The synergy of germline C634Y and V292M RET mutations in a northern Chinese family with multiple endocrine neoplasia type 2A.

Abstract: Genetic analysis for germline mutations of RET proto-oncogene has provided a basis for individual management of medullary thyroid carcinoma (MTC) and pheochromocytoma. Most of compound mutations have more aggressive phenotypes than single point mutations, but the compound C634Y/V292M variant in MTC has never been reported. Thus, we retrospectively investigated synergistic effect of C634Y and V292M RET germline mutations in family members with multiple endocrine neoplasia type 2A. Nine of 14 family members in a northern Chinese family underwent RET mutation screening using next-generation sequencing and PCR followed by direct bidirectional DNA sequencing. Clinical features of nine individuals were retrospectively carefully reviewed. In vitro, the scratch-wound assay was used to investigate the difference between the cells carrying different mutations. We find no patients died of MTC. All 3 carriers of the V292M variant were asymptomatic and did not have biochemical or structural evidence of disease (age: 82, 62 and 58). Among 4 C634Y mutation carriers, 2 patients had elevated calcitonin with the highest (156 pg/mL) in an 87-year-old male. Two carriers of compound C634Y/V292M trans variant had bilateral MTC with pheochromocytoma or lymph node metastasis (age: 54 and 41 years, respectively). Further, the compound C634Y/V292M variant had a faster migration rate than either single point mutation in vitro (P < .05). In conclusion, the V292M RET variant could be classified as 'likely benign' according to ACMG (2015). The compound variant V292M/C634Y was associated with both more aggressive clinical phenotype and faster cell growth in vitro than was either single mutation.

Yang|Zheng|Z|
Qi|Xinmeng|X|
Gross|Neil|N|
Kou|Xiujuan|X|
Bai|Yunlong|Y|
Feng|Yaru|Y|
Wang|Bochun|B|
Zafereo|Mark E|ME|
Li|Guojun|G|0000-0001-9505-1502
Sun|Chuanzheng|C|
Li|Huihui|H|
Chen|Xiaohong|X|
Huang|Zhigang|Z|

D018813:Multiple Endocrine Neoplasia Type 2a

RET proto-oncogene
compound mutation
MEN2
hereditary medullary thyroid carcinoma


Microphthalmia-associated transcription factor mutations are associated with white-spotted coat color in swamp buffalo.

Abstract: A candidate gene analysis of the microphthalmia-associated transcription factor (MITF) gene was used in an attempt to identify the genetic basis for a white-spotted coat color phenotype in the Asian swamp buffalo (Bubalus bubalis carabanensis). Ninety-three buffaloes-32 solid, 38 spotted and 23 white individuals-were Sanger-sequenced for all MITF exons as well as highly conserved intronic and flanking regions. MITF cDNA representing skin and iris tissue from six spotted, nine solid and one white buffaloes was also Sanger-sequenced to confirm detected mutations. Two independent loss-of-function mutations, a premature stop codon (c.328C>T, p.Arg110*) and a donor splice-site mutation (c.840+2T>A, p.Glu281_Leu282Ins8), both of which cause white-spotted coat color in swamp buffaloes, were identified. The nonsense mutation leads to a premature stop codon in exon 3, and likely removal of the resulting mRNA via nonsense-mediated decay pathway, whereas the donor splice-site mutation leads to aberrant splicing of exon 8 that encodes part of a highly conserved region of MITF. The resulting insertion of eight amino acid residues is expected to perturb the leucine zipper part in the basic helix-loop-helix leucine zipper (bHLH-Zip) domain and will most likely influence dimerization and DNA binding capacity. Electrophoretic mobility shift assay was performed using mutant and wild-type MITF proteins and showed that the mutant MITF protein resulting from the splice-site mutation decreased in vitro DNA binding capacity compared to wild-type MITF. White-spotted buffalo bulls are sacrificed in funeral ceremonies in Tana Toraja, Indonesia, because they are considered holy, and our results show that genetic variation causes a tie to the cultural use of these buffaloes.

Yusnizar|Y|Y|
Wilbe|M|M|
Herlino|A O|AO|
Sumantri|C|C|
Noor|R Rachman|RR|
Boediono|A|A|
Andersson|L|L|
Andersson|G|G|

MITF
Bubalus bubalis
donor splice-site mutation
nonsense mutation


Medication associated with hearing loss: 25 years of medical malpractice cases in the United States.

Abstract:
OBJECTIVES
Many medications have the potential for ototoxicity. To potentiate management of this risk, this study examines malpractice litigation trends of lawsuits involving hearing loss associated with medication use. As experts in hearing loss, it may benefit otolaryngologists to be familiar with this information.

STUDY DESIGN
Retrospective review.

SETTING
All US civil trials.

SUBJECTS AND METHODS
Court records of legal trials from 1987 to 2012 were obtained from 2 major computerized databases. Data were compiled on the demographics of the defendant and plaintiff, use of otolaryngologists as expert witnesses, medication used, legal allegations, verdicts, and judgments.

RESULTS
Forty-six unique cases met inclusion criteria and were selected for review. Antibiotics (72%), specifically aminoglycosides (47%), were the most common medications cited as causing hearing loss. Eleven (22%) cases were resolved through a settlement before a verdict was reached. Verdicts in favor of the plaintiffs (37%) were awarded an average of $1,134,242. Pediatric patients were more likely to have outcomes in their favor (P = .03) compared to adults. Of the cases found in favor of the plaintiff, the most common reasons cited were inappropriate medication, dose, or duration (59%); failure to properly monitor (39%); and failure to choose a less toxic medication (18%).

CONCLUSIONS
Physicians must be aware of the potential effects of the medications they prescribe. An understanding of potential drug interactions, proper monitoring, and appropriate substitution with less toxic medications are important to improve patient care. Analyzing litigation trends may be used to prevent future lawsuits and improve physician awareness.

Ruhl|Douglas S|DS|
Cable|Benjamin B|BB|
Martell|David W|DW|

medication
hearing loss
medical malpractice
ototoxicity


Impact of spreading olive mill waste water on agricultural soils for leaching of metal micronutrients and cations.

Abstract: Olive mill waste water (OMWW) is an acidic (pH 4-5), saline (EC ∼ 5-10 mS cm-1), blackish-red aqueous byproduct of the three phase olive oil production process, with a high chemical oxygen demand (COD) of up to 220,000 mg L-1. OMWW is conventionally disposed of by uncontrolled dumping into the environment or by semi-controlled spreading on agricultural soils. It was hypothesized that spreading such liquids on agricultural soils could result in the release and mobilization of indigenous soil metals. The effect of OMWW spreading on leaching of metal cations (Na, K, Mg, Mn, Fe, Cu, Zn) was tested in four non-contaminated agricultural soils having different textures (sand, clay loam, clay, and loam) and chemical properties. While the OMWW contributed metals to the soil solution, it also mobilized indigenous soil metals as a function of soil clay content, cation exchange capacity (CEC), and soil pH-buffer capacity. Leaching of soil-originated metals from the sandy soil was substantially greater than from the loam and clay soils, while the clay loam was enriched with metals derived from the OMWW. These trends were attributed to cation exchange and organic-metal complex formation. The organic matter fraction of OMWW forms complexes with metal cations; these complexes may be mobile or precipitate, depending on the soil chemical and physical environment.

Aharonov-Nadborny|R|R|
Tsechansky|L|L|
Raviv|M|M|
Graber|E R|ER|

D057919:Biological Oxygen Demand Analysis

Metals
OMWW
Cation exchange
Complex formation
Olive mill wastewater
Soil spreading


Bowel perforation in newborn with anorectal malformation and no fistula at presentation.

Abstract:
PURPOSE
Anorectal malformation (ARM) in newborns with no fistula at presentation resembles intestinal obstruction. The aim of this study is to study the factors associated with bowel perforation in this group of patients.

METHODS
From 2000 to 2012, 106 newborns with ARM were managed in our hospital. Thirty neonates without fistula at presentation were included in this study. Demographic data and the incidence of bowel perforation were studied.

RESULTS
Twenty-nine male and 1 female were included in the study. Five patients were born premature and six patients had low birth weight. Six patients had Down's syndrome and 12 patients had associated anomalies. Cross-table lateral x-ray in prone position was performed from 20 to 24 hours after birth. All operations were performed within 48 hours after birth. One neonate underwent primary anoplasty. Twenty-nine neonates underwent colostomy. Two males developed bowel perforation before surgery (at 33 and 36 hours after birth). Perforation was associated with low birth weight (p=0.034) and was not associated with prematurity (p=0.31), Down's syndrome (p=0.634) or the presence of other associated anomalies (p=0.687).

CONCLUSIONS
In newborns with ARM, bowel perforation can occur within 36 hours after birth. Forty-eight hours of waiting is too long as it risks perforation. In this study, a neonate with low birth weight was trended toward bowel perforation.

Chan|Kin Wai Edwin|KW|
Lee|Kim Hung|KH|
Tsui|Siu Yan Bess|SY|
Wong|Yuen Shan|YS|
Pang|Kit Yi Kristine|KY|
Mou|Jennifer Wai Cheung|JW|
Tam|Yuk Him|YH|

D000015:Abnormalities, Multiple
D000071056:Anorectal Malformations
D001006:Anus, Imperforate
D003125:Colostomy
D057210:Delayed Diagnosis
D003937:Diagnosis, Differential
D004314:Down Syndrome
D042241:Early Diagnosis
D005260:Female
D006801:Humans
D007230:Infant, Low Birth Weight
D007231:Infant, Newborn
D007234:Infant, Premature
D007235:Infant, Premature, Diseases
D007415:Intestinal Obstruction
D007416:Intestinal Perforation
D008297:Male
D011859:Radiography
D012189:Retrospective Studies
D013997:Time Factors
D016896:Treatment Outcome

Perforation
Anorectal malformation
Fistula


Influence of El Niño Southern Oscillation phenomenon on coastal phytoplankton in a mixohaline ecosystem on the southeastern of South America: Río de la Plata estuary.

Abstract: The aim of this study was to analyze the density, diversity, biomass and assemblage composition of the phytoplankton in relation to environmental conditions (physical, chemical, hydrological and meteorological variables), measured under the different scenarios caused by the ENSO phenomenon in the period between 2005 and 2012, in six sampling sites in the tidal freshwater zone of the Río de la Plata estuary, covering almost 100km of coastline. The results revealed changes in the structure of the phytoplankton, such as a significant reduction of diversity, and decreases in biomass and phytoplankton density, particularly during El Niño phases. Cyanobacteria were more abundant in the neutral periods, Chlorophyceae dominated La Niña phase while Bacyllariophyceae dominated El Niño. However, no complete replacement of species between cycles was observed. The results obtained were highly variable due to the inherent natural variability of the Río de la Plata, emphasized by the anthropogenic impact in this area.

Sathicq|María Belén|MB|
Bauer|Delia Elena|DE|
Gómez|Nora|N|

El Niño Southern Oscillation phenomenon
Phytoplankton
Río de la Plata estuary
Freshwater tidal zone
Structural responses


The validity of suspected blood indicator software in capsule endoscopy: a systematic review and meta-analysis.

