Do baseline estrogen and testosterone affect lower urinary tract symptoms (LUTS) prior to or after pharmacologic treatment with tadalafil?

Abstract: Little is known about how total testosterone and estradiol-17β influence lower urinary tract symptoms (LUTS) in men with benign prostatic hypertrophy (BPH). We analyzed data from a subset of men aged ≥18 years randomized to tadalafil 5 mg once-daily or placebo who had ≥6 month history of LUTS and an International Prostate Symptom Score (IPSS)≥13 enrolled in one of three randomized, placebo-controlled tadalafil clinical trials (N = 958). Three specific aims were addressed, as follows: (i) To characterize enrolled men by treatment randomization and testosterone level; (ii) to assess cross-sectional associations of estradiol-17β, testosterone, and LUTS prior to treatment with tadalafil; and, (iii) to assess longitudinal associations between baseline estradiol-17β and testosterone and improvements or worsening of LUTS during a 12-week period of tadalafil or placebo administration. LUTS were assessed by total IPSS, IPSS voiding sub-score (IPSS-V) and IPSS storage sub-score (IPSS-S) for cross-sectional analyses, and change in total IPSS (ΔIPSS), ΔIPSS-V, and ΔIPSS-S between baseline and 12-week visit for longitudinal analyses. Correlation analyses and linear regression examined associations. Baseline testosterone was not significantly associated with IPSS. In contrast, estradiol-17β was inversely correlated with IPSS (r = -0.08; p < 0.05) and IPSS-S (r = -0.14; p < 0.05). Tadalafil treatment resulted in greater IPSS improvements in men with lower baseline estradiol-17β versus those with higher baseline estradiol-17β. Lower baseline estradiol-17β was significantly associated with modestly improved ΔIPSS-V (p = 0.04) and Δtotal IPSS (p = 0.05) but not with ΔIPSS-S, following treatment which may substantiate the role of bladder dysfunction because of nerve and smooth muscle changes in the bladder in addition to benign prostatic enlargement in LUTS. Circulating baseline testosterone did not predict ΔIPSS. Men with lower baseline estradiol-17β levels showed greater responsiveness to tadalafil 5 mg treatment than those with higher baseline estradiol-17β levels when responsiveness was measured using total IPSS and IPSS-V.

Egan|K B|KB|
Miner|M M|MM|
Suh|M|M|
McVary|K|K|
Ni|X|X|
Roehrborn|C G|CG|
Wittert|G|G|
Wong|D G|DG|
Rosen|R C|RC|

testosterone
lower urinary tract symptoms
tadalafil
International Prostate Symptom Score
benign prostatic hyperplasia
estradiol


Genome-wide association study of sepsis in extremely premature infants.

Abstract:
OBJECTIVE
To identify genetic variants associated with sepsis (early-onset and late-onset) using a genome-wide association (GWA) analysis in a cohort of extremely premature infants.

STUDY DESIGN
Previously generated GWA data from the Neonatal Research Network's anonymised genomic database biorepository of extremely premature infants were used for this study. Sepsis was defined as culture-positive early-onset or late-onset sepsis or culture-proven meningitis. Genomic and whole-genome-amplified DNA was genotyped for 1.2 million single-nucleotide polymorphisms (SNPs); 91% of SNPs were successfully genotyped. We imputed 7.2 million additional SNPs. p Values and false discovery rates (FDRs) were calculated from multivariate logistic regression analysis adjusting for gender, gestational age and ancestry. Target statistical value was p<10-5. Secondary analyses assessed associations of SNPs with pathogen type. Pathway analyses were also run on primary and secondary end points.

RESULTS
Data from 757 extremely premature infants were included: 351 infants with sepsis and 406 infants without sepsis. No SNPs reached genome-wide significance levels (5×10-8); two SNPs in proximity to FOXC2 and FOXL1 genes achieved target levels of significance. In secondary analyses, SNPs for ELMO1, IRAK2 (Gram-positive sepsis), RALA, IMMP2L (Gram-negative sepsis) and PIEZO2 (fungal sepsis) met target significance levels. Pathways associated with sepsis and Gram-negative sepsis included gap junctions, fibroblast growth factor receptors, regulators of cell division and interleukin-1-associated receptor kinase 2 (p values<0.001 and FDR<20%).

CONCLUSIONS
No SNPs met genome-wide significance in this cohort of extremely low birthweight infants; however, areas of potential association and pathways meriting further study were identified.

D048868:Adaptor Proteins, Signal Transducing

extreme prematurity
Genetics
ELBW
infection


Informing the future of PrEP navigation: Findings from a five-site cluster evaluation.

Abstract: The PrEP (pre-exposure prophylaxis) Implementation, Data to Care and Evaluation (PrIDE) demonstration project funded 12 health departments (HD) (2016-2019) to scale up PrEP among sexual minorities at risk for HIV. Each health department (HD) conducted an evaluation of at least one local strategy, and, to maximize crossvalidation, an adapted cluster evaluation approach was employed. As a result, five HDs with similar evaluation questions regarding PrEP navigation were identified. Overall, PrEP navigation fit in well with HD clinics and community-based organizations. A hybrid model of patient, peer, and systems navigation linking clients to PrEP and social services was commonly used. Although there were no differences by setting regarding linking clients to PrEP providers, one HD demonstrated that having all PrEP services in the same location contributed the most to PrEP uptake. Navigator skill for case management and rapport building facilitated navigation, whereas staff turnover and lack of client health insurance were challenges. While one HD in a non-Medicaid expansion state was affected by health insurance issues the most, another HD demonstrated that providing payment assistance increased client PrEP use. The findings pinpoint PrEP navigation hybrid modality and having health insurance as promising strategies to increase PrEP uptake among priority groups.

Salabarría-Peña|Yamir|Y|
Douglas|Chelsea|C|
Brantley|Meredith|M|
Johnson|Amy K|AK|

PrEP
PrEP navigation
Navigation
Cluster evaluation
HIV
Systems navigation
MSM
Patient navigation
Peer navigation
Transgender


Storkhead box 2 and melanoma inhibitory activity promote oral squamous cell carcinoma progression.

Abstract:
BACKGROUND
Storkhead box protein 2 (STOX2) is a transcriptional factor associated with pre-eclampsia with fetal growth restriction. We recently reported that melanoma inhibitory activity (MIA) promotes oral squamous cell carcinoma (OSCC) progression. However, the relationship between STOX2 and MIA remains unknown in malignancies.

METHODS
We used immunohistochemistry and PCR to investigate MIA and STOX2 expression in OSCC. We also performed functional analysis in human OSCC cells.

RESULTS
MIA and STOX2 mRNA levels were higher in OSCCs than in normal oral epithelial cells, and upregulation of STOX2 was significantly correlated with overexpression of MIA. Immunostaining for STOX2 was associated with nodal metastasis (P = 0.0002) and MIA expression (P < 0.0001). Furthermore, MIA expression (P = 0.0035) and STOX2 expression (P = 0.0061) were associated with poor outcome in OSCCs. In vitro analysis using OSCC cells revealed that MIA increased expression of STOX2 by paracrine manner. Moreover, STOX2 accelerated OSCC cell growth, invasion, suppressed apoptosis, and enhanced resistance to paclitaxel, cisplatin, and 5-FU.

CONCLUSIONS
Our results suggest that MIA-STOX2 signaling may be a useful diagnostic and therapeutic target in OSCCs.

Sasahira|Tomonori|T|
Nishiguchi|Yukiko|Y|
Fujiwara|Rina|R|
Kurihara|Miyako|M|
Kirita|Tadaaki|T|
Bosserhoff|Anja Katrin|AK|
Kuniyasu|Hiroki|H|

D000077195:Squamous Cell Carcinoma of Head and Neck

STOX2
MIA
metastasis
multidrug resistance
oral cancer


A Systematic Review of ASL Perfusion MRI in Mild TBI.

Abstract: Mild traumatic brain injury (mTBI) is a major public health concern. Cerebrovascular alterations play a significant role in the evolution of injury sequelae and in the process of post-traumatic brain repair. Arterial spin labeling (ASL) is an advanced perfusion magnetic resonance imaging technique that permits noninvasive quantification of cerebral blood flow (CBF). This is the first systematic review of ASL research findings in patients with mTBI. Our approach followed the American Academy of Neurology (AAN) and PRISMA guidelines. We searched Ovid/MEDLINE, Web of Science, Scopus, and the Cochrane Index for relevant articles published as of February 20, 2020. Full-text results were combined into Rayyan software for further evaluation. Data extraction, including risk of bias ratings, was performed using American Academy of Neurology's four-tiered classification scheme. Twenty-three articles met inclusion criteria comprising data on up to 566 mTBI patients and 654 control subjects. Of the 23 studies, 18 reported some type of regional CBF abnormality in mTBI patients at rest or during a cognitive task, with more findings of decreased than increased CBF. The evidence supports the conclusion that mTBI likely causes ASL-derived CBF anomalies. However, synthesis of findings was challenging due to substantial methodological variations across studies and few studies with low risk of bias. Thus, larger-scale prospective cohort studies are needed to more definitively chart the course of CBF changes in humans after mTBI and to understand how individual difference factors contribute to post-injury CBF changes.

Mild traumatic brain injury
Arterial spin labeling
Magnetic resonance imaging
Cerebral blood flow
Concussion


The Influence of Smoking on the Peri-Implant Microbiome.

Abstract: Smokers are at high risk for 2 bacterially driven oral diseases: peri-implant mucositis and peri-implantitis. Therefore, the purpose of this investigation was to use a deep-sequencing approach to identify the effect of smoking on the peri-implant microbiome in states of health and disease. Peri-implant biofilm samples were collected from 80 partially edentulous subjects with peri-implant health, peri-implant mucositis, and peri-implantitis. Bacterial DNA was isolated and 16S ribsomal RNA gene libraries sequenced using 454-pyrosequencing targeting the V1 to V3 and V7 to V9 regions. In total, 790,692 classifiable sequences were compared against the HOMD database for bacterial identification. Community-level comparisons were carried out using UniFrac and nonparametric tests. Microbial signatures of health in smokers exhibited lower diversity compared to nonsmokers, with significant enrichment for disease-associated species. Shifts from health to mucositis were accompanied by loss of several health-associated species, leading to a further decrease in diversity. Peri-implantitis did not differ significantly from mucositis in species richness or evenness. In nonsmokers, by contrast, the shift from health to mucositis resembled primary ecological succession, with acquisition of several species without replacement of pioneer organisms, thereby creating a significant increase in diversity. Again, few differences were detected between peri-implantitis and mucositis. Thus, our data suggest that smoking shapes the peri-implant microbiomes even in states of clinical health, by supporting a pathogen-rich community. In both smokers and nonsmokers, peri-implant mucositis appears to be a pivotal event in disease progression, creating high-at-risk-for-harm communities. However, ecological succession follows distinctly divergent pathways in smokers and nonsmokers, indicating a need for personalized therapeutics for control and prevention of disease in these 2 cohorts.

Tsigarida|A A|AA|
Dabdoub|S M|SM|
Nagaraja|H N|HN|
Kumar|P S|PS|

peri-implantitis
biofilms
16S ribosomal RNA
high-throughput nucleotide sequencing
microbiota
tobacco


The Use of Flow Diverter in Ruptured, Dissecting Intracranial Aneurysms of the Posterior Circulation.

Abstract:
OBJECTIVE
Acute dissecting aneurysms of the posterior circulation are a rare cause of subarachnoid hemorrhage. Established endovascular treatment options include parent artery occlusion and stent-assisted coiling, but appear to be associated with an increased risk of ischemic stroke. Vessel reconstruction with flow diverters is an alternative treatment option; however, its safety and efficacy in the acute stage remains unclear.

