Bears habituate to the repeated exposure of a novel stimulus, unmanned aircraft systems.

Abstract: Unmanned aircraft systems (UAS; i.e. 'drones') provide new opportunities for data collection in ecology, wildlife biology and conservation. Yet, several studies have documented behavioral or physiological responses to close-proximity UAS flights. We experimentally tested whether American black bears (Ursus americanus) habituate to repeated UAS exposure and whether tolerance levels persist during an extended period without UAS flights. Using implanted cardiac biologgers, we measured heart rate (HR) of five captive bears before and after the first of five flights each day. Spikes in HR, a measure of stress, diminished across the five flights within each day and over the course of 4 weeks of twice-weekly exposure. We halted flights for 118 days, and when we resumed, HR responses were similar to that at the end of the previous trials. Our findings highlight the capacity of a large mammal to become and remain habituated to a novel anthropogenic stimulus in a relatively short time (3-4 weeks). However, such habituation to mechanical noises may reduce their wariness of other human threats. Also, whereas cardiac effects diminished, frequent UAS disturbances may have other chronic physiological effects that were not measured. We caution that the rate of habituation may differ between wild and captive animals: while the captive bears displayed large initial spikes in HR change (albeit not as large as wild bears), these animals were accustomed to regular exposure to humans and mechanical noises that may have hastened habituation to the UAS.

Ditmer|Mark A|MA|0000-0003-4311-3331
Werden|Leland K|LK|0000-0002-3579-4352
Tanner|Jessie C|JC|
Vincent|John B|JB|
Callahan|Peggy|P|
Iaizzo|Paul A|PA|
Laske|Timothy G|TG|0000-0001-5847-3415
Garshelis|David L|DL|

bears
habituation
Drone
cardiac biologger
stress
unmanned aerial system


Malignant tumours of temporomandibular joint.

Abstract:
BACKGROUND
Malignant tumours of the temporomandibular joint (MTTMJ) are extremely rare. Studies describing its unique epidemiology, clinicopathological features, treatment and prognosis comprehensively are limited. To address these issues, current investigation was performed.

METHODS
A retrospective research was carried out by using population-based data from the Surveillance, Epidemiology, and End Results database (1973-2016).

RESULTS
Data for a total of 734 patients, including 376 men and 358 women, was found. The median age was 47 years. The 5-year and 10-year disease specific survival (DSS) rates were 69.2 and 63.6%, respectively. Significant differences in DSS were found according to age, race, tumour type, AJCC/TNM stage, surgery, radiotherapy, chemotherapy and different treatment modalities (P < 0.05). In the multivariate survival analysis, age > 44 years and AJCC stage III and IV were associated with poor DSS.

CONCLUSION
MTTMJ was mostly found in white people with a median age of 47 years without any sex predominance. Patient's age and AJCC stage was independent predictor of DSS.

Malignant tumour
Temporomandibular joint
SEER analysis


Real-world effectiveness and safety of sensor-augmented insulin pump therapy in adults with type 1 diabetes: Long-term follow-up.

Abstract:
OBJECTIVE
To evaluate the effectiveness and safety of sensor-augmented insulin pump therapy (SAP) in addition to a comprehensive diabetes program on glycated hemoglobin (HbA1c), severe hypoglycemia, ketoacidosis, and the hospital admission rate in patients with type 1 diabetes under real-world settings during a 2-year follow-up.

METHODS
This was a retrospective real-life study comparing diabetes control before and after SAP therapy initiation. Patients ≥18 years old with type 1 diabetes were included. They were followed for 2 years with clinical assessments at months 3, 6, 12, 18, and 24. Effectiveness was estimated by difference in medians of HbA1c from baseline and at each follow-up visit. Safety was assessed by comparing the annual rates of severe hypoglycemia, hyperglycemic crisis, and hospital admission related to diabetes.

RESULTS
162 patients were included, median age 32 years, women 73%). The main indication for SAP was poor metabolic control (51.2%). At 2 years HbA1c decreased from 8.4% to 7.5% (-0.9%, 95% CI: 0.5-1.2; p<0.0001), HbA1c ≤7% improved from 14.2% to 25.3% (11.1%, 95% CI: 19.7-2.5; p=0.006), and severe hypoglycemia decreased from 22.2% to 14.1% (-8.1%, 95% CI: -16.5 to 0.3; p=0.03).

CONCLUSIONS
SAP therapy improved glycemic control after the third month of use and for up to 2 years of follow-up, with lower rates of hospital admission and severe hypoglycemia. More studies are needed to assess the add-on impact of education programs and technologies for diabetes care.

Coronel-Restrepo|Nicolás|N|
Blanco|Víctor Manuel|VM|
Palacio|Andres|A|
Ramírez-Rincón|Alex|A|
Arbeláez|Sebastián|S|
Duque|Valentina|V|
Pino|Juan José|JJ|
Carvajal|Javier|J|
Bedoya|Jorge|J|
Cuesta|Diana Paola|DP|
Botero|José Fernando|JF|

Sistemas de infusión continua de insulina

Terapia con bomba de insulina aumentada por sensor


Characterization of a glycoside hydrolase family 78 α-l-rhamnosidase from Bacteroides thetaiotaomicron VPI-5482 and identification of functional residues.