Abstract: Software tools have been developed as capsule endoscopy (CE) reading aids. The suspected blood indicator (SBI) tags possible areas of haemorrhage in the gastrointestinal (GI) tract. This meta-analysis aims to investigate the diagnostic accuracy of SBI in CE. Areas covered: A systematic literature search was conducted for studies on the use of SBI in CE. Sensitivity, specificity and diagnostic odds ratio (DOR) of SBI in diagnosing GI bleeding was evaluated. 2040 patients from 16 studies underwent 2049 CE examinations. The overall sensitivity of SBI for bleeding or potentially bleeding lesions was 0.553, specificity 0.578, DOR 12.354. The sensitivity of SBI for active bleeding was 0.988, specificity 0.646, DOR 229.89. Expert commentary: Currently, SBI has limited validity in CE reading. However, in active GI bleeding, it has good sensitivity, supporting its use in the acute setting.

Yung|Diana E|DE|
Sykes|Catherine|C|
Koulaouzidis|Anastasios|A|

suspected blood indicator
Capsule endoscopy
systematic review
meta-analysis
obscure gastrointestinal bleeding
small bowel bleeding


Establishing SW1353 Chondrocytes as a Cellular Model of Chondrolysis.

Abstract: Osteoarthritis (OA) is the most common degenerative joint disease characterised by chondrocyte cell death. An in vitro model of chondrocyte cell death may facilitate drug discovery in OA management. In this study, the cytotoxicity and mode of cell death of SW1353 chondrocytes treated with 24 h of OA inducers, including interleukin-1β (IL-1β), hydrogen peroxide (H2O2) and monosodium iodoacetate (MIA), were investigated. The microscopic features, oxidative (isoprostane) and inflammatory markers (tumour necrosis factor-alpha; TNF-α) for control and treated cells were compared. Our results showed that 24 h of H2O2 and MIA caused oxidative stress and a concentration-dependent reduction of SW1353 cell viability without TNF-α level upregulation. H2O2 primarily induced chondrocyte apoptosis with the detection of blebbing formation, cell shrinkage and cellular debris. MIA induced S-phase arrest on chondrocytes with a reduced number of attached cells but without significant cell death. On the other hand, 24 h of IL-1β did not affect the cell morphology and viability of SW1353 cells, with a significant increase in intracellular TNF-α levels without inducing oxidative stress. In conclusion, each OA inducer exerts differential effects on SW1353 chondrocyte cell fate. IL-1β is suitable in the inflammatory study but not for chondrocyte cell death. H2O2 and MIA are suitable for inducing chondrocyte cell death and growth arrest, respectively.

hydrogen peroxide
monosodium iodoacetate
oxidative stress
inflammation
interleukin-1 beta


Ameliorative effect of aqueous leaf extract of Solanum aethiopicum on phenylhydrazine-induced anaemia and toxicity in rats.

Abstract: Solanum aethiopicum is used in ethnomedicine for the treatment of overweight, constipation and anaemia. This study evaluated the ameliorative effect of aqueous leaf extract of S. aethiopicum on phenylhydrazine-induced anaemia in rats. Acute toxicity was determined in male and female rats (n = 5/group/sex) by oral administration of single dose of up to 5000 mg/kg of the S. aethiopicum extract. The experimental rats were randomly grouped into five (5) groups of 6 rats each. Group (i) served as normal control, group (ii) negative control, group (iii) standard drug-5 mg/kg ferrous sulphate, groups (iv) and (v), 200 and 400 mg/kg of S. aethiopicum extract respectively. Phenylhydrazine (PHZ) was administered intraperitoneally at the dose of 50 mg/kg body weight for two consecutive days to groups (ii-v). After 14 days, the rats were sacrificed; blood, liver and kidney were collected. The haematological, lipid profile, liver and kidney function parameters were determined and the histopathology of the liver and kidney were examined. In acute toxicity study, no signs of toxicity or death were recorded. The study shows an observable significant (P < 0.05) increase in packed cell volume, haemoglobin and red blood cell counts at 400 mg/kg S. aethiopicum extract in both the male and female rats when compared to other groups. Solanum aethiopicum extract at the dose of 400 mg/kg reduced aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), urea, creatinine and chloride. The results of this study lent credence to the use of S. aethiopicum leaf as an anti-anaemic tonic with a wide margin of safety and hepato/reno-protective potentials.

Ekweogu|Celestine Nwabu|CN|
Ude|Victor Chibueze|VC|
Nwankpa|Promise|P|
Emmanuel|Okezie|O|
Ugbogu|Eziuche Amadike|EA|

Solanum aethiopicum
Anaemia
Toxicity
Liver and kidney
Haematology


Insights into the field carcinogenesis of ovarian cancer based on the nanocytology of endocervical and endometrial epithelial cells.

Abstract: Ovarian cancer ranks fifth in cancer fatalities among American women. Although curable at early stages with surgery, most women are diagnosed with symptoms of late-stage metastatic disease. Moreover, none of the current diagnostic techniques are clinically recommended for at-risk women as they preferentially target low-grade tumors (which do not affect longevity) and fail to capture early signatures of more lethal serous tumors which originate in the fimbrae region of the fallopian tubes. Hence, the early detection of ovarian cancer is challenging given the current strategy. Recently, our group has developed a novel optical imaging technique, partial wave spectroscopic (PWS) microscopy, that can quantify the nanoscale macromolecular density fluctuations within biological cells via a biomarker, disorder strength (Ld ). Using the concept of field carcinogenesis, we propose a method of detecting ovarian cancer by PWS assessment of endometrial and endocervical columnar cells. The study includes 26 patients (controls = 15, cancer = 11) for endometrium and 23 (controls = 13, cancer = 10) for endocervix. Our results highlight a significant increase in Ld (% fold-increase > 50%, p-value < 0.05) for columnar epithelial cells obtained from cancer patients compared to controls for both endocervix and endometrium. Overall, the quantification of field carcinogenic events in the endometrium and the novel observation of its extension to the cervix are unique findings in the understanding of ovarian field carcinogenesis. We further show independent validation of the presence of cervical field carcinogenesis with micro-RNA expression data.

Damania|Dhwanil|D|
Roy|Hemant K|HK|
Kunte|Dhananja|D|
Hurteau|Jean A|JA|
Subramanian|Hariharan|H|
Cherkezyan|Lusik|L|
Krosnjar|Nela|N|
Shah|Maitri|M|
Backman|Vadim|V|

ovarian cancer
endometrium
endocervix
field-carcinogenesis
nano-architecture


Nuts and bolts of PMMC flap in oral cancer and its clinical outcome in 168 indian patients: A retrospective analysis.

Abstract:
Introduction
The gold standard for reconstruction is the microvascular free flaps, whereas pedicled flaps are generally employed as a rescue procedure. Pectoralis major myocutaneous flap (PMMC) flap being a reliable flap is associated with high rate of complication. So, the purpose of this study was to check and assess the predictability of PMMC Flap and its clinical outcome in 168 Indian patients.

Materials and method
We conducted a retrospective study of PMMC flap which was harvested in 168 Indian oral cancer patients in 3 years time span. Patients were kept on follow up for 1-3 years. Rate of complication were documented for flap necrosis and wound dehiscence; and patient related data like neck bulk acceptance and range of motion were recorded. Gender comparison of complications were also documented.

Results
The most common complication was wound dehiscence in 11 (6.5%) patients. Partial flap necrosis was observed in 3 (1.8%) female patients. There was no case of total flap necrosis. Questionare method was used for patients to record neck bulk acceptance. Range of motion was evaluated during follow up period. Follow up period of all the patients was 1-3 years.

Conclusion
PMMC flap is still a well founded 'workhorse' flap for reconstruction in head and neck cancer patients and can be used successfully with acceptable morbidity.

Girhe|Vijaykumar|V|
Auti|Akanksha A|AA|
Girhe|Prachi|P|
Wagre|Rohinee|R|

PMMC Flap
Neck bulk acceptance
Range of motion
Post-operative complications


Ultrathin ZnIn2 S4 Nanosheets Anchored on Ti3 C2 TX MXene for Photocatalytic H2 Evolution.

Abstract: Photocatalysts derived from semiconductor heterojunctions that harvest solar energy and catalyze reactions still suffer from low solar-to-hydrogen conversion efficiency. Now, MXene (Ti3 C2 TX ) nanosheets (MNs) are used to support the in situ growth of ultrathin ZnIn2 S4 nanosheets (UZNs), producing sandwich-like hierarchical heterostructures (UZNs-MNs-UZNs) for efficient photocatalytic H2 evolution. Opportune lateral epitaxy of UZNs on the surface of MNs improves specific surface area, pore diameter, and hydrophilicity of the resulting materials, all of which could be beneficial to the photocatalytic activity. Owing to the Schottky junction and ultrathin 2D structures of UZNs and MNs, the heterostructures could effectively suppress photoexcited electron-hole recombination and boost photoexcited charge transfer and separation. The heterostructure photocatalyst exhibits improved photocatalytic H2 evolution performance (6.6 times higher than pristine ZnIn2 S4 ) and excellent stability.

MXene
photocatalytic H2 evolution
ZnIn2S4 nanosheets
photoexcited charge separation
two-dimensional heterostructures


Flood susceptibility assessment in Hengfeng area coupling adaptive neuro-fuzzy inference system with genetic algorithm and differential evolution.

Abstract: Floods are among Earth's most common natural hazards, and they cause major economic losses and seriously affect peoples' lives and health. This paper addresses the development of a flood susceptibility assessment that uses intelligent techniques and GIS. An adaptive neuro-fuzzy inference system (ANFIS) was coupled with a genetic algorithm and differential evolution for flood spatial modelling. The model considers thirteen hydrologic, morphologic and lithologic parameters for the flood susceptibility assessment, and Hengfeng County in China was chosen for the application of the model due to data availability and the 195 total flood events. The flood locations were randomly divided into two subsets, namely, training (70% of the total) and testing (30%). The Step-wise Weight Assessment Ratio Analysis (SWARA) approach was used to assess the relation between the floods and influencing parameters. Subsequently, two data mining techniques were combined with the ANFIS model, including the ANFIS-Genetic Algorithm and the ANFIS-Differential Evolution, to be used for flood spatial modelling and zonation. The flood susceptibility maps were produced, and their robustness was checked using the Receiver Operating Characteristic (ROC) curve. The results showed that the area under the curve (AUC) for all models was >0.80. The highest AUC value was for the ANFIS-DE model (0.852), followed by ANFIS-GA (0.849). According to the RMSE and MSE methods, the ANFIS-DE hybrid model is more suitable for flood susceptibility mapping in the study area. The proposed method is adaptable and can easily be applied in other sites for flood management and prevention.

Hong|Haoyuan|H| Panahi|Mahdi|M| Shirzadi|Ataollah|A| Ma|Tianwu|T| Liu|Junzhi|J| Zhu|A-Xing|AX| Chen|Wei|W| Kougias|Ioannis|I| Kazakis|Nerantzis|N|

Flood susceptibility
Genetic algorithm
Differential evolution
ANFIS
Hengfeng County
Climate change


The use of non-pharmacological interventions for dementia behaviours in care homes: findings from four in-depth, ethnographic case studies.

Abstract:
BACKGROUND
antipsychotic medications have been used to manage behavioural and psychological symptoms of dementia (BPSD). Due to the potential risks associated with these medications for people with dementia, non-pharmacological interventions (NPIs) have been recommended as safer alternatives. However, it is unknown if, or how, these interventions are used in care homes to help people experiencing BPSD.

AIM
to explore the use of NPIs in care homes to manage BPSD.

METHODS
In-depth, ethnographic case studies were conducted in four care homes; in total, they included interviews with 40 care-home staff and 384 hours of participant observations.