METHODS
This is a multicentric retrospective analysis of 15 consecutive acutely ruptured dissecting posterior circulation aneurysms treated with flow diverters. The primary end point was favorable aneurysm occlusion, defined as OKM C1-3 and D (O'Kelly Marotta scale). Secondary end points were procedure-related complications and clinical outcome.

RESULTS
Nine of 15 aneurysms (60%) arose from the intradural portion of the vertebral artery, 3 were located on the posterior inferior cerebellar artery and 1 each on the anterior inferior cerebellar artery, posterior cerebral artery, and basilar artery. Flow diverter placement was technically successful in 14 of 15 cases (93%). After endovascular treatment, none of the ruptured aneurysms rebled. Median clinical follow-up was 217 days and median angiographic follow-up was 203 days. Favorable occlusion was observed in 7 of 14 aneurysms (50%) directly after flow diverter placement; of those, 5 were completely occluded (36%). Seven patients (47%) with poor-grade subarachnoid hemorrhage died in the acute phase. Favorable clinical outcome (modified Rankin scale ≤2) was observed in 4 of 15 patients (27%) and a moderate outcome (modified Rankin scale 3/4) was observed in 5 of 15 patients (33%). All aneurysms showed complete occlusion at follow-up.

CONCLUSIONS
Flow diverters might be a feasible, alternative treatment option for acutely ruptured dissecting posterior circulation aneurysms and may effectively prevent rebleeding. Larger cohort studies are required to validate these results.

Maus|Volker|V|
Mpotsaris|Anastasios|A|
Dorn|Franziska|F|
Möhlenbruch|Markus|M|
Borggrefe|Jan|J|
Stavrinou|Pantelis|P|
Abdullayev|Nuran|N|
Barnikol|Utako Birgit|UB|
Liebig|Thomas|T|
Kabbasch|Christoph|C|

Flow diverter
Intracranial aneurysms
Acutely dissecting aneurysms
SAH


Developing future medical educators in an Australian medical program: supervisors' reflections on the first four years of MD Professional Project implementation.

Abstract:
BACKGROUND
Increasingly, professional bodies expect doctors to not only provide patient care but also educate students, trainees and patients. Few medical students, however, receive formal tuition in terms of the theory and practice of medical education. A curriculum restructure from an MBBS to a Doctor of Medicine (MD) program provided an opportunity to develop three Masters streams: Clinical research, Capstones and educational Professional Projects. This submission describes how one Australian medical school is preparing some students for their future roles as medical educators through MD Professional Projects.

DESIGN
Framed by the 12 roles of the medical 'teacher', most students undertaking these projects take on Resource Developer (including simulation) and Assessor roles. For those choosing resource development (excluding simulation) or assessment, the Association for Medical Education (AMEE) Student Essential Skills in Medical Education (ESME) Course is compulsory. For those choosing educational research, the ESME Course is optional.

OUTCOMES
By December 2020, four MD cohorts will have graduated with 69 students having undertaken educational MD Professional Projects, with fifty-one completing the ESME Course. MD students have created a range of resources for the curriculum, their colleagues and the local healthcare community. In addition to the expected learning we identified additional value-added outcomes for learners (e.g. skill development), the curriculum (e.g. areas of difficulty), academic supervisors' roles (e.g. role-modelling) and for the health care community (e.g. as expert reviewers).

CONCLUSIONS
Engaging in scholarly activities such the ESME Course and developing learning resources not only provided MD students with a more in-depth theoretical knowledge in a range of clinical areas, but also developed skills that would prepare them for their future roles as medical educators. As supervisors, we identified the value these projects add to the broader health community as well as personal and professional benefits for ourselves.

Association for Medical Education in Europe (AMEE)


Natural history of ovarian cancer.

Abstract: Ovarian cancer is a disease laden with paradigms, and it is a serious health problem. It is important to know its natural history, as it is multifactorial in origin, and also to understand its behaviour given its risk factors which can lead to death from metastasis in patients. It continues to be a challenge for oncologists. An analytical literature review was performed to update the latest concepts of its origin, evolution, risk factors, pre-clinical horizon, and its clinical manifestations; until the death of the patient.


Effectiveness of a telephone intervention based on motivational health coaching for improving the mental health of caregivers of people with dementia: A randomised controlled trial.

Abstract:
OBJECTIVES
Caring for a family member with dementia is considered one of the activities with the greatest negative impact on a person's mental health. Developing long-lasting and effective strategies is a challenge for caregivers. This study sought to evaluate the impact of an intervention based on a programme of motivational coaching delivered by telephone in a group of caregivers of patients with dementia compared to a control group.

METHODS
A randomised controlled trial with a control group and an intervention group. (CONSORT guidelines were used). Telephone calls were made during six weeks, involving a process of coaching and motivational interviews. The following variables were measured in caregivers: self-efficacy of caring, depression, perceived stress, frequency of problematic behaviours and dysfunctional thoughts. Assessments were conducted at three time points: baseline, post-intervention and three months' post-intervention.

RESULTS
In total, 106 caregivers participated (53 subjects in the control group and 53 in the intervention group). Statistically significant differences (ANCOVA) were found between both groups for the self-efficacy and stress variables, with improved results in the intervention group (p < .01). Furthermore, statistically significant differences were found in the intervention group between the baseline and post-intervention assessments, with improvements in self-efficacy, decreased stress and decreased dysfunctional thoughts (p < .05). The results were maintained over time for both groups.

CONCLUSIONS
An intervention based on telephone calls using a health coaching approach with motivational interviewing appears to be effective for the improvement of self-efficacy and mental health of caregivers of people with moderate dementia. Furthermore, these effects appear to be maintained over time.

coaching
caregivers
dementia
randomised controlled trial
motivational interviewing
eHealth
older people


Feasibility and acceptance of the CaringGuidance web-based, distress self-management, psychoeducational program initiated within 12 weeks of breast cancer diagnosis.

Abstract:
OBJECTIVE
Limited clinical resources create barriers to quality management of cancer-related distress. CaringGuidance After Breast Cancer Diagnosis is a web-based, patient-controlled, psychoeducational program of cognitive-behavioral, coping and problem-solving strategies aimed at early post-diagnosis distress reduction without clinical resources. This study evaluated the feasibility of recruiting and retaining newly diagnosed women to 12 weeks of CaringGuidance and program acceptance.

METHODS
Women with stage 0 to II breast cancer diagnosed within the prior 3 months were recruited from clinics and communities in four states, from 2013 to 2015 and randomized to 12 weeks of CaringGuidance plus usual care (n = 57) or usual care alone (n = 43). Recruitment, retention, and program use were tracked. Using standard and study-derived measures, demographic and psychological variables were assessed at baseline and monthly and program satisfaction at 12 weeks.

RESULTS
Of 139 women screened, 100 enrolled, five withdrew, and 12 were lost to follow-up (83% retention rate). Total program engagement was positively associated with greater baseline intrusive/avoidant thoughts. Intervention participants (92%) believed CaringGuidance would benefit future women and was easy to use. Sixty-six percent believed CaringGuidance helped them cope. Women used program content to change thoughts (49%) or behaviors (40%). Stress in the previous year was positively associated with reports that CaringGuidance was reassuring and helpful.

CONCLUSIONS
Feasibility and acceptance of CaringGuidance was demonstrated pointing to the program's potential as a cancer-distress self-management intervention. Future research will explore program feasibility and acceptability in other regions of the United States, leading to clinical implementation trials.

Lally|Robin M|RM|0000-0003-0323-127X
Bellavia|Gina|G|
Gallo|Steven|S|
Kupzyk|Kevin|K|
Helgeson|Vicki|V|
Brooks|Catherine|C|
Erwin|Deborah|D|
Brown|Jean|J|

D010342:Patient Acceptance of Health Care

self-management
cancer
breast neoplasm
eHealth
oncology
psychological adjustment


Isolation and characterization of Bacillus subtilis CH16 strain from chicken gastrointestinal tracts for use as a feed supplement to promote weight gain in broilers.

Abstract: Spore-forming bacterial strains were isolated from chicken gastrointestinal tracts to develop a heat-stable feed supplement that promotes weight gain in broilers. Seven Bacillus strains having more than 90% sporulation were screened from the isolates and identified to be closely related with Bacillus subtilis and Bacillus licheniformis. Of the seven strains, B. subtilis CH16 was selected to develop a feed supplement for broilers, because it formed 100% heat-stable spores, grew rapidly at 42°C and quickly formed a biofilm. In large-scale trials in broilers (n ≥ 1150 per group), the group fed CH16 (3 × 10(6) CFU g(-1) pellet) showed higher average daily gain (ADG = 61·16) and lower food conversion ratio (FCR = 1·696) than did the group fed B. licheniformis CH22 (ADG = 57·10 and FCR = 1·792), the group fed B. subtilis HU58 (ADG = 51·90 and FCR = 1·868), BioPlus group (ADG = 59·32 and FCR = 1·807) and the control group (ADG = 56·02 and FCR = 1·880). In conclusion, CH16 spores significantly increased ADG by 9·17% and reduced FCR by 9·79% in broilers. The result supports the use of B. subtilis CH16 of chicken intestinal origin as a feed supplement that promote weight gain in broilers. Significance and impact of the study: This study reports screening of Bacillus strains isolated from chicken gastrointestinal tracts for development of a feed supplement that promote weight gain in broilers. Of the seven Bacillus isolates with high sporulation efficiency (≥90%), Bacillus subtilis CH16 strain showed the best growth and biofilm formation at body temperature of broilers (42°C). In large-scale trials in broilers (n ≥ 1150 per group), CH16 spores induced a 9·17% increase in daily weight gain (ADG) and a 9·79% reduction in FCR while the commercial BioPlus(®) YC induced only a 5·89% increase in ADG and a 3·88% reduction in FCR.

Nguyen|A T V|AT|
Nguyen|D V|DV|
Tran|M T|MT|
Nguyen|L T|LT|
Nguyen|A H|AH|
Phan|T-N|TN|

D000821:Animal Feed
D000818:Animals
D001412:Bacillus subtilis
D001483:Base Sequence
D018441:Biofilms
D002645:Chickens
D027081:DNA Gyrase
D004269:DNA, Bacterial
D019587:Dietary Supplements
D041981:Gastrointestinal Tract
D008460:Meat
D019936:Probiotics
D012336:RNA, Ribosomal, 16S
D017422:Sequence Analysis, DNA
D013171:Spores, Bacterial
D015430:Weight Gain

gastrointestinal tract
feed supplement
weight gain
broiler
Bacillus spore
probiotic


Lamprey Immune Protein Mediates Apoptosis of Lung Cancer Cells Via the Endoplasmic Reticulum Stress Signaling Pathway.

Abstract: Lamprey immune protein (LIP), a novel protein derived from the Lampetra japonica, has been shown to exert efficient tumoricidal actions without concomitant damage to healthy cells. Our study aimed to ascertain the mechanisms by which LIP inhibits lung cancer cells, thus delineating potential innovative therapeutic strategies. LIP expression in lung cancer cells was evaluated by western blotting and immunohistochemistry. Functional assays, such as high-content imaging, 3D-structured illumination microscopy (3D-SIM) imaging, flow cytometry, and confocal laser scanning microscopy, were performed to examine the proliferation and lung cancer cell apoptosis. Tumor xenograft assays were performed using an in vivo imaging system. We observed that LIP induces the decomposition of certain lung cancer cell membranes by destroying organelles such as the microtubules, mitochondria, and endoplasmic reticulum (ER), in addition to causing leakage of cytoplasm, making the maintenance of homeostasis difficult. We also demonstrated that LIP activates the ER stress pathway, which mediates lung cancer cell apoptosis by producing reactive oxygen species (ROS). In addition, injection of LIP significantly retarded the tumor growth rate in nude mice. Taken together, these data revealed a role of LIP in the regulation of lung cancer cell apoptosis via control of the ER stress signaling pathway, thus revealing its possible application in lung cancer treatment.

Song|Xiaoping|X| Xu|Xiangting|X| Lu|Jiali|J| Chi|Xiaoyuan|X| Pang|Yue|Y| Li|Qingwei|Q|

lamprey
apoptosis
lung cancer
endoplasmic reticulum stress
LIP
cytotoxicity


Risk factors associated with musculoskeletal disorders of the neck and shoulder in the personnel of Kerman University of Medical Sciences.

Abstract:
BACKGROUND
Musculoskeletal disorders (MSDs) of the neck and shoulder are the most common and most influential factors causing disorder in the performance and absenteeism of work in administrative personnel.

AIM
To identify risk factors which affect musculoskeletal disorders of neck and shoulder areas in headquarters staff of Kerman University of Medical Sciences.

METHODS
The present cross-sectional study was conducted in 2015 on 282 headquarters personnel of Kerman University of Medical Sciences (Kerman, Iran). The desired headquarters staff were selected from seven Deputy Vice-Chancellors of Kerman University of Medical Sciences, including Deputy of Health; Deputy of Treatment; Deputy of Education; Deputy of Students and Cultural Affairs; Deputy of Food and Drugs; Deputy of Management Development and Resource Planning; Deputy of Research and Technology, and data were gathered by using a standard Nordic musculoskeletal questionnaire NMQ (Nordic) and were analyzed by using SPSS version 16. The impact of various factors on the most common complications (neck and shoulder pains) was analyzed separately through logistic regression analysis and detailed Odds Ratio (OR) was calculated for each individual.

RESULTS
The occurrence of neck and shoulder pains in headquarters staff were 42.14% and 40.71%, respectively. In the prevalence of neck pain variables such as marital status (single than married p=0.01, OR=0.24), work experience (p=0.03, OR=1.07 ), education (bachelor's degree and lower than master's degree and higher p=0.003, OR=2.69), right / left-handedness (left than right p=0.03, OR=0.33), weight (p=0.04, OR=1.04), place of work (p<0.05); as well as in the prevalence of shoulder pain variables such as marital status (single than married p=0.04, OR=0.48), work experience (p=0.01, OR=1.20), education (bachelor and lower than master and higher p=0.04, OR=1.97), right / left handedness (left than right p=0.01, OR=0.42), age (p=0.02, OR=1.05), and gender (male than female p=0.03, OR=0.65) affected.

CONCLUSION
The results of this study showed that the prevalence of neck and shoulder pains is influenced by various risk factors and some of which were identified and an amount of their influence in this study was found. Therefore, it is suggested by considering the risk factors and planning control programs, a major step is taken in reducing the musculoskeletal disorders of office staff.

Madadizadeh|Farzan|F| Vali|Leila|L| Rafiei|Sima|S| Akbarnejad|Zahra|Z|

Risk factor
Musculoskeletal disorders
Shoulder pain
Neck pain
Office staff


The proximal tubule is the primary target of injury and progression of kidney disease: role of the glomerulotubular junction.

Abstract: There is an alarming global increase in the incidence of end-stage kidney disease, for which early biomarkers and effective treatment options are lacking. Largely based on the histology of the end-stage kidney and on the model of unilateral ureteral obstruction, current investigation is focused on the pathogenesis of renal interstitial fibrosis as a central mechanism in the progression of chronic kidney disease (CKD). It is now recognized that cumulative episodes of acute kidney injury (AKI) can lead to CKD, and, conversely, CKD is a risk factor for AKI. Based on recent and historic studies, this review shifts attention from the glomerulus and interstitium to the proximal tubule as the primary sensor and effector in the progression of CKD as well as AKI. Packed with mitochondria and dependent on oxidative phosphorylation, the proximal tubule is particularly vulnerable to injury (obstructive, ischemic, hypoxic, oxidative, metabolic), resulting in cell death and ultimately in the formation of atubular glomeruli. Animal models of human glomerular and tubular disorders have provided evidence for a broad repertoire of morphological and functional responses of the proximal tubule, revealing processes of degeneration and repair that may lead to new therapeutic strategies. Most promising are studies that encompass the entire life cycle from fetus to senescence, recognizing epigenetic factors. The application of techniques in molecular characterization of tubule segments and the development of human kidney organoids may provide new insights into the mammalian kidney subjected to stress or injury, leading to biomarkers of early CKD and new therapies.

D000818:Animals
D006801:Humans
D007674:Kidney Diseases
D007678:Kidney Glomerulus
D007684:Kidney Tubules
D007687:Kidney Tubules, Proximal

proximal tubule
unilateral ureteral obstruction
chronic kidney disease
acute kidney injury
atubular glomeruli


Soft Tissue Management in Facial Trauma.

Abstract: The management of soft tissue injury after facial trauma poses unique challenges to the plastic surgeon, given the specialized nature of facial tissue and the aesthetic importance of the face. The general principles of trauma management and wound care are applied in all cases. The management of severe injuries to the face is discussed in relation to the location and the mechanism of injury. Facial transplants have arisen in the past decade for the management of catastrophic soft tissue defects, although high morbidity and mortality after these non-life-saving operations must be considered in patient selection.

Braun|Tara L|TL|
Maricevich|Renata S|RS|

facial trauma
facial transplants
facial animal bites
soft tissue reconstruction


An iterative learning strategy for the auto-tuning of the feedforward and feedback controller in type-1 diabetes.

Abstract: This paper proposes a scheme for the control of the blood glucose in subjects with type-1 diabetes mellitus based on the subcutaneous (s.c.) glucose measurement and s.c. insulin administration. The tuning of the controller is based on an iterative learning strategy that exploits the repetitiveness of the daily feeding habit of a patient. The control consists of a mixed feedback and feedforward contribution whose parameters are tuned through an iterative learning process that is based on the day-by-day automated analysis of the glucose response to the infusion of exogenous insulin. The scheme does not require any a priori information on the patient insulin/glucose response, on the meal times and on the amount of ingested carbohydrates (CHOs). Thanks to the learning mechanism the scheme is able to improve its performance over time. A specific logic is also introduced for the detection and prevention of possible hypoglycaemia events. The effectiveness of the methodology has been validated using long-term simulation studies applied to a set of nine in silico patients considering realistic uncertainties on the meal times and on the quantities of ingested CHOs.

feedback control
type-1 diabetes
artificial pancreas
iterative learning control
physiological model


An audit to assess the perspectives of U.S. wound care specialists regarding the importance of proteases in wound healing and wound assessment.

Abstract: Chronic wounds represent an aberrant biochemistry that creates a toxic proteolytic milieu which can be detrimental to the healing process. Rebalancing the wound microenvironment and addressing elevated protease activity (EPA) could therefore help facilitate healing. To understand how clinicians currently diagnose and manage excessive proteolytic activity, 183 survey responses from US wound specialists were collated and analysed to find out their perceptions on the role of proteases. The majority of respondents (>98%) believed proteases were important in wound healing and that a point-of-care (POC) protease test could be useful. This study yielded a low response rate (7.1%, n = 183); however, there were adequate data to draw significant conclusions. Specialists perceived that fibrin, slough, granulation tissue and rolled wound edges could indicate EPA. About 43% of respondents, however, failed to give a correct response when asked to review photographs to determine if excessive protease activity was present, and the perceived visual signs for EPA did not correlate with the wounds that had EPA; no statistical differences between professions were observed. Respondents chose debridement, wound cleansing and advanced therapies as important in reducing excessive protease activity. It was concluded that specialists have a need for POC diagnostic tests. On the basis of the responses to wound photos, it was determined that there were no visual cues clinicians could use in determining excessive protease activity. Additional research is recommended to evaluate the efficacy of a POC diagnostic test for protease activity and the treatments and therapies applied when EPA is found.

Snyder|Robert J|RJ|
Cullen|Breda|B|
Nisbet|Lorraine T|LT|

Wound care
Proteases
Human neutrophil elastase
Matrix metalloproteases
Point‐of‐care diagnostic tests
Serine proteases


Corrigendum: Genetic Mapping of a Light-Dependent Lesion Mimic Mutant Reveals the Function of Coproporphyrinogen III Oxidase Homolog in Soybean.

Abstract: [This corrects the article DOI: 10.3389/fpls.2020.00557.].

Ma|Jingjing|J|
Yang|Suxin|S|
Wang|Dongmei|D|
Tang|Kuanqiang|K|
Feng|Xing Xing|XX|
Feng|Xian Zhong|XZ|

coproporphyrinogen III oxidase
Glycine max
lesion mimic mutant 2
pathogen resistance
tetrapyrrole biosynthesis


Transcription Factor Hepatocyte Nuclear Factor-1β Regulates Renal Cholesterol Metabolism.

Abstract: HNF-1β is a tissue-specific transcription factor that is expressed in the kidney and other epithelial organs. Humans with mutations in HNF-1β develop kidney cysts, and HNF-1β regulates the transcription of several cystic disease genes. However, the complete spectrum of HNF-1β-regulated genes and pathways is not known. Here, using chromatin immunoprecipitation/next generation sequencing and gene expression profiling, we identified 1545 protein-coding genes that are directly regulated by HNF-1β in murine kidney epithelial cells. Pathway analysis predicted that HNF-1β regulates cholesterol metabolism. Expression of dominant negative mutant HNF-1β or kidney-specific inactivation of HNF-1β decreased the expression of genes that are essential for cholesterol synthesis, including sterol regulatory element binding factor 2 (Srebf2) and 3-hydroxy-3-methylglutaryl-CoA reductase (Hmgcr). HNF-1β mutant cells also expressed lower levels of cholesterol biosynthetic intermediates and had a lower rate of cholesterol synthesis than control cells. Additionally, depletion of cholesterol in the culture medium mitigated the inhibitory effects of mutant HNF-1β on the proteins encoded by Srebf2 and Hmgcr, and HNF-1β directly controlled the renal epithelial expression of proprotein convertase subtilisin-like kexin type 9, a key regulator of cholesterol uptake. These findings reveal a novel role of HNF-1β in a transcriptional network that regulates intrarenal cholesterol metabolism.

Aboudehen|Karam|K|
Kim|Min Soo|MS|
Mitsche|Matthew|M|
Garland|Kristina|K|
Anderson|Norma|N|
Noureddine|Lama|L|
Pontoglio|Marco|M|
Patel|Vishal|V|
Xie|Yang|Y|
DeBose-Boyd|Russell|R|
Igarashi|Peter|P|

D051539:Hepatocyte Nuclear Factor 1-beta

transcription factors
lipids
polycystic kidney disease


BCL2 and related prosurvival proteins require BAK1 and BAX to affect autophagy.

Abstract: It is widely thought that prosurvival BCL2 family members not only inhibit apoptosis, but also block autophagy by directly binding to BECN1/Beclin 1. To distinguish whether BCL2, BCL2L1/BCL-XL, or MCL1 influence autophagy directly, or indirectly, through their effects on apoptosis, we compared normal cells to those lacking BAX and BAK1. In cells able to undergo mitochondria-mediated apoptosis, inhibiting the endogenous prosurvival BCL2 family members induces both autophagy and cell death, but when BAX and BAK1 are deleted, neither inhibiting nor overexpressing BCL2, BCL2L1, or MCL1 causes any detectable effect on LC3B lipidation, LC3B turnover, or autolysosome formation. These results show that prosurvival BCL2 family members influence autophagy only indirectly, by inhibiting activation of BAX and BAK1.

D050998:bcl-2 Homologous Antagonist-Killer Protein


Shoulder activity level is not associated with the severity of symptomatic, atraumatic rotator cuff tears in patients electing nonoperative treatment.

Abstract:
BACKGROUND
Patient activity level may be an important prognostic variable relating to outcomes in patients with shoulder disorders. Little is known about the predictors of activity level in patients with shoulder disorders.

HYPOTHESIS
Tear size and patient variables would be predictive of shoulder activity level in a cohort of patients who have selected initial nonoperative treatment for a symptomatic, atraumatic rotator cuff tear on magnetic resonance imaging (MRI).

STUDY DESIGN
Cross-sectional study; Level of evidence, 3.

METHODS
Patients with an atraumatic rotator cuff tear on MRI were prospectively enrolled in the Multicenter Orthopaedic Outcomes Network (MOON) shoulder study of nonoperative treatment. As part of routine data collection, these patients were asked to complete a previously validated shoulder activity scale. A regression analysis was performed to assess the association of shoulder activity level to rotator cuff tear characteristics, including tendon involvement and retraction, and patient factors such as age, sex, smoking, and occupation.

RESULTS
A total of 434 patients (220 male, 214 female) with a mean age of 62.7 years (range, 31-90 years) completed the activity scale. Shoulder activity was not associated with severity of the rotator cuff tear, but it was negatively associated with age (P = .0001) and female sex (P = .001). The only other factor associated with shoulder activity level in this cohort was occupation (P = .0006).

CONCLUSION
Shoulder activity level in patients with an atraumatic rotator cuff tear confirmed on MRI is not associated with severity of the tear but is affected by age, sex, and occupation.

Brophy|Robert H|RH|
Dunn|Warren R|WR|
Kuhn|John E|JE|
|||

shoulder
activity level
rotator cuff tear


Correlation of foot posture index with plantar pressure and radiographic measurements in pediatric flatfoot.

Abstract:
OBJECTIVE
To investigate the correlation between the Foot Posture Index (FPI) (including talar head palpation, curvature at the lateral malleoli, inversion/eversion of the calcaneus, talonavicular bulging, congruence of the medical longitudinal arch, and abduction/adduction of the forefoot on the rare foot), plantar pressure distribution, and pediatric flatfoot radiographic findings.

METHODS
Nineteen children with flatfoot (age, 9.32±2.67 years) were included as the study group. Eight segments of plantar pressure were measured with the GaitView platform pressure pad and the FPI was measured in children. The four angles were measured on foot radiographs. We analyzed the correlation between the FPI, plantar pressure characteristics, and the radiographic angles in children with flatfoot.

RESULTS
The ratio of hallux segment pressure and the second through fifth toe segment pressure was correlated with the FPI (r=0.385, p=0.017). The FPI was correlated with the lateral talo-first metatarsal angle (r=0.422, p=0.008) and calcaneal pitch (r=-0.411, p=0.01).

CONCLUSION
Our results show a correlation between the FPI and plantar pressure. The FPI and pediatric flatfoot radiography are useful tools to evaluate pediatric flatfoot.

Lee|Jung Su|JS|
Kim|Ki Beom|KB|
Jeong|Jin Ook|JO|
Kwon|Na Yeon|NY|
Jeong|Sang Mi|SM|


Genetic Characterization of Middle East Respiratory Syndrome Coronavirus, South Korea, 2018.

Abstract: We evaluated genetic variation in Middle East respiratory syndrome coronavirus (MERS-CoV) imported to South Korea in 2018 using specimens from a patient and isolates from infected Caco-2 cells. The MERS-CoV strain in this study was genetically similar to a strain isolated in Riyadh, Saudi Arabia, in 2017.

Chung|Yoon-Seok|YS|
Kim|Jeong Min|JM|
Man Kim|Heui|H|
Park|Kye Ryeong|KR|
Lee|Anna|A|
Lee|Nam-Joo|NJ|
Kim|Mi-Seon|MS|
Kim|Jun Sub|JS|
Kim|Chi-Kyeong|CK|
Lee|Jae In|JI|
Kang|Chun|C|

D065207:Middle East Respiratory Syndrome Coronavirus

Middle East respiratory syndrome
coronavirus
South Korea
Caco-2 cells
S gene
spike gene
sputum
throat swab
viruses


Green synthesis of silver nanoparticles using Annona squamosa L. seed extract: characterization, photocatalytic and biological activity assay.

Abstract: The aqueous seed extract of Annona squamosa L. was used as a reducing and stabilizing agent for the synthesis of silver nanoparticles (AgNPs). The formation of AgNPs in aqueous silver nitrate solution after the addition of the extract was indicated by a colour change from pale yellow to dark brown corresponding to a λmax at 430 nm. The phytochemicals in the extract, responsible for efficient capping and stabilization of the nanoparticles, were identified by FTIR. Powder XRD pattern demonstrated the polycrystalline nature of the AgNPs. TEM image confirmed that AgNPs were spherical in shape and the average particle size was found to be 22 nm. Further, the nanoparticles exhibited good catalytic activity towards the degradation of coomassie brilliant blue dye and demonstrated significant antibacterial activity. Their larvicidal activity against mosquito larvae showed a LC50 value 22.44 μg/mL against III instars. In addition, AgNPs positively influenced the germination of chickpea seeds.

Jose|Vimala|V|
Raphel|Lidiya|L|
Aiswariya|K S|KS|
Mathew|Paulson|P|

Silver nanoparticles
Annona squamosa L.
Bioactivity
Photocatalysis


Dexmedetomidine post-conditioning attenuates cerebral ischemia following asphyxia cardiac arrest through down-regulation of apoptosis and neuroinflammation in rats.

Abstract:
BACKGROUND
Neuroprotection strategies after cardiac arrest (CA)/cardiopulmonary resuscitation (CPR) remain key areas of basic and clinical research. This study was designed to investigate the neuroprotective effects of dexmedetomidine following resuscitation and potential mechanisms.

METHODS
Anesthetized rats underwent 6-min asphyxia-based cardiac arrest and resuscitation, after which the experimental group received a single intravenous dose of dexmedetomidine (25 μg/kg). Neurological outcomes and ataxia were assessed after the return of spontaneous circulation. The serum levels and brain expression of inflammation markers was examined, and apoptotic cells were quantified by TUNEL staining.

RESULTS
Neuroprotection was enhanced by dexmedetomidine post-conditioning after the return of spontaneous circulation. This enhancement was characterized by the promotion of neurological function scores and coordination. In addition, dexmedetomidine post-conditioning attenuated the serum levels of the pro-inflammatory cytokine tumor necrosis factor (TNF)-α at 2 h, as well as interleukin IL-1β at 2, 24, and 48 h. TUNEL staining showed that the number of apoptotic cells in the dexmedetomidine post-conditioning group was significantly reduced compared with the control group. Further western blot analysis indicated that dexmedetomidine markedly reduced the levels of caspase-3 and nuclear factor-kappa B (NF-κB) in the brain.

CONCLUSIONS
Dexmedetomidine post-conditioning had a neuroprotective effect against cerebral injury following asphyxia-induced cardiac arrest. The mechanism was associated with the downregulation of apoptosis and neuroinflammation.

Li|Guangqian|G| LeiQian||| Gu|Pan|P| Fan|Dan|D|0000-0003-3245-7702

Dexmedetomidine
Post-conditioning
Cerebral ischemia
Apoptosis
Neuroinflammation
Asphyxiacardiac arrest


One-year clinical evaluation of different types of bulk-fill composites.

Abstract:
AIM
In the present study, we evaluated the 1-year clinical performance of a conventional posterior composite resin and three bulk-fill composite resins.

METHODS
Fifty patients with four class II restorations under occlusion were enrolled in the present study. A total of 200 restorations were placed in the cavity, 50 for each material (Clearfil Photo Posterior, Filtek Bulk-Fill Flowable and Filtek P60, Tetric EvoCeram Bulk-Fill, and SonicFill). One operator placed the restorations in the cavity, and 1 week later the patients were called for baseline examination. Two calibrated examiners evaluated the restorations once every 3 months for 1 year, according to United States Public Health Service criteria. The data were analyzed using SPSS. Non-parametric tests (Kruskal-Wallis, Mann-Whitney U-test, and Friedman) were used for the analysis at a confidence level of 95%.

RESULTS
The 1-year recall rate was 86%. All restorations showed minor modifications after 1 year. However, no statistically-significant differences were detected between the materials' performance at baseline and after 1 year for all criteria (P > 0.05).

CONCLUSIONS
The bulk-fill composite resin materials showed similar clinical performance when compared with a conventional posterior composite resin. Further evaluations are necessary for the long-term clinical performance of these materials.

Bayraktar|Yusuf|Y|
Ercan|Ertuğrul|E|
Hamidi|Mehmet Mustafa|MM|
Çolak|Hakan|H|

clinical evaluation
bulk-fill composite
clinical performance
posterior composite
class II restoration


A case of mistaken identity: Saksenaea vasiformis of the orbit.

Abstract: The authors describe a rare presentation of invasive fungal rhino-orbital cellulitis caused by Saksenaea vasiformis in an immunocompetent child. The patient was initially diagnosed and treated as Mucoraceae, which has a high mortality rate and is primarily seen in immunocompromised patients. Though of the same order, Mucorales, the families Mucoraceae and Saksenaeacae, may be difficult to differentiate on histologic examination and must be distinguished by fungal culture and speciation. Our patient responded well to sino-orbital debridement and systemic treatment with amphotericin and posaconazole.

Chen|Allison J|AJ|
Ediriwickrema|Lilangi S|LS|
Verma|Rohan|R|
Vavinskaya|Vera|V|
Shaftel|Solomon|S|
Deconde|Adam S|AS|
Korn|Bobby S|BS|
Kikkawa|Don O|DO|
Liu|Catherine Y|CY|

Saksenaea
mucorales
Saksenaeacae
Invasive fungal sinusitis
liposomal amphotericin B
mucormycosis
orbital cellulitis


A clinical evaluation to determine the safety, pharmacokinetics, and pharmacodynamics of an inositol-stabilized arginine silicate dietary supplement in healthy adult males.

Abstract:
PURPOSE
The purpose of this study was to characterize the pharmacokinetics (PKs) and pharmacodynamics (PDs) of an oral inositol-stabilized arginine silicate dietary supplement.

SUBJECTS AND METHODS
Ten healthy males, 26.7±5.4 years, took three 500 mg arginine silicate capsules (active product) for 14 days. The subjects attended test visits on Days 1 and 14. Fasting blood and saliva collections were performed predose and at 0.5 hours, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 5 hours, and 6 hours postdose for plasma arginine, serum silicon, and salivary nitric oxide (NO) + nitrite.

RESULTS
Day 1 PK parameters (adjusted for body weight) for arginine were peak serum concentration (C Max) 30.06±7.80 μg/mL, time it takes to reach peak serum concentration (t Max) 1.13±0.52 hours, and time required to reach half its original concentration (t 1/2) 15.93±9.55 hours and for silicon were C Max 2.99±0.63 μg/mL, t Max 2.44±2.05 hours, and t 1/2 34.56±16.56 hours. After Day 1 dose, arginine levels increased at 0.5 hours, 1 hour, 1.5 hours, 2 hours, 3 hours, and 5 hours (P<0.01) and silicon levels increased at 1 hour and 1.5 hours (P<0.05). After Day 14 dose, arginine levels increased at 0.5 hours, 1 hour, and 1.5 hours (P<0.05) and silicon levels increased at 1 hour, 1.5 hours, 2 hours, and 3 hours (P<0.01). After 14 days of use, baseline arginine trended toward being higher than baseline Day 1 (P=0.0645), and 4-hour postdose plasma arginine was significantly higher (P=0.0488) at Day 14 than Day 1. Although not a significant difference, NO, as measured as salivary nitrate, increased in four subjects and stayed the same in six subjects at 0.5 hours after the first dose (P=0.125). After 14 days of use, baseline NO levels increased in six subjects and stayed the same in four subjects; this shift was significant (P=0.031).

CONCLUSION
The arginine silicate dietary supplement increases blood levels of arginine after a single dose within 30 minutes and blood levels of silicon for up to 1.5 hours. Blood levels of arginine, silicon, and NO (salivary nitrite) were elevated consistently after 14 days of use. The observed increase in baseline salivary nitrite is supporting information that there was some improvement in NO production. Further study on the effect of this supplement on NO production and the resulting physiological effect is warranted. Within the specific protocol of this study, the product was found to be safe.

Kalman|Douglas S|DS|
Feldman|Samantha|S|
Samson|Adam|A|
Krieger|Diane R|DR|

pharmacokinetics
pharmacodynamics
arginine
dietary supplements
silicon
nitric oxide
vasodilation


Cardiac metastasis in a patient with oral squamous cell carcinoma.

Abstract: A 55-year-old man initially presented with an undifferentiated, HPV-p16-negative squamous cell carcinoma (SCC) in the left tonsillar region (cT4a N0 M0), which was treated with a combination of radiotherapy and chemotherapy. Several months later, the patient developed osteoradionecrosis on the left side of the mandible as well as a second primary lesion at the left base of the tongue. Surgical resection and mandibular reconstruction with a free vascularised fibula flap was performed. Regional clinical and radiologic follow-up showed no signs of tumour recurrence. However, routine positron emission tomography (PET)-CT showed a hypermetabolic mass intracardially. MRI confirmed the presence of a mass intramurally in the left ventricle, highly indicative of metastasis. Cardiac metastasis following oral cancer is rare and usually asymptomatic. Therefore, it can be missed easily and is mostly described as a finding postmortem. Reporting these cases is important for contributing to the insight into the uncommon development of metastasis.


Seroprevalences and Correlates of Hepatitis B and C Among Cameroonian Pregnant Women.

Abstract:
Background and rationale
Viral hepatitis B (VHB) and viral hepatitis C (VHC) are major public health issues in resource-poor countries where vertical transmission remains high.

Aim
To assess prevalences and correlates of VHB and VHC among women attending antenatal clinic.

Methods
A cross-sectional study at the Yaounde Central Hospital from January 1 to June 30, 2016. We included 360 pregnant women who were screened for hepatitis B virus surface antigen (HbsAg) and VHCAb by rapid diagnostic test (DiaSpot Diagnostics, USA) followed by confirmation of positive results by a reference laboratory. Odds ratios (95% confidence interval [CI]) were used to measure associations between variables. Statistical significance was set for P-value <.05.

Results
Mean age was 27.9 ± 5.6 years. The prevalences of HbsAg and VHCAb were 9.4% (n = 34) and 1.7% (n = 6), respectively. Multiplicity of sex partners was significantly associated with HbsAg positivity (adjusted odds ratio [aOR]: 11.6; 95% CI: 5.1-26.7; P < .001) while none of the studied factors was associated with VHCAb.

Conclusion
The high prevalence of hepatitis B among pregnant women supports systematic screening and free vaccination of pregnant women and women of childbearing age.

Fouelifack|Florent Ymele|FY|
Fouedjio|Jeanne Hortence|JH|
Fouogue|Jovanny Tsuala|JT|
Fouelifa|Loic Dongmo|LD|

correlates
viral hepatitis B
viral hepatitis C
Prevalence
Cameroon
pregnancy


Coupling coordination and interaction between urbanization and eco-environment in Cheng-Yu urban agglomeration, China.

Abstract: We built a comprehensive evaluation index system of urbanization in Chengdu-Chongqing (Cheng-Yu) urban agglomeration from four subsystems, including the economic, social, ecological, and urban and rural coordination. The comprehensive evaluation index system of eco-environment was constructed by combining ecological environment carrying capacity and ecological flexibi-lity. The coupling coordination degree model was applied to quantify the coupling coordination degree between urbanization and eco-environment in the prefecture-level cities of Cheng-Yu urban agglo-meration from 2005 to 2018. With GIS spatial analysis, phenomenon analysis and Tapio model, we analyzed the interaction type, evolution path and path of decoupling between urbanization and eco-environment in the prefecture-level cities of Cheng-Yu urban agglomeration. The results showed that the urbanization quality of Cheng-Yu urban agglomeration showed a trend of fluctuation and rise during the study period. Both Chengdu and Chongqing as high value areas showed "double-core" radia-ting to the surrounding areas. The eco-environment quality showed a slowly rising trend. The spatial pattern was a " U " shape with a north opening, high perimeter and low center. The degree of coupling coordination between the urbanization system and the eco-environment system was rising, with a spatial pattern of low in the middle and high in the east and west. The overall level of coupling coordination was relatively high. The type of coupling coordination degree was gradually evolving from near-disorder and reluctant coordination to moderate coordination. The evolution paths of urbanization and eco-environmental interaction were divided into two categories: stable and changing. The stable type included 20 cities in 5 subcategories, with Chengdu, Deyang, Mianyang, etc. being always well-coordination. The change type included 16 cities in 9 subcategories. The coordination degree of Chongqing main urban area, Tongliang and most other cities was improved, showing "rising" development. Hechuan, Zigong and a few other cities showed "sinking" development. The growth rates of both ecological environment and urbanization were positive. The decoupling state of urbanization and ecological environment was mainly characterized by weak decoupling and expansion connection.

Yang|Liang-Jie|LJ| Zhang|Xiao-Hong|XH| Pan|Jing-Hu|JH| Yang|Yong-Chun|YC|

D003247:Conservation of Natural Resources

Cheng-Yu urban agglomeration
Tapio model
urbanization quality
coupled coordination model
eco-environmental quality


Clinical development of HER3-targeting monoclonal antibodies: Perils and progress.

Abstract: The human epidermal growth factor receptor (HER) family consists of four transmembrane receptor tyrosine kinases: epidermal growth factor receptor (EGFR), HER2, HER3, and HER4. They are part of a complex signalling network and stimulate intracellular pathways regulating cell growth and differentiation. So far, monoclonal antibodies (mAbs) and small molecule tyrosine kinase inhibitors targeting EGFR and HER2 have been developed and approved. Recently, focus has turned to HER3 as it may play an important role in resistance to EGFR- and HER2-targeting therapies. HER3-targeting agents have been undergoing clinical evaluation for the last 10 years and currently thirteen mAbs are in phase 1 or 2 clinical studies. Single agent activity has proven to be limited, however, the tolerability was favourable. Thus, combinations of HER3-binding mAbs with other HER-targeting therapies or chemotherapies have been pursued in various solid tumor entities. Data indicate that the HER3-binding ligand heregulin may serve as a response prediction marker for HER3-targeting therapy. Within this review the current status of clinical development of HER3-targeting compounds is described.

Jacob|Wolfgang|W| James|Ian|I| Hasmann|Max|M| Weisser|Martin|M|

D000911:Antibodies, Monoclonal
D066246:ErbB Receptors
D006801:Humans
D058990:Molecular Targeted Therapy
D009369:Neoplasms
D047428:Protein Kinase Inhibitors
D020893:Receptor, ErbB-3

Monoclonal antibody
HER3
Heregulin
Biomarker


Rab11-mediated post-Golgi transport of the sialyltransferase ST3GAL4 suggests a new mechanism for regulating glycosylation.

Abstract: Glycosylation, the most common posttranslational modification of proteins, is a stepwise process that relies on tight regulation of subcellular glycosyltransferase location to control the addition of each monosaccharide. Glycosyltransferases primarily reside and function in the endoplasmic reticulum (ER) and the Golgi apparatus; whether and how they traffic beyond the Golgi, how this trafficking is controlled, and how it impacts glycosylation remain unclear. Our previous work identified a connection between N-glycosylation and Rab11, a key player in the post-Golgi transport that connects recycling endosomes and other compartments. To learn more about the specific role of Rab11, we knocked down Rab11 in HeLa cells. Our findings indicate that Rab11 knockdown results in a dramatic enhancement in the sialylation of N-glycans. Structural analyses of glycans using lectins and LC-MS revealed that α2,3-sialylation is selectively enhanced, suggesting that an α2,3-sialyltransferase that catalyzes the sialyation of glycoproteins is activated or upregulated as the result of Rab11 knockdown. ST3GAL4 is the major α2,3-sialyltransferase that acts on N-glycans; we demonstrated that the localization of ST3GAL4, but not the levels of its mRNA, protein, or donor substrate, was altered by Rab11 depletion. In knockdown cells, ST3GAL4 is densely distributed in the trans-Golgi network, compared with the wider distribution in the Golgi and in other peripheral puncta in control cells, whereas the α2,6-sialyltransferase ST6GAL1 is predominantly localized to the Golgi regardless of Rab11 knockdown. This indicates that Rab11 may negatively regulate α2,3-sialylation by transporting ST3GAL4 to post-Golgi compartments (PGCs), which is a novel mechanism of glycosyltransferase regulation.

Kitano|Masato|M| Kizuka|Yasuhiko|Y| Sobajima|Tomoaki|T| Nakano|Miyako|M| Nakajima|Kazuki|K| Misaki|Ryo|R| Itoyama|Saki|S| Harada|Yoichiro|Y| Harada|Akihiro|A| Miyoshi|Eiji|E| Taniguchi|Naoyuki|N|

sialyltransferase
ST3GAL4
glycosylation
posttranslational modification
glycosyltransferase
Rab11
glycan
α2,3-sialylation
N-linked glycosylation
membrane traffic


Geographic trends and risk of gastrointestinal cancer among patients with celiac disease in Europe and Asian-Pacific region.

Abstract: Celiac disease is an autoimmune disorder that affects genetically predisposed individuals upon the ingestion of gluten. It is now considered one of the most common genetic disorders in Europe and Asian Pacific region with a prevalence of up to 2.67% of the population. The true prevalence of celiac disease may still be underestimated. Studies remain limited by sample size and selection bias. Celiac disease predisposes to the development of gastrointestinal malignancies, especially lymphomas and small bowel adenocarcinoma. The risk of developing a celiac disease associated malignancies remains uncertain, despite numerous studies. In Middle Eastern countries, the literature regarding celiac disease has expanded significantly in recent years. These studies reported have largely concentrated on the epidemiology of Celiac disease and there is an absolute and relative paucity of published research regarding celiac disease associated malignancy. The aim of this article is to review the current literature and evaluate the risk of gastrointestinal malignancies among patients with celiac disease and then review studies from the Asian Pacific region of the world.

Rostami Nejad|Mohammad|M|
Aldulaimi|David|D|
Ishaq|Sauid|S|
Ehsani-Ardakani|Mohammad Javad|MJ|
Zali|Mohammad Reza|MR|
Malekzadeh|Reza|R|
Rostami|Kamran|K|

Celiac disease
Europe
Asian Pacific region
Lymphoma
Adenocarcinoma


Feasibility of ultrasound-guided absorbable retaining thread needle localization for nonpalpable breast lesions.

Abstract:
PURPOSE
Absorbable retaining thread (ART) needle localization utilizes a guiding needle with a thread; this technique was invented to reduce patient discomfort and wire migration. We investigated the feasibility of ultrasound (US)-guided ART needle localization for nonpalpable breast lesions.

METHODS
ART needle localization was performed for 26 nonpalpable breast lesions in 26 patients who were scheduled to undergo surgical excision the day after localization. Seventeen breast lesions were initially diagnosed as invasive ductal carcinoma, six as ductal carcinomas in situ, and one as fibrocystic change. The other two cases without an initial pathologic diagnosis had suspicious US features, and excision was planned concomitantly with contralateral breast cancer surgery. The primary outcome was the technical success rate of ART needle localization confirmed by US immediately after the procedure, and the secondary outcomes were the percentage of clear margins on pathology and the complication rate of ART needle localization.

RESULTS
The technical success rate of ART needle localization was 96.2% (25 of 26 patients), and the ART was located 1 cm away from the mass in one patient (3.8%). The lesions were successfully removed with clear margins in all 26 patients. No significant complications related to ART needle localization were observed.

CONCLUSION
ART needle localization can be an alternative to wire needle localization for nonpalpable breast lesions.

Park|Seo Young|SY|
Kim|Hye Jung|HJ|
Kim|Won Hwa|WH|
Cheon|Hye Jin|HJ|
Lee|Hoseok|H|
Park|Ho Yong|HY|
Jung|Jin Hyang|JH|
Park|Ji Young|JY|

Breast neoplasms
Image-guided surgery
Ultrasonography


Ocean acidification alters fish-jellyfish symbiosis.

Abstract: Symbiotic relationships are common in nature, and are important for individual fitness and sustaining species populations. Global change is rapidly altering environmental conditions, but, with the exception of coral-microalgae interactions, we know little of how this will affect symbiotic relationships. We here test how the effects of ocean acidification, from rising anthropogenic CO2 emissions, may alter symbiotic interactions between juvenile fish and their jellyfish hosts. Fishes treated with elevated seawater CO2 concentrations, as forecast for the end of the century on a business-as-usual greenhouse gas emission scenario, were negatively affected in their behaviour. The total time that fish (yellowtail scad) spent close to their jellyfish host in a choice arena where they could see and smell their host was approximately three times shorter under future compared with ambient CO2 conditions. Likewise, the mean number of attempts to associate with jellyfish was almost three times lower in CO2-treated compared with control fish, while only 63% (high CO2) versus 86% (control) of all individuals tested initiated an association at all. By contrast, none of three fish species tested were attracted solely to jellyfish olfactory cues under present-day CO2 conditions, suggesting that the altered fish-jellyfish association is not driven by negative effects of ocean acidification on olfaction. Because shelter is not widely available in the open water column and larvae of many (and often commercially important) pelagic species associate with jellyfish for protection against predators, modification of the fish-jellyfish symbiosis might lead to higher mortality and alter species population dynamics, and potentially have flow-on effects for their fisheries.

Nagelkerken|Ivan|I|
Pitt|Kylie A|KA|
Rutte|Melchior D|MD|
Geertsma|Robbert C|RC|

global change
juvenile fish
behaviour
commensalism
jellyfish blooms


Cor triatriatum dexter associated with atrial septal defect: Management in a complex clinical case.

Abstract: The coexistence of an atrial septal defect and a prominent eustachian valve is a rare congenital anomaly, rarely reported in literature. Differentiation between a giant eustachian valve and cor triatriatum dexter can be difficult. A case of a large atrial septal defect associated with cor triatriatum dexter diagnosed by echocardiography in an asymptomatic woman is reported. A watchful waiting strategy was adopted.

cor triatriatum dexter
atrial septal defect
prominent eustachian valve
echocardiography
cardiac magnetic resonance imaging


Low-level fluoride exposure reduces glycemia in NOD mice.

Abstract:
Water fluoridation is the most widespread measure to prevent dental caries but its relationship with the development of type-1 diabetes (T1D), which has been increasing by 2-5% worldwide, is not quite well understood.

AIM
This study evaluated if fluoride (F) administered in the drinking water can prevent or reduce the development of T1D in non-obese diabetic (NOD) mice, as well as to explore the underlying mechanisms.

MATERIALS AND METHODS
Twenty-four weaning NOD mice received water containing 0, 10 or 50 ppm F for 21 days. Plasma glucose and insulin were analyzed. Quantitative proteomic analysis was conducted in the liver and gastrocnemius muscle.

RESULTS
Animals treated with 10 ppm F had significantly lower glucose levels than the control group, but there was no significant difference among the groups in relation to insulin. The % of β-cell function was significantly higher in the 10 ppm F group. Changes in the proteomic profile of muscle and liver were seen among the groups. In the muscle, the 10 ppm F group presented, when compared with control, increased expression of proteins involved in energy metabolism. The 50 ppm F group, compared with control, presented increased expression of proteins related to muscle contraction, differentiation of brown adipose tissue and apoptosis. For the liver, the 10 ppm F group had increase in proteins involved in energy metabolism and protein synthesis, in respect to control. There was also an increase in isoforms of Glutathione S transferase, which was confirmed by Western blotting. In the group treated with 50 ppm F, proteins related to ROS metabolism and energetic metabolism were altered.

CONCLUSION
Increased expression of antioxidant proteins by treatment with low F concentration may possibly help to explain protection against the development of T1D, which should be better explored in future mechanistic studies.

Malvezzi|Maria Aparecida Pereira Nunes|MAPN|

Pereira|Heloisa Aparecida Barbosa Silva|HABS|

Glycemia
Water fluoridation
Diabetes
Proteomic Analysis
Liver
Insulinemia


SEEG-guided radiofrequency thermocoagulation of epileptic foci in the paediatric population: Feasibility, safety and efficacy.

Abstract:
PURPOSE
Focal epilepsy in children may be refractory to pharmacological treatment and surgical resection may be an appropriate option. When invasive electroencephalogram is required in the presurgical evaluation, depth electrodes can be used to create focal lesions in the epileptogenic zone using radiofrequency thermocoagulation (RFTC), to disrupt the epileptogenic zone.

METHODS
This study aimed to assess the efficacy and safety of RFTC in a paediatric population of 46 patients.

RESULTS
The mean age of onset was 3.3 years and the mean age at SEEG was 8.2 years. MRI lesions were identified in 71.7% of the series, among them 60% of malformation of cortical development. 43.5% of the patients were seizure free at 1 month, 26.1% were responders. The mean duration of improvement was 6.8 months. 8 children were seizure free for >8 months and among them, 6 are currently seizure free for 8-24 months. 5 patients had functional deficits post-procedures, transient in 4 patients and prolonged in one of whom. 3/5 were anticipated following the results of cortical stimulation. Multivariate analysis found 3 independent criteria linked to RFTC efficiency one month after RFTC: frequency of the seizures before RFTC, age and number of contacts used.

CONCLUSION
RFTC is a safe method for the paediatric population providing important predictive information for surgical resection. An improvement in seizure frequency, often transient, is seen in 2/3 of our patients. RTFC could be useful as a palliative technique for children with an epileptogenic zone overlapping with eloquent areas, with minimal risk of sequelae.

Chipaux|Mathilde|M|
Taussig|Delphine|D|
Dorfmuller|Georg|G|
Dorison|Nathalie|N|
Tisdall|Martin M|MM|
Boyd|Stewart G|SG|
Thornton|Rachel|R|
Eltze|Christin|C|
Fohlen|Martine|M|
Cross|Helen J|HJ|
Ferrand-Sorbets|Sarah|S|

Thermocoagulation
Paediatrics
Epilepsy
Children
Epilepsy surgery
Invasive EEG
stereoEEG


REST promotes ETS1-dependent vascular growth in medulloblastoma.

Abstract: Expression of the RE1-silencing transcription factor (REST), a master regulator of neurogenesis, is elevated in medulloblastoma (MB) tumors. A cell-intrinsic function for REST in MB tumorigenesis is known. However, a role for REST in the regulation of MB tumor microenvironment has not been investigated. Here, we implicate REST in remodeling of the MB vasculature and describe underlying mechanisms. Using RESTTG mice, we demonstrate that elevated REST expression in cerebellar granule cell progenitors, the cells of origin of sonic hedgehog (SHH) MBs, increased vascular growth. This was recapitulated in MB xenograft models and validated by transcriptomic analyses of human MB samples. REST upregulation was associated with enhanced secretion of proangiogenic factors. Surprisingly, a REST-dependent increase in the expression of the proangiogenic transcription factor E26 oncogene homolog 1, and its target gene encoding the vascular endothelial growth factor receptor-1, was observed in MB cells, which coincided with their localization at the tumor vasculature. These observations were confirmed by RNA-Seq and microarray analyses of MB cells and SHH-MB tumors. Thus, our data suggest that REST elevation promotes vascular growth by autocrine and paracrine mechanisms.

REST
medulloblastoma
tumor microenvironment
vasculature
NRSF


Impact of a Patient Blood Management monitoring and feedback programme on allogeneic blood transfusions and related costs.

Abstract: A Patient Blood Management programme was established at the University Hospital of Zurich, along with a monitoring and feedback programme, at the beginning of 2014 with a first analysis reported in 2015. Our study aimed to investigate the further impact of this Patient Blood Management monitoring and feedback programme on transfusion requirements and related costs. We included adult patients discharged between 2012 and 2017. A total of 213,882 patients underwent analysis: 66,659 patients in the baseline period (2012-2013); 35,309 patients in the year after the introduction of the Patient Blood Management monitoring and feedback programme (2014) and 111,914 patients in the continued sustainability period (2015-2017). The introduction of the Patient Blood Management monitoring and feedback programme reduced allogeneic blood product transfusions by 35%, from 825 units per 1000 hospital discharges in 2012 to 536 units in 2017. The most sustained effect was an approximately 40% reduction in red blood cell transfusions, from 535 per 1000 discharges to 319 units. Fewer patients were transfused in the periods after the introduction of the Patient Blood Management monitoring and feedback programme (6251 (9.4%) vs. 2932 (8.3%) vs. 8196 (7.3%); p < 0.001). Compared with 2012, the yearly OR for being exposed to any blood transfusion declined steadily after the introduction of the Patient Blood Management monitoring and feedback programme to 0.64 (95%CI 0.61-0.68; p < 0.001) in 2017. For patients requiring extracorporeal membrane oxygenation, transfusion requirements were also sustainably reduced. This reduction in allogeneic blood transfusions led to savings of 12,713,754 Swiss francs (£ 9,497,000 sterling; EUR 11,100,000; US$ 12,440,000) in blood product acquisition costs over 4 years. In-hospital mortality was not affected by the programme. The Patient Blood Management monitoring and feedback programme sustainably reduced transfusion requirements and related costs, without affecting in-hospital mortality.

Kaserer|A|A|
Rössler|J|J|
Braun|J|J|
Farokhzad|F|F|
Pape|H-C|HC|
Dutkowski|P|P|
Plass|A|A|
Horisberger|T|T|
Volbracht|J|J|
Manz|M G|MG|
Spahn|D R|DR|

Patient Blood Management
adverse outcomes, mortality
allogeneic transfusion
healthcare costs
patient outcomes, monitoring


Serum oxytocin concentrations in current and recent suicide survivors are lower than in healthy controls.

Abstract:
BACKGROUND
Suicide and suicide attempts are dramatic events both for the individuals concerned and for their social circles. From a psychopathological perspective, suicidal behavior could be understood as a severe breakdown in relations with their social worlds. Oxytocin is a neuropeptide highly involved in the perception of facets of social relationship such as their quality feelings of belongingness, and mutual trust. Given this, we expected that serum oxytocin concentrations would be lower in current and recent suicide survivors than in healthy controls.

METHODS
A total of 48 participants (mean age: 27 years; 62.5% females) took part in the study. Of these, 16 (62.5% females) survived a suicide attempt 12-24 h ago; 16 (62.5% females) had made a suicide attempt about 12 weeks ago, and 16 (62.5% females) were healthy age- and gender-matched controls. Blood samples were taken in the morning to assess serum oxytocin concentrations. Participants also completed questionnaires covering sociodemographic information and a scale assessing suicidal ideation.

RESULTS
Compared to healthy controls, suicide survivors had significantly lower serum oxytocin concentrations, but these levels did not differ between current and recent suicide survivors. Compared to healthy controls and recent suicide attempters, current suicide attempters recorded significantly higher scores on the Beck scale for suicidal ideation. Across the sample as a whole, higher scores for suicidal ideation were associated with lower serum oxytocin concentrations. Serum oxytocin concentrations and scores on the Beck scale for suicidal ideation did not differ between females and males.

CONCLUSIONS
Given that oxytocin is a neurobiological correlate of subjectively perceived quality of social interaction and social relationships, the results support the notion that suicide attempts are closely linked to suicide survivors' perceptions of the quality of their social lives. Speculatively, and based on the serum oxytocin concentrations, it also appears that 12 weeks after a suicide attempt, the survivor's perceived quality of social life has not significantly improved.

Jahangard|Leila|L|
Shayganfard|Mehran|M|
Ghiasi|Farahnaz|F|
Salehi|Iraj|I|
Haghighi|Mohammad|M|
Ahmadpanah|Mohammad|M|
Sadeghi Bahmani|Dena|D|
Brand|Serge|S|

Serum
Oxytocin
Suicide
Suicide attempts
Social world


Change in Antibiotic Use in Secondary and Tertiary Hospitals Nationwide After a National Antimicrobial Stewardship Campaign Was Launched in China, 2011-2016: An Observational Study.

Abstract:
BACKGROUND
An antimicrobial stewardship campaign was launched in 2011 by the Ministry of Health. This study aimed to assess the achievements and trends in the clinical use of antibiotics in secondary and tertiary hospitals following this campaign in China.

METHODS
This observational study analyzed nationwide hospital antibiotic procurement and consumption data and antibiotic-resistance surveillance data based on claims filed in 2010-2016.

RESULTS
After a 6-year national campaign, the proportion of outpatients and surgical patients who received antibiotic treatment decreased from 19.5% to 8.5% and from 97.9% to 38.3%, respectively. The intensity of antibiotic use among inpatients decreased from 85.3±29.8 defined daily dosage (DDD) per 100 patient days to 48.5±8.0 DDD per 100 patient days. Moreover, the antibiotic procurement expenditure among hospitals declined from 22.3% of total drug procurement costs in 2010 to 12.1% in 2016, although total drug procurement costs doubled during that time. The incidence of methicillin-resistant Staphylococcus aureus isolates also dropped (from 54.4% in 2010 to 34.4% in 2016), as did the proportion of carbapenem-resistant Pseudomonas aeruginosa isolates (from 30.8% to 22.3%).

CONCLUSIONS
The 6-year campaign successfully reduced antibiotic consumption and irrational drug use in Chinese hospitals which was associated with declines in the prevalence of common antibiotic-resistant bacteria.

Xiao|Yonghong|Y| Shen|Ping|P| Zheng|Beiwen|B| Zhou|Kai|K| Luo|Qixia|Q| Li|Lanjuan|L|

stewardship
China
antimicrobial resistance


Variation in intraabdominal pressure in patients with acute heart failure according to left ventricular ejection fraction. Results of an intraabdominal pressure study.

Abstract:
BACKGROUND
The increase in intraabdominal pressure (IAP) has been correlated with increased creatinine levels in patients with heart failure with severely reduced left ventricular ejection fraction (HFrEF). However, IAP has not been examined in more stable patients or those with heart failure with preserved ejection fraction (HFpEF).

PATIENTS AND METHOD
We conducted an observational, prospective descriptive study that measured the IAP of patients hospitalised for decompensated heart failure (HF). The sample was stratified according to left ventricular ejection fraction (LVEF), with a cut-off of 50%. The objective was to analyse the IAP, the baseline characteristics and degree of congestion using clinical ultrasonography and impedance audiometry.

RESULTS
The study included 56 patients, 22 with HFrEF and 34 with HFpEF. The patients with HFrEF presented a higher prevalence of ischaemic heart disease (11% vs. 6%; p = 0.010) and chronic obstructive pulmonary disease/asthma (6% vs. 2%; p = 0.025). The IAP was higher in the patients with HFrEF (17.2 vs. 13.3 mmHg; p = 0.004), with no differences in renal function at admission according to the LVEF (CKD-EPI creatinine) (HFrEF 55.0 mL/min/1.73 m2 [32.6-83.6] vs. HFpEF 55.0 mL/min/1.73 m2 [44.0-74.9]; p = 0.485). The patients with HFrEF presented a more congestive profile determined through ultrasonography (inferior vena cava collapse [26% vs. 50%; p = 0.001]), impedance audiometry (total body water at admission, 46 L vs. 41 L; p = 0.052; and at 72 h, 50.2 L vs. 39.1 L; p = 0.038) and CA125 concentration (68 U/mL vs. 39 U/mL; p = 0.037).

CONCLUSIONS
During the decompensation episodes, the patients with HFrEF had a greater increase in IAP and a higher degree of systemic congestion.

Rubio Gracia|J|J|
Giménez López|I|I|
Josa Laorden|C|C|
Sánchez Marteles|M|M|
Garcés Horna|V|V|
de la Rica Escuín|M L|ML|
Pérez Calvo|J I|JI|

Intraabdominal pressure
Heart failure
Ventricular ejection fraction
Congestion
Cardiorenal syndrome
Congestión
Fracción de eyección ventricular
Insuficiencia cardíaca
Presión intraabdominal
Síndrome cardio-renal


Exposure to household air pollution from biomass cookstoves and self-reported symptoms among women in rural Honduras.

Abstract: Household air pollution from combustion of solid fuels is an important risk factor for morbidity and mortality, causing an estimated 2.6 million premature deaths globally in 2016. Self-reported health symptoms are a meaningful measure of quality of life, however, few studies have evaluated symptoms and quantitative measures of exposure to household air pollution. We assessed the cross-sectional association of self-reported symptoms and exposures to household air pollution among women in rural Honduras using stove type (traditional [n = 76]; cleaner-burning Justa [n = 74]) and 24-hour average personal and kitchen fine particulate matter (PM2.5) concentrations. The odds of prevalent symptoms were higher among women using traditional stoves vs Justa stoves (e.g. headache: odds ratio = 2.23; 95% confidence interval = 1.13-4.39). Associations between symptoms and measured PM2.5 were generally consistent with the null. These results add to the evidence suggesting reduced exposures and better health-related quality of life among women using cleaner-burning biomass stoves.


Thiomers--from bench to market.

Abstract: Thiolated polymers or designated thiomers are obtained by immobilization of sulhydryl bearing ligands on the polymeric backbone of well-established polymers such as poly(acrylates) or chitosans. This functionalization leads to significantly improved mucoadhesive properties compared to the corresponding unmodified polymers, as disulfide bonds between thiol groups of thiomers and cysteine-rich glycoproteins of the mucus gel layer are formed. Furthermore, enzyme- and efflux-pump inhibiting as well as improved permeation-enhancing properties are advantages of thiolization. By the covalent attachment of mercaptonicotinamide substructures via disulfide bonds to thiolated polymers these properties are even substantially further improved and stability towards oxidation even in aqueous media can be provided. Meanwhile, more than 50 research groups worldwide are working on thiolated polymers. For certain thiomers the scale up process for industrial production has already been done and GMP material is available. Furthermore, safety of thiolated poly(acrylic acid), thiolated chitosan and thiolated hyaluronic acid could be demonstrated via orientating studies in human volunteers and via various clinical trials. The first product (Lacrimera® eye drops, Croma-Pharma) containing a chitosan-N-acetylcysteine conjugate for treatment of dry eye syndrome will enter the European market this year. It is the only product providing a sustained protective effect on the ocular surface due to its comparatively much more prolonged residence time worldwide. Various further products utilizing, for instance, thiolated hyaluronic acid in ocular surgery are in the pipeline.

Thiomers
Mucoadhesion
In vivo studies
Permeation enhancement


Long-delayed expression of the immediate early gene Arc/Arg3.1 refines neuronal circuits to perpetuate fear memory.

Abstract: Fear memories typically persist for long time periods, and persistent fear memories contribute to post-traumatic stress disorder. However, little is known about the cellular and synaptic mechanisms that perpetuate long-term memories. Here, we find that mouse hippocampal CA1 neurons exhibit biphasic Arc (also known as Arg3.1) elevations after fear experience and that the late Arc expression regulates the perpetuation of fear memoires. An early Arc increase returned to the baseline after 6 h, followed by a second Arc increase after 12 h in the same neuronal subpopulation; these elevations occurred via distinct mechanisms. Antisense-induced blockade of late Arc expression disrupted memory persistence but not formation. Moreover, prolonged fear memories were associated with the delayed, specific elimination of dendritic spines and the reactivation of neuronal ensembles formed during fear experience, both of which required late Arc expression. We propose that late Arc expression refines functional circuits in a delayed fashion to prolong fear memory.

Nakayama|Daisuke|D| Iwata|Hirokazu|H| Teshirogi|Chie|C| Ikegaya|Yuji|Y| Matsuki|Norio|N| Nomura|Hiroshi|H|

Arc/Arg3.1
dendritic spines
BDNF
fear conditioning
hippocampus
memory engram


The Long Non-coding RNA-ORLNC1 Regulates Bone Mass by Directing Mesenchymal Stem Cell Fate.

Abstract: Bone marrow-derived mesenchymal stem cells (BMSCs) have the potential to differentiate into osteoblasts or adipocytes, and the shift between osteogenic and adipogenic differentiation determines bone mass. The aim of this study was to identify whether lncRNAs are involved in the differentiation commitment of BMSCs during osteoporosis. Here, we found ORLNC1, a functionally undefined lncRNA that is highly conserved, which exhibited markedly higher expression levels in BMSCs, bone tissue, and the serum of OVX-induced osteoporotic mice than sham-operated counterparts. Notably, a similar higher abundance of lncRNA-ORLNC1 expression was also observed in the bone tissue of osteoporotic patients. The transgenic mice overexpressing lncRNA-ORLNC1 showed a substantial increase in the osteoporosis-associated bone loss and decline in the osteogenesis of BMSCs. The BMSCs pretreated with lncRNA-ORLNC1-overexpressing lentivirus vector exhibited the suppressed capacity of osteogenic differentiation and oppositely enhanced adipogenic differentiation. We then established that lncRNA-ORLNC1 acted as a competitive endogenous RNA (ceRNA) for miR-296. Moreover, miR-296 was found markedly upregulated during osteoblast differentiation, and it accelerated osteogenic differentiation by targeting Pten. Taken together, our results indicated that the lncRNA-ORLNC1-miR-296-Pten axis may be a critical regulator of the osteoporosis-related switch between osteogenesis and adipogenesis of BMSCs and might represent a plausible therapeutic target for improving osteoporotic bone loss.

Yang|Lei|L| Li|Yuan|Y| Gong|Rui|R| Gao|Manqi|M| Feng|Chao|C| Liu|Tianyi|T| Sun|Yi|Y| Jin|Mengyu|M| Wang|Dawei|D| Yuan|Ye|Y| Yan|Gege|G| He|Mingyu|M| Idiiatullina|Elina|E| Ma|Wenya|W| Han|Zhenbo|Z| Zhang|Lai|L| Huang|Qi|Q| Ding|Fengzhi|F| Cai|Benzhi|B| Yang|Fan|F|

BMSCs
adipogenic differentiation
lncRNA
osteoporosis
osteogenic differentiation
miR-296
Pten
bone formation


Poster - Thur Eve - 28: Optimization of a prostate cancer IGRT protocol.

Abstract: Our image-guided radiation therapy (IGRT) protocol for post-prostatectomy patients involves acquiring a kV cone beam computed tomography (CBCT) dataset at each fraction and shifting the treatment couch to align the surgical clips. This IGRT strategy requires significant resources, and delivers non-negligible dose to normal tissues. The objective of this work is to evaluate this IGRT protocol against two alternative strategies in terms of the dose-volume statistics for target and organ at risk regions. Our method involves deforming the planning CT to the CBCT dataset acquired at each fraction, computing dose on the deformed dataset, and inversely transforming the dose back onto the original planning CT dataset. The treatments of six patients were evaluated assuming three IGRT scenarios: no IGRT, daily IGRT using the clinically employed couch shifts, and alternating day IGRT. The doses delivered to the clinical target volumes are within approximately 3.2, 1.3, and 2.1% of the plan for the non-IGRT, daily, and alternating day IGRT protocols, respectively. Doses to relevant portions of the organs at risk deviate from the plan by up to 10.5, 13.1 and 10.7% for non-IGRT, daily IGRT, and alternating day IGRT protocols, respectively. Some cases do not differ significantly between IGRT and non-IGRT protocols in terms of cumulative DVHs, highlighting the difficult task of correcting prostate bed deformations via the treatment couch translations. In general, the alternating day IGRT protocol was found to result in a clinically insignificant deviation in delivered dose while providing a significant reduction in resource use and patient imaging dose.

Dona|O|O| Diamond|K|K| Ostapiak|O|O| Wierzbicki|M|M|

Cancer
Radiation therapy
Cone beam computed tomography
Computed tomography
Tissues
Anatomy
Dosimetry
Image guided radiation therapy
Medical imaging
Radiation treatment


Hypoxia-preconditioned mesenchymal stem cells attenuate microglial pyroptosis after intracerebral hemorrhage.

Abstract:
Background
Microglia plays a vital role in neuroinflammation, contributing to the pathogenesis of intracerebral hemorrhage (ICH)-induced brain injury. Mesenchymal stem cells (MSCs) hold great potential for treating ICH. We previously revealed that MSCs ameliorate the microglial pyroptosis caused by an ischemic stroke. However, whether MSCs can modulate microglial pyroptosis after ICH remains unknown. This study aimed to investigate the neuroprotective effects of hypoxia-preconditioned olfactory mucosa MSCs (OM-MSCs) on ICH and the possible mechanisms.

Methods
ICH was induced in mice via administration of collagenase IV. At 6 h post-ICH, 2-4×105 normoxic/hypoxic OM-MSCs or saline were intracerebrally administered. To evaluate the neuroprotective effects, the behavioral outcome, apoptosis, and neuronal injury were measured. Microglia activation and pro-inflammatory cytokines were applied to detect neuroinflammation. Microglial pyroptosis was determined by western blotting, immunofluorescence staining, and transmission electron microscopy (TEM).

Results
The two OM-MSC-transplanted groups exhibited significantly improved functional recovery and reduced neuronal injury, especially the hypoxic OM-MSCs group. Hypoxic OM-MSCs attenuated microglial activation as well as the levels of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). Moreover, we found that hypoxia-preconditioned OM-MSCs ameliorated pyroptosis by diminishing the levels of pyroptosis-associated proteins in peri-hematoma brain tissues, decreasing the expression of the microglial nod-like receptor family protein 3 (NLRP3) and caspase-1, and reducing the membrane pores on microglia post-ICH.

Conclusions
Our study showed that hypoxic preconditioning augments the therapeutic efficacy of OM-MSCs, and hypoxia-preconditioned OM-MSCs alleviate microglial pyroptosis in the ICH model.

Liu|Jianyang|J| He|Jialin|J| Huang|Yan|Y| Ge|Lite|L| Xiao|Han|H| Zeng|Liuwang|L| Jiang|Zheng|Z| Lu|Ming|M| Hu|Zhiping|Z|

pyroptosis
microglia
Mesenchymal stem cells (MSCs)
hypoxic preconditioning
intracerebral hemorrhage (ICH)


Small Improvements in Postoperative Outcome with Gap Balancing Technique Compared with Measured Resection in Total Knee Arthroplasty.

Abstract:
Background
There is ongoing debate about how to obtain correct rotational alignment in total knee arthroplasty (TKA). Two commonly used techniques are the measured resection (MR) and the gap balancing (GB) technique.

Objective
The objective of the present study was to analyze which of these two techniques confers a clinical advantage up to 10 years postoperatively.

Methods
Two hundred patients were randomized to either MR or GB. The primary outcome was the Knee Society Knee Score (KS) 10 years postoperatively. Secondary outcomes were passive range of motion, the Knee Society Function Score (FS), and the Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC), along with implant survival. We employed a two one-sided test (TOST) and linear mixed models to assess clinical outcomes.

Results
Mean KS was 82 (95% confidence interval (CI), 80 - 83) and 77 (95% CI, 76 - 79) in the GB and MR group, respectively. The TOST test and linear mixed model both revealed statistical significance (p < 0.001). In addition, GB yielded better postoperative FS and WOMAC. However, between-group differences were consistently small. Implant survival rates at 10 years, with survival for any reason as the endpoint of interest, were 93.7% (95% CI, 86.4% and 97.1%) and 89.8% (95% CI, 81.9% - 94.4%) for the GB group and the MR group, respectively (p = 0.302).

Conclusion
Gap-balancing is a safe and reliable technique. KS for the two study groups at 10 years can be considered equivalent, and the small postoperative advantages may not extend beyond clinical relevance.

Hommel|Hagen|H| Kunze|Daniel|D| Hommel|Peggy|P| Fennema|Peter|P|

Gap balancing
Measured resection
Total knee arthroplasty
Knee
Osteoarthritis
Ligament balancing
Randomized clinical trial


Diversity of Virulence Genes in Multidrug Resistant Escherichia coli from a Hospital in Western China.

Abstract:
Background
Escherichia coli strains are the most commonly isolated bacteria in hospitals. The normally harmless commensal E. coli can become a highly adapted pathogen, capable of causing various diseases both in healthy and immunocompromised individuals, by acquiring a combination of mobile genetic elements. Our aim was to characterize E. coli strains from a hospital in western China to determine their virulence and antimicrobial resistance potential.

Methods
A total of 97 E. coli clinical isolates were collected from the First Affiliated Hospital of Chengdu Medical College from 2015 to 2016. Microbiological methods, PCR, and antimicrobial susceptibility tests were used in this study.

Results
The frequency of occurrence of the virulence genes fimC, irp2, fimH, fyuA, lpfA, hlyA, sat, and cnf1 in the E. coli isolates was 93.81, 92.78, 91.75, 84.54, 41.24, 32.99, 28.86, and 7.22%, respectively. Ninety-five (97.9%) isolates carried two or more different virulence genes. Of these, 44 (45.4%) isolates simultaneously harbored five virulence genes, 24 (24.7%) isolates harbored four virulence genes, and 17 (17.5%) isolates harbored six virulence genes. In addition, all E. coli isolates were multidrug resistant and had a high degree of antimicrobial resistance.

Conclusion
These results indicate a high frequency of occurrence and heterogeneity of virulence gene profiles among clinical multidrug resistant E. coli isolates. Therefore, appropriate surveillance and control measures are essential to prevent the further spread of these isolates in hospitals.

Li|Xue|X| Luo|Qi|Q| Yu|Xinyu|X| Zhang|Yanling|Y| Cao|Xiaoyue|X| Li|Dan|D|

virulence genes
Escherichia coli
antimicrobial resistance
clinical isolates
MDR


Promoting and delivering antenatal care in rural Jimma Zone, Ethiopia: a qualitative analysis of midwives' perceptions.

Abstract:
BACKGROUND
Despite improvements in recent years, Ethiopia faces a high burden of maternal morbidity and mortality. Antenatal care (ANC) may reduce maternal morbidity and mortality through the detection of pregnancy-related complications, and increased health facility-based deliveries. Midwives and community-based Health Extension Workers (HEWs) collaborate to promote and deliver ANC to women in these communities, but little research has been conducted on the professional working relationships between these two health providers. This study aims to generate a better understanding of the strength and quality of professional interaction between these two key actors, which is instrumental in improving healthcare performance, and thereby community health outcomes.

METHODS
We conducted eleven in-depth interviews with midwives from three rural districts within Jimma Zone, Ethiopia (Gomma, Kersa, and Seka Chekorsa) as a part of the larger Safe Motherhood Project. Interviews explored midwives' perceptions of strengths and weaknesses in ANC provision, with a focus as well on their engagement with HEWs. Thematic content analysis using Atlas.ti software was used to analyse the data using an inductive approach.

RESULTS
Midwives interacted with HEWs throughout three key aspects of ANC promotion and delivery: health promotion, community outreach, and provision of ANC services to women at the health centre and health posts. While HEWs had a larger role in promoting ANC services in the community, midwives functioned in a supervisory capacity and provided more clinical aspects of care. Midwives' ability to work with HEWs was hindered by shortages in human, material and financial resources, as well as infrastructure and training deficits. Nevertheless, midwives felt that closer collaboration with HEWs was worthwhile to enhance service provision. Improved communication channels, more professional training opportunities and better-defined roles and responsibilities were identified as ways to strengthen midwives' working relationships with HEWs.

CONCLUSION
Enhancing the collaborative interactions between midwives and HEWs is important to increase the reach and impact of ANC services and improve maternal, newborn and child health outcomes more broadly. Steps to recognize and support this working relationship require multipronged approaches to address imminent training, resource and infrastructure deficits, as well as broader health system strengthening.

Antenatal care
Ethiopia
Midwives
Health extension workers
Teamwork


Neotropical Monogenoidea. 60. Two new species of Gyrodactylus (Monogenoidea: Gyrodactylidae) from the armored-catfish, Pareiorhaphis parmula Pereira (Loricariidae) and from the cascarudo, Callichthys callichthys (Linnaeus) (Callichthyidae) from Brazil.

Abstract: Two new species of Gyrodactylus are described from the body surface of two catfish species from southern Brazilian rivers. Gyrodactylus anaspidus n. sp. is described from the armored-catfish, Pareiorhaphis parmula (Loricariidae) and Gyrodactylus polyadenus n. sp. is described from the cascarudo, Callichthys callichthys (Callichthyidae). The new species differ from previously described neotropical species of Gyrodactylus by the relative morphology of their haptoral hard structures and male copulatory organ (MCO). Gyrodactylus anaspidus n. sp. has a superficial bar without a shield and an MCO with one row of spinelets (9-11 spinelets). Gyrodactylus polyadenus n. sp. presents a shield associated to a superficial bar, a deep bar with narrow extremities connected to the anchors, a subrectangular hooklet with a short point, and an MCO with one row of six spinelets. We also report that G. anaspidus n. sp. co-occurs with oviparous species of Gyrodactylidae on their respective loricariid hosts.

Vianna|RogÉrio T|RT|
Boeger|Walter A|WA|

Platyhelminthes, Gyrodactylus anaspidus n. sp., Gyrodactylus polyadenus n. sp., Pareiorhaphis parmula, Callichthys callichthys, Neotropical region