Abstract: A putative glycoside hydrolase family 78 α-l-rhamnosidase BtRha78A from Bacteroides thetaiotaomicron VPI-5482 was heterologously over-expressed in Escherichia coli. Enzymatic properties of recombinant BtRha78A were characterized in detail. Recombinant BtRha78A might efficiently hydrolyze p-nitrophenyl α-l-rhamnopyranoside. BtRha78A displayed the highest activity at 60 °C in pH 6.5. BtRha78A exhibited a good pH stability and relatively high thermostability. BtRha78A could be tolerant of a low concentration of alcohols. These attractive advantages made it a promising alternative biocatalyst for industrial applications. The catalytic general acid Asp335 and general base Glu595 of BtRha78A were confirmed by site-directed mutagenesis. Alanine scanning mutagenesis based on sequence alignment and structural analysis revealed that the conserved residues Asp330, Arg334, Trp339, Asp342, Tyr383, Trp440, and His620 were crucial for enzyme catalysis. Most functional residues located at the conserved general acid motif (Asp330-Asp342) and were completely conserved in the subfamily I Rha78s.

Li|Binchun|B| Ji|Yaru|Y| Li|Yanqin|Y| Ding|Guobin|G|

Glycoside hydrolase family 78
α-l-Rhamnosidase
General acid
General base
General acid motif


Hyperbaric oxygen therapy in acute stroke: is it time for Justitia to open her eyes?

Abstract: Hypoxia is a critical component of neuronal death in patients with stroke. Therefore increasing oxygenation of brain tissue seems to be a logical therapy against cerebral ischemia. Oxygen therapy exists in two modalities: normobaric hyperoxia therapy and hyperbaric oxygen therapy (HBO). HBO is a therapeutic procedure in which pure (100%) oxygen is administered at greater than atmospheric pressure in HBO therapy chambers. In this review article, we aimed to summarize the current knowledge regarding the therapeutic use of HBO in acute stroke patients. Literature review and electronic search were performed using PubMed, Medscape, and UpToDate with the keywords stroke, acute stroke, hyperbaric oxygen therapy, and hyperoxia. According to the reviewed literature, the use of HBO as routine stroke therapy cannot be justified in acute stage of stroke. More randomized, controlled studies are needed regarding safety and especially effectives of HBO in stroke patients. Also, standardized definitionof HBO should be proposed and used in all future studies.

Hyperbaric oxygen therapy
Stroke
Normobaric hyperoxia therapy
Hyperoxia


Development of Teaching Materials of Dementia by Incorporating a Communications Robot for Schoolchildren Who Are Dementia Supporters.

Abstract: In this study, we aimed to teach elementary school students how to practically deal with elderly people with dementia and developed and evaluated teaching materials using a communication robot called Pepper. The teaching material used the robot to model representative symptoms seen in elderly people with dementia in a realistic context. We applied the two principles of Merrill's first principle and the ARCS model to achieve learning objectives and sustain learning motivation. Furthermore, to verify the effectiveness of the teaching materials, we conducted a questionnaire survey on five experts in community welfare. As a result, it was speculated that by using Pepper, motivation for learning increases and learning can be effectively accomplished. In the future, we aim to introduce the function to the teaching materials based on the evaluation and introduce it to kids' dementia supporter training course.

Murashima|Kotoka|K| Majima|Yukie|Y| Masuda|Seiko|S| Nakamura|Yumiko|Y| Fukayama|Kaori|K|


Controlling Monomer Feeding Rate to Achieve Highly Crystalline Covalent Triazine Frameworks.

Abstract: The synthesis of highly crystalline covalent triazine frameworks (CTFs) with ultrastrong covalent bonds (aromatic CN) from the triazine linkage presents a great challenge to synthetic chemists. Herein, the synthesis of highly crystalline CTFs via directly controlling the monomer feeding rate is reported. By tuning the feeding rate of monomers, the crystallization process can be readily governed in a controlled manner in an open system. The sample of CTF-HUST-HC1 with abundant exposed {001} crystal facets has the better crystallinity and thus is selected to study the effect of high crystallinity on photoelectric properties. Owing to the better separation of photogenerated electron-hole pairs and charge transfer, the obtained highly ordered CTF-HUST-HC1 has superior performance in the photocatalytic removal of nitric oxide (NO) than its lesser crystalline counterparts and g-C3 N4 .

covalent triazine frameworks
high crystallinity
controlling feeding rate
covalent organic frameworks
photocatalysis


Left atrial appendage function assessment and thrombus identification.

Abstract:
BACKGROUND
The diagnosis of thrombus in the left atrium in patients with persistent atrial fibrillation (AF) and may be inconsistent because of variability in thrombus morphology. In some cases it is challenging and requires unusual approach. New Doppler-derived methods might be helpful to identify such thrombi. We evaluated quantitative differences in mechanical function of the left atrial appendage (LAA) basal segments using tissue Doppler imaging (TDI)and speckle tracking echocardiography (STE) in patients with non-valvular AF with and without LAA thrombus and compared them with SR patients.

METHODS
A total of 80 patients with normal left ventricular ejection fraction underwent transesophageal echocardiography (40 patients with SR and 40 patients with AF on oral anticoagulants including patients with LAA thrombus). We analyzed the basal segments of LAA including left lateral ridge (LLR) and baso-medial appendage segment (BMAS). Quantitative analysis was used to calculate peak velocity, average velocity, strain, strain rate and deformation.

RESULTS
In patients with AF the lower LLR strain rate was the sole new STE significant parameter differentiating patients with and without LAA thrombi: - 0.9(- 1.2; - 0.1)s- 1 vs. - 1.6(- 1.9; - 1.3)s- 1, (p = 0.004). Additionally, patients in SR demonstrated significantly better peak velocity, average velocity, strain, strain rate and deformation than those with AF (p < 0.001).

CONCLUSIONS
LLR appeared to be an appropriate site for measuring Doppler derived parameters. It is possible that the strain rate in LLR area may be a novel parameter correlating with the presence of thrombus in patients with AF.

Appendage
Thrombus
Atrial fibrillation
Strain
Strain rate
Sinus rhythm


Environmental risk of nickel in aquatic Arctic ecosystems.

Abstract: The Arctic faces many environmental challenges, including the continued exploitation of its mineral resources such as nickel (Ni). The responsible development of Ni mining in the Arctic requires establishing a risk assessment framework that accounts for the specificities of this unique region. We set out to conduct preliminary assessments of Ni exposure and effects in aquatic Arctic ecosystems. Our analysis of Ni source and transport processes in the Arctic suggests that fresh, estuarine, coastal, and marine waters are potential Ni-receiving environments, with both pelagic and benthic communities being at risk of exposure. Environmental concentrations of Ni show that sites with elevated Ni concentrations are located near Ni mining operations in freshwater environments, but there is a lack of data for coastal and estuarine environments near such operations. Nickel bioavailability in Arctic freshwaters seems to be mainly driven by dissolved organic carbon (DOC) concentrations with bioavailability being the highest in the High Arctic, where DOC levels are the lowest. However, this assessment is based on bioavailability models developed from non-Arctic species. At present, the lack of chronic Ni toxicity data on Arctic species constitutes the greatest hurdle toward the development of Ni quality standards in this region. Although there are some indications that polar organisms may not be more sensitive to contaminants than non-Arctic species, biological adaptations necessary for life in polar environments may have led to differences in species sensitivities, and this must be addressed in risk assessment frameworks. Finally, Ni polar risk assessment is further complicated by climate change, which affects the Arctic at a faster rate than the rest of the world. Herein we discuss the source, fate, and toxicity of Ni in Arctic aquatic environments, and discuss how climate change effects (e.g., permafrost thawing, increased precipitation, and warming) will influence risk assessments of Ni in the Arctic.

Gauthier|Patrick T|PT|
Blewett|Tamzin A|TA|
Garman|Emily R|ER|
Schlekat|Christian E|CE|
Middleton|Elizabeth T|ET|
Suominen|Emily|E|
Crémazy|Anne|A|

Nickel
Arctic
Bioavailability
Toxicity
Climate change
Water quality


Subthalamic nucleus high-frequency stimulation modulates neuronal reactivity to cocaine within the reward circuit.

Abstract: The subthalamic nucleus (STN) is a critical component of a complex network controlling motor, associative and limbic functions. High-frequency stimulation (HFS) of the STN is an effective therapy for motor symptoms in Parkinsonian patients and can also reduce their treatment-induced addictive behaviors. Preclinical studies have shown that STN HFS decreases motivation for cocaine while increasing that for food, highlighting its influence on rewarding and motivational circuits. However, the cellular substrates of these effects remain unknown. Our objectives were to characterize the cellular consequences of STN HFS with a special focus on limbic structures and to elucidate how STN HFS may interfere with acute cocaine effects in these brain areas. Male Long-Evans rats were subjected to STN HFS (130 Hz, 60 μs, 50-150 μA) for 30 min before an acute cocaine injection (15 mg/kg) and sacrificed 10 min following the injection. Neuronal reactivity was analyzed through the expression of two immediate early genes (Arc and c-Fos) to decipher cellular responses to STN HFS and cocaine. STN HFS only activated c-Fos in the globus pallidus and the basolateral amygdala, highlighting a possible role on emotional processes via the amygdala, with a limited effect by itself in other structures. Interestingly, and despite some differential effects on Arc and c-Fos expression, STN HFS diminished the c-Fos response induced by acute cocaine in the striatum. By preventing the cellular effect of cocaine in the striatum, STN HFS might thus decrease the reinforcing properties of the drug, which is in line with the inhibitory effect of STN HFS on the rewarding and reinforcing properties of cocaine.

Hachem-Delaunay|Sabira|S|
Fournier|Marie-Line|ML|
Cohen|Candie|C|
Bonneau|Nicolas|N|
Cador|Martine|M|
Baunez|Christelle|C|
Le Moine|Catherine|C|

Addiction
Arc
c-Fos
Striatum
Basal ganglia
Deep brain stimulation
Nucleus accumbens
Parkinson
catFISH


Anatomo-functional characterization of interatrial septum for catheter-based interventions.

Abstract: Secundum Atrial septal defect (ASD) and Patent foramen ovale (PFO) is becoming the most popular field of interest for catheter-based interventions. While there is a common agreement about the management of ASD patients, there is no complete agreement on which is the best management of PFO patients. In PFO patients, the real challenge for the clinician, beside secondary prevention of recurrent stroke, is to understand which the higher risk patients to refer for treatment are and which is the proper device to use. In this setting, the anatomo-functional characterization of interatrial septum seems to be of paramount importance for both ASD and PFO, not only for the device selection but also for therapeutic decision-making. In the present review the author overviews the main anatomic a functional characteristics of interatrial septum, obtained with the current available diagnostic tools, such as transcranial Doppler, transthoracic and transesophageal echocardiography and intracardiac echocardiography, and discusses the impact of such characteristics on catheter based closure.

anatomo-functional characterization
catheter-based interventions
Secundum Atrial septal defect (ASD)
Patent foramen ovale (PFO)


The Speed of Increasing milk Feeds: a randomised controlled trial.

Abstract:
BACKGROUND
In the UK, 1-2% of infants are born very preterm (<32 weeks of gestation) or have very low birth weight (<1500 g). Very preterm infants are initially unable to be fed nutritional volumes of milk and therefore require intravenous nutrition. Milk feeding strategies influence several long and short term health outcomes including growth, survival, infection (associated with intravenous nutrition) and necrotising enterocolitis (NEC); with both infection and NEC being key predictive factors of long term disability. Currently there is no consistent strategy for feeding preterm infants across the UK. The SIFT trial will test two speeds of increasing milk feeds with the primary aim of determining effects on survival without moderate or severe neurodevelopmental disability at 24 months of age, corrected for prematurity. The trial will also examine many secondary outcomes including infection, NEC, time taken to reach full feeds and growth.

METHODS/DESIGN
Two thousand eight hundred very preterm or very low birth weight infants will be recruited from approximately 30 hospitals across the UK to a randomised controlled trial. Infants with severe congenital anomaly or no realistic chance of survival will be excluded. Infants will be randomly allocated to either a faster (30 ml/kg/day) or slower (18 ml/kg/day) rate of increase in milk feeds. Data will be collected during the neonatal hospital stay on weight, infection rates, episodes of NEC, length of stay and time to reach full milk feeds. Long term health outcomes comprising vision, hearing, motor and cognitive impairment will be assessed at 24 months of age (corrected for prematurity) using a parent report questionnaire.

DISCUSSION
Extensive searches have found no active or proposed studies investigating the rate of increasing milk feeds. The results of this trial will have importance for optimising incremental milk feeding for very preterm and/or very low birth weight infants. No additional resources will be required to implement an optimal feeding strategy, and therefore if successful, the trial results could rapidly be adopted across the NHS at low cost.

TRIAL REGISTRATION
ISRCTN Registry; ISRCTN76463425 on 5 March, 2013.

Abbott|Jane|J| Berrington|Janet|J| Bowler|Ursula|U| Boyle|Elaine|E| Dorling|Jon|J|0000-0002-1691-3221 Embleton|Nicholas|N| Juszczak|Edmund|E| Leaf|Alison|A| Linsell|Louise|L| Johnson|Samantha|S| McCormick|Kenny|K| McGuire|William|W| Roberts|Tracy|T| Stenson|Ben|B| |||

D002675:Child, Preschool
D002985:Clinical Protocols
D002658:Developmental Disabilities
D004750:Enteral Nutrition
D005260:Female
D005500:Follow-Up Studies
D006801:Humans
D007223:Infant
D007231:Infant, Newborn
D007234:Infant, Premature
D007235:Infant, Premature, Diseases
D019102:Infant, Very Low Birth Weight
D015931:Intensive Care, Neonatal
D008297:Male
D008895:Milk, Human
D010288:Parenteral Nutrition
D011446:Prospective Studies
D013997:Time Factors

Milk feeds
Preterm infants
NEC
Prematurity
Milk volume
Neurodevelopment
Parenteral nutrition
RCT
Sepsis


Excitatory amino acid receptors in the dorsomedial hypothalamic area contribute to the chemoreflex tachypneic response.

Abstract: This study evaluated the effect of blockade of the excitatory amino acid (EAA) receptors in the dorsomedial hypothalamic (DMH) area on the ventilatory and cardiovascular responses of the chemoreflex activation in conscious rats. Bilateral microinjection of kynurenic acid (2.7 nmol, n = 6) into the DMH area reduced the tachypneic (+ 264 ± 13 versus + 204 ± 14 cpm, P < 0.05) and pressor (+ 52 ± 5 versus + 31 ± 6 mmHg, P < 0.05) components of chemoreflex but had no effect on the bradycardic component (-214 ± 7 versus -244 ± 17 bpm) of the chemoreflex. The magnitudes of the reduction in pressor and tachypneic chemoreflex responses were not significantly correlated (r = 0.308, P = 0.330). These data indicate that neurons located in the DMH area are activated by chemoreflex; that this activation is mediated via EAA receptors; and that it is essential for the full expression of the respiratory component of the chemoreflex.

Silva|Nathália T|NT|
Nalivaiko|Eugene|E|
da Silva|Luiz G|LG|
Haibara|Andréa S|AS|

D018691:Excitatory Amino Acid Antagonists

Excitatory amino acid receptor
Chemoreflex
Tachypneic response
Dorsomedial hypothalamus


Differential Role of Rapamycin in Epidermis-Induced IL-15-IGF-1 Secretion via Activation of Akt/mTORC2.

Abstract:
Backgroud/Aims: The effects of rapamycin (RPM) on wound healing have been previously studied. However, reciprocal contradictory data have been reported, and the underlying mechanism remains unclear. This study aims to uncover differential role of RPM in regulation of wound healing and explore the possible mechanism.

METHODS
C57BL/6J mice and epidermal cells were treated with different doses of RPM. The wound re-epithelialization was observed by hematoxylin and eosin (HE) staining. The expression of IL-15 and IGF-1 were detected by immunohistochemistry and quantitative real-time PCR. Epidermal cell survival was determined by CCK-8 assays. Moreover, the mTORC1 and mTORC2 pathway were examined by western blot analysis.

RESULTS
This study showed that differential doses of RPM could lead to separate consequences in epidermis. Histological analyses showed that low-dose RPM promoted wound healing, and enhanced the expression of IL-15 and IGF-1. Furthermore, western blot analysis showed that the effect of low-dose RPM in epidermis were not through mTORC1 pathway. Instead, activation of the Akt/mTORC2 pathway was involved in low-dose RPM-induced IL-15 and IGF-1 production in epidermis, while high-dose RPM inhibited the expression of IL-15 and IGF-1 and the activity of mTORC1 and mTORC2 pathway.

CONCLUSION
This study for the first time demonstrated that RPM-mediated wound healing was dose-dependent.

Bai|Yang|Y| Xu|Rui|R| Zhang|Xueyuan|X| Zhang|Xiaorong|X| Hu|Xiaohong|X| Li|Yashu|Y| Li|Haisheng|H| Liu|Meixi|M| Huang|Zhenggen|Z| Yan|Rongshuai|R| He|Weifeng|W| Luo|Gaoxing|G| Wu|Jun|J|

D000076225:Mechanistic Target of Rapamycin Complex 2

D060888:Real-Time Polymerase Chain Reaction


Inter-rater agreement in the choice of prophylactic treatment for vestibular migraine and role of an assisted algorithm for this choice.

Abstract:
BACKGROUND AND OBJECTIVE
Vestibular migraine (VM) is a cause of episodic vestibular syndrome. There are many drugs available for its prophylaxis and currently the choice is mainly made according to the patient's comorbidities. The aim of this article was to measure the agreement of a group of otorhinolaryngologists in the choice of a prophylactic treatment and to evaluate the role of an assisted algorithm in the choice of this prophylaxis.

MATERIAL AND METHOD
The medical records of 10 patients with VM were offered to 10 otolaryngologists who were asked to select for each patient the drug they considered most appropriate among five possible options. The Fleiss' κ index was calculated among the 10 otolaryngologists alone, recalculating it including the algorithm as the eleventh evaluator, and Cohen's κ index was calculated between each otolaryngologist and the answers of the algorithm. The otolaryngologists were offered the option to change their responses after knowing the responses of the algorithm and then both indexes were calculated again.

RESULTS
The Fleiss' κ index was .302. This index was raised to .343 after introducing the algorithm as an evaluator. After offering the responses proposed by the algorithm, Cohen's κ was improved in 9 of the 10 evaluators, and Fleiss' κ rose to .711.

CONCLUSIONS
The agreement between otorhinolaryngologists in choosing prophylaxis for MV can be defined as "fair". The responses of the algorithm for the choice of prophylaxis were close to the average opinion of the otolaryngologists, raising the agreement between them to "substantial".

Domínguez-Durán|Emilio|E| Baños-López|Pablo|P| Martín-Castillo|Elena|E| Galera-Ruiz|Hugo|H|

Treatment
Vestibular migraine
Algorithms
Prophylaxis
Algoritmos
Migraña vestibular
Profilaxis
Tratamiento


A Randomized Phase II Study to Determine the Effect of 2 Different Doses of Aflibercept in Patients With Metastatic Renal Cell Carcinoma (ECOG-ACRIN [E4805]).

Abstract:
BACKGROUND
Aflibercept is a recombinantly produced fusion protein that has potent anti-vascular endothelial growth factor (VEGF) activity. We tested whether aflibercept has clinical activity in clear-cell renal cell carcinoma (ccRCC). The recommended phase II dose was 4 mg/kg but several patients (pts) treated at 1 mg/kg showed prolonged progression-free survival. We therefore tested both doses in a parallel group randomized trial.

PATIENTS AND METHODS
Eligible pts had histologically confirmed advanced or metastatic ccRCC and previous treatments included exposure to a VEGF receptor tyrosine kinase inhibitor. Pts received aflibercept (either 1 mg/kg or 4 mg/kg) on day 1 of a 14-day cycle until disease progression. Pts randomized to 1 mg/kg could crossover to 4 mg/kg at the time of disease progression. The primary end point was proportion alive and progression-free at 8 weeks. A Simon 2-stage design was used for each arm with 33 and 24 eligible pts per arm enrolled in stages 1 and 2.

RESULTS
Ninety-four pts were enrolled, 59 and 35 to 4 mg and 1 mg doses, respectively. Seventy-two percent had 1 previous treatment most commonly sunitinib. Sixteen eligible pts crossed over at the time of disease progression to the 4-mg dose. Most common adverse events were hypertension, proteinuria, and fatigue. Only 4 pts reported Grade 4 or higher toxicity. With 36 of 59 pts (61%) progression-free at 8 weeks, the 4-mg/kg dose met protocol-specified efficacy criteria.

CONCLUSION
Aflibercept is active in previously treated ccRCC and might be worthy of further study.

Pili|Roberto|R|
Jegede|Opeyemi|O|
Carducci|Michael A|MA|
Manola|Judith|J|
Groteluschen|David L|DL|
Appleman|Leonard L|LL|
Liu|Glenn|G|
Shanks|James C|JC|
Dakhil|Shaker R|SR|
Dutcher|Janice|J|
DiPaola|Robert S|RS|

D040262:Receptors, Vascular Endothelial Growth Factor

Angiogenesis inhibitor
Antiangiogenesis
Drug resistance
VEGF blocker


High-Dose Insulin Euglycemic Therapy in the Treatment of a Massive Caffeine Overdose.

Abstract: A 33-year-old woman experienced 90 min of in-hospital cardiac arrest following an intentional overdose of anhydrous caffeine powder. In the face of prolonged and apparently futile resuscitation attempts, high-dose insulin euglycemic therapy was initiated. A loading dose of 1 IU/kg/h of IV insulin resulted in a dramatic improvement in perfusion. This was augmented by a 72-h infusion reaching a maximal rate of 10 IU/kg/h. The patient recovered full neurologic function and survived to discharge. Although high-dose insulin is effective in beta-blocker, calcium channel blocker, and tricyclic antidepressant overdose, this is seemingly the first description of its successful use in caffeine toxicity.

high-dose insulin euglycemic therapy
insulin
caffeine
overdose
toxicity


Changes in nonhuman primate brain function following chronic alcohol consumption in previously naïve animals.

Abstract:
INTRODUCTION
Chronic alcohol abuse is associated with neurophysiological changes in brain activity; however, these changes are not well localized in humans. Non-human primate models of alcohol abuse enable control over many potential confounding variables associated with human studies. The present study utilized high-resolution magnetoencephalography (MEG) to quantify the effects of chronic EtOH self-administration on resting state (RS) brain function in vervet monkeys.

METHODS
Adolescent male vervet monkeys were trained to self-administer ethanol (n=7) or an isocaloric malto-dextrin solution (n=3). Following training, animals received 12 months of free access to ethanol. Animals then underwent RS magnetoencephalography (MEG) and subsequent power spectral analysis of brain activity at 32 bilateral regions of interest associated with the chronic effects of alcohol use.

RESULTS
demonstrate localized changes in brain activity in chronic heavy drinkers, including reduced power in the anterior cingulate cortex, hippocampus, and amygdala as well as increased power in the right medial orbital and parietal areas.

DISCUSSION
The current study is the first demonstration of whole-head MEG acquisition in vervet monkeys. Changes in brain activity were consistent with human electroencephalographic studies; however, MEG was able to extend these findings by localizing the observed changes in power to specific brain regions. These regions are consistent with those previously found to exhibit volume loss following chronic heavy alcohol use. The ability to use MEG to evaluate changes in brain activity following chronic ethanol exposure provides a potentially powerful tool to better understand both the acute and chronic effects of alcohol on brain function.

Rowland|Jared A|JA|
Stapleton-Kotloski|Jennifer R|JR|
Alberto|Greg E|GE|
Davenport|April T|AT|
Kotloski|Robert J|RJ|
Friedman|David P|DP|
Godwin|Dwayne W|DW|
Daunais|James B|JB|

Primate Alcohol Magnetoencephalography Vervet


Inequality and heterogeneity in health-related quality of life: findings based on a large sample of cross-sectional EQ-5D-5L data from the Swedish general population.

Abstract:
PURPOSE
This study aimed to investigate inequality and heterogeneity in health-related quality of life (HRQoL) and to provide EQ-5D-5L population reference data for Sweden.

METHODS
Based on a large Swedish population-based survey, 25,867 respondents aged 30‒104 years, HRQoL is described by sex, age, education, income, economic activity, health-related behaviours, self-reported diseases and conditions. Results are presented by EQ-5D-5L dimensions, respondents rating of their overall health on the EQ visual analogue scale (EQ VAS), VAS index value and TTO (time trade-off) index value allowing for calculation of quality-adjusted life years (QALYs). Ordinary Least Squares and multivariable logistic regression analyses were used to study inequalities in observed EQ VAS score between socioeconomic groups and the likelihood to report problems on the dimensions, respectively, adjusted for confounders.

RESULTS
In total, 896 different health states were reported; 24.1% did not report any problems. Most problems were reported with pain/discomfort. Women reported worse HRQoL than men, and health deteriorated with age. The strongest association between diseases and conditions and EQ VAS score was seen for depression and mental health problems. There was a socioeconomic gradient in HRQoL; adjusting for health-related behaviours, diseases and conditions slightly reduced the differences between educational groups and income groups, but socioeconomic inequalities largely remained.

CONCLUSION
EQ-5D-5L population reference (norms) data are now available for Sweden, including socioeconomic differentials. Results may be used for comparisons with disease-specific populations and in health economic evaluations. The observed socioeconomic inequality in HRQoL should be of great importance for policy makers concerned with equity aspects.

EQ-5D-5L
General population
Reference data
Sweden
Socioeconomic group
Inequalities in health status


Exposure to extremely low frequency electromagnetic fields during pregnancy and the risk of spontaneous abortion: a case-control study.

Abstract:
BACKGROUND
Exposure to extremely low frequency electromagnetic fields is increasingly common, but the potential influence on pregnant women has not been thoroughly investigated.

METHODS
In this case-control study, 58 women who had an unexplained spontaneous abortion at < 14 weeks gestation and 58 matched pregnant women >14 weeks gestation were enrolled in 2012. The women completed the questionnaire, which was used to collect data about socioeconomic and obstetric characteristics, medical and reproductive histories. Then, to evaluate the extremely low frequency electromagnetic fields , we determined the magnitude of electromagnetic fields in the participants' houses by an exposure level tester (3D EMF tester/ Model: ELF-828; Taiwan).The instrument covers a limited frequency range (30 HZ to 3 KHZ).

RESULTS
The magnitude of extremely low frequency electromagnetic fields in the participants' houses was significantly different between the two groups (P<0.001).

CONCLUSIONS
Extremely low frequency electromagnetic fields exposure is probably related to early spontaneous abortions.

Shamsi Mahmoudabadi|Fatemeh|F|
Ziaei|Saeideh|S|
Firoozabadi|Mohammad|M|
Kazemnejad|Anoshirvan|A|


Regulation of translation by upstream translation initiation codons of surfactant protein A1 splice variants.

Abstract: Surfactant protein A (SP-A), a molecule with roles in lung innate immunity and surfactant-related functions, is encoded by two genes in humans: SFTPA1 (SP-A1) and SFTPA2 (SP-A2). The mRNAs from these genes differ in their 5'-untranslated regions (5'-UTR) due to differential splicing. The 5'-UTR variant ACD' is exclusively found in transcripts of SP-A1, but not in those of SP-A2. Its unique exon C contains two upstream AUG codons (uAUGs) that may affect SP-A1 translation efficiency. The first uAUG (u1) is in frame with the primary start codon (p), but the second one (u2) is not. The purpose of this study was to assess the impact of uAUGs on SP-A1 expression. We employed RT-qPCR to determine the presence of exon C-containing SP-A1 transcripts in human RNA samples. We also used in vitro techniques including mutagenesis, reporter assays, and toeprinting analysis, as well as in silico analyses to determine the role of uAUGs. Exon C-containing mRNA is present in most human lung tissue samples and its expression can, under certain conditions, be regulated by factors such as dexamethasone or endotoxin. Mutating uAUGs resulted in increased luciferase activity. The mature protein size was not affected by the uAUGs, as shown by a combination of toeprint and in silico analysis for Kozak sequence, secondary structure, and signal peptide and in vitro translation in the presence of microsomes. In conclusion, alternative splicing may introduce uAUGs in SP-A1 transcripts, which in turn negatively affect SP-A1 translation, possibly affecting SP-A1/SP-A2 ratio, with potential for clinical implication.

Tsotakos|Nikolaos|N| Silveyra|Patricia|P| Lin|Zhenwu|Z| Thomas|Neal|N| Vaid|Mudit|M| Floros|Joanna|J|

D037662:Pulmonary Surfactant-Associated Protein A

uAUG
ribosome binding site
scanning mechanism
translation regulation


Evaluation of High-Resolution Melting for Rapid Differentiation of Phytophthora Hybrids and Their Parental Species.

Abstract: Phytophthora species hybrids have been repeatedly reported as causing damaging diseases to cultivated and wild plants. Two known hybrids, P. andina and P. × pelgrandis, are pathogens of Solanaceae and ornamentals, respectively, although the extent of their host ranges are unknown. P. andina emerged from hybridization of P. infestans and an unidentified related species, whereas P. × pelgrandis emerged from P. nicotianae and P. cactorum. Considering that hybrids and parental species can coexist in the same regions and to distinguish them usually requires cloning or whole genome sequencing, we aimed to develop a rapid tool to distinguish them. Specifically, we used high-resolution melting (HRM) assays to differentiate genotypes based on their amplicon melting profiles. We designed primers for P. × pelgrandis and parental species based on available sequences of P. nicotianae and P. cactorum nuclear genes containing polymorphisms between species. For P. andina, heterozygous sites from Illumina short reads were used for the same purpose. We identified multiple amplicons exhibiting differences in melting curves between parental species and hybrids. We propose HRM as a rapid method for differentiation of P. andina and P. × pelgrandis hybrids from parental species that could be employed to advance research on these pathogens.

D017931:DNA Primers
D006824:Hybridization, Genetic
D058889:Molecular Typing
D010838:Phytophthora
D019657:Solanaceae
D044366:Transition Temperature


The relationship between stigma and a rehabilitation framework [international classification of functioning, disability and health (ICF)]: three case studies of women living with HIV in Lusaka, Zambia.

Abstract:
PURPOSE
To explore how the International Classification of Functioning, Disability and Health, a rehabilitation framework, can provide a holistic understanding of stigma experiences of three women living with human immunodeficiency virus in Lusaka, Zambia.

METHODS
A secondary analysis of three cases by drawing on interview transcripts collected as part of a larger longitudinal study with eighteen women living with the virus. The interview tool used the rehabilitation framework to ask questions about the impact of the virus on the body, daily activities, social participation and the future. Vignettes were produced for each of the eighteen women including information on stigma and the rehabilitation framework. Three case studies were developed from women who provided comprehensive accounts of stigma and the International Classification of Functioning, Disability and Health.

RESULTS
Stigma experiences aligned well with three dimensions of the International Classification of Functioning, Disability and Health: participation restrictions, environmental and personal factors. These domains were used to understand stigma in three forms (i.e. enacted, self and structural stigma) as experienced by these women.

CONCLUSIONS
More research is needed to ascertain how stigma and rehabilitation are related in other environments and populations and to explore how to mitigate stigma within the rehabilitation context.IMPLICATIONS FOR REHABILITATIONRehabilitation professionals deal with aspects of stigma and discrimination in their clinical work and this analysis offers a way to consider HIV-related stigma within rehabilitation in an organized and theoretically-informed way.The insights from this study are important for the field of HIV and for advancing understanding of the complexities of stigma in the context of rehabilitation more broadly.This analysis offers guidance to rehabilitation providers about the nuanced and multi-faceted ways that stigma can occur in the context of rehabilitation, including within their own clinical practice.

D064702:International Classification of Functioning, Disability and Health


A Comparative Assessment of Effects of Major Mediators of Acute Phase Response (IL-1, TNF-α, IL-6) on Breathing Pattern and Survival Rate in Rats with Acute Progressive Hypoxia.

Abstract: A pressing issue of the day is the identification of therapeutic targets to suppress the "cytokine storm" in COVID-19 complicated by acute respiratory distress syndrome (ARDS) with concomitant hypoxemia. However, the key cytokine and its relative contribution to the pathogenesis of ARDS, which leads to high mortality, are unknown. A comparative assessment of the effect of elevated systemic levels of pro-inflammatory cytokines IL-1β, TNF-1α and IL-6 on the respiratory patterns and survival rate in rats was carried out under progressively increasing acute hypoxia. Increasing hypoxia was simulated by a rebreathing method (from normoxia to apnea). The recorded parameters were the breathing pattern components (tidal volume and respiratory rate), minute ventilation (MV), oxygen saturation, apnea onset time, and posthypoxic survival rate. A comparative analysis was carried out under mild, moderate and severe hypoxia (at FIO2 = 15, 12 and 8%, respectively). It was shown that increasing hypoxia was accompanied by an acute suppression of the compensatory elevation of MV in rats with increased systemic levels of IL-1β and TNF-1α. By contrast, IL-6 caused an intensive elevation of MV with increasing hypoxia. Acute hypoxia (FIO2 < 8%), in all experimental series, was accompanied by an impairment of the respiratory rhythm up to the development of apnea. Posthypoxic breathing restoration (survival rate) was 50% with IL-1β and TNF-1α and only 10% with IL-6. The obtained results indicate that the elevated IL-6 level, despite the absence of respiratory disorders at the initial stage of the developing pathologic process, leads to a higher mortality in rats compared to IL-1β and TNF-1α. This allows considering IL-6 as an early prognostic biomarker of a high risk of mortality under severe hypoxemia.

Donina|Zh A|ZA|
Baranova|E V|EV|
Aleksandrova|N P|NP|

cytokine storm
acute respiratory distress syndrome
apnea
increasing hypoxemia


Multiresidue analysis of 85 persistent organic pollutants in small human serum samples by modified QuEChERS preparation with different ionization sources in mass spectrometry.

Abstract: In this study, a multiresidue analytical method was developed, validated, and applied for quantifying 85 persistent organic pollutants (POPs), including 38 polychlorinated biphenyls (PCBs), 23 polybrominated diphenyl ethers (PBDEs), and 24 organochlorine pesticides (OCPs) from 200 μL of human serum. A modified QuEChERS (Quick, Easy, Cheap, Effective, Rugged, and Safe) method was applied to minimize the required sample amount and optimize various conditions including the extraction solvent and the number of extractions. The extraction efficiency was optimized using double extraction with an ethyl acetate/hexane/acetone mixture. Gas chromatography coupled with triple-quadrupole mass spectrometry was used for analysis, and two different ionization sources, electron impact ionization (EI) and atmospheric pressure chemical ionization (APCI), were used to compare their sensitivity. The APCI source employed soft ionization at atmospheric pressure, producing abundant molecular ion formation with minimal fragmentation, in contrast to extensive fragmentation caused by EI. Of the 85 POPs analyzed, 59 target compounds (69.4%) showed lower limits of detection that were two- to fifty-fold lower in APCI than those determined using EI. The developed method was validated for its detection limit (0.5-10 pg/mL for PCBs, 2-20 pg/mL for PBDEs, and 2-40 pg/mL for OCPs), precision (0.8%-34.3% of coefficient of variation), recovery (49.6%-77.1%), matrix effect (46.7%-156.9%), and accuracy (81.2%-113.1% for PCBs, 85.8%-112.2% for PBDEs, and 55.2%-113.9% for OCPs). Its linearity was R2 > 0.99 for 84 compounds, and 96% average accuracy (for APCI) was obtained using the National Institute of Standards and Technology (NIST) standard reference materials (NIST 1957 and 1958). These ionization methods were compared by analyzing 25 real human serum samples. The observed species were 1.1-24.6 pg/mL of 28 PCBs, 2.5 pg/mL of BDE-47, and 6.5-195.1 pg/mL of 6 organochlorine pesticides (median concentration for each species), and only 11 compounds were detected with APCI owing to its enhanced sensitivity.

Lee|Joo Eun|JE|
Oh|Han Bin|HB|
Im|Hosub|H|
Han|Sang Beom|SB|
Kim|Ki Hun|KH|

Atmospheric pressure chemical ionization


Agreement Between 35 Published Frailty Scores in the General Population.

Abstract: In elderly populations, frailty is associated with higher mortality risk. Although many frailty scores (FS) have been proposed, no single score is considered the gold standard. We aimed to evaluate the agreement between a wide range of FS in the English Longitudinal Study of Ageing (ELSA). Through a literature search, we identified 35 FS that could be calculated in ELSA wave 2 (2004-2005). We examined agreement between each frailty score and the mean of 35 FS, using a modified Bland-Altman model and Cohen's kappa (κ). Missing data were imputed. Data from 5,377 participants (ages ≥60 years) were analyzed (44.7% men, 55.3% women). FS showed widely differing degrees of agreement with the mean of all scores and between each pair of scores. Frailty classification also showed a very wide range of agreement (Cohen's κ = 0.10-0.83). Agreement was highest among "accumulation of deficits"-type FS, while accuracy was highest for multidimensional FS. There is marked heterogeneity in the degree to which various FS estimate frailty and in the identification of particular individuals as frail. Different FS are based on different concepts of frailty, and most pairs cannot be assumed to be interchangeable. Research results based on different FS cannot be compared or pooled.

Aguayo|Gloria A|GA|
Donneau|Anne-Françoise|AF|
Vaillant|Michel T|MT|
Schritz|Anna|A|
Franco|Oscar H|OH|
Stranges|Saverio|S|
Malisoux|Laurent|L|
Guillaume|Michèle|M|
Witte|Daniel R|DR|

agreement
frailty scores
elderly population
Bland-Altman model
accuracy
Cohen's kappa coefficient
disability
reliability


Insights into the Progression of Labile Hb A1c to Stable Hb A1c via a Mechanistic Assessment of 2,3-Bisphosphoglycerate Facilitation of the Slow Nonenzymatic Glycation Process.

Abstract: Nonenzymatic glycation (NEG) of human hemoglobin (Hb A) consists of initial non covalent, reversible steps involving glucose and amino acid residues, which may also involve effector reagent(s) in the formation of labile Hb A1c (the conjugate acid of the Schiff base). Labile Hb A1c can then undergo slow, largely irreversible, formation of stable Hb A1c (the Amadori product). Stable Hb A1c is measured to assess diabetic progression after labile Hb A1c removal. This study aimed to increase the understanding of the distinctions between labile and stable Hb A1c from a mechanistic perspective in the presence of 2,3-bisphosphoglycerate (2,3-BPG). 2,3-Bisphosphoglycerate is an effector reagent that reversibly binds in the Hb A1c pocket and modestly enhances overall NEG rate. The deprotonation of C2 on labile Hb A1c in the formation of the Amadori product was previously proposed to be rate-limiting. Computational chemistry was used here to identify the mechanism(s) by which 2,3-BPG facilitates the deprotonation of C2 on labile Hb A1c. 2,3-Bisphosphoglycerate is capable of abstracting protons on C2 and the α-nitrogen of labile Hb A1c and can also deprotonate water and/or amino acid residues, therefore preparing these secondary reagents to deprotonate labile Hb A1c. Parallel reactions not leading to an Amadori product were found that include formation of the neutral Schiff base, dissociation of glucose from the protein, and cyclic glycosylamine formation. These heretofore under appreciated parallel reactions may help explain both the selective removal of labile from stable Hb A1c and the slow rate of NEG.

Mottishaw|Christina R|CR|
Becker|Stephanie|