FINDINGS
NPIs, some of which are the focus of efficacy research, were used in care homes but predominantly as activities to improve the quality of life of all residents and not identified by staff as meeting individual needs in order to prevent or manage specific behaviours. Socially relevant activities such as offering a cup of tea were used to address behaviours in the moment. Residents with high levels of need experienced barriers to inclusion in the activities.

CONCLUSIONS
there is a gap between rhetoric and practice with most NPIs in care homes used as social activities rather than as targeted interventions. If NPIs are to become viable alternatives to antipsychotic medications in care homes, further work is needed to embed them into usual care practices and routines. Training for care-home staff could also enable residents with high needs to gain better access to suitable activities.

Backhouse|Tamara|T| Killett|Anne|A| Penhale|Bridget|B| Gray|Richard|R|

D007722:Health Knowledge, Attitudes, Practice

non-pharmacological intervention
dementia
care home
BPSD
activities
older people


The Responders' Gender Stereotypes Modulate the Strategic Decision-Making of Proposers Playing the Ultimatum Game.

Abstract: Despite the wealth of studies investigating factors affecting decisions, not much is known about the impact of stereotypical beliefs on strategic economic decision-making. In the present study, we used the ultimatum game paradigm to investigate how participants playing as proposer modulate their strategic economic behavior, according to their game counterparts' stereotypical identity (i.e., responders). The latter were introduced to the participants using occupational role nouns stereotypically marked with gender paired with feminine or masculine proper names (e.g., linguist-Anna; economist-David; economist-Cristina; linguist-Leonardo). When playing with male-stereotyped responders, proposers quickly applied the equity rule, behaving fairly, while they adopted a strategic behavior with responders characterized by female stereotypes. They were also longer to make their offers to female than to male responders but both kinds of responders received comparable offers, suggesting a greater cognitive effort to treat females as equally as males. The present study explicitly demonstrates that gender stereotypical information affect strategic economic decision-making and highlights a possible evolution of gender discrimination into a more insidious discrimination toward individuals with female characteristics.

Fabre|Eve F|EF|
Causse|Mickael|M|
Pesciarelli|Francesca|F|
Cacciari|Cristina|C|

gender stereotypes
strategic decision-making
proposer
ultimatum game


Global prevalence and reasons for case cancellation on the intended day of surgery: A systematic review and meta-analysis.

Abstract:
Background
Cancellation of operation on the intended day of surgery affects the efficiency of Operation Room which incurs a significant financial loss for the patient, hospital, and health care cost of a country at large. This systematic and Meta-Analysis was intended to provide evidence on the global prevalence and determinants of case cancellation on the intended day of surgery.

Methods
A comprehensive search was conducted in PubMed/Medline; Science direct and LILACS from January 2010 to May 2020 without language restriction. The Heterogeneity among the included studies was checked with forest plot, χ2 test, I2 test, and the p-values. All observational studies reporting prevalence and determinants were included.

Results
A total of 1207 articles were identified from different databases with an initial search. Fort-eight articles were selected for evaluation after the successive screening. Thirty-three Articles with 306,635 participants were included. The Meta-Analysis revealed that the global prevalence of case cancellation on the intended day of surgery was 18% (95% CI: 16 to 20). The Meta-Analysis also showed that lack of operation theatre facility accounted for the major reason for cancellation followed by no attendant and change in medical condition.

Conclusion
The meta-analysis revealed that the prevalence of case cancellation was very high in low and middle-income countries and the majorities were avoidable which entails rigorous activities on operation theatre facilities, preoperative evaluation and preparation, patient and health care provider communications.

Registration
This Systematic Review and Meta-Analysis was registered in a research registry (researchregistry5746) available at https://www.researchregistry.com/browse-the-registry#home/.

Abate|Semagn Mekonnen|SM|
Chekole|Yigrem Ali|YA|
Minaye|Solomon Yimer|SY|
Basu|Bivash|B|

Global Prevalence Cancellation Surgery Determinants


Software Defined Networking for Improved Wireless Sensor Network Management: A Survey.

Abstract: Wireless sensor networks (WSNs) are becoming increasingly popular with the advent of the Internet of things (IoT). Various real-world applications of WSNs such as in smart grids, smart farming and smart health would require a potential deployment of thousands or maybe hundreds of thousands of sensor nodes/actuators. To ensure proper working order and network efficiency of such a network of sensor nodes, an effective WSN management system has to be integrated. However, the inherent challenges of WSNs such as sensor/actuator heterogeneity, application dependency and resource constraints have led to challenges in implementing effective traditional WSN management. This difficulty in management increases as the WSN becomes larger. Software Defined Networking (SDN) provides a promising solution in flexible management WSNs by allowing the separation of the control logic from the sensor nodes/actuators. The advantage with this SDN-based management in WSNs is that it enables centralized control of the entire WSN making it simpler to deploy network-wide management protocols and applications on demand. This paper highlights some of the recent work on traditional WSN management in brief and reviews SDN-based management techniques for WSNs in greater detail while drawing attention to the advantages that SDN brings to traditional WSN management. This paper also investigates open research challenges in coming up with mechanisms for flexible and easier SDN-based WSN configuration and management.

Ndiaye|Musa|M|
Hancke|Gerhard P|GP|
Abu-Mahfouz|Adnan M|AM|

software defined networks for sensor nodes


Exponential correlations among neuropathic components, pain intensity, and catastrophic thoughts in patients with musculoskeletal pain disorder.

Abstract:
BACKGROUND
Neuropathic components and catastrophic thoughts contribute to the quality of life impairments in patients with chronic pain. This retrospective cross-sectional observational study examined the extent to which neuropathic components affect pain intensity and catastrophic thoughts using a mathematical model.

METHODS
Participants with chronic pain with spinal or joint disorders were rated for pain intensity using a numerical rating scale (NRS), painDETECT questionnaire (PDQ), and pain catastrophizing scale (PCS). We plotted to scatter plots between PDQ and either NRS or PCS and drew best-fit lines for patients with leg pain only. We divided patients with both leg and back pain into two clusters: located above or below the baselines, and then we drew the best-fit lines for each cluster. We performed factor analysis on PDQ items and developed and validated a discriminant to identify patients located above the baseline in another cohort of musculoskeletal disorders.

RESULTS
We analyzed 163 patients with lumbar disorders and 205 patients with joint disorders. PDQ correlated exponentially with NRS and PCS of the patients located above the baseline in both disorder groups and correlated linearly or logarithmically in patients located below the baseline. Factor analysis revealed three sets of pain characteristics for each disorder. We developed the discriminant from PDQ items to identify patients showing exponential correlations and then validated it in another cohort of 137 patients. The coefficient for "pressure-evoked pain" was the highest in the discriminant.

CONCLUSIONS
Mathematical models indicate neuropathic components demonstrate linear correlations with NRS and PCS generally, but exponential correlations in a cluster of the patients with musculoskeletal pain. We developed and validated the discriminant based on pain characteristics to identify such patients; "pressure-evoked pain" was the most significant contributor.

Saita|Kosuke|K| Sumitani|Masahiko|M| Nikaido|Takuya|T| Sekiguchi|Miho|M| Inoue|Reo|R| Abe|Hiroaki|H| Konno|Shinichi|S| Uchida|Kanji|K|

D059350:Chronic Pain
D003430:Cross-Sectional Studies
D006801:Humans
D059352:Musculoskeletal Pain
D009437:Neuralgia
D011788:Quality of Life
D012189:Retrospective Studies
D011795:Surveys and Questionnaires

musculoskeletal pain
mathematical model
painDETECT
Pain catastrophizing
neuropathic pain


The Dietary Furocoumarin Imperatorin Increases Plasma GLP-1 Levels in Type 1-Like Diabetic Rats.

Abstract: Imperatorin, a dietary furocoumarin, is found not only in medicinal plants, but also in popular culinary herbs, such as parsley and fennel. Recently, imperatorin has been shown to activate GPR119 in cells. Another GPR, GPR131, also called TGR5 or G-protein-coupled bile acid receptor 1 (GPBAR1), is known to regulate glucose metabolism. Additionally, TGR5 activation increases glucagon-like peptide (GLP-1) secretion to lower blood sugar levels in animals. Therefore, the present study aims to determine whether the effects of imperatorin on GLP-1 secretion are mediated by TGR5. First, we transfected cultured Chinese hamster ovary cells (CHO-K1 cells) with the TGR5 gene. Glucose uptake was confirmed in the transfected cells using a fluorescent indicator. Moreover, NCI-H716 cells, which secrete GLP-1, were used to investigate the changes in calcium concentrations and GLP-1 levels. In addition, streptozotocin (STZ)-induced type 1-like diabetic rats were used to identify the effects of imperatorin in vivo. Imperatorin dose-dependently increased glucose uptake in CHO-K1 cells expressing TGR5. In STZ diabetic rats, similar to the results in NCI-H716 cells, imperatorin induced a marked increase of GLP-1 secretion that was reduced, but not totally abolished, by a dose of triamterene that inhibited TGR5. Moreover, increases in GLP-1 secretion induced by imperatorin and GPR119 activation were shown in NCI-H716 cells. We demonstrated that imperatorin induced GLP-1 secretion via activating TGR5 and GPR119. Therefore, imperatorin shall be considered as a TGR5 and GPR119 agonist.

Wang|Lin-Yu|LY| Cheng|Kai-Chun|KC| Li|Yingxiao|Y| Niu|Chiang-Shan|CS| Cheng|Juei-Tang|JT| Niu|Ho-Shan|HS|

imperatorin GPR119 TGR5 transfection triamterene sitagliptin


Selective Estrogen Receptor Modulator (SERM)-like Activities of Diarylheptanoid, a Phytoestrogen from Curcuma comosa, in Breast Cancer Cells, Pre-osteoblast Cells, and Rat Uterine Tissues.

Abstract: Diarylheptanoids from Curcuma comosa, of the Zingiberaceae family, exhibit diverse estrogenic activities. In this study we investigated the estrogenic activity of a major hydroxyl diarylheptanoid, 7-(3,4 -dihydroxyphenyl)-5-hydroxy-1-phenyl-(1E)-1-heptene (compound 092) isolated from C. comosa. The compound elicited different transcriptional activities of estrogen agonist at low concentrations (0.1-1 μM) and antagonist at high concentrations (10-50 μM) using luciferase reporter gene assay in HEK-293T cells. In human breast cancer (MCF-7) cells, compound 092 showed an anti-estrogenic activity by down-regulating ERα-signaling and suppressing estrogen-responsive genes, whereas it attenuated the uterotrophic effect of estrogen in immature ovariectomized rats. Of note, compound 092 promoted mouse pre-osteoblastic (MC3T3-E1) cell differentiation and the related bone markers, indicating its positive osteogenic effect. Our findings highlight a new, nonsteroidal, estrogen agonist/antagonist of catechol diarylheptanoid from C. comosa, which is scientific evidence supporting its potential as a dietary supplement to prevent bone loss with low risk of breast and uterine cancers in postmenopausal women.

D020845:Selective Estrogen Receptor Modulators

diarylheptanoid
phytoestrogens
Curcuma comosa
breast cancer
estrogen agonist
bone
estrogen antagonist
uterus


Anatomy of Master Knot of Henry: A morphometric study on cadavers.

Abstract:
OBJECTIVE
The objective of this study was to evaluate the features of flexor hallucis longus (FHL), flexor digitorum longus (FDL) and flexor digitorum accessorius (FDA) muscles with relevance to the tendon grafts and to reveal the location of Master Knot of Henry (MKH).

METHODS
Twenty feet from ten formalin fixed cadavers were dissected, which were in the inventory of Anatomy Department of Medicine Faculty, Mersin University. The location of MKH was identified. Interconnections of FHL and FDL were categorized. According to incision techniques, lengths of FHL and FDL tendon grafts were measured. Attachment sites of FDA were assessed.

RESULTS
MKH was 12.61 ± 1.11 cm proximal to first interphalangeal joint, 1.75 ± 0.39 cm below to navicular tuberosity and 5.93 ± 0.74 cm distal to medial malleolus. The connections of FHL and FDL were classified in 7 types. Tendon graft lengths of FDL according to medial and plantar approaches were 6.14 ± 0.60 cm and 9.37 ± 0.77 cm, respectively. Tendon graft lengths of FHL according to single, double and minimal invasive incision techniques were 5.75 ± 0.63 cm, 7.03 ± 0.86 cm and 20.22 ± 1.32 cm, respectively. FDA was found to be inserting to FHL slips in all cases and it inserted to various surfaces of FDL.

CONCLUSION
The exact location of MKH and slips was determined. Two new connections not recorded in literature were found. It was observed that the main attachment site of FDA was the FHL slips. The surgical awareness of connections between the FHL, FDL and FDA, which participated in the formation of long flexor tendons of toes, could be important for reducing possible loss of function after tendon transfers postoperatively.

Beger|Orhan|O| Elvan|Özlem|Ö| Keskinbora|Mert|M| Ün|Burçin|B| Uzmansel|Deniz|D| Kurtoğlu|Zeliha|Z|

Master knot of Henry
Flexor hallucis longus
Flexor digitorum longus
Flexor digitorum accessorius
Slip
Tendon transfer


Network meta-analysis: application and practice using Stata.

Abstract: This review aimed to arrange the concepts of a network meta-analysis (NMA) and to demonstrate the analytical process of NMA using Stata software under frequentist framework. The NMA tries to synthesize evidences for a decision making by evaluating the comparative effectiveness of more than two alternative interventions for the same condition. Before conducting a NMA, 3 major assumptions-similarity, transitivity, and consistency-should be checked. The statistical analysis consists of 5 steps. The first step is to draw a network geometry to provide an overview of the network relationship. The second step checks the assumption of consistency. The third step is to make the network forest plot or interval plot in order to illustrate the summary size of comparative effectiveness among various interventions. The fourth step calculates cumulative rankings for identifying superiority among interventions. The last step evaluates publication bias or effect modifiers for a valid inference from results. The synthesized evidences through five steps would be very useful to evidence-based decision-making in healthcare. Thus, NMA should be activated in order to guarantee the quality of healthcare system.

Network meta-analysis
Biostatistic
Mixed treatment comparison
Treatment outcome


Lipoprotein (a) and aortic valve calcium in South Asians compared to other race/ethnic groups.

Abstract:
BACKGROUND AND AIMS
South Asians are at increased risk for cardiovascular disease (CVD). Aortic valve calcium (AVC) is associated with CVD risk and aortic stenosis. Elevated Lp(a) is a heritable risk factor for CVD and AVC. AVC prevalence and its association with Lp(a) have not been studied in South Asians.

METHODS
Among participants in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study (n = 695), AVC prevalence and extent were compared to four race/ethnic groups in the Multi-Ethnic Study of Atherosclerosis (MESA) (n = 4671). Multivariable regression was performed to evaluate associations between Lp(a) and AVC stratified by race/ethnic groups, adjusting for cardiovascular risk factors.

RESULTS
After age and sex adjustment, South Asians had higher median Lp(a) (17.0 mg/dL) compared to Whites (12.9 mg/dL), Hispanics (13.1 mg/dL) and Chinese Americans (12.9 mg/dL), and Blacks had highest Lp(a) levels (35.1 mg/dL). There were no differences in the odds of AVC in South Asians compared with Whites or Hispanics, after age and sex adjustment (p = 0.64 and 0.63, respectively). Odds of AVC was lower in Chinese (OR 0.35; 95%CI 0.23-0.54) and somewhat lower in Blacks compared with South Asians (OR 0.76; 0.56-1.04). There were no associations between Lp(a) and AVC presence or extent in South Asians. Lp(a) was associated with AVC only among Blacks and Whites.

CONCLUSIONS
Although present in Whites and Blacks, there were no associations between Lp(a) and AVC in South Asians. These differences may be due to statistic power or race specific modifying factors that influences the effect of Lp(a) particles on AVC pathogenesis.

Makshood|Minhal|M|
Joshi|Parag H|PH|
Kanaya|Alka M|AM|
Ayers|Colby|C|
Budoff|Matthew|M|
Tsai|Michael Y|MY|
Blaha|Michael|M|
Michos|Erin D|ED|
Post|Wendy S|WS|

Lipoprotein (a)
Aortic valve calcium
South asians
MASALA


Maxillary Permanent First Premolars With Three Canals: Incidence Analysis Using Cone Beam Computerized Tomographic Techniques.

Abstract:
Aim
This study aimed to analyze incidence of three canals in human permanent maxillary first premolar teeth using cone beam tomographic techniques.

Materials and Methods
The samples were divided into three groups namely Group (GP) I (single rooted [n = 255]), GP II (two rooted [n = 326]), and GP III (three rooted [n = 8)]. The teeth were processed, mounted in arches, coded, and subjected to cone beam tomographic scanning. Incidence of three canals was evaluated by cone beam tomography, compared, and statistically analyzed.

Results
The percentage of incidence of three canals in human permanent maxillary first premolar teeth was 1.7% and there was no statistically significant difference of incidence of three canals between studies using cone beam and non-cone beam methodologies.

Conclusion
Clinicians should be aware of the variations they may encounter when endodontically treating a maxillary first permanent premolar and should apply this knowledge in a clinical scenario systematically.

Karunakaran|Jeyaraman Venkataraman|JV|
Ganeshamoorthy|Thiyagarajan|T|
Anbarasi|Kaliayaperumal|K|
Ragavendran|Nagappan|N|
Karthick|Arthanari Kaneesh|AK|

three canals
maxillary first premolar
cone beam tomography
Canal configuration


Occurrence and Molecular Characteristics of Extended-Spectrum Beta-Lactamase-Producing Enterobacterales Recovered From Chicken, Chicken Meat, and Human Infections in Sao Paulo State, Brazil.

Abstract: This study aimed to investigate the phylogenetic diversity and epidemiology of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae from chicken, chicken meat, and human clinical isolates in Sao Paolo, Brazil, and characterize their respective ESBL-encoding plasmids. Three hundred samples from chicken cloaca, chicken meat, and clinical isolates were phenotypically and genotypically assessed for ESBL resistance. Isolates were identified by MALDI TOF-MS and further characterized by MLST analysis and phylogenetic grouping. ESBL genes were characterized and their location was determined by I-Ceu-I-PFGE and Southern blot, conjugation, transformation, and PCR-based replicon typing experiments. Thirty-seven ESBL-producing isolates (28 E. coli and 9 K. pneumoniae) that were positive for the bla  or bla  gene groups were obtained. Two isolates were negative in the transformation assay, and the chromosomal location of the genes was deduced by Southern blot. The bla  genes identified were carried on plasmid replicon-types X1, HI2, N, FII-variants, I1 and R. The E. coli isolates belonged to nine sequence types, while the K. pneumoniae isolates belonged to four sequence types. The E. coli isolates belonged to phylotype classification groups A, B1, D, and F. This study demonstrated that isolates from cloacal swabs, chicken meat, and human feces had genetic diversity, with a high frequency of bla  among chickens, chicken meat, and human feces. Thus, this reinforces the hypothesis that chickens, as well as their by-products, could be an important source of transmission for ESBL-producing pathogens to humans in South America.

Cardozo|Marita Vedovelli|MV|
Liakopoulos|Apostolos|A|
Brouwer|Michael|M|
Kant|Arie|A|
Pizauro|Lucas José Luduvério|LJL|
Borzi|Mariana Monezi|MM|
Mevius|Dik|D|
de Ávila|Fernando Antonio|FA|

extended spectrum beta lactamases (ESBLs)


At discharge gait speed and independence of patients provides a challenges for rehabilitation after total joint arthroplasty: an observational study.

Abstract:
Background
The level of functioning in people discharged from hospital after hip arthroplasty is very heterogeneous and prognostic factors are not fully understood. The aim of this study was to determine the mean level of autonomy achieved by such patients at discharge from hospital using the Iowa Level of Assistence (ILOA) scale as a measurement tool and to investigate the possible predictive factors of this autonomy.

Methods
It was conducted a prospective cohort study including hip arthroplasty patients treated consecutively in 2012. Hip arthroplasty patients following fractures, revision surgery and partial replacement were excluded, as well as patients with concomitant neurologic or rheumatologic diseases or postoperative complications that did not allow to continue the rehabilitation program, and patients with a hospitalization of more than 7 days. During the last 24 h of hospital stay the physiotherapist filled in the ILOA scale and collected all data (age, gender, number of physiotherapy treatments, length of hospitalization). Statistical analysis (univariate and multivariate analysis) was performed between the variables collected and the ILOA Score.

Results
The sample was composed of 167 patients. The mean score of the ILOA was 16.6 (±6.5) and gait speed had the poorest outcome 0.19 m/s - 0.43 m/s. Multivariate analysis showed that older women are most at risk of not achieving good levels of autonomy.

Conclusions
In hip arthroplasty patients at discharge from hospital gait speed is severely impaired. The challenge for rehabilitation should be to recover walking ability and efficiency starting from the early post-operative period. Gender- and age-tailored rehabilitation programs should be considered by placing particular attention on elderly women.

Rehabilitation
Hip replacement arthroplasty
Patient outcome assessment
Recovery of function


Based Natural Products as Quorum Sensing Inhibitors in E. Coli: A Critical Review.

Abstract: The existence of multidrug-resistant (MDR) E .coli (superbugs) is a global health issue confronting humans, livestock, food processing units, and pharmaceutical industries. The quorum sensing (QS) controlling ability of the E .coli to form biofilms has become one of the important reasons for the emergence of multidrug-resistant pathogens. Quorum signaling activation and formation of biofilm lead to the emergence of antimicrobial resistance of the pathogens increasing the therapy difficulty for treating bacterial diseases. There is a crucial need, therefore, to reinforce newer therapeutic designs to overcome this resistance. As the infections caused by E .coli are attributed via the QS-regulated biofilm formation, easing this system by QS inhibitors is a possible strategy for treating bacterial diseases. Plant based natural products have been reported to bind to QS receptors and interrupt the QS systems of pathogens by inhibiting biofilm formation and disrupting the formed biofilms, thus minimizing the chances to develop a resistance mechanism. The present report reviews critically the QS capability of E .coli to form biofilms leading to multidrug resistant pathogens and the investigations that have been carried out so far on plant acquired natural products as QS inhibitors.

Cardiliya|A P|AP|
Selvaraj|A|A|
Nanjan|M J|MJ|
Chandrasekar|M J N|MJN|

quorum sensing (QS)
bacterial
biofilm formation
multidrug resistant bacteria


Effect of pharmacological treatment for urinary incontinence in the elderly and frail elderly: A systematic review.

Abstract:
AIM
The prevalence and severity of urinary incontinence (UI) increase with age and comorbidity. The benefits of pharmacotherapy for UI in the elderly are questionable. The aim of the present study was to systematically review the efficacy of pharmacological treatment for UI in the elderly and frail elderly.

METHODS
We searched PubMed, EMBASE, Cochrane library and Cinahl databases through October 2013 to identify prospective controlled trials that evaluated pharmacological treatment for UI in persons aged ≥65 years. Elderly persons living in nursing homes were regarded as frail elderly. Outcomes were urinary leakage, quality of life and adverse events.

RESULTS
We screened 1038 abstracts and assessed 309 full-text articles. We identified 13 trials of high or moderate quality; 11 evaluated anticholinergic drugs and two evaluated duloxetine. Oxybutynin, the only drug studied in the frail elderly population, had no effect on urinary leakage or quality of life in elderly with urgency UI (UUI). Seven trials evaluated the effects of darifenacin, fesoterodine, solifenacin, tolterodine or trospium. Urinary leakage decreased (standard mean difference: -0.24, 95% confidence interval -0.32-0.15), corresponding to a reduction of half a leakage per 24 h. Common side-effects of treatment were dry mouth and constipation. Data were insufficient for evaluation of the effect on quality of life or cognition. The evidence was insufficient to evaluate the effects of duloxetine. No eligible studies on mirabegron and estrogen were found.

CONCLUSIONS
Anticholinergics have a small, but significant, effect on urinary leakage in older adults with UUI. Treatment with drugs for UUI in the frail elderly is not evidence based.

Samuelsson|Eva|E| Odeberg|Jenny|J| Stenzelius|Karin|K| Molander|Ulla|U| Hammarström|Margareta|M| Franzen|Karin|K| Andersson|Gunnel|G| Midlöv|Patrik|P|

urinary incontinence
elderly
frail elderly
systematic review
pharmacotherapy


Ovarian biomarkers predict controlled ovarian stimulation for in vitro fertilisation treatment in Singapore.

Abstract:
INTRODUCTION
Ovarian biomarkers have been shown to predict responses to controlled ovarian hyperstimulation (COH) during in vitro fertilisation (IVF) in predominantly Caucasian populations, with limited studies performed in Southeast Asian women in Singapore.

METHODS
We evaluated the performance of serum anti-Müllerian hormone (AMH), follicle-stimulating hormone and oestradiol levels, antral follicle count (AFC), body mass index, ovarian volume, and age to establish thresholds for the prediction of poor (< 4 oocytes retrieved) and excessive responses (> 19 oocytes retrieved) in 263 women undergoing COH. Univariate and multivariate logistic regression analysis and receiver operating characteristic curves were used to calculate probabilities for poor and excessive responders to COH.

RESULTS
36 (13.7%) and 50 (19.0%) women had poor and excessive response to COH, respectively. An AMH value of 0.69 ng/mL predicted poor ovarian response with positive likelihood ratio (LR) of 2.94, compared to an AFC of ≤ 5 when the positive LR is 2.36. Conversely, an AMH value of ≥ 3.06 ng/mL predicted excessive ovarian response with positive LR of 2.24, compared to an AFC cut-off of ≥ 12 with positive LR of 1.93.

CONCLUSION
AMH levels and AFC are equivalent in the prediction of both poor and excessive ovarian response in women undergoing IVF. Our study highlights the importance of establishing population-specific cut-off biomarker values so that protocols can be tailored to optimise IVF treatment.

Lee|Ryan Wai Kheong|RWK|
Khin|Lay Wai|LW|
Hendricks|Marianne Sybille|MS|
Tan|Heng Hao|HH|
Nadarajah|Sadhana|S|
Tee|Nancy Wen Sim|NWS|
Loh|Seong-Feei|SF|
Tai|Bee Choo|BC|
Chan|Jerry Ky|JK|

ovarian biomarkers stimulation fertilisation


Predictive validity of short term scar quality on final burn scar outcome using the Patient and Observer Scar Assessment Scale in patients with minor to moderate burn severity.

Abstract:
BACKGROUND
The aim of this study was to assess the predictive validity of the Patient and Observer Assessment Scale (POSAS), in order to determine whether it can be used to predict final scar quality.

METHODS
Patients with a maximum TBSA burned of 20% who were treated in a Dutch burn center and participated in two scar assessments at 3 months and >18 months post-burn were included. Scar quality assessment consisted of the POSAS, Dermaspectrometer® (color) and Cutometer® (elasticity). Predictive validity was determined in three ways: (1) the discriminative ability to distinguish good from reduced long term scar quality, (2) correlations between POSAS items score at the two subsequent assessments and (3) linear regression was conducted to identify POSAS items as independent predictors. Additionally, reliability, construct validity and interpretability were assessed.

RESULTS
A total of 141 patients were included with a mean TBSA burned of 5.2% (±4.5). The ability of the Patient scale to discriminate between good and reduced long term scar quality was adequate with an area under the curve (AUC) of 0.728 (CI 0.640-0.804), the ability of the Observer scale was good with an AUC of 0.854 (CI 0.781-0.911). Correlations between items scored T3 and T>18 were at least adequate. On item level, pain and stiffness (Patient) and pliability and relief (Observer) were identified as significant predictors for reduced long term scar quality. The POSAS was reliable, construct validity was adequate at three months but declined at >18 months.

CONCLUSION
This study found that final scar quality can be adequately predicted by an early POSAS assessment at three months.

Goei|H|H|
van der Vlies|C H|CH|
Tuinebreijer|W E|WE|
van Zuijlen|P P M|PPM|
Middelkoop|E|E|
van Baar|M E|ME|

Predictive validity
Scars
Burns
POSAS
Outpatient burn care
PROMs


Barriers for Antiretroviral Therapy Adherence and Viral Suppression in Members of the Key Population in Mumbai, India: Implications for Interventions.

Abstract:
Background
Poor adherence to antiretroviral therapy (ART) is associated with poor virologic control and drug resistance in people living with HIV/AIDS. Some barriers to ART adherence are cost, lack of information, stigma, or dissatisfaction with health services.

Aims and Objectives
To study the association between barriers for ART adherence and viral suppression, and explore the role of "missing ART dose" as a potential mediator in high-risk groups.

Materials and Methods
Demographic, clinical, and behavioral data from 50 "virally suppressed" (viral load [VL] <1000 copies/ml) and 48 "not suppressed" (VL > 1000 copies/ml) individuals belonging to the key population in Mumbai were collected. Sociodemographic, behavioral, and other characteristics were compared, and mediation analysis was used to identify the mediator in the pathway to viral suppression.

Results
Those who had missed their ART at least once in the past three months (37% versus 60%, P = 0.03) and stayed alone were less likely to be virally suppressed (31% versus 69%, P = 0.002). Individuals who had negative perception about ART (adjusted odds ratio [aOR]: 0.11, 95% confidence interval [CI]: 0.02, 0.47; P = 0.002), poor ART-related knowledge/behaviors (aOR: 0.14, 95% CI: 0.03, 0.60; P = 0.007), and poor pill taking practices (aOR: 0.10, 95% CI: 0.02, 0.61; P = 0.01) were significantly less likely to be virally suppressed. The mediation pathway "adherence theme > missed ART in the past three months > viral suppression" was significant in these themes.

Conclusions
The factors associated with low viral suppression were knowledge/behaviors, perceptions about ART, and poor pill taking practices. Thus, it is important to provide correct information about ART, its effects, side effects, and potential limitations to marginalized population. Involving brothel keepers and Gurus (head of male-to-female transgendered people/Hijras clans), and technology enabled customized counseling sessions will be helpful.

Acharya|Shrikala|S|
Parthasarathy|M|M|
Palkar|Amol|A|
Keskar|Padmaja|P|
Setia|Maninder Singh|MS|

barriers
Adherence
viral suppression
ART
mediation


Win-Stay, Lose-Sample: a simple sequential algorithm for approximating Bayesian inference.

Abstract: People can behave in a way that is consistent with Bayesian models of cognition, despite the fact that performing exact Bayesian inference is computationally challenging. What algorithms could people be using to make this possible? We show that a simple sequential algorithm "Win-Stay, Lose-Sample", inspired by the Win-Stay, Lose-Shift (WSLS) principle, can be used to approximate Bayesian inference. We investigate the behavior of adults and preschoolers on two causal learning tasks to test whether people might use a similar algorithm. These studies use a "mini-microgenetic method", investigating how people sequentially update their beliefs as they encounter new evidence. Experiment 1 investigates a deterministic causal learning scenario and Experiments 2 and 3 examine how people make inferences in a stochastic scenario. The behavior of adults and preschoolers in these experiments is consistent with our Bayesian version of the WSLS principle. This algorithm provides both a practical method for performing Bayesian inference and a new way to understand people's judgments.

Bonawitz|Elizabeth|E|
Denison|Stephanie|S|
Gopnik|Alison|A|
Griffiths|Thomas L|TL|

Bayesian inference
Causal learning
Algorithmic level


Predictors for High Microsatellite Instability in Patients with Colorectal Cancer Fulfilling the Revised Bethesda Guidelines.

Abstract:
BACKGROUND
The revised Bethesda guidelines (rBG) are generally used for screening of Lynch syndrome, and few researchers have investigated the associations between microsatellite instability (MSI) status and each item of the rBG.

PATIENTS AND METHODS
This retrospective study included patients with colorectal cancer who were classified into those fulfilling the rBG (Bethesda group) and those not (control group). The breakdown of each item in the rBG and predictors of high MSI (MSI-H) were determined in the Bethesda group.

RESULTS
Of 809 consecutive patients, 161 (19.9%) were found to fulfil the rBG criteria. As a predictor of MSI-H, items 2 or 5 of the rBG showed a sensitivity of 93.3%. Item 5 and right-sided tumour location were independent predictors of MSI-H in patients fulfilling the rBG (odds ratio(OR)=4.49 and 25.1; p=0.0260 and <0.0001, respectively).

CONCLUSION
Item 5 of the rBG and right-sided tumour location are significant predictors of MSI-H.

Arakawa|Keiichi|K| Hata|Keisuke|K| Kawai|Kazushige|K| Tanaka|Toshiaki|T| Nishikawa|Takeshi|T| Sasaki|Kazuhito|K| Shuno|Yasutaka|Y| Kaneko|Manabu|M| Hiyoshi|Masaya|M| Emoto|Shigenobu|S| Murono|Koji|K| Nozawa|Hiroaki|H|

D003123:Colorectal Neoplasms, Hereditary Nonpolyposis

Colorectal cancer
Bethesda guidelines
Lynch syndrome


Multiscale simulation of the interaction of calreticulin-thrombospondin-1 complex with a model membrane microdomain.

Abstract: Cell surface calreticulin (CRT) binding to thrombospondin-1 (TSP1), regulates cell adhesion, migration, anoikis resistance, and collagen production. Due to the essential role of membrane microdomains in CRT-mediated focal adhesion disassembly, we previously studied the effect of raft-like bilayers on TSP1-CRT interactions with all-atom molecular dynamics (AAMD) simulations. However, the simulated systems of protein on the surface of the bilayer(s) in the explicit solvent are too large for long timescale AAMD simulations due to computational expense. In this study, we adopted a multiscale modeling approach of combining AAMD, coarse-grained molecule dynamics (CGMD), and reversed AAMD (REV AAMD) simulations to investigate the interactions of single CRT or of the TSP1-CRT complex with a membrane microdomain at microsecond timescale. Results showed that CRT conformational stabilization by binding of TSP1 in AAMD simulation was undetectable in CGMD simulation, but it was recovered in REV AAMD simulation. Similarly, interactions of the CRT N-domain and TSP1 with the membrane microdomain were lost in CGMD simulations but they were re-gained in the REV AAMD simulations. There was the higher coordination of the CRT P-domain in the TSP1-CRT complex with the lipid components of membrane microdomain compared to that of single CRT, which could directly affect the conformation of CRT and further mediate CRT recruitment of LDL receptor-related protein for signaling events. This study provides structural and molecular insights into TSP1-CRT interactions in a membrane microdomain environment and demonstrates the feasibility of using multiscale simulations to investigate the interactions between protein and membrane microdomains at a long timescale.

Wang|Lingyun|L|
Murphy-Ullrich|Joanne E|JE|
Song|Yuhua|Y|

D037282:Calreticulin
D021962:Membrane Microdomains
D056004:Molecular Dynamics Simulation
D011485:Protein Binding
D017433:Protein Structure, Secondary
D013816:Thermodynamics
D019700:Thrombospondin 1

multiscale simulation
membrane microdomain
calreticulin
thrombospondin-1
protein–membrane interactions


Association of physical activity with risk of metabolic syndrome: findings from a cross-sectional study conducted in rural area, Nantong, China.

Abstract: The prevalence of metabolic syndrome increases rapidly worldwide, and its association with physical activity (PA) varies with race and lifestyles. Little is known about the association in rural China. The Nantong Metabolic Syndrome Study recruited 13,505 female and 6997 male participants in 2007 and 2008. Socio-demographic characteristics, and physiological and behavioural data were collected. Logistic regression model was applied to estimate associations of metabolic syndrome and its components with different PAs. The overall metabolic syndrome prevalence was 21.6% in current study. Increasing total PA or moderate-to-vigorous-intensity occupational PA was associated with decreasing 5%-60% risk of having metabolic syndrome and abnormal metabolic syndrome components in both genders. An association between leisure-time PA and blood pressure was found in men, but no associations between leisure-time PA and metabolic syndrome components were found in women. Commuting PA, such as walking and taking bus, by bicycle and walking only, was associated with decrease of 20%-45% risk of several abnormal metabolic syndrome components in women. This study provides information for future investigation into the nature of these associations so that recommendations can be developed to reduce the prevalence of metabolic syndrome and its components among rural population in China.

Xiao|Jing|J| Wu|Chuanli|C| Xu|Guangfei|G| Huang|Jianping|J| Gao|Yuexia|Y| Lu|Qingyun|Q| Hua|Tianqi|T| Cai|Hui|H|

Association
metabolic syndrome
metabolic syndrome components
commuting physical activity
leisure-time physical activity
occupational physical activity


Role of circular RNA in hematological malignancies.

Abstract: Compared with linear RNA, circular RNAs (circRNAs) form a covalently closed circular continuous loop and are highly conserved, stable and tissue-specific. In recent years, circRNAs received considerable attention in the diagnosis, classification, treatment and prognosis of hematological tumors. circRNAs function as microRNA sponges and competitive endogenous RNAs that play an essential role in the translation, regulation and interaction of proteins. The present review discussed the fundamental properties and functions of circRNAs and the latest advancements in the context of circRNAs in the clinical research of hematological malignancies, namely acute and chronic myeloid leukemia, and chronic lymphocytic leukemia. circRNAs show potential in the diagnosis and prognosis of various diseases and can be used as therapeutic targets and biomarkers for disease.

Mei|Mei|M| Wang|Yingjun|Y| Li|Zhaoming|Z| Zhang|Mingzhi|M|

circRNA
hematological tumor
miRNA sponge
tumor biomarker


Use of human islets to understand islet biology and diabetes: progress, challenges and suggestions.

Abstract: Over the last two decades, improved access to human islets and the development of human islet distribution networks have enabled the use of millions of human islets in hundreds of scientific research projects, leading to a dramatic increase in our understanding of human islet biology. Here we discuss recent scientific advances as well as methodological and experimental challenges that impact human islet quality, experimental outcomes and the reporting of human islets used in scientific publications. In a survey of over 200 scientific publications with human islet experimentation, we found that the reporting of critical information was quite variable, sometimes obscure, and often failed to adequately outline the experiments and results using human islets. As the complexity of human islet research grows, we propose that members of the human islet research ecosystem work together to develop procedures and approaches for accessible and transparent collecting and reporting of crucial human islet characteristics and, through this, enhance collaboration, reproducibility and rigour, leading to further advances in our understanding of human islet biology.

Hart|Nathaniel J|NJ|
Powers|Alvin C|AC|0000-0003-1941-5786

D016381:Islets of Langerhans Transplantation

Human
Islets
Diabetes
Research
Reporting
Transparency
Rigour
Insulin
Pancreas
Resource
Review
Unique identifier


MUC1: The First Respiratory Mucin with an Anti-Inflammatory Function.

Abstract: MUC1 is a membrane-bound mucin expressed on the apical surfaces of most mucosal epithelial cells. In normal lung epithelia, MUC1 is a binding site for Pseudomonas aeruginosa, an opportunistic human pathogen of great clinical importance. It has now been established that MUC1 also serves an anti-inflammatory role in the airways that is initiated late in the course of a bacterial infection and is mediated through inhibition of Toll-like receptor (TLR) signaling. MUC1 expression was initially shown to interfere with TLR5 signaling in response to P. aeruginosa flagellin, but has since been extended to other TLRs. These new findings point to an immunomodulatory role for MUC1 during P. aeruginosa lung infection, particularly during the resolution phase of inflammation. This review briefly summarizes the recent characterization of MUC1's anti-inflammatory properties in both the respiratory tract and extrapulmonary tissues.

Kato|Kosuke|K|
Lillehoj|Erik P|EP|
Lu|Wenju|W|
Kim|Kwang Chul|KC|

MUC1
lung
Pseudomonas aeruginosa
Toll-like receptor
inflammation
membrane-tethered mucin


Sensitive polarographic electrochemical determination of clarithromycin in blood serum.

Abstract: Clarithromycin is an antibacterial widely used for the treatment of a myriad of infections. Various methods including HPLC have been reported for its drug plasma concentration but they are more complex. In this study, we developed an electrochemical method for estimation of clarithromycin in blood using differential pulse polarography (DPP) after oral administration of pure clarithromycin suspension. The differential pulse polarography of clarithromycin showed peak with peak potential Ep is -1460 mV SCE at pH 6.5 ± 0.1. The developed electrochemical method was standardized and validated for the determination of clarithromycin in blood serum of albino rats. PK analysis included C max, T max, AUC0-24, elimination rate constant (Kel) and t1/2. C max were found to be 1.34 ± 0.16 mg/ml and 1.99 ± 0.22 mg/ml for plain clarithromycin and suspension formulation, respectively. Effects of ammonium tartarate concentration and pH were also studied as specificity parameters. Developed electrochemical method was found to be simple, accurate method for to estimate blood-clarithromycin profile and can also be used similarly for various dosage forms.

Electrochemical Clarithromycin Serum Polarography


Semi-volatile components of PM2.5 in an urban environment: volatility profiles and associated oxidative potential.

Abstract: The volatility profiles of PM2.5 semi-volatile compounds and relationships to the oxidative potential of urban airborne particles were investigated in central Los Angeles, CA. Ambient and thermodenuded fine (PM2.5) particles were collected during both warm and cold seasons by employing the Versatile Aerosol Concentration Enrichment System (VACES) combined with a thermodenuder. When operated at 50 °C and 100 °C, the VACES/thermodenuder system removed about 50% and 75% of the PM2.5 volume concentration, respectively. Most of the quantified PM2.5 semi-volatile species including organic carbon (OC), water soluble organic carbon (WSOC), polycyclic aromatic hydrocarbons (PAHs), organic acids, n-alkanes, and levoglucosan, as well as inorganic ions (i.e., nitrate, sulfate, and ammonium) exhibited concentration losses in the ranges of 40-66% and 67-92%, respectively, as the thermodenuder temperature increased to 50 °C and 100 °C. Species in the PM2.5 such as elemental carbon (EC) and inorganic elements (including trace metals) were minimally impacted by the heating process - thus can be considered refractory. On average, nearly half of the PM2.5 oxidative potential (as measured by the dichlorodihydrofluorescein (DCFH) alveolar macrophage in vitro assay) was associated with the semi-volatile species removed by heating the aerosols to only 50 °C, highlighting the importance of this quite volatile compartment to the ambient PM2.5 toxicity. The fraction of PM2.5 oxidative potential lost upon heating the aerosols to 100 °C further increased to around 75-85%. Furthermore, we document statistically significant correlations between the PM2.5 oxidative potential and different semi-volatile organic compounds originating from primary and secondary sources, including OC (Rwarm, and Rcold) (0.86, and 0.74), WSOC (0.60, and 0.98), PAHs (0.88, and 0.76), organic acids (0.76, and 0.88), and n-alkanes (0.67, and 0.83) in warm and cold seasons, respectively, while a strong correlation between oxidative potential and levoglucosan, a tracer of biomass burning, was observed only during the cold season (Rcold=0.81).

Pirhadi|Milad|M|
Mousavi|Amirhosein|A|
Taghvaee|Sina|S|
Shafer|Martin M|MM|
Sioutas|Constantinos|C|

volatility
thermodenuder
PM2.5 oxidative potential
DCFH assay
gas-particle partitioning
semi-volatile organic compounds (SVOCs)


MicroRNA-19 restores vascular endothelial cell function in lower limb ischemia-reperfusion injury through the KLF10-dependent TGF-β1/Smad signaling pathway in rats.

Abstract: Ischemia-reperfusion injury (IRI) is a severe problem patients diagnosed with acute limb ischemia. Recently, microRNAs (miR) have emerged as regulators of IRI as well as ischemic preconditioning and ischemic postconditioning. Therefore, using rat models, this study aims to explore all of the possible mechanisms that miR-19 exhibits with its relation to the transforming growth factor beta (TGF-β1)/Smad signaling pathway in the lower limb IRI. An immunofluorescence staining method was used to identify the Krueppel-like factor 10 (KLF10) positive expression and the location of KLF10 expression. The targeting relationship that miR-19 has with KLF10 was verified by the dual-luciferase reporter gene assay. Vascular endothelial cells (VECs) were treated with elevated or suppressed miR-19 or KLF10 knockdown. A 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay was used to test cell proliferation, and flow cytometry was employed to detect both cell cycle and apoptosis. The KLF10-positive expression in the VECs (both in cytoplasm and nucleus) was found to be elevated in the IRI rats. We found that miR-19 was downregulated, KLF10 upregulated, and the TGF-β1/Smad signaling pathway activated in the vascular epithelial tissues of IRI rats. KLF10 is a target gene of miR-19. Overexpression of miR-19 decreased the expression of KLF10, TGF-β1, and Smad2/3. Decreased miR-19 inhibited VEC proliferation, arrested VECs at the G1 phase, and promoted the apoptosis of VECs following their lower limb I/R injury. These results indicate miR-19 as being an inhibitor in the VEC injury of IRI via the TGF-β1/Smad signaling pathway by suppression of KLF10.

Xu|Yong-Le|YL| Zhang|Min-Hong|MH| Guo|Wei|W| Xue|Yan|Y| Du|Xin|X| Zhang|Tao|T| Wu|Na|N| Wu|Ye|Y|0000-0001-7040-4076

D053773:Transforming Growth Factor beta1

transforming growth factor beta 1 (TGF-β1)/Smad signaling pathway


The role of cell cycle progression for the apoptosis of cancer cells induced by palladium(II)-saccharinate complexes of terpyridine.

Abstract:
OBJECTIVES
Palladium complexes are potent and less toxic molecules in comparison to other metal based agents. Here, we characterized two palladium(II) saccharinate complexes with terpyridine for their cell cycle specificity.

MATERIALS AND METHODS
Cells were arrested at G1, G1/S boundary or mitosis using mimosine, double-Thymidine block, aphidicolin, nocodazole or colcemid, and evaluated based on morphology and flow cytometry. Synchronized cells were treated with the Pd(II) complexes, and viability was measured via MTT assay.

RESULTS
While treatment of arrested cells with the Pd(II) complexes resulted in no significant change in cell death in HCT-116 and MDA-MB-231 cells, HeLa cells were more sensitive in S/G1. The main form of cell death was found to be apoptosis.

CONCLUSIONS
Pd(II) complexes appear to be cell-cycle non-specific, while cell line dependent differences may be observed. Cells die through apoptosis regardless of the cell cycle stage, which makes these complexes more promising as anti-cancer agents.

Kacar|Omer|O|
Cevatemre|Buse|B|
Hatipoglu|Ibrahim|I|
Arda|Nazli|N|
Ulukaya|Engin|E|
Yilmaz|Veysel T|VT|
Acilan|Ceyda|C|

D004354:Drug Screening Assays, Antitumor

Apoptosis
Cancer
Cell cycle specific
Cell cycle arrest
Cytotoxicity
Metal based anticancer agents
Palladium(II) complex


Oral and Dental Examinations Findings in 15 Zoo Bolivian Squirrel Monkeys (Saimiri boliviensis) and Black-Tufted Marmosets (Callithrix penicillata).

Abstract: As part of an annual wellness evaluation, we performed oral and dental examination under general anesthesia in 7 zoo Bolivian squirrel monkeys aged 10 and 15 years, and 8 zoo black-tufted marmosets aged between 1 and 7 years. No oral discomfort was observed in any animal prior to the procedure. Apart from dilacerated roots of second mandibular incisor teeth in Bolivian squirrel monkeys and one case of presumably odontodysplasia in a black-tufted marmoset, no major variations in number and shape of the present teeth and roots were revealed. All 15 animals had gingivitis, but periodontitis was only diagnosed in 3 black-tufted marmosets. Most commonly diagnosed dental pathology in Bolivian squirrel monkeys was attrition/abrasion, affecting 11.9% of all teeth, followed by caries, which was only diagnosed in older animals. Altogether 8 fractured teeth were diagnosed in Bolivian squirrel monkeys only, with root fracture being the most common type, followed by complicated crown fracture and complicated crown-root fracture. Radiographic signs of endodontic disease were found in 10 teeth in Bolivian squirrel monkeys and in one nonvital tooth with intact crown in a black-tufted marmoset. We associated high occurrence of caries in the older Bolivian squirrel monkeys with their diet and saliva characteristics of these animals. Lack of any periodontitis in Bolivian squirrel monkeys may partially be attributed to limitations of radiography technique, although squirrel monkeys appear to be far less susceptible to naturally occurring periodontitis than marmosets.

periodontitis
caries
dental radiography
new world monkeys
oral examination


PsT1: A Low-Cost Optical Simulator for Psychomotor Skills Training in Neuroendoscopy.

Abstract:
BACKGROUND
Well-developed psychomotor skills are important for competence in minimally invasive surgery. Neuroendoscopy is no exception, and adaptation to different visual perspectives and careful handling of the surgical instruments are mandatory. Few training systems, however, focus on developing psychomotor skills for neuroendoscopy. Here, we introduce a new training system called PsT1 that provides visual feedback via the use of simple optics that emulate the endoscope at 0° and 30°. Time and error metrics are generated automatically with integrated software to ensure objective assessment.

METHODS
Neuroendoscopic optics were emulated with a low-cost, commercially available universal serial bus 2.0 camera and a light-emitting diode light source. Visual feedback of 30° was obtained by displacing the optical axis of the universal serial bus camera by 30°, and metrics (time, precision, and errors) were generated automatically by the software. Three evaluation modules were developed (spatial adaptation, depth adaptation, and dissection), and 35 expert and nonexpert neurosurgeons performed an initial evaluation of the system.

RESULTS
A total of 81% and 90% of surgeons agreed that the visuals were satisfactory and movement and control were accurately replicated, respectively. The advantages and disadvantages of the system were compared.

CONCLUSIONS
Here, we present a novel, low-cost, and easy-to-implement training system for developing basic neuroendoscopic psychomotor skills. The use of objective metrics, surgical instruments, and emulation of the neuroendoscope at 0° and 30° are competitive advantages of the current system.

Espinoza|Daniel Lorias|DL|
González Carranza|Vicente|V|
Chico-Ponce de León|Fernando|F|
Martinez|Arturo Minor|AM|

Neuroendoscopy
Metrics
Angled optics
Box trainer
Degrees of freedom


Persulfate-enhanced sonochemical degradation of naphthol blue black in water: Evidence of sulfate radical formation.

Abstract: This work explores the effect of persulfate (PS) on the sonochemical degradation of organic pollutants taking naphthol blue black (NBB), an anionic diazo dye, as a substrate model. The sonolytic experiments were conducted in the absence and presence of PS under various experimental conditions including acoustic power (10-80W), frequency (20 and 585kHz) and saturating gas (argon, air and nitrogen). Experimental results showed that PS decomposition into sulfate radical (SO4-) takes place by sonolysis and increasing PS concentration up to 1g/L would result in an increase in the NBB degradation rate. It was found that the PS-enhanced effect was strongly operating parameters dependent. The positive effect of PS decreased with increasing power and the best enhancing effect was obtained for the lowest acoustic power. Correspondingly, the PS-enhanced effect was more remarkable at low frequency (20kHz) than that observed at high frequency ultrasound (585kHz). Nitrogen saturating gas gave the best enhanced effect of PS than argon and air atmospheres. Theoretical (computer simulation of bubble collapse) and experimental measurements of the yields of free radical generation under the different experimental conditions have been made for interpreting the obtained effects of PS on the sonochemical degradation of the dye pollutant. The experimental findings were attributed to the fact that radical-radical recombination reactions occur at faster rate than the radical-organic reaction when the concentration of free radicals is too high (at higher sonochemical conditions).

Ferkous|Hamza|H| Merouani|Slimane|S| Hamdaoui|Oualid|O| Pétrier|Christian|C|

Sonochemical degradation
Persulfate (PS)
Naphthol blue black (NBB)
Computer simulation
()OH radical
SO(4)(−) radical


Prevalence and relationship between burnout and depression in our future doctors: a cross-sectional study in a cohort of preclinical and clinical medical students in Ireland.

Abstract:
OBJECTIVES
This cross-sectional study was designed to measure burnout and its impact on risk of depression in a medical student population, comparing the preclinical and clinical years.

DESIGN
We conducted a survey of 269 medical school students in both preclinical and clinical years at the Royal College of Surgeons in Ireland, using the Beck Depression Inventory-Fast Screen (BDI-FS), the Maslach Burnout Inventory-Student Survey and items assessing willingness to use mental health services. Burnout scores were calibrated to probability of depression caseness and classified as low risk (<25%), intermediate (25%-50%) and high risk (>50%) of depression.

RESULTS
There was a 39% (95% CI 33% to 45%) prevalence of depressive caseness based on a score of ≥6 on the BDI-FS. Prevalence did not vary significantly between clinical and preclinical years. The rate of burnout varied significantly between years (p=0.032), with 35% in the high-burnout category in clinical years compared with 26% in preclinical years. Those in the low burnout category had a 13% overall prevalence of depressive symptoms, those in the intermediate category had a 38% prevalence and those in the high category had a 66% prevalence of depressive symptoms. Increasing emotional exhaustion (OR for one-tertile increase in score 2.0, p=0.011) and decreasing academic efficacy (OR 2.1, p=0.007) increased the odds of being unwilling to seek help for mental health problems (11%).

CONCLUSION
While previous studies have reported significant levels of burnout and depression, our method of calibrating burnout against depression allows burnout scores to be interpreted in terms of their impact on mental health. The high prevalences, in line with previous research, point to an urgent need to rethink the psychological pressures of health professions education.

Fitzpatrick|Orla|O|
Biesma|Regien|R|
Conroy|Ronán M|RM|
McGarvey|Alice|A|

burnout
depression
medical students
mental health


Thrombosis in immune thrombocytopenia - current status and future perspectives.

Abstract: Immune thrombocytopenia (ITP) is an autoimmune disorder in which a combination of defective platelet production and enhanced clearance leads to thrombocytopenia. The primary aim for therapy in patients with this condition is the prevention of bleeding. However, more recently, increased rates of venous and arterial thrombotic events have been reported in ITP, even in the context of marked thrombocytopenia. In this review we discuss the epidemiology, aetiology and management of thrombotic events in these patients. We consider the impact of ITP therapies on the increased thrombotic risk, in particular the use of thrombopoietin-receptor agonists (TPO-RAs), as well as factors inherent to ITP itself. We also discuss the limited evidence available to guide clinicians in the treatment of these complex cases.

thrombosis thrombocytopenia bleeding anticoagulation antiplatelet


Orthosiphon pallidus, a Potential Treatment for Patients with Breast Cancer.

Abstract:
Objective
Orthosiphon pallidus (O. pallidus), which belongs to the Lamiaceae family, is a popular garden plant that is widely used for the treatment of various diseases, such as urinary lithiasis, fever, hepatitis, cancer and jaundice. The objective of the present work was to investigate the antioxidant free-radical scavenging and the anticancer activities of O. pallidus against human breast-cancer cell lines.

Methods
The antioxidant activity of Orthosiphon pallidus aqueous extract (OPAE) was investigated using different models, such as the 1,1-diphenyl-2-picrylhydrazyl (DPPH) and the 2, 2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) models, as were the Fe+ chelation, the hydroxyl radical and superoxide radical scavenging, and total reducing power activities. The anticancer activities of the extract were determined by using the 3-(4, 5- dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) and the sulforhodamine (SRB) assays on the MCF-7 and the MDA-MB-231 cancer cell lines.

Results
The aqueous Orthosiphon pallidus extract showed potent activity in in-vitro models. It significantly inhibited the scavenging of hydroxyl and superoxide radicals, but induced a remarkable Fe+ chelation activity. For both cell lines, the percent cytotoxicity was found to increase steadily with increasing OPAE concentration up to 240 μg/mL.

Conclusion
These results suggest that Orthosiphon pallidus has excellent antioxidant, antimicrobial, and anticancer activities against human breast-cancer cell lines.

Singh|Mukesh K|MK|
Dhongade|Hemant|H|
Tripathi|Dulal Krishna|DK|

Orthosiphon pallidus
antioxidant activity
cytotoxicity assay
total flavonoid content (TFC)
total phenol content (TPC)


Population Pharmacodynamic Analysis of Uric Acid-Lowering Effects of Febuxostat Based on Electronic Medical Records in Two Hospitals.

Abstract: The aim of this study was to develop a population pharmacodynamic (PPD) model to describe uric acid (UA)-lowering effects in patients treated with febuxostat based on electronic medical records in 2 independent hospitals (university and city hospitals). Interhospital differences in the PPD model were also evaluated. We conducted the following 2 approaches to build the PPD models. A PPD model was developed separately using individual hospital data, and structural models and covariates between the two hospitals were compared (approach A). Another PPD model was developed using all available data from both hospitals, and differences between the 2 hospitals were evaluated by performing a covariate analysis on all PPD parameters (approach B). PPD analyses were performed by NONMEM using data from 358 patients. In both approaches, one indirect response model was established. In approach A, 2 diuretics (loops and thiazides) and renal function tests (Scr or BUN) were selected as covariates for the UA baseline level (serum UA levels just before the febuxostat treatment), whereas 2 diuretics and BUN were selected in approach B. A covariate analysis indicated that loops and thiazides increased UA baseline levels by 7%-14% and 6%-11%, respectively. In approach B, "hospital" was identified as a significant covariate for the UA baseline level; the baseline level was 7% higher in the city hospital. A PPD analysis may provide a precise description of the time course of the UA-lowering effects of febuxostat and quantitatively detect an interhospital difference in the UA baseline level.

Muraki|Shota|S| Moriki|Kuniaki|K| Shigematsu|Saki|S| Fukae|Masato|M| Kakara|Makoto|M| Yamashita|Daiki|D| Hirota|Takeshi|T| Takane|Hiroshi|H| Shimada|Miki|M| Hirakawa|Masaaki|M| Ieiri|Ichiro|I|

population pharmacodynamics
febuxostat
electronic medical records
uric acid
interhospital difference
NONMEM


Coinfection and the evolution of drug resistance.

Abstract: Recent experimental work in the rodent malaria model has shown that when two or more strains share a host, there is competitive release of drug-resistant strains upon treatment. In other words, the propagule output of a particular strain is repressed when competing with other strains and increases upon the removal of this competition. This within-host effect is predicted to have an important impact on the evolution and growth of resistant strains. However, how this effect translates to epidemiological parameters at the between-host level, the level at which disease and resistance spread, has yet to be determined. Here we present a general, between-host epidemiological model that explicitly takes into account the effect of coinfection and competitive release. Although our model does show that when there is coinfection competitive release may contribute to the emergence of resistance, it also highlights an additional between-host effect. It is the combination of these two effects, the between-host effect and the within-host effect, that determines the overall influence of coinfection on the emergence of resistance. Therefore, even when competitive release of drug-resistant strains occurs, within an infected individual, it is not necessarily true that coinfection will result in the increased emergence of resistance. These results have important implications for the control of the emergence and spread of drug resistance.

model
competitive release
Epidemiology
antibiotics
infectious disease


Food waste in Italian households during the Covid-19 pandemic: a self-reporting approach.

Abstract: Food waste prevention and reduction are an economic, social and environmental concern included among the 17 Sustainable Development Goals (SDGs) within Agenda 2030 for Sustainable Development. The third target under SDG 12 (Target 12.3) on Responsible Production and Consumption aims to halve food waste by 2030 at retail and consumer levels, considering that more than half of its quantity is generated by final consumers, both indoor and outdoor. However, the Covid-19 pandemic outbreak at the beginning of 2020 imposed several food consumption behaviors and lifestyle changes: food service facilities (e.g., restaurants, pubs, cafés, hotels, resorts) have been closed roughly all over the world, generating a sharp domestic consumption and an expected increase in household waste. The authors conducted an explorative research through the food diary approach. The purpose of this paper is to have a better understanding of household food consumption and wastage trends during Covid-19 pandemic testing, as well as food diary methodology strengths and weaknesses. Food diaries, even with their intrinsic limitations and biases, represent a valuable technique to obtain detailed qualitative and quantitative knowledge on daily food consumption and consumers' behavior. Through the limited but significant results achieved, the authors highlight the logistics of the methodology and the food waste generation trends among a small sample of Italian families during the Covid-19 pandemic. Further, healthier work-life balances, adequate time management and smart food delivery seem to be good opportunities for food waste reduction in households.

Food waste
COVID-19 pandemic
Sustainability
Food diaries
Food waste behavior


Choroidal vascularity index and choriocapillary changes in retinal vein occlusions.

Abstract:
PURPOSE
To evaluate the changes in the choroidal structure in the setting of retinal vein occlusion (RVO).

METHODS
Changes in the structure of the choroid were studied in sixty-four eyes with unilateral central or branch RVO using optical coherence tomography (OCT) with enhanced depth imaging and OCT-angiography (OCT-A). Choroidal vascularity index (CVI), Haller layer/choroidal thickness (H/C) ratio, and choriocapillaris flow density were used to compare the structural characteristics of the choroid with fellow eyes and the eyes of thirty-four age-, gender-, and systemic co-morbidity-matched controls.

RESULTS
Eyes with RVO had a higher H/C ratio but a lower choriocapillaris flow density compared to both fellow and control eyes (p < 0.001). CVI was significantly lower in both eyes of the patients with RVO compared with control eyes (p < 0.05) with a more robust decrease in the eye that had developed RVO (p < 0.001). The H/C ratio (r = 0.303 p < 0.001), CVI (r = - 0.268, p = 0.001), and choriocapillaris flow density (r = - 0.237, p = 0.003) were all correlated with logMAR visual acuity, and other clinical features.

CONCLUSION
Retinal vein occlusions alter the hemodynamic properties of the choroid leading to structural changes. These changes may be secondary to a compensatory mechanism to supply oxygen to hypoxic retina.

D002829:Choroid
D005451:Fluorescein Angiography
D006801:Humans
D012170:Retinal Vein Occlusion
D012189:Retrospective Studies
D041623:Tomography, Optical Coherence
D014792:Visual Acuity

Optical coherence tomography angiography


A Light-Field Metasurface for High-Resolution Single-Particle Tracking.

Abstract: Three-dimensional (3D) single-particle tracking (SPT) is a key tool for studying dynamic processes in the life sciences. However, conventional optical elements utilizing light fields impose an inherent trade-off between lateral and axial resolution, preventing SPT with high spatiotemporal resolution across an extended volume. We overcome the typical loss in spatial resolution that accompanies light-field-based approaches to obtain 3D information by placing a standard microscope coverslip patterned with a multifunctional, light-field metasurface on a specimen. This approach enables an otherwise unmodified microscope to gather 3D information at an enhanced spatial resolution. We demonstrate simultaneous tracking of multiple fluorescent particles within a large 0.5 × 0.5 × 0.3 mm3 volume using a standard epi-fluorescent microscope with submicron lateral and micron-level axial resolution.

Light-field metasurface
single-particle tracking
Mie resonance
interleaved metasurface
microlens array
point spread function engineering


Meditation for adults with non-specific low back pain: a systematic review and meta-analysis.

Abstract:
OBJECTIVES
We aim to determine the effectiveness of meditation for adults with non-specific low back pain.

METHODS
We searched PubMed, EMBASE, PEDro, Scopus, Web of Science, Cochrane Library, and PsycINFO databases for randomized controlled trials that investigated the effectiveness of meditation in adults with non-specific low back pain. Two reviewers rated risk of bias using the PEDro scale and the certainty of the evidence using the GRADE approach. Primary outcomes were pain intensity and disability.

RESULTS
We included eight trials with a total of 1,234 participants. Moderate-certainty evidence shows that meditation is better than usual care for disability at short-term (SMD = -0.22; 95% CI = -0.42 to -0.02). We also found that meditation is better than usual care for pain intensity at long-term (SMD = -0.28; 95% CI = -0.54 to -0.02). There is no significant difference for pain intensity between meditation and minimal intervention or usual care at short and intermediate-term. We did not find differences between meditation and minimal intervention for disability at intermediate-term or usual care in any follow-up period.

CONCLUSIONS
We found small effect sizes and moderate-certainty evidence that meditation is slightly better than minimal intervention in the short-term for disability. Low-certainty of evidence suggests that meditation is slightly better than usual care for pain in the long-term. Meditation appears to be safe with most trials reporting no serious adverse events.

meditation
pain
review
chronic low back pain


Cerebrospinal Fluid Monoamine Metabolite Analysis in Pediatric Movement Disorders.

Abstract: Abnormal concentrations of dopamine and serotonin metabolites in the cerebrospinal fluid is the diagnostic hallmark of a group of treatable conditions known as the monoamine neurotransmitter disorders. We assessed cerebrospinal fluid dopamine and serotonin metabolite concentrations in a series of 69 patients affected by movement disorders of unknown etiology. Abnormal results were disclosed in 13/69 subjects (19%). Both primary and secondary monoamine neurotransmitter disorders were observed. The clinical presentation of both forms was hypokinetic-rigid syndrome or dystonia. L-Dopa treatment resulted in significant improvement of the clinical picture in the majority of primary neurotransmitter disorders. Eight patients presented a secondary neurotransmitter disorder. One suffered from a GM2 gangliosidosis and one from infantile bilateral striatal necrosis. Etiologic diagnoses were not established in the others. L-Dopa was started in four patients, leading to a significant improvement of hypokinesia in the patient suffering from GM2 gangliosidosis and a slight improvement in 3 unclassified patients.

Tonduti|Davide|D| Zorzi|Giovanna|G| Ghezzi|Daniele|D| Zibordi|Federica|F| Garavaglia|Barbara|B| Nardocci|Nardo|N|

movement disorders
neurotransmitter disorders
hypokinetic-rigid syndrome
dystonia


Prognostic value of risk stratification using blood parameters for nivolumab in Japanese patients with metastatic renal-cell carcinoma.

Abstract:
BACKGROUND
Nivolumab is a standard treatment for previously treated advanced renal-cell carcinoma. However, nivolumab is effective in only a limited number of patients; therefore, we evaluated the prognostic value of several biomarkers, including inflammation-based prognostic scores and changes in these scores following nivolumab treatment in Japanese patients with metastatic renal-cell carcinoma.

METHODS
We retrospectively reviewed the medical records of 65 patients with previously treated metastatic renal-cell carcinoma and who received nivolumab. Inflammation-based prognostic scores, including neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, lymphocyte/monocyte ratio, and Glasgow prognostic score before and 6 weeks after the treatment were recorded. Categorical variables influencing disease-specific survival were compared using Cox proportional-hazards regression models.

RESULTS
Univariate analysis showed that Memorial Sloan-Kettering Cancer Center risk score (P = 0.0052), lactate dehydrogenase (P = 0.0266), lymphocyte/monocyte ratio (P = 0.0113), and platelet/lymphocyte ratio (P = 0.0017) had a significant effect on disease-specific survival. Multivariate analyses showed that platelet/lymphocyte ratio and lactate dehydrogenase were found to be independent prognostic factors for disease-specific survival (P = 0.0008, risk ratio (RR) = 7.95, 95% confidence interval, 2.16-51.64 and P = 0.0123, RR = 3.92, 95% confidence interval, 1.37-10.80, respectively). The combination of platelet/lymphocyte ratio and lactate dehydrogenase was the most significant prognostic biomarker in metastatic renal-cell carcinoma (P < 0.0001). Changes in lymphocyte/monocyte ratio and platelet/lymphocyte ratio in response to nivolumab were significant prognostic factors for disease-specific survival (P < 0.0001 and P = 0.0477, respectively).

CONCLUSIONS
The combination of platelet/lymphocyte ratio and lactate dehydrogenase may be a potential biomarker for estimating disease-specific survival in Japanese patients with metastatic renal-cell carcinoma treated by nivolumab.

Yamamoto|Yoshiaki|Y| Matsuyama|Hideyasu|H| Matsumoto|Hiroaki|H| Sakano|Shigeru|S| Fuji|Nakanori|N| Oba|Kazuo|K| Yamamoto|Mitsutaka|M| Kamiryo|Yoriaki|Y| Hiragino|Takeshi|T| Nagao|Kazuhiro|K| Takai|Kimio|K| Aoki|Akihiko|A|

nivolumab
renal-cell carcinoma
inflammation-based prognostic score
platelet/lymphocyte ratio
lactate dehydrogenase