Outcome of gastro-oesophageal reflux-related respiratory manifestations after laparoscopic fundoplication.

Abstract:
AIMS
Patients with refractory respiratory symptoms related to gastro-oesophageal reflux disease (GORD) such as asthma and cough are being referred for laparoscopic fundoplication (LFP), as recommended by the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES). However there are limited data regarding symptomatic response to fundoplication in this group of patients.

METHOD
A 7 year retrospective review was performed to study the efficacy of LFP in the treatment of patients with respiratory manifestations of GORD. Patients were followed up from 4 to 6 weeks (short-term) to 6-12 months (long-term) post-operatively.

RESULTS
Of 208 patients who underwent LFP, 73 (35%) patients were eligible for inclusion into the study. 55 (75%) patients had improved respiratory symptoms at short-term follow-up. At long-term follow-up, 7 of these patients had recurrence of respiratory symptoms, while 4 patients had improvement not initially apparent. No significant predictive factor for the success or failure of surgery was identified. 190 (91%) of 208 patients had symptomatic improvement in GORD at short-term follow-up.

CONCLUSION
LFP is effective with the response rates over 75% in the control of respiratory manifestation of GORD, compared to over 91% response rate in the control GOR symptoms alone. More research is needed to identify factors to aid patient selection to improve response rate.

Adaba|Franklin|F|
Ang|Chin W|CW|
Perry|Anthony|A|
Wadley|Martin S|MS|
Robertson|Charles S|CS|

Respiratory manifestations
Laparoscopic fundoplication
Gastro-oesophageal reflux


Effects of two human chorionic gonadotropin doses administered to the ovarian states during the in vitro fertilization and embryo transfer program.

Abstract: The aim of the present study was to examine the effects of the human chorionic gonadotropin (hCG) dose on the pulsatility indices (PI) of the intraovarian artery on the day of follicle aspiration and the oocyte quality, intrafollicular oxidative stress and luteinization. PI was also measured on the day of hCG administration. A total of 15 patients were undergoing the in vitro fertilization and embryo transfer (IVF-ET) program. To estimate whether there was any difference between the intraovarian artery blood flow and oocyte development of the same patients treated with 5,000 or 10,000 IU hCG, the intraovarian artery blood flow was measured by transvaginal color ultrasonography pulsed wave Doppler, and the follicular fluids and the granulosa cells were collected at follicle aspiration. There were statistically significant differences between the same patients undergoing the two different hCG-dose treatments in which the first protocol included 10,000 IU and the second protocol included 5,000 IU hCG treatment. These differences were apparent in the PI of intraovarian artery blood flow on the day of follicle aspiration (P=0.0023), in the incidence of apoptosis in cumulus (ApoC) and mural (ApoM) granulosa cells (ApoC, P=0.0077; ApoM, P=0.0128), in the total oocytes retrieved (P=0.0342) and in the follicle fluid progesterone concentration (P=0.0044). There were no significant differences between the two protocols in the PI of intraovarian artery blood flow on the day of hCG administration (P=0.4326), serum steroid on the day of follicle aspiration [serum P, P>0.9999; serum estradiol (E2), P=0.8589], follicle fluid E2 concentration (P=0.8939), mature oocyte rate (P=0.3743) and total mature oocytes retrieved (P=0.2026). In conclusion, the dose of hCG administration can significantly affect the intraovarian artery blood flow and the development of follicles and oocytes in an IVF-ET program.

Ma|Mingxing|M| Wang|Jialin|J| Xu|Lijun|L| Zhang|Qinxi|Q| DU|Botao|B| Jiang|Xiaoying|X| Shi|Qingli|Q| Zhou|Lili|L| Li|Baoxin|B| Saito|Hidekazu|H| Kurachi|Hirohisa|H|

human chorionic gonadotropin
intraovarian artery blood flow
granulosa cells
oocyte maturation
pulsatility index


Evaluation of the effect of time dependent dosing on pharmacokinetic and pharmacodynamics of amlodipine in normotensive and hypertensive human subjects.

Abstract: In clinical practice, circadian rhythms play a prominent role in pharmacokinetics and cell responses to therapy, hence necessitating in designing a defined protocol for drug administration. Clinical evidence for chronopharmacological behavior of cardiovascular active drugs in human subjects has been limited for amlodipine. Hence, the present study was undertaken to study the chronopharmacokinetic and chronopharmacodynamic phenomena of amlodipine and evaluate the effect of time of dosage in hypertensive subjects. Single oral dose of amlodipine was administered to the hypertensive/normotensive subjects either morning or evening to assess the pharmacokinetic profile after morning dosing or evening dosing, respectively. PK parameters obtained revealed that Tmax was shorter and Cmax was greater after evening dosing than the morning dosing in both hypertensive and normotensive subjects. These observations were comparable with the hypothesis that amlodipine is absorbed rapidly when it is given during the night time. Also, the changes in systolicBP, DiastolicBP, and heart rate in comparison to the respective circadian baseline values were markedly different depending on the time and dosing. SBP and HR were significantly reduced after evening dosing with slight difference in measurement of DBP in hypertensive patients. Hence, it can be concluded that prescription of antihypertensive medications containing amlodipine, to be administered at night offers highly efficacious means to control BP without the need to increase either the dose or number of medications. The current treatment strategy method involves delivery of medications, so that they are synchronized in time to biological need that varies according to the chronobiology of the targeted tissues.

Khodadoustan|Samira|S|
Nasri Ashrafi|Iran|I|
Vanaja Satheesh|K|K|
Kumar|Chethan|C|
Hs|Shekar|S|
S|Chikkalingaiah|C|

D018660:Blood Pressure Monitoring, Ambulatory

Amlodipine normotensive hypertensive chronopharmacokinetics chronopharmacodynamic


Supporting laparoscopic general surgery training with digital technology: The United Kingdom and Ireland paradigm.

Abstract: Surgical training in the UK and Ireland has faced challenges following the implementation of the European Working Time Directive and postgraduate training reform. The health services are undergoing a digital transformation; digital technology is remodelling the delivery of surgical care and surgical training. This review aims to critically evaluate key issues in laparoscopic general surgical training and the digital technology such as virtual and augmented reality, telementoring and automated workflow analysis and surgical skills assessment. We include pre-clinical, proof of concept research and commercial systems that are being developed to provide solutions. Digital surgical technology is evolving through interdisciplinary collaboration to provide widespread access to high-quality laparoscopic general surgery training and assessment. In the future this could lead to integrated, context-aware systems that support surgical teams in providing safer surgical care.

Digital technology
Surgical training
Telementoring
Artificial intelligence
Laparoscopic surgery
Nontechnical skills
Simulation
Virtual reality mobile application


New-Onset Diabetes in the Setting of Beta-Cell Dysfunction in a Young Patient With COVID-19 Infection.

Abstract: Reciprocal relationships between viral illness and chronic diseases have been established. Such relationships augment one another and increase the potential harm. The coronavirus 2019 pandemic proved that the most vulnerable populations are the ones with underlying chronic diseases, especially diabetes mellitus. As new data are evolving, viral illnesses, like COVID-19, have been speculated to potentially induce diabetes mellitus. Here we report a 20-year-old male with no past medical history who presented with polyuria, polydipsia, and dry mouth. He was found to have significant hyperglycemia. He had COVID-19-like symptoms a few weeks prior to admission and was tested positive for COVID-19, but the symptoms had resolved prior to his presentation. He was managed with intravenous fluids (IVFs), electrolytes replacement, and insulin. He was diagnosed with new-onset diabetes mellitus likely secondary to a recent COVID-19 infection and was discharged home on insulin, oral antidiabetic medications, and outpatient follow-up with primary care clinic and endocrinology clinic.

Alshamam|Mohsen S|MS|
Nso|Nso|N|
Idrees|Zarwa|Z|
Iqbal|Saba|S|
Ghernautan|Victoria|V|
Sumbly|Vikram|V|
Agladze|Mariam|M|
Khan|Saifullah|S|
Sachmechi|Issac|I|

beta-cell dysfunction
covid hyperglycemia
covid-19 and diabetes
post infectious diabetes
sars-cov-2


Evaluating an emergency department-based mental health liaison nurse service: A multi-site translational research project.

Abstract:
OBJECTIVE
We aimed to translate and evaluate a model of mental health liaison nursing (MHLN) care that was embedded within EDs.

METHODS
The 12 month mixed-methods translational research study incorporated descriptive data on ED presentations, waiting times for MHLN intervention, time spent in ED and discharge arrangements across three EDs in New South Wales. The study involved an inner-city ED (where the model was first established) and two rural sites. Surveys were conducted on a subset of ED patients (n = 58), and emergency and psychiatry staff (n = 52).

RESULTS
Triage category 3 presentations accounted for 49% of the MHLN team workload. Response times and ED length of stay varied between city and rural sites, with rural sites demonstrating prompt response times and reduced ED length of stay. The model was strongly endorsed by patients and staff, with 95% of staff and 85% of patients across the three sites recommending the model be implemented in other emergency settings. The need for adequate resources to maintain designated levels of staffing and sustain this model of care was highlighted.

CONCLUSION
Findings from the present study indicate that a model of ED-based MHLN care developed in a metropolitan setting was successfully translated to two rural sites. However, the model needs to adhere to certain key principles, and be adequately resourced in order to be sustainable and improve outcomes for ED patients and access to community care.

mental health
translational research
emergency department
patient satisfaction
staff satisfaction


BMP-2 upregulates the AKT/mTOR pathway in breast cancer with microcalcification and indicates a poor prognosis.

Abstract:
BACKGROUND
As a reliable biomarker of breast cancer, breast microcalcification has been reported to be correlated with poor prognosis. Bone morphogenetic protein 2 (BMP-2) plays an important role in microcalcification of breast cancer. Studies in other tissues have shown an association between BMP-2 and AKT/mTOR pathway, while their relationship in breast cancer still remains largely undetermined. To clarify the relationship of these three factors, we collected patients of invasive breast cancer with/without microcalcification and immunohistochemical examination was performed.

METHOD/PATIENTS
A total of 272 patients with primary invasive breast cancer were selected from the First Hospital of China Medical University from January 2010 to January 2012. Immunohistochemical examination of the BMP-2, p-AKT and p-mTOR was performed on 4-µm tissue microarray (TMA) sections. Then, we analyzed the relationship of BMP-2, p-AKT, and p-mTOR and their correlation with disease-free survival (DFS) in breast cancer with/without microcalcification.

RESULTS
We found that breast cancer patients with microcalcification were correlated with HER-2 positive expression and poor prognosis. Immunohistochemical examination showed that the expressions of BMP-2 and p-mTOR were increased in breast cancer with microcalcification and the expressions of BMP-2, p-AKT, and p-mTOR were correlated with each other. Moreover, the high expressions of BMP-2, p-AKT, and p-mTOR were significantly correlated with poor prognosis.

CONCLUSIONS
Based on the abovementioned findings, we hypothesized that the high expression of BMP-2 not only played a vital role in the formation of microcalcification, but also activated the AKT/mTOR pathway. Collectively, breast cancer patients with microcalcification were more likely to be resistant to targeted or endocrine therapy and be correlated with poor prognosis.

BMP-2
AKT
mTOR
Breast cancer
Microcalcification
Prognosis


National German Guideline (S2k): Guideline for the Diagnosis and Treatment of Endometriosis: Long Version - AWMF Registry No. 015-045.

Abstract: In this guideline, recommendations and standards for optimum diagnosis and treatment of endometriosis are presented. They are based on the analysis of the available scientific evidence as published in prospective randomized and retrospective studies as well as in systematic reviews. The guideline working group consisted of experts from Austria, Germany, Switzerland, and the Czech Republic.

Ulrich|U|U|
Buchweitz|O|O|
Greb|R|R|
Keckstein|J|J|
von Leffern|I|I|
Oppelt|P|P|
Renner|S P|SP|
Sillem|M|M|
Stummvoll|W|W|
De Wilde|R-L|RL|
Schweppe|K-W|KW|
|||

endometriosis
health care
laparoscopy
reproductive medicine


School Factors and Alcohol Use: The Moderating Effect of Nativity in a National Sample of Latino Adolescents.

Abstract:
BACKGROUND
School is an important developmental context for adolescents and may be related to adolescent alcohol use. Less is known as to whether the relationships between school factors and alcohol use differ between Latino youth born outside of the United States versus those born in the United States.

OBJECTIVE
The aim of this study is to test nativity as a moderator of the relationship between school factors and alcohol use among Latino adolescents.

METHODS
This study used data from Waves I and II of the National Longitudinal Study of Adolescent Health (Add Health) to test nativity as a moderator of the relationship between school factors and alcohol use in a subsample of Latino adolescents.

RESULTS
Results found that during adolescence, nativity moderates the relationship between school connectedness and Wave I alcohol use. For those born outside of the United States, school connectedness was not related to alcohol use. Significant main effects emerged for grades in school and truancy. Better grades were associated with less alcohol use, while truancy was associated with greater alcohol use. The longitudinal relationships between school factors and Wave II alcohol use were not statistically significant.

CONCLUSIONS
School connectedness is a contemporaneous risk factor for alcohol use among those born in the United States. Prevention efforts that address school contextual factors may be important for all Latino students to reduce engagement in alcohol use and optimize well-being.

Vaughan|Ellen L|EL|
Martinez|Sylvia|S|
Escobar|Oscar S|OS|
Denton|Lisa K|LK|

alcohol use
nativity
Adolescents
school connectedness
truancy
Hispanic/Latino


Molecular phylogeography of the brown bear (Ursus arctos) in Northeastern Asia based on analyses of complete mitochondrial DNA sequences.

Abstract: To further elucidate the migration history of the brown bears (Ursus arctos) on Hokkaido Island, Japan, we analyzed the complete mitochondrial DNA (mtDNA) sequences of 35 brown bears from Hokkaido, the southern Kuril Islands (Etorofu and Kunashiri), Sakhalin Island, and the Eurasian Continent (continental Russia, Bulgaria, and Tibet), and those of four polar bears. Based on these sequences, we reconstructed the maternal phylogeny of the brown bear and estimated divergence times to investigate the timing of brown bear migrations, especially in northeastern Eurasia. Our gene tree showed the mtDNA haplotypes of all 73 brown and polar bears to be divided into eight divergent lineages. The brown bear on Hokkaido was divided into three lineages (central, eastern, and southern). The Sakhalin brown bear grouped with eastern European and western Alaskan brown bears. Etorofu and Kunashiri brown bears were closely related to eastern Hokkaido brown bears and could have diverged from the eastern Hokkaido lineage after formation of the channel between Hokkaido and the southern Kuril Islands. Tibetan brown bears diverged early in the eastern lineage. Southern Hokkaido brown bears were closely related to North American brown bears.

Hirata|Daisuke|D|
Mano|Tsutomu|T|
Abramov|Alexei V|AV|
Baryshnikov|Gennady F|GF|
Kosintsev|Pavel A|PA|
Vorobiev|Alexandr A|AA|
Raichev|Evgeny G|EG|
Tsunoda|Hiroshi|H|
Kaneko|Yayoi|Y|
Murata|Koichi|K|
Fukui|Daisuke|D|
Masuda|Ryuichi|R|

phylogeography
brown bear
Ursus arctos
complete mitochondrial DNA
Hokkaido


Neurovascular Coupling During Visual Stimulation in Multiple Sclerosis: A MEG-fMRI Study.

Abstract: The process of neurovascular coupling ensures that increases in neuronal activity are fed by increases in cerebral blood flow. Evidence suggests that neurovascular coupling may be impaired in Multiple Sclerosis (MS) due to a combination of brain hypoperfusion, altered cerebrovascular reactivity and oxygen metabolism, and altered levels of vasoactive compounds. Here, we tested the hypothesis that neurovascular coupling is impaired in MS. We characterized neurovascular coupling as the relationship between changes in neuronal oscillatory power within the gamma frequency band (30-80 Hz), as measured by magnetoencephalography (MEG), and associated hemodynamic changes (blood oxygenation level dependent, BOLD, and cerebral blood flow, CBF) as measured by functional MRI. We characterized these responses in the visual cortex in 13 MS patients and in 10 matched healthy controls using a reversing checkerboard stimulus at five visual contrasts. There were no significant group differences in visual acuity, P100 latencies, occipital gray matter (GM) volumes and baseline CBF. However, in the MS patients we found a significant reduction in peak gamma power, BOLD and CBF responses. There were no significant differences in neurovascular coupling between groups, in the visual cortex. Our results suggest that neuronal and vascular responses are altered in MS. Gamma power reduction could be an indicator of GM dysfunction, possibly mediated by GABAergic changes. Altered hemodynamic responses confirm previous reports of a vascular dysfunction in MS. Despite altered neuronal and vascular responses, neurovascular coupling appears to be preserved in MS, at least within the range of damage and disability studied here.

Stickland|Rachael|R|
Allen|Marek|M|
Magazzini|Lorenzo|L|
Singh|Krish D|KD|
Wise|Richard G|RG|
Tomassini|Valentina|V|

neurovascular coupling
Multiple Sclerosis
cerebral blood flow
magnetoencephalography
functional MRI
visual function


The number of injected same-day preschool vaccines relates to preadolescent needle fear and HPV uptake.

Abstract:
PURPOSE
Fear of needles develops at approximately five years of age, and decreases compliance with healthcare. We sought to examine the relationship of preschool vaccine history, parent and preadolescent needle fear, and subsequent compliance with optional vaccines.

METHODS
As part of a private practice randomized controlled trial, parents and 10-12year olds rated needle anxiety on a 100mm visual analog scale. This follow-up cohort study compared their needle anxiety to previous vaccination records, including number of vaccinations between ages four and six years (total and same-day maximum), and subsequent initiation of the HPV vaccine through age 13.

RESULTS
Of the 120 preadolescents enrolled between 4.28.09 and 1.19.2010, 117 received preschool vaccinations between ages four and six years. The likelihood of being in the upper quartile of fear (VAS≥83) five years later increased with each additional same-day injection (OR=3.108, p=0.0100 95%CI=1.311, 7.367), but was not related to total lifetime or total four-to-six year injections. Only 12.5% (15) of parents reported anxiety about their preadolescents' vaccines (VAS>50). Parent and child anxiety was weakly correlated (r=0.15). Eight children in the upper fear quartile began their HPV series (26.67%) compared to 14 in the lower quartile (48.28% VAS<32) (OR 2.57, p=0.0889, 95%CI 0.864-7.621); there was no difference in HPV uptake between upper and lower quartile of parent anxiety.

CONCLUSIONS
The more same-day preschool injections between 4 and 6years of age, the more likely a child was to fear needles five years later. Preadolescent needle fear was a stronger predictor than parent vaccine anxiety of subsequent HPV vaccine uptake.

Baxter|Amy L|AL|
Cohen|Lindsey L|LL|
Burton|Mark|M|
Mohammed|Anaam|A|
Lawson|M Louise|ML|

Needle fear
HPV
Adherence
Pain
Vaccine Hesitancy
phobia


Early exposure to distinct sources of lipids affects differently the development and hepatic inflammatory profiles of 21-day-old rat offspring.

Abstract:
Introduction
Maternal diet composition of fatty acids during pregnancy and lactation seems to modify the fetal programming, epigenetic pattern and offspring phenotype.

Aim
Herein, we investigated the effects of maternal consumption of normal-fat diets with distinct lipid sources during pregnancy and lactation on the somatic development and proinflammatory status of 21-day-old rat offspring.

Materials and Methods
On the first day of pregnancy, female Wistar rats were divided into four groups as follows: soybean oil (M-SO), lard (M-L), hydrogenated vegetable fat (M-HVF) and fish oil (M-FO). Diets were maintained during pregnancy and lactation. Male offspring constituted the SO, L, HVF and FO groups. Pups were weighed and measured weekly. Lipopolysaccharide serum concentration was determined. Tumor necrosis factor alpha, interleukin (IL)-6 and IL-10 in the liver were evaluated by enzyme-linked immunosorbent assay. Liver gene expressions were determined by real-time polymerase chain reaction. Protein expressions in the liver were analyzed by Western blotting.

Results
We observed an increase in body weight and adiposity in L and HVF groups. Moreover, HVF group showed an increase in the toll-like receptor 4 mRNA levels, IL10Rα and phosphorylated form of IκB kinase (IKK; p-IKKα+β) protein expression. The FO group presented a decrease in body weight, relative weight of retroperitoneal adipose tissue, ADIPOR2 gene expression, lipopolysaccharide and p-IKKα+β and phosphorylated form of nuclear transcription factor kappa B (NFκB) p50 (p-NFκB p50) protein expression.

Conclusion
Summarily, whereas maternal intake of normal-fat diets based on L and HVF appear to affect the somatic development negatively, only early exposure to HVF impairs the pups' proinflammatory status. In contrast, maternal diets based on FO during pregnancy and lactation have been more beneficial to the adiposity and toll-like receptor 4 signaling pathway of the 21-day-old rat offspring, particularly when compared to L or HVF diets.

do Nascimento|Claudia Maria da Penha Oller|CMDPO|

fatty acids
pregnancy and lactation
proinflammatory status
pups
adiposity


Oncogenic role and therapeutic target of leptin signaling in colorectal cancer.

Abstract:
INTRODUCTION
Obesity is characterized by high secretion of several cytokines from adipose tissue and is a recognized risk factor for many cancers. Among these cytokines, leptin mainly produced by adipose tissue and cancer cells is the most studied adipokine. Leptin is an activator of cell proliferation, an antiapoptotic molecule and inducer of cancer stem cells in many cell types, and its critical roles in obesity-related tumorigenesis are based on its oncogenic, mitogenic, pro-inflammatory and pro-angiogenic actions.

AREAS COVERED
These leptin-induced signals and action are critical for their biological effects on energy balance, adiposity, endocrine systems, immunity, angiogenesis as well as oncogenesis. This review focuses on the up-to-date knowledge on the oncogenic role of leptin signaling, clinical significance and specific drug target development in colorectal cancer (CRC). Additionally, leptin-induced angiogenic ability and molecular mechanisms in CRC cells are discussed.

EXPERT OPINION
Stringent binding affinity of leptin/Ob-R and overexpression of leptin/Ob-R and their targets in cancer cells make it a unique drug target for prevention and treatment of CRC, particularly in obesity colorectal patients.

Zhou|Weiqiang|W| Tian|Yuwang|Y| Gong|Hangjun|H| Guo|Shanchun|S| Luo|Chengyu|C|

leptin
leptin signaling
colorectal cancer
leptin antagonist
tumor angiogenesis


School Breakfast Club Programs in Australian Primary Schools, Not Just Addressing Food Insecurity: A Qualitative Study.

Abstract: Background. Many Australian primary schools have established school breakfast clubs (SBCs) to address concerns about children arriving at school hungry and the subsequent impact on learning but their effectiveness is uncertain. This study aimed to identify the perceived benefits, impacts, operational practices, and challenges of running SBCs. Method. Case studies with 10 Australian primary schools from different socioeconomic and geographic areas. Focus groups or interviews were held with 142 participants including students, parents/carers, school staff, and funding body representatives between July 2016 and October 2017. Results. There were no eligibility criteria to attend SBCs with all students able to attend, regardless of household income. Thus, participating in the SBC was often reported as a matter of choice rather than a consequence of food insecurity. Participants, including children, discussed the many social benefits of SBCs (i.e., social eating, relationship building, school connection, and engagement) as well as perceived improved classroom behavior. Challenges for program delivery included resource limitations, particularly, the reliance on volunteers and sourcing food. Discussion/Conclusion. SBCs offered a range of benefits beyond their primary goal of addressing food security. SBCs were highly valued by members of the school community for their social, welfare, well-being, and educational benefits, but program sustainability is constrained by resource limitations.

Jose|Kim|K|0000-0002-9346-6429
MacDonald|Fiona|F|
Vandenberg|Miriam|M|
Williams|Julie|J|
Abbott-Chapman|Joan|J|
Venn|Alison|A|
Smith|Kylie J|KJ|

well-being
child health
school health
social capital
social connection


Micropulse transscleral cyclophotocoagulation in a Taiwanese population: 2-year clinical outcomes and prognostic factors.

Abstract:
PURPOSE
To evaluate the 2-year efficacy and safety of micropulse transscleral cyclophotocoagulation (MP-TSCPC) in Taiwanese patients with glaucoma.

METHODS
We included the patients who received standardized MP-TSCPC with follow-up examinations on a regular basis for 24 months. Treatment success was defined as the attainment of a postoperative intraocular pressure (IOP) between 6 and 21 mmHg or a ≥ 20% reduction in IOP from baseline without an increase in glaucoma medications.

RESULTS
A total of 60 eyes from 56 patients who underwent MP-TSCPC for refractory glaucoma were included. The median age at MP-TSCPC intervention was 58.9 ± 12.4 years. The percentage of treatment success was 88.3% at 3 months, 83.3% at 6 months, 78.3% at 12 months, and 75.0% at 24 months. The mean baseline IOP prior to MP-TSCPC was 34 ± 11.9 mmHg (range 14-56 mmHg). The mean postoperative IOP decreased to 20.9 ± 10.0 mmHg, 18.0 ± 7.8 mmHg, 17.5 ± 6.4 mmHg, and 18.2 ± 7.1 mmHg after 3 months, 6 months, 12 months, and 24 months, respectively, in successful cases. The mean number of glaucoma medications at baseline was 3.8 ± 0.2, and the mean numbers of glaucoma medications at postoperative months 3, 6, 12, and 24 were 2.6 ± 0.7, 2.8 ± 0.6, 2.5 ± 1.4 and 2.6 ± 1.4, respectively, in successful cases. Younger age and prior CW-TSCPC significantly contributed to surgical failure in the multivariate model. Complications after MP-TSCPC included mild anterior chamber inflammation, conjunctival hemorrhage, hypotony, and mydriasis, and all subsided after treatment. None of the eyes developed vitreous hemorrhage, cystoid macular edema, or phthisis bulbi in the late postoperative period.

CONCLUSIONS
This study demonstrated that younger age and prior CW-TSCPC were risk factors for MP-TSCPC failure within 2 years. MP-TSCPC might be safe and effective for refractory glaucoma patients with maximal antiglaucoma medications.

Micropulse
Glaucoma
Intraocular pressure
Treatment lasers


Electroanatomic guidance versus conventional fluoroscopy during transseptal puncture for atrial fibrillation ablation.

Abstract:
INTRODUCTION
Technological advancement in the setting of atrial fibrillation (AF) ablation has decreased radiation exposure and complications associated with the procedure. Yet, transseptal puncture (TSP) remains a challenging step that necessitates accurate guidance. We describe our experience performing TSP under electroanatomic (EA) guidance.

METHODS AND RESULTS
The analysis included 145 consecutive EA-guided ablation procedures performed between June 2018 and April 2019 and 145 consecutive standard ablations performed before June 2018. EA guidance utilized the CARTO 3 three-dimensional mapping system to reconstruct anatomic and electrical characteristics of the right atrium and fossa ovalis. Patients with a history of previous cardiac surgery were excluded. For EA-guided procedures, the mean patient age was 60 ± 10 years, 75.2% were male, and 69.0% had paroxysmal AF. Similarly, the mean age for conventional procedures was 60 ± 11 years, 71.0% were male, and 71.7% had paroxysmal AF. The fossa ovalis was detected as a region of low voltage, <0.75 mV. EA guidance yielded shorter fluoroscopy times (EA vs. conventional, 3.6 ± 2.5 vs. 13.5 ± 10.5 min; p < .001) and a lower dose area product than conventional guidance (13 ± 11 Gy* cm2 vs. 28 ± 27  Gy* cm2 ; p < .001). The total procedure duration was similar between groups (146 ± 48 vs. 148 ± 54 min). There were no significant complications related to TSP.

CONCLUSION
During AF ablation, TSP with EA guidance facilitated safe access to the left atrium while reducing radiation risk to both patients and operators.

Troisi|Federica|F|0000-0002-4133-2664
Quadrini|Federico|F|
Di Monaco|Antonio|A|0000-0002-1297-2056
Vitulano|Nicola|N|
Caruso|Rosa|R|
Guida|Pietro|P|0000-0002-6936-350X
Langialonga|Tommaso|T|
Grimaldi|Massimo|M|

fluoroscopy
atrial fibrillation
ablation
atrial transseptal puncture
electroanatomic mapping


Isolation and characterization of extracellular polysaccharide Thelebolan produced by a newly isolated psychrophilic Antarctic fungus Thelebolus.

Abstract: The present investigation is on a newly isolated psychrophilic Antarctic filamentous Ascomycetous fungus that has been identified as Thelebolus sp. and given the designation of Thelebolus sp. IITKGP-BT12. The culture was primarily identified through morphological studies, and was further confirmed by 18S rRNA sequencing (GenBank Accession No. KC191572), which revealed its close relatedness with Thelebolus microsporus. The exopolysaccharide (EPS) produced (1.94 g L(-1)) by the fungus was isolated, purified and characterized as glucan having an average molecular mass of 5×10(5)Da. The structure of EPS was determined by gas chromatography with tandem mass spectrometry (GC-MS/MS), Fourier transform infrared spectroscopy (FT-IR) and nuclear magnetic resonance (NMR) studies ((1)H, (13)C and HSQC). NMR analysis indicated the presence of (1→3)-linked β-d-glucan backbone with (1→6)-linked branches of β-d-glucopyranosyl units. Antiproliferative activity of EPS was demonstrated in B16-F0 cells, with IC50 of 275.42 μg m L(-1). Flow cytometry analysis and DNA fragmentation studies revealed that the cytotoxic action of the EPS mediated apoptosis in cancer cells. This is the first ever report on bioactive EPS thelebolan from Thelebolus sp.

Mukhopadhyay|Sourav K|SK|
Chatterjee|Soumya|S|
Gauri|Samiran S|SS|
Das|Shibendu S|SS|
Mishra|Abheepsa|A|
Patra|Moumita|M|
Ghosh|Ananta K|AK|
Das|Amit K|AK|
Singh|Shiv M|SM|
Dey|Satyahari|S|

Psychrophiles Antarctic Thelebolus Exopolysaccharide Glucan Antiproliferative


Multi-tissue integration of transcriptomic and specialized metabolite profiling provides tools for assessing the common bean (Phaseolus vulgaris) metabolome.

Abstract: Common bean (Phaseolus vulgaris L.) is an important legume species with a rich natural diversity of landraces that originated from the wild forms following multiple independent domestication events. After the publication of its genome, several resources for this relevant crop have been made available. A comprehensive characterization of specialized metabolism in P. vulgaris, however, is still lacking. In this study, we used a metabolomics approach based on liquid chromatography-mass spectrometry to dissect the chemical composition at a tissue-specific level in several accessions of common bean belonging to different gene pools. Using a combination of literature search, mass spectral interpretation, 13 C-labeling, and correlation analyses, we were able to assign chemical classes and/or putative structures for approximately 39% of all measured metabolites. Additionally, we integrated this information with transcriptomics data and phylogenetic inference from multiple legume species to reconstruct the possible metabolic pathways and identify sets of candidate genes involved in the biosynthesis of specialized metabolites. A particular focus was given to flavonoids, triterpenoid saponins and hydroxycinnamates, as they represent metabolites involved in important ecological interactions and they are also associated with several health-promoting benefits when integrated into the human diet. The data are presented here in the form of an accessible resource that we hope will set grounds for further studies on specialized metabolism in legumes.

Perez de Souza|Leonardo|L|
Scossa|Federico|F|
Proost|Sebastian|S|
Bitocchi|Elena|E|
Papa|Roberto|R|
Tohge|Takayuki|T|
Fernie|Alisdair R|AR|

transcriptomics
common bean
Phaseolus vulgaris
metabolomics
natural diversity
specialized metabolism


Unethical human research in the field of neuroscience: a historical review.

Abstract: Understanding the historical foundations of ethics in human research are key to illuminating future human research and clinical trials. This paper gives an overview of the most remarkable unethical human research and how past misconducts helped develop ethical guidelines on human experimentation such as The Nuremberg Code 1947 following WWII. Unethical research in the field of neuroscience also proved to be incredibly distressing. Participants were often left with life-long cognitive disabilities. This emphasizes the importance of implicating strict rules and ethical guidelines in neuroscience research that protect participants and respects their dignity. The experiments conducted by German Nazi in the concentration camps during WWII are probably the most inhumane and brutal ever conducted. The Nuremberg Code of 1947, one of the few positive outcomes of the Nazi experiments, is often considered the first document to set out ethical regulations of human research. It consists of numerous necessary criteria, to highlight a few, the subject must give informed consent, there must be a concrete scientific basis for the experiment, and the experiment should yield positive results that cannot be obtained in any other way. In the end, we must remember, the interest of the patient must always prevail over the interest of science or society.

Neuroscience
Ethics
Unethical research
History


Mercury and methylmercury bioaccumulation in a contaminated bay.

Abstract: The bioaccumulation and the main source of total Hg (THg) and methylmercury (MMHg) in the deposit-feeding polychaete Neanthes japonica collected in Jinzhou Bay, China, were investigated. Compared with the historical data, THg bioaccumulation in polychaetes collected in sediment of Jinzhou Bay was distinctly higher due to higher sediment THg concentration, but MMHg bioaccumulation was significantly lower. THg accumulation in polychaetes mainly derived from its accumulation in sediment. However, MMHg bioaccumulation in polychaetes did not correlate with Hg concentration in sediment. Besides sediment ingestion, MMHg accumulation in polychaetes may partially source from the process of in vivo transformation. The in vivo Hg methylation may take place in polychaetes, according to the excellent correlation between MMHg concentration and THg and inorganic Hg concentration in polychaetes. The biochemical characters in polychaete body, the oxidation-reduction environment and the microbial activity in polychaete gut may be beneficial to in vivo Hg methylation.

Xu|Zhizhen|Z| Fan|Wenhong|W| Shi|Zhiwei|Z| Tan|Cheng|C| Cui|Minming|M| Tang|Shichuan|S| Qiu|Guangle|G| Feng|Xinbin|X|

Mercury
Methylmercury
Bioaccumulation
In vivo
Methylation


RalA exerts an inhibitory effect on IL-1β/IL-18 secretion by blocking NLRP3 inflammasome activation in levornidazole-treated human THP-1 macrophages.

Abstract: The NLRP3 inflammasome is an important mediator of inflammatory responses and its regulation is an active area of research. RalA is a Ras-like GTPase, which play pivotal roles in the biology of cells. So far, there have been very few studies on RalA regulating inflammatory responses. Bioinformatics analysis predicted that RalA might participate in the regulatory network of NLRP3 inflammasome, which has been confirmed in THP-1 macrophages. After virtual screening of compounds, it was found that levonidazole selected from our virtual small molecule compound library has the potential to bind to RalA. Of note, the interaction of RalA/levornidazole was verified by Surface Plasmon Resonance-Biacore T200, LC/MS analysis and Western blotting analysis. Molecular dynamics simulations revealed that the conformational changes of RalA might be regulated by levornidazole. Additionally, IL-1β/IL-18 secretion from ATP + LPS stimulated THP-1-derived macrophages was RalA-dependently suppressed by levornidazole, suggesting that RalA might have an inhibitory effect on NLRP3 inflammasome activation. The results of co-immunoprecipitation and RalA depletion experiments showed that levornidazole could induce RalA to block the assembly of NLRP3/ASC/pro-caspase-1 complex, thereby reducing the levels of cleaved-caspase-1 and IL-1β/IL-18 secretion. Our study has suggested an anti-inflammatory function of RalA and identified its targeting chemical compound. Overall, this study clarifies a novel pharmacological mechanism by which RalA/levornidazole inhibits NLRP3 inflammasome activation and IL-1β/IL-18 secretion.

Wang|Xingqi|X| Gou|Lingshan|L| Gao|Yuzhi|Y| Huang|Yuqing|Y| Kuai|Rui|R| Li|Yu|Y| Wang|Yujing|Y| Chen|Yanhong|Y| Li|Jun|J| Cheng|Chao|C| Feng|Zhaojun|Z| Wu|Xuefeng|X| Yao|Ruiqin|R|

D000071199:NLR Family, Pyrin Domain-Containing 3 Protein


Diagnosis of an adenocarcinoma of Müllerian origin made as a result of its metastasis in the mouth floor.

Abstract: Metastases derived from primary tumours distant to the oral and maxillofacial region account for only 1% of all malignancies at that location, usually with a poor prognosis. In women, the primary tumours that most frequently metastasise to the oral cavity are breast adenocarcinomas affecting the jawbones and soft tissues (41% and 24%, respectively), followed by adrenal glands and female genital organs to the jawbones (8%), and female genital organs to the soft tissues (15%). Metastatic tumours of the mouth are a challenging diagnosis because of their exceptional occurrence. We report on the case of an 83-year-old woman who consulted for a bleeding ulcerated tumour on the floor of the mouth. A biopsy-confirmed metastasis of an adenocarcinoma of Müllerian origin. The oral lesion was the first sign of undetected cancer. The patient agreed to surgical resection and was further referred to palliative care for her symptoms.

Gandolfo|Mariana Silva|MS|
Denninghoff|Valeria|V|
Avagnina|Alejandra|A|
Adler|Lidia Isabel|LI|

mouth
gynecological cancer
head and neck cancer
oral and maxillofacial surgery
pathology


Impact of preformed and de novo anti-HLA DP antibodies in renal allograft survival.

Abstract: The influence of antibodies against HLA-DP antigens detected with solid-phase assays on graft survival after kidney transplantation (KT) is uncertain. We evaluated with Luminex® the prevalence of pre- and posttransplant DP antibodies in 440 KT patients and their impact on graft survival. For 291 patients with available pretransplant samples, DP antibodies were present in 39.7% KT with pretransplant HLA antibodies and 47.7% with DSA. Graft survival of KT with pretransplant class-II DSA was worse than with non-DSA (p=0.01). DP antibodies did not influence graft survival. Of 346 patients monitored post-KT, 17.1% had HLA class-II antibodies, 56% with DP antibodies. Class-II DSA was detected in 39%, 60.9% of them had DP antibodies. Graft survival was worse in patients with class-II DSA (p=0.022). DP antibodies did not change these results. The presence of isolated DP antibodies was a rare event both pre- and posttransplantation (1.03 and 0.86%). The presence of pretransplant and posttransplant DSA is associated with a negative impact on graft survival. However, the presence of DP antibodies does not modify this impact significantly.

Redondo-Pachón|Dolores|D|
Pascual|Julio|J|
Pérez-Sáez|María J|MJ|
García|Carmen|C|
Hernández|Juan José|JJ|
Gimeno|Javier|J|
Mir|Marisa|M|
Crespo|Marta|M|

Graft survival
HLA-DP antibodies
Renal transplant


Electrospun Scaffolds Containing Silver-Doped Hydroxyapatite with Antimicrobial Properties for Applications in Orthopedic and Dental Bone Surgery.

Abstract: Preventing the development of osteomyelitis while enhancing bone regeneration is challenging, with relatively little progress to date in translating promising technologies to the clinic. Nanoscale hydroxyapatite (nHA) has been employed as a bone graft substitute, and recent work has shown that it may be modified with silver to introduce antimicrobial activity against known pathogens. The aim of this study was to incorporate silver-doped nHA into electrospun scaffolds for applications in bone repair. Silver-doped nHA was produced using a modified, rapid mixing, wet precipitation method at 2, 5, 10 mol.% silver. The silver-doped nHA was added at 20 wt.% to a polycaprolactone solution for electrospinning. Bacteria studies demonstrated reduced bacterial presence, with Escherichia coli and Staphylococcus aureus undetectable after 96 h of exposure. Mesenchymal stem cells (MSCs) were used to study both toxicity and osteogenicity of the scaffolds using PrestoBlue® and alkaline phosphatase (ALP) assays. Innovative silver nHA scaffolds significantly reduced E. coli and S. aureus bacterial populations while maintaining cytocompatibility with mammalian cells and enhancing the differentiation of MSCs into osteoblasts. It was concluded that silver-doped nHA containing scaffolds have the potential to act as an antimicrobial device while supporting bone tissue healing for applications in orthopedic and dental bone surgery.

Paterson|Thomas E|TE|
Shi|Rui|R|
Tian|Jingjing|J|
Harrison|Caroline J|CJ|
De Sousa Mendes|Mailys|M|
Hatton|Paul V|PV|
Li|Zhou|Z|0000-0002-9952-7296
Ortega|Ilida|I|

antimicrobial
bone regeneration
silver
electrospinning
toxicity
nano-hydroxyapatite


CHC for pelvic pain in women with endometriosis: ineffectiveness or discontinuation due to side-effects.

Abstract:
STUDY QUESTION
What are the use patterns and factors associated with combined hormonal contraception (CHC) ineffectiveness or discontinuation due to side-effects in patients with endometriosis and pelvic pain?

SUMMARY ANSWER
Worse chronic pelvic pain (CPP) severity and pelvic floor myalgia were associated with continuous CHC ineffectiveness, while poorer quality-of-life was associated with continuous CHC discontinuation due to side-effects.

WHAT IS KNOWN ALREADY
CHC is a first line of therapy for endometriosis-associated pelvic pain in women. However, some patients state that CHC is ineffective for their pain, while others have to discontinue CHC due to side-effects.

STUDY DESIGN SIZE DURATION
Analysis of a prospective patient database from a tertiary care referral center for patients with endometriosis and pelvic pain between December 2013 and April 2015 was carried out.

PARTICIPANTS/MATERIALS SETTING AND METHODS
A total of 373 patients of reproductive age with endometriosis from the database were included in the study. Data included patient self-reported questionnaires, physical examination findings and validated instruments. There were four variables of interest: history of cyclical CHC ineffectiveness (yes/no), history of cyclical CHC discontinuation due to side-effects (yes/no), history of continuous CHC ineffectiveness (yes/no) and history of continuous CHC discontinuation due to side-effects (yes/no). The primary outcome was CPP severity for the past 3 months (score of 0-10), and secondary outcomes were other pelvic pain scores, quality-of-life on the Endometriosis Health Profile 30 (EHP-30) and underlying conditions including irritable bowel syndrome, painful bladder syndrome, abdominal wall pain, pelvic floor myalgia and depression, anxiety and pain catastrophizing.

MAIN RESULTS AND THE ROLE OF CHANCE
Among the 373 cases in the dataset, prior cyclical CHC use was reported by 228 (61.1%) women, of which 103 (27.6%) stated it was ineffective for their pain and 94 (25.2%) stated they discontinued CHC due to side-effects. Previous continuous CHC use was reported by 175 (46.9%) women, of which 67 (18.0%) stated it was ineffective and 59 (15.8%) stated they discontinued due to side-effects. Worse CPP severity in the last 3 months was associated with a history of continuous CHC ineffectiveness (P < 0.001). Poorer quality-of-life was present in women who reported a history of continuous CHC discontinuation due to side-effects (P = 0.005). Among the underlying conditions, pelvic floor tenderness (as a marker of pelvic floor myalgia) was associated with CHC ineffectiveness.

LIMITATIONS AND REASONS FOR CAUTION
This study involved patient recall and no longitudinal follow-up. Also, we do not have data on the type of side-effect that led to discontinuation. Medication ineffectiveness was reported subjectively by the patient rather than using standardized criteria. Finally, the diagnosis of endometriosis was based on previous surgery or a current nodule or endometrioma on examination/ultrasound; without prospective surgical data on all the patients, it was not possible to do a sub-analysis by current surgical features (e.g. stage).

WIDER IMPLICATIONS OF THE FINDINGS
In women with endometriosis, CHC ineffectiveness was associated with worse CPP and pelvic floor myalgia, which suggests myofascial or nervous system contributors to CPP that does not respond to hormonal suppression. A tender pelvic floor, as a sign of pelvic floor myalgia, may be a clinical marker of patients with endometriosis who are less likely to have an optimal response to hormonal suppression. For women who discontinue CHC due to side-effects, research is needed to help alleviate these side-effects as these patients report worse quality-of-life.

STUDY FUNDING/COMPETING INTERESTS
This work was supported by a Canadian Institutes of Health Research (CIHR) Transitional Open Operating Grant (MOP-142273) as well as BC Women's Hospital and the Women's Health Research Institute. PY is also supported by a Health Professional Investigator Award from the Michael Smith Foundation for Health Research. MB/CA has financial affiliations with Abbvie and Allergan; the other authors have no conflicts of interest.

endometriosis
combined hormonal contraception
chronic pelvic pain
pelvic floor myalgia
combined oral contraceptives


Role of Hepatocyte Paraffin 1 antigen in the course of colorectal carcinogenesis.

Abstract:
BACKGROUND
Few studies have reported the expression of Hepatocyte Paraffin 1 (Hep Par 1) in colorectal carcinomas with contradictory results. Reported rate of expression ranged from 4-50%. Moreover, the correlation between Hep Par 1 expression and clinicopathological parameters has not been investigated. The objective of the present study was to investigate the role of CPS1 (using Hep Par 1) in colonic carcinogenesis and characterize carcinomas which express it.

MATERIAL AND METHOD
Comparative analysis was done between Hep Par 1 expression in normal colonic mucosa (n=10), adenomatous polyps (n=29) and sporadic adenocarcinoma (n=40) and was correlated with clinicopathologic parameters.

RESULTS
Normal colonic mucosa did not express Hep Par 1. In contrast, it was expressed in dysplastic glands and neoplastic cells of well-moderately differentiated non-mucinous adenocarcinomas. Hep Par 1 was found in 47.5% of colonic carcinomas, 41.7% of polyps with high grade dysplasia (HGD) and 23.5% of polyps with low grade dysplasia (LGD). Mean Hep Par-1 score, likewise, was highest in carcinoma, high in polyps with HGD and lowest in polyps with LGD. Hep Par 1 expression inversely correlated with some conventional prognostic parameters including tumour type, grade, lymph node metastasis and AJCC stage. It did not correlate with depth of invasion or lymphovascular invasion.

CONCLUSION
Hep Par 1 (i.e. CPS1) might play an active role in initiation of dysplasia and progression of multistep colorectal carcinogenesis. However, it seems that CPS1 is not involved in invasion and tumour spread. Conversely, it might be in the play of suppressing cancer progression. These findings could have both prognostic and therapeutic applications.

Hep Par 1
Adenomatous polyp
colonic carcinoma
progression


Custom-made 3D-printed prosthesis and free vascularised fibula for humeral reconstruction after osteosarcoma resection in a 13-year-old patient.

Abstract: Surgical reconstruction after humeral resection represents a challenging issue in orthopaedic oncology. Particularly in paediatric patients, the main concerns are maintaining limb function and reconstruction longevity. We describe a novel strategy of humeral reconstruction based on the use of a three-dimensional-printed custom-made prosthesis in a 13-year-old patient diagnosed with osteosarcoma. The implant was specifically designed to sustain the native head, which was spared, as it was not involved by the neoplastic tissue. The mechanical support the prosthesis provided was associated with the biological stimulus of a free vascularised fibular graft to obtain an anatomic, functional and stable construct. This solution has had good longevity, and after 3 years of follow-up, the patient still shows excellent limb function and personal satisfaction.

Beltrami|Giovanni|G|
Nucci|Anna Maria|AM|
Tamburini|Angela|A|
Innocenti|Marco|M|

orthopaedics
paediatric oncology
plastic and reconstructive surgery


Comparison of Thessaly Test with Joint Line Tenderness and McMurray Test in the Diagnosis of Meniscal Tears.

Abstract:
Introduction
Meniscus injuries are the most frequent problem of the knee. The aim of this study was to investigate the accuracy of the Thessaly test and comparing it with those of McMurray and Joint-line tenderness tests for diagnosing meniscal tears.Materials and methods: This study was designed as a prospective observational one done in an outpatient clinic at a university hospital. 106 patients with knee pain and 82 age-matched control were included during study period (from February 2014 to January 2015). Each patient was clinically examined with McMurray, Thessaly, and joint line tenderness tests. Then, the findings were matched by MRI and arthroscopic findings. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy were calculated as main outcomes.

Results
Based on MRI, Thessaly was the most sensitive for medial meniscus tears (56.2%), while McMurray and joint-line tenderness were more specific (89.1% and 88.0%, respectively). For lateral meniscus tears, McMurray was the most sensitive (56.2%) and all were specific (McMurray 89.6%, Thessaly 88.4%, joint-line tenderness 90.2%). With arthroscopy, Thessaly was the most sensitive for medial meniscus (76.6%), while McMurray and joint-line tenderness were more specific (81.0%, and 81.0%). Agreement with arthroscopy was the highest with McMurray (for medial meniscus kappa=0.40, p<0.001, and for lateral meniscus kappa=0.38, p=0.002).

Conclusion
The Thessaly can be used to screen for medial meniscus tears. McMurray and joint-line tenderness should be used for suspected medial meniscus tears. For lateral meniscus, McMurray is appropriate for screening and all the tests are useful in clinic.

Shekarchi|B|B|
Panahi|A|A|
Raeissadat|S A|SA|
Maleki|N|N|
Nayebabbas|S|S|
Farhadi|P|P|

Thessaly
joint line tenderness
McMurray
meniscal tears


Epac1-/- mice have elevated baseline permeability and do not respond to histamine as measured with dynamic contrast-enhanced magnetic resonance imaging with contrast agents of different molecular weights.

Abstract:
AIM
Epac1-/- mice, but not Epac2-/- mice have elevated baseline permeability to albumin. This study extends the investigations of how Epac-dependent pathways modulate transvascular exchange in response to the classical inflammatory agent histamine. It also evaluates the limitations of models of blood-to-tissue exchange in transgenic mice in DCE-MRI measurements.

METHODS
We measured DCE-MRI signal intensity in masseter muscle of wt and Epac1-/- mice with established approaches from capillary physiology to determine how changes in blood flow and vascular permeability contribute to overall changes of microvascular flux. We used two tracers, the high molecular weight tracer (Gadomer-17, MW 17 kDa, apparent MW 30-35 kDa) is expected to be primarily limited by diffusion and therefore less dependent on changes in blood flow and the low molecular weight tracer (Dotarem (MW 0.56 kDa) whose transvascular exchange is determined by both blood flow and permeability. Paired experiments in each animal combined with analytical methods provided an internally consistent description of microvascular transport.

RESULTS
Epac1-/- mice had elevated baseline permeability relative to wt control mice for Dotarem and Gadomer-17. In contrast to wt mice, Epac1-/- mice failed to increase transvascular permeability in response to histamine. Dotarem underestimated blood flow and vascular volume and Gadomer-17 has limited sensitivity in extravascular accumulation.

CONCLUSION
The study suggests that the normal barrier loosening effect of histamine in venular microvessels do not function when the normal barrier tightening effect of Epac1 is already compromised. The study also demonstrated that the numerical analysis of DCE-MRI data with tracers of different molecular weight has significant limitations.

D020662:Guanine Nucleotide Exchange Factors

histamine
Dotarem
Epac1
capillary permeability
compartment model
deconvolution


Promiscuous activation of transient receptor potential vanilloid 1 (TRPV1) channels by negatively charged intracellular lipids: the key role of endogenous phosphoinositides in maintaining channel activity.

Abstract: The regulation of the heat- and capsaicin-activated transient receptor potential vanilloid 1 (TRPV1) channels by phosphoinositides is controversial. Data in cellular systems support the dependence of TRPV1 activity on phosphoinositides. The purified TRPV1, however, was recently shown to be fully functional in artificial liposomes in the absence of phosphoinositides. Here, we show that several other negatively charged phospholipids, including phosphatidylglycerol, can also support TRPV1 activity in excised patches at high concentrations. When we incorporated TRPV1 into planar lipid bilayers consisting of neutral lipids, capsaicin-induced activity depended on phosphatidylinositol 4,5-bisphosphate. We also found that TRPV1 activity in excised patches ran down and that MgATP reactivated the channel. Inhibition of phosphatidylinositol 4-kinases or enzymatic removal of phosphatidylinositol abolished this effect of MgATP, suggesting that it activated TRPV1 by generating endogenous phosphoinositides. We conclude that endogenous phosphoinositides are positive cofactors for TRPV1 activity. Our data highlight the importance of specificity in lipid regulation of ion channels and may reconcile discordant data obtained in various experimental settings.

Lukacs|Viktor|V| Rives|Jan-Michael|JM| Sun|Xiaohui|X| Zakharian|Eleonora|E| Rohacs|Tibor|T|

TRPV1
Phosphoinositides
Ion Channels
Electrophysiology
Inositol Phospholipid
TRP Channels


How to Study the Proteomes and Phosphoproteomes of Anther and Pollen.

Abstract: Proteomics analysis was a powerful technology for characterizing proteins and protein posttranslational modification (PTMs). Recently, many anther and pollen-related proteomic analyses have been reported, which have expanded our understanding of anther and pollen development and regulation. In this chapter, we describe a detailed, optimized protocol for the separation, digestion, tagging, and subsequent mass spectrometry-based identification and quantification of proteins and phosphoproteins from anther and pollen.

Zhang|Chi|C| Feng|Xiaobing|X| Hu|Menghui|M| Zhang|Zaibao|Z|

Liquid chromatography–mass spectrometry (LC-MS/MS)


Prevalence of latent tuberculosis infection, hepatitis B, hepatitis C, and syphilis among newly arrived unaccompanied minors living in reception centers in Rome.

Abstract:
OBJECTIVE
This study aimed to address the prevalence of infectious diseases in a population of unaccompanied immigrant minors living in reception centres of Rome, Italy.

METHODS
The study was carried out from January 2013 to January 2019. All unaccompanied immigrant minors were screened for hepatitis B, hepatitis C, syphilis and latent tuberculosis infection.

RESULTS
A total of 879 unaccompanied immigrant minors, 858 males and 21 females, aged 13-18 years old were studied. Of these, 615 were from Africa, 179 from Asia and 84 from Eastern Europe. A low prevalence of HBsAg carriage (2.5%) was observed as was very low prevalence of hepatitis C (0.72%) and latent syphilis (0.4%); latent tuberculosis, defined as tuberculin skin test (TST)+ X-ray case, was diagnosed in 102 (12%) minors.

CONCLUSIONS
Similar to previous studies, these data demonstrate that migrant minors are generally healthy. However, given the relatively high prevalence of hepatitis B and latent tuberculosis, systematic screening for these diseases among immigrant minors immigrants is highly recommended for early detection and treatment of potentially transmissible diseases.

Marrone|Rosalia|R| Baglio|Giovanni|G| Bruscino|Giusy|G| Costanzo|Gianfranco|G| Cavani|Andrea|A| Mirisola|Concetta|C|

Tuberculosis
Hepatitis
Syphilis
Infectious diseases
Screening
Unaccompanied migrant minors


Immunopathological and Modulatory Effects of Cag A Genotype on Gastric Mucosa, Inflammatory Response, Pepsinogens, and Gastrin-17 Secretion in Iraqi Patients infected with H. pylori.

Abstract:
OBJECTIVE
To determine the immunopathological correlation between Cag A+ H. pylori-specific IgG; pepsinogen I&II (PI&PII); gastrin-17 (G-17); status of gastric and duodenal mucosa and inflammatory activities on different gastroduodenal disorders.

METHODOLOGY
Eighty gastroduodenal biopsies were taken from patients with gastroduodenal disorders for histopathological evaluation and H. pylori diagnosis. Serum samples were used for evaluation of gastric hormones and detection of H. pylori-specific IgG antibodies. The tissue expression of H. pylori Cag A gene was detected by in situ hybridisation.

RESULTS
H. pylori IgG antibodies were detected in (88.8%) of enrolled patients. According to Cag A gene expression, Significant difference (P value ˂ 0.05) was detected in levels of PG I; PGII, PG I/PG II among patients with gastric disorders. Serum G-17 level was negatively correlated with Cag A gene expression (P-value = 0.04). There was a significant correlation between H. pylori IgG and PG I; PG II; G-17. The current study revealed that corpus atrophic gastritis was diagnosed histologically with (5%) gastric ulcer cases; (3.75%) of duodenal ulcer cases; (3.75%) of duodenitis cases; (1.25%) of gastropathy cases and (8.75%) of gastritis cases. At the same time H. pylori gastritis diagnosed concurrently with (8.75%) of gastric ulcer cases; (11.25%) of duodenal ulcer cases; (17.5%) of gastropathy cases; (3.75%) of duodenitis cases and (2.5%) of prepyloric ulcer cases. A significant correlation was reported between the Immunopathological status of gastric mucosa and endoscopic mucosal finding among duodenal ulcer cases and gastritis cases only. A positive correlation was reported between serum levels of PGI; PGII; PGI/PGII; G-17; PMNs grade and Immunopathological status of the gastroduodenal mucosa of H. pylori Infected patients. A significant difference was reported in lymphocyte grades among gastric disorders without correlation with immunohistopathological changes in the mucosa (P-value = 0.002). A significant difference was reported in lymphocyte grades among different disorders according to H. pylori IgG. A significant difference was reported in serum level of PG I; PG II; PG I/PG II; G-17 according to PMN and lymphocyte grades (P-value ˂ 0.01). PMNs grades positively correlated with gastric Cag A expression; H. pylori IgG; PG II; G-17 levels. PG I; PG I/ PG II correlated with lymphocyte grades (P-value ˂ 0.05); while PGII has a negative correlation (P-value = 0.039).

CONCLUSION
Endoscopic mucosal finding does not reflect exactly the actual immunopathological changes of gastric mucosa during H. pylori infection. Secretion of gastrin was not affected by the presence of Cag A in gastric tissue. Instead, the fluctuation in the hormone level appears to be due to the presence of H. pylori infection in gastric tissue. Gastric tissue infiltration with PMNs & lymphocytes inflammatory infiltrates has a direct effect on PGs and gastrin levels in serum of infected patients. The level of PG I; PG II; G-17 secretion correlated with the development of immune response against H. pylori and production of specific H. pylori IgG. Finally, H. pylori can modulate gastric secretions through Cag A dependent and independent pathways.

gastric mucosa
pepsinogens
gastrin-17
H. pylori
CagA
Iraq


Using Metabolic and Biochemical Indicators to Predict Diabetic Retinopathy by Back-Propagation Artificial Neural Network.

Abstract:
Purpose
Timely diagnosis of diabetic retinopathy (DR) can significantly improve the prognosis of patients. In this study, we established a prediction model by analyzing the relationship between diabetic retinopathy and related metabolic and biochemical indicators.

Methods
A total of 427 type 2 diabetes mellitus (T2DM) patients were selected from the datadryad website data. Logistic regression (MLR) was used to input layer variables of the model were screened. Then, Tan-Sigmoid was selected as the transfer function of the hidden layer node, and the linear function was used as the output layer function to establish the back propagation artificial neural network (BP-ANN) model. The model was applied to 183 patients with type 2 diabetes mellitus (T2DM) in our hospital to predict DR.

Results
A total of 167 patients (39.2%) with DR were obtained from the Datadryad database. Input variables were screened by MLR model, and it was concluded that the age, sex, albumin and creatinine, diabetes course were independently associated with the occurrence of DR. The above variables were used to establish BP-ANN model. The area under receiver operating characteristic curve (AUC) was significantly higher than that of MLR model (0.88 vs 0.74, P<0.05), the probability threshold of the model was 0.3. Type 2 diabetes mellitus (T2DM) were selected in our hospital, including 92 patients with DR (50.2%). The above BP-ANN model was used to predict the incidence of DR, and the AUC area was significantly higher than that of the MLR model (0.77 vs 0.70, P<0.05), the probability threshold was 0.7.

Conclusion
We established the BP-ANN model and applied it to diagnose DR. Taking diabetic course, age, sex, albumin and creatinine as the inputs of BP-ANN, the existence of DR could be well predicted. Meanwhile, the generalization ability of the model could be improved by selecting different probability thresholds in different ROC curves.

diabetic retinopathy
type 2 diabetes
BP-ANN
probability threshold


Effects of environmental tobacco smoke on the oral health of preschool children.

Abstract:
AIMS
This study investigated the association between the prevalence of oral health problems (caries, gingivitis, mucosal pigmentation and enamel defects in one to 5 year-old children exposed and not exposed to environmental tobacco smoke before and/or after birth. Exposure to environmental tobacco smoke (ETS) in childhood may have significant health effects.

METHODS
A structured questionnaire was used to collect data on a child's current and previous illnesses, oral health behaviours, dietary habits, parental smoking behaviours and parents' dental history. The intraoral examination recorded dental caries (dmfs), enamel defects, gingival health, melanin pigmentation and soft tissue health. Stimulated saliva was collected. Total sIgA levels were quantified using indirect competitive ELISA with a SalimetricsTM kit.

RESULTS
The 44 children (aged 15-69 months) recruited were divided into two groups: ETS and non-ETS (control). There were 22 children in each: 16 who were exposed to ETS during and after gestation were identified as the ETSB subgroup. Participants exposed to ETS were more likely to have had upper respiratory tract and middle ear infections during the neonatal period and had higher mean dmft, mean dmfs, mean percent of surfaces with demarcated opacities and mean GI than the non-ETS participants. The children exposed to ETS before and after birth had the highest occurrence of enamel opacities showed a higher risk for dental caries even though more children in this group used the recommended fluoride toothpaste (1000 ppm fluoride). Mothers who smoked either never breastfed their children or breastfed their children for less than the recommended period of 6 months. Children exposed to ETS were shown to have higher mean total sIgA (μg/ml) than the children in the control group.

CONCLUSIONS
Associations between ETS exposure before and after gestation and oral health, including salivary changes in young children were shown in the present study. Dental health professionals should include a question about household smoking in children's dental histories, which would allow opportunities to discuss the impact of smoking on child oral health. Longitudinal oral health studies should include a history of maternal smoking during pregnancy and afterwards.

B Hasmun|N N|NN|
Drummond|B K|BK|
Milne|T|T|
Cullinan|M P|MP|
Meldrum|A M|AM|
Coates|D|D|


The functional neuroanatomy of emotion processing in frontotemporal dementias.

Abstract: Impaired processing of emotional signals is a core feature of frontotemporal dementia syndromes, but the underlying neural mechanisms have proved challenging to characterize and measure. Progress in this field may depend on detecting functional changes in the working brain, and disentangling components of emotion processing that include sensory decoding, emotion categorization and emotional contagion. We addressed this using functional MRI of naturalistic, dynamic facial emotion processing with concurrent indices of autonomic arousal, in a cohort of patients representing all major frontotemporal dementia syndromes relative to healthy age-matched individuals. Seventeen patients with behavioural variant frontotemporal dementia [four female; mean (standard deviation) age 64.8 (6.8) years], 12 with semantic variant primary progressive aphasia [four female; 66.9 (7.0) years], nine with non-fluent variant primary progressive aphasia [five female; 67.4 (8.1) years] and 22 healthy controls [12 female; 68.6 (6.8) years] passively viewed videos of universal facial expressions during functional MRI acquisition, with simultaneous heart rate and pupillometric recordings; emotion identification accuracy was assessed in a post-scan behavioural task. Relative to healthy controls, patient groups showed significant impairments (analysis of variance models, all P < 0.05) of facial emotion identification (all syndromes) and cardiac (all syndromes) and pupillary (non-fluent variant only) reactivity. Group-level functional neuroanatomical changes were assessed using statistical parametric mapping, thresholded at P < 0.05 after correction for multiple comparisons over the whole brain or within pre-specified regions of interest. In response to viewing facial expressions, all participant groups showed comparable activation of primary visual cortex while patient groups showed differential hypo-activation of fusiform and posterior temporo-occipital junctional cortices. Bi-hemispheric, syndrome-specific activations predicting facial emotion identification performance were identified (behavioural variant, anterior insula and caudate; semantic variant, anterior temporal cortex; non-fluent variant, frontal operculum). The semantic and non-fluent variant groups additionally showed complex profiles of central parasympathetic and sympathetic autonomic involvement that overlapped signatures of emotional visual and categorization processing and extended (in the non-fluent group) to brainstem effector pathways. These findings open a window on the functional cerebral mechanisms underpinning complex socio-emotional phenotypes of frontotemporal dementia, with implications for novel physiological biomarker development.

Marshall|Charles R|CR|
Hardy|Christopher J D|CJD|
Russell|Lucy L|LL|
Bond|Rebecca L|RL|
Sivasathiaseelan|Harri|H|
Greaves|Caroline|C|
Moore|Katrina M|KM|
Agustus|Jennifer L|JL|
van Leeuwen|Janneke E P|JEP|
Wastling|Stephen J|SJ|
Rohrer|Jonathan D|JD|
Kilner|James M|JM|
Warren|Jason D|JD|

D000342:Affective Symptoms
D000368:Aged
D018888:Aphasia, Primary Progressive
D001341:Autonomic Nervous System
D001931:Brain Mapping
D004644:Emotions
D005149:Facial Expression
D005260:Female
D057180:Frontotemporal Dementia
D006339:Heart Rate
D006801:Humans
D008032:Limbic System
D008279:Magnetic Resonance Imaging
D008297:Male
D008875:Middle Aged
D009415:Nerve Net
D009483:Neuropsychological Tests
D011680:Pupil

emotion
frontotemporal dementia
functional MRI
autonomic
cardiac


Determination of sulfur in crude oil using high-resolution continuum source molecular absorption spectrometry of the SnS molecule in a graphite furnace.

Abstract: An analytical method for the determination of sulfur, as the tin mono-sulfide (SnS) molecule, in crude oil using high-resolution continuum source graphite furnace molecular absorption spectrometry (HR-CS GF MAS) has been developed. The molecular absorbance of the SnS has been measured using the wavelength at 271.624 nm and the crude oil samples were prepared as micro-emulsions due to their high viscosity. Several chemical modifiers (Ir, Pd, Ru, Zr) were tested and palladium was chosen, because it exhibited the best performance. The heating program was optimized by comparing the pyrolysis and vaporization curves obtained for an aqueous sulfur standard and a micro-emulsion of a crude oil certified reference material (CRM). The optimum pyrolysis and vaporization temperatures were found to be 600 and 2000°C, respectively. The limit of detection and the characteristic mass using micro-emulsion analysis of crude oil samples were 5.8 and 13.3 ng S. Accuracy and precision of the method has been evaluated using two crude oil CRM (NIST 2721 and NIST 2722), showing good agreement with the informed or certified values.

Cadorim|Heloisa R|HR|
Pereira|Éderson R|ÉR|
Carasek|Eduardo|E|
Welz|Bernhard|B|
de Andrade|Jailson B|JB|

Crude oil
Molecular absorption
HR-CS GF MAS
Sulfur determination
Tin sulfide


Saliva Proteomics as Fluid Signature of Inflammatory and Immune-Mediated Skin Diseases.

Abstract: Saliva is easy to access, non-invasive and a useful source of information useful for the diagnosis of serval inflammatory and immune-mediated diseases. Following the advent of genomic technologies and -omic research, studies based on saliva testing have rapidly increased and human salivary proteome has been partially characterized. As a proteomic protocol to analyze the whole saliva proteome is not currently available, the most common aim of the proteomic analysis is to discriminate between physiological and pathological conditions. The salivary proteome has been initially investigated in several diseases: oral squamous cell carcinoma and oral leukoplakia, chronic graft-versus-host disease, and Sjögren's syndrome. Otherwise, salivary proteomics studies in the dermatological field are still in the initial phase, thus the aim of this review is to collect the best research evidence on the role of saliva proteomics analysis in immune-mediated skin diseases to understand the direction of research in this field. The results of PRISMA analysis reported herein suggest that human saliva analysis could provide significant data for the diagnosis and prognosis of several immune-mediated and inflammatory skin diseases in the next future.

saliva
atopic dermatitis
blistering diseases
oral lichen plants
psoriasis
vitiligo


Epigenetic Mechanisms of Tamoxifen Resistance in Luminal Breast Cancer.

Abstract: Breast cancer is one of the most common cancers and the second leading cause of cancer death in the United States. Estrogen receptor (ER)-positive cancer is the most frequent subtype representing more than 70% of breast cancers. These tumors respond to endocrine therapy targeting the ER pathway including selective ER modulators (SERMs), selective ER downregulators (SERDs) and aromatase inhibitors (AIs). However, resistance to endocrine therapy associated with disease progression remains a significant therapeutic challenge. The precise mechanisms of endocrine resistance remain unclear. This is partly due to the complexity of the signaling pathways that influence the estrogen-mediated regulation in breast cancer. Mechanisms include ER modifications, alteration of coregulatory function and modification of growth factor signaling pathways. In this review, we provide an overview of epigenetic mechanisms of tamoxifen resistance in ER-positive luminal breast cancer. We highlight the effect of epigenetic changes on some of the key mechanisms involved in tamoxifen resistance, such as tumor-cell heterogeneity, ER signaling pathway and cancer stem cells (CSCs). It became increasingly recognized that CSCs are playing an important role in driving metastasis and tamoxifen resistance. Understanding the mechanism of tamoxifen resistance will provide insight into the design of novel strategies to overcome the resistance and make further improvements in breast cancer therapeutics.

epigenetics
tamoxifen resistance
luminal breast cancer
cancer stem cells
DNA methylation
histone modification
microRNA


Paracoccus jeotgali sp. nov., isolated from Korean salted and fermented shrimp.

Abstract: A Gram-stain-negative and facultatively aerobic bacterium, designated as strain CBA4604T, was isolated from a traditional Korean salted and fermented shrimp food (saeu-jeot). Phylogenetic analysis based on 16S rRNA gene sequences showed that strain CBA4604T formed a clearly distinct phyletic lineage from closely related species within the genus Paracoccus. Strain CBA4604T was the most closely related to P. koreensis Ch05T (97.5% 16S rRNA gene sequence similarity) and other type strains (≤ 97.0%). The genome comprised a chromosome and two plasmids of 3,299,166 bp with 66.5% G+C content. The DNA-DNA relatedness values between strain CBA4604T and P. koreensis Ch05T, P. alcaliphilus DSM 8512T, and P. stylophorae KTW-16T were 30.5%, 22.9%, and 16.7%, respectively. Cells of the strain were short rod-shaped and oxidase- and catalase-positive. The growth of strain CBA-4604T was observed at 10-40°C (optimum, 37°C), pH 6.0-10.0 (optimum, pH 7.0), and in the presence of 0-8.0% (w/v) NaCl (optimum, 0-2.0%). Strain CBA4604T contained ubiquinone 10 as the sole isoprenoid quinone and summed feature 8 (C18:1ω7c/C18:1ω6c) and C18:0 as the major cellular fatty acids. The polar lipids consisted of phosphatidylcholine, phosphatidylglycerol, diphosphatidylglycerol, phospholipid, an unidentified aminolipid, an unidentified glycolipid, and three unidentified lipids. Based on its phylogenetic, genomic, phenotypic, and chemotaxonomic features, we concluded that strain CBA-4604T represents a novel species in the genus Paracoccus and we propose the name Paracoccus jeotgali sp. nov. The type strain is CBA4604T (= KACC 19579T = JCM 32510T).

Kim|Juseok|J|
Kim|Joon Yong|JY|
Song|Hye Seon|HS|
Cha|In-Tae|IT|
Roh|Seong Woon|SW|
Lee|Se Hee|SH|

D015373:Bacterial Typing Techniques
D001482:Base Composition
D004269:DNA, Bacterial
D005227:Fatty Acids
D005285:Fermentation
D000074421:Fermented Foods
D016680:Genome, Bacterial
D006863:Hydrogen-Ion Concentration
D009693:Nucleic Acid Hybridization
D010230:Paracoccus
D010802:Phylogeny
D012336:RNA, Ribosomal, 16S
D056910:Republic of Korea
D017747:Seafood
D017422:Sequence Analysis, DNA
D012965:Sodium Chloride
D014451:Ubiquinone

Paracoccus jeotgali
salted and fermented shrimp
new taxon
polyphasic taxonomy


Sudden cardiac death in young athletes; a literature review and special considerations in Asia.

Abstract: Sudden cardiac death (SCD) in a young athlete is rare, but catastrophic. Exercise acts as a risk factor for SCD in people with cardiovascular disease. A diversity of cardiovascular disorders including hypertrophic cardiomyopathy, congenital coronary anomalies, arrhythmogenic right ventricular dysplasia, dilated cardiomyopathy, aortic rupture due to Marfan syndrome, myocarditis, valvular disease and electrical disorders (Wolff-Parkinson-White syndrome, long QT syndrome, Brugada syndrome), as well as commotio cordis represent the common causes of SCD in young athletes.As the outcome of lethal cardiovascular disorders is not reversible except in few cases, effective measures should be addressed to reduce the burden of sudden cardiac death in young athletes. Currently, two types of recommendations are proposed by American and European countries.It seems that there are some special considerations in Asia, entirely different from North America or Europe, which warrant more comprehensive research on epidemiology and etiology of SCD in young Asian athletes by country and evaluation of current national preventive strategies and their achievements in decreasing the risk. Using these data and considering regional restrictions, an expert group will be able to plan a practical and feasible preventive strategy.

Sudden Cardiac Death
Athletes
Asia
Sports
Young Adult


Clinical review of two fatal equine cases of infection with the insectivorous bat strain of Australian bat lyssavirus.

Abstract:
CASE SERIES
The first two confirmed cases of Australian bat lyssavirus (ABLV) infection in horses are presented. Both cases occurred in the same week in May 2013 in paddock mates in south-east Queensland. Australia has been one of only a few countries considered free from rabies-like viruses in domestic animal species. ABLV infection had previously only been confirmed in bats and humans. All three confirmed human cases were fatal, the latest in February 2013. An additional human case of possible abortive infection in 1996 has also been reported. Both equine cases reported here resulted in euthanasia. The risks of infection across other mammalian species are still to be determined.

CONCLUSIONS
These two equine cases highlight that ABLV should be considered as a differential diagnosis in animals with similar clinical presentations in Australia. There is a need for greater awareness regarding the zoonotic risk, use of personal protective equipment, pre- and post-exposure prophylactic measures and laboratory diagnostic options. The authors recommend ABLV testing for all Australian cases of progressive equine neurological disease.

D060888:Real-Time Polymerase Chain Reaction

Australian bat lyssavirus
equine encephalitis
equine rabies
zoonoses


Costs of a school-based dental mobile service in South Africa.

Abstract:
BACKGROUND
The burden of untreated tooth decay remains high and oral healthcare utilisation is low for the majority of children in South Africa. There is need for alternative methods of improving access to low cost oral healthcare. The mobile dental unit of the University of the Witwatersrand (Wits) has been operational for over 25 years, providing alternative oral healthcare to children and adults who otherwise would not have access. The aim of this study was to conduct a cost-analysis of a school based oral healthcare program in the Wits mobile dental unit. The objectives were to estimate the general costs of the school based program, costs of oral healthcare per patient and the economic implications of providing services at scale.

METHODS
In 2012, the Wits mobile dental unit embarked on a 5 month project to provide oral healthcare in four schools located around Johannesburg. Cost and service use data were retrospectively collected from the program records for the cost analysis, which was undertaken from a provider perspective. The costs considered included both financial and economic costs. Capital costs were annualised and discounted at 6 %. One way sensitivity tests were conducted for uncertain parameters.

RESULTS
The total economic costs were R813.701 (US$76,048). The cost of screening and treatment per patient were R331 (US$31) and R743 (US$69) respectively. Furthermore, fissure sealants cost the least out of the treatments provided. The sensitivity analysis indicated that the Wits mobile dental unit was cost efficient at 25 % allocation of staff time and that a Dental Therapy led service could save costs by 9.1 %.

CONCLUSIONS
Expanding the services to a wider population of children and utilising Dental Therapists as key personnel could improve the efficiency of mobile dental healthcare provision.

Molete|M P|MP|
Chola|L|L|
Hofman|K J|KJ|

School based program
Cost analysis
Mobile dental care
Oral health


Dyadic effects of distress on sleep duration in advanced cancer patients and spouse caregivers.

Abstract:
OBJECTIVE
Short sleep duration is a common problem for both advanced cancer patients and their spouse caregivers. Sleep and distress have been shown to be interdependent in patient-caregiver and spouse dyads, yet virtually, no work has explored the dyadic effects of psychological distress on sleep in advanced cancer patients and spouse caregivers. The goal of the present study was to examine the dyadic impact of anxiety and depression on sleep duration in a sample of advanced cancer patients and their spouse caregivers. It was hypothesized that, for both patients and caregivers, anxiety and depression in individuals would be associated with sleep duration in both themselves (actor effects) and in their spouses (partner effects).

METHOD
Advanced cancer patients and their spouse caregivers (N = 87 dyads) completed cross-sectional questionnaires assessing demographic variables, subjective health, subjective sleep duration, and anxiety and depression symptoms.

RESULTS
Controlling for sex, age, and subjective health, individuals' anxiety was negatively associated with their own and their partner's sleep duration. No significant actor or partner effects were found for depression.

CONCLUSIONS
Results provided partial support for hypotheses. Although past work has demonstrated links between subjective sleep disturbance and anxiety/psychological distress, this is one of the first studies to examine partner effects of distress on sleep disturbance in advanced cancer patients and spouse caregivers.

Otto|Amy K|AK|0000-0003-3712-6435
Gonzalez|Brian D|BD|0000-0001-5108-5735
Heyman|Richard E|RE|
Vadaparampil|Susan T|ST|
Ellington|Lee|L|
Reblin|Maija|M|0000-0003-3108-465X

sleep
cancer
patients
spouses
caregivers
anxiety
depression
couples
observational study
oncology


Enhanced methane production from waste activated sludge by potassium ferrate combined with ultrasound pretreatment.

Abstract: This study explored the effect of potassium ferrate (PF) combined with ultrasound (US) pretreatment on methane generation from sludge by a series of experiments and simulations. Batch experiments showed that the pretreatment of PF coupled with US exhibited positively synergy on the methane yield. And by the pretreatment of 0.05 g/g TSS (total suspended solids) PF cooperated with US (1 W/mL, 25 kHz, 15 min), the methane yield was enhanced from 180.62 ± 3.26 to 228.83 ± 4.76 mL/g VSS (volatile suspended solids). Mechanism studies confirmed that the co-pretreatment of PF and US efficiently promoted sludge disintegration, and the biodegradability of sludge organics was obviously enhanced. Microbial community analysis showed that the functional microorganisms participating in sludge anaerobic digestion were enriched by PF cooperated with US pretreatment, with the total abundance enhanced from 12.96% in the control to 17.96% in PF + US pretreated reactor.

Guo|Bing|B| Hu|Jiawei|J| Zhang|Jingsi|J| Wu|Zhigen|Z| Li|Zhuo|Z|

Methane
Wasted activated sludge
Potassium ferrate
Ultrasound pretreatment
Anaerobic digestion


Strategies to optimize bonding of adhesive materials to molar-incisor hypomineralization-affected enamel: A systematic review.

Abstract:
BACKGROUND
Children with first permanent molar affected by molar-incisor hypomineralization (MIH) show high treatment failure rate.

AIM
To conduct a systematic review on bonding of adhesive materials to MIH-affected enamel, so as to identify all the methods suggested to optimize it and to determine the best bonding protocol(s).

DESIGN
An exhaustive literature search was conducted on MEDLINE/PubMed, the Cochrane Library, and Web of Science databases, up to October 2018. Laboratory and clinical studies, involving adhesive restorations bonded to MIH-affected enamel, with at least a comparative group were included. Two authors independently selected studies, collected data, and assessed bias risk.

RESULTS
After title and abstract review and duplicate exclusion, 14 articles were selected on the 496 eligible papers. After full reading, 4 articles were excluded. Finally, 10 studies (6 laboratory and 4 clinical studies) were included.

CONCLUSIONS
Bond strength of composite was not significantly different when using self-etch compared with etch-and-rinse adhesives. Deproteinization after etching for etch-and-rinse adhesives enhanced bond strength; this could allow to keep MIH-affected enamel. Icon® showed an erratic penetration; however, a preliminary deproteinization after etching could improve bond strength. A study reported no significant differences in sealant retention rate, whereas another recommended to previously apply an adhesive.

D000134:Acid Etching, Dental
D002648:Child
D003188:Composite Resins
D001840:Dental Bonding
D003738:Dental Cements
D003743:Dental Enamel
D017220:Dentin-Bonding Agents
D006801:Humans
D007180:Incisor
D008422:Materials Testing
D008963:Molar
D019279:Resin Cements
D033081:Shear Strength

bonding
adhesive
MIH
bond strength
deproteinization
resin infiltration


Training volume and soft tissue injury in professional and non-professional rugby union players: a systematic review.

Abstract:
AIM
To investigate the relationship between training volume and soft tissue injury incidence, and characterise soft tissue injury in rugby union players.

DESIGN
A systematic search of electronic databases was performed. The search strategy combined terms covering: training volume and injury, and rugby union, and players of all levels.

DATA SOURCES
Medline, SPORTDiscus, Web of Science, Embase, PubMed.

ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Studies were included if they reported: male rugby union players, a clear definition of a rugby union injury, the amount of training volume undertaken by participants, and epidemiological data for soft-tissue injuries including the number or incidence.

RESULTS
15 studies were eligible for inclusion. Overall match and training injury incidence ranged from 3.3 to 218.0 injuries/1000 player match hours and 0.1-6.1 injuries/1000 player training hours, respectively. Muscle and tendon as well as joint (non-bone) and ligament injuries were the most frequently occurring injuries. The lower limb was the most prevalent injury location. Injury incidence was higher in professional rugby union players than non-professional players. Contact events were responsible for the greatest injury incidence. For non-contact mechanisms, running was responsible for the highest injury incidence. Inconsistent injury definitions hindered reliable comparison of injury data. The lack of reporting training volumes in hours per player per week limited the ability to investigate associations between training volume and injury incidence.

CONCLUSIONS
A higher level of play may result in higher match injury incidence. Muscle and tendon injuries were the most common type of soft tissue injury, while the lower limb was the most common location of injury in rugby union players, and running was responsible for the highest injury incidence during non-contact events.

Contact sports
Football
Muscle injury
Sporting injuries
Training load


Pre-operative neoadjuvant chemotherapy cycles and survival in newly diagnosed ovarian cancer: what is the optimal number? A Memorial Sloan Kettering Cancer Center Team Ovary study.

Abstract:
OBJECTIVE
Although trials of neoadjuvant chemotherapy in ovarian cancer use 3 neoadjuvant cycles, real-world practice varies. We sought to evaluate the influence of increasing pre-operative cycles on survival, accounting for surgical outcomes.

METHODS
We identified 199 women with newly diagnosed ovarian cancer recommended for neoadjuvant chemotherapy who underwent interval debulking surgery from July 2015 to December 2018. Non-parametric tests were used to compare clinical characteristics by neoadjuvant cycles. The Kaplan-Meier method was used to estimate differences in progression-free and overall survival. The log-rank test was used to assess the relationship of covariates to outcome.

RESULTS
The median number of neoadjuvant cycles was 4 (range 3-8), with 56 (28%) women receiving ≥5 cycles. Compared with those receiving 3 or 4, women with ≥5 neoadjuvant cycles received fewer or no post-operative cycles (p<0.001) but had no other differences in clinical factors (p>0.05). Complete gross resection rates were similar among those receiving 3, 4, and ≥5 neoadjuvant cycles (68.5%, 70%, and 71.4%, respectively, p=0.96). There were no significant differences in progression-free or overall survival when comparing 3 versus 4 neoadjuvant cycles. However, more cycles (≥5 vs 4) were associated with worse progression-free survival, even after adjustment for BRCA status and complete gross resection (HR 2.20, 95% CI 1.45 to 3.33, p<0.001), and worse overall survival, even after adjustment for histology, response on imaging, and complete gross resection rates (HR 2.78, 95% CI 1.37 to 5.63, p=0.016). The most common reason for receiving ≥5 cycles was extent of disease requiring more neoadjuvant chemotherapy.

CONCLUSIONS
Despite maximal cytoreduction, patients receiving ≥5 neoadjuvant cycles have a poorer prognosis than those receiving 3-4 cycles. Future studies should focus on reducing surgical morbidity and optimizing novel therapies in this high-risk group.

Liu|Ying L|YL|
Zhou|Qin C|QC|
Iasonos|Alexia|A|
Chi|Dennis S|DS|
Zivanovic|Oliver|O|
Sonoda|Yukio|Y|
Gardner|Ginger|G|
Broach|Vance|V|
O'Cearbhaill|Roisin|R|
Konner|Jason A|JA|
Grisham|Rachel|R|
Aghajanian|Carol A|CA|
Abu-Rustum|Nadeem R|NR|
Tew|William|W|
Long Roche|Kara|K|

D000971:Antineoplastic Combined Chemotherapy Protocols

D016032:Randomized Controlled Trials as Topic


Single-Cell Transcriptomics Reveal Immune Mechanisms of the Onset and Progression of IgA Nephropathy.

Abstract: IgA nephropathy (IgAN) is the leading cause of kidney failure due to an incomplete understanding of its pathogenesis. We perform single-cell RNA sequencing (RNA-seq) on kidneys and CD14+ peripheral blood mononuclear cells (PBMCs) collected from IgAN and normal samples. In IgAN, upregulation of JCHAIN in mesangial cells provides insight into the trigger mechanism for the dimerization and deposition of IgA1 in situ. The pathological mesangium also demonstrates a prominent inflammatory signature and increased cell-cell communication with other renal parenchymal cells and immune cells, suggesting disease progress from the mesangium to the entire kidney. Specific gene expression of kidney-resident macrophages and CD8+ T cells further indicates abnormal regulation associated with proliferation and inflammation. A transitional cell type among intercalated cells with fibrosis signatures is identified, suggesting an adverse outcome of interstitial fibrosis. Altogether, we systematically analyze the molecular events in the onset and progression of IgAN, providing a promising landscape for disease treatment.

Zheng|Ying|Y| Lu|Ping|P| Deng|Yiyao|Y| Wen|Lu|L| Wang|Yong|Y| Ma|Xin|X| Wang|Zhongxin|Z| Wu|Lingling|L| Hong|Quan|Q| Duan|Shuwei|S| Yin|Zhong|Z| Fu|Bo|B| Cai|Guangyan|G| Chen|Xiangmei|X| Tang|Fuchou|F|

IgA nephropathy
immune cellsmesangial cell
single-cell RNA seq


Magainin-modified polydopamine nanoparticles for photothermal killing of bacteria at low temperature.

Abstract: Photothermal therapy (PTT) is a promising method to kill bacteria because of the broad-spectrum of antibacterial activity and the ability of spatiotemporal regulation. In the previously reported systems, light induced high temperature (˜70 °C) was essential for effectively killing of bacteria, which, however, would also damage nearby nontarget cells or tissues. Here we report photothermal nanoparticles (NPs) for more targeting and killing bacteria at a relative low temperature. Polydopamine (PDA) was chosen to prepare NPs because of its excellent capability of photothermal conversion. Magainin I (MagI) which is an antimicrobial peptide was used to modify NPs' surface because it can specifically interact with bacteria. We demonstrate that MagI-PEG@PDA NPs effectively killed E. coli at a low temperature of ˜45 °C upon near-infrared (NIR) light irradiation. In contrast, the native PDA NPs under light irradiation or the MagI-PEG@PDA NPs themselves showed no bacteria killing ability. This work highlights the importance of close interaction between the target bacteria and the photothermal materials and may promote the practical clinical applications of the PTT.

Fan|Xiao-Li|XL| Li|He-Yang|HY| Ye|Wan-Ying|WY| Zhao|Ming-Qi|MQ| Huang|Dan-Ni|DN| Fang|Yu|Y| Zhou|Bin-Quan|BQ| Ren|Ke-Feng|KF| Ji|Jian|J| Fu|Guo-Sheng|GS|

Polydopamine
Low temperature
Photothermal therapy
Magainin
Antibacterial nanoparticles


A New Variant of Dual Left Anterior Descending Artery Anomaly: Type XI.

Abstract: A dual left anterior descending (LAD) artery is a rare congenital anomaly which is classified into different types based on the origin, course and termination of the short and long LAD arteries. To date, 10 variants of dual LAD artery anomalies have been described. We report a 44-year-old woman who was referred to the Department of Radiology, Royal Hospital, Muscat, Oman, in 2017. Coronary computed tomography angiography revealed a dual LAD artery anomaly in which the short and long LAD arteries shared a common ostium with the right coronary artery from the right coronary sinus. To the best of the authors' knowledge, this type of variant has not been previously reported in the literature.

Al-Umairi|Rashid S|RS|
Al-Kindi|Faiza A|FA|
Al-Tai|Saqar A|SA|

Oman
Case Report
Congenital Abnormality
Coronary Angiography
Coronary Vessel Anomalies


Antitumor effects of curcumin on the proliferation, migration and apoptosis of human colorectal carcinoma HCT‑116 cells.

Abstract: Curcumin is the main component of the Chinese herbal plant turmeric, which has been demonstrated to possess antitumor and other pharmacological properties. The aim of the present study was to investigate the effects of curcumin on the viability, migration and apoptosis of human colorectal carcinoma HCT‑116 cells, and to explore the underlying molecular mechanisms. In addition, it was investigated whether the antitumor effect of curcumin on HCT‑116 cells could match that of the chemotherapeutic drug 5‑fluorouracil (5‑FU). HCT‑116 cells were treated with curcumin (10, 20 and 30 µM) and 5‑FU (500 µM), and cell viability and proliferation were detected by Cell Counting Kit‑8 and colony formation assays, respectively. The migration and invasion of treated cells were determined using Transwell and carboxyfluorescein succinimidyl amino ester fluorescent labeling assays. Cell cycle distribution and apoptosis rates were detected by flow cytometry. Furthermore, cell morphology changes associated with apoptosis were observed by fluorescence microscopy with acridine orange/ethidium bromide dual staining. To investigate the possible underlying molecular mechanisms, the gene and protein levels of Fas, Fas‑associated via death domain (FADD), caspase‑8, caspase‑3, matrix metalloproteinase (MMP)‑9, nuclear factor (NF)‑κB, E‑cadherin and claudin‑3 were detected using quantitative PCR analysis, zymography and western blotting. The results revealed that curcumin markedly inhibited the viability and proliferation of HCT‑116 cells in a dose‑ and time‑dependent manner. The migration, aggregation and invasion of HCT‑116 cells into the lungs of mice were decreased by curcumin treatment in a dose‑dependent manner. S‑phase arrest and gradually increased apoptotic rates of HCT‑116 cells were observed with increasing curcumin concentrations. Additionally, the mRNA and protein levels of apoptosis‑associated proteins (Fas, FADD, caspase‑8 and caspase‑3) and E‑cadherin in HCT‑116 cells were upregulated following treatment with curcumin in a dose‑dependent manner. By contrast, the expression of migration‑associated proteins, including MMP‑9, NF‑κB and claudin‑3, was downregulated with increasing curcumin concentrations. These data suggested that the inhibitory effect of curcumin on HCT‑116 cells may match that of 5‑FU. Therefore, curcumin induced cell apoptosis and inhibited tumor cell metastasis by regulating the NF‑κB signaling pathway, and its therapeutic effect may be comparable to that of 5‑FU.

Xiang|Lei|L| He|Bin|B| Liu|Qiang|Q| Hu|Dongdong|D| Liao|Wenjing|W| Li|Ruochan|R| Peng|Xinyi|X| Wang|Qian|Q| Zhao|Gang|G|

D023041:Xenograft Model Antitumor Assays

curcumin
apoptosis
colorectal carcinoma
5-fluorouracil
HCT-116 cells
Fas death receptor pathway
nuclear factor-κB
epithelial-to-mesenchymal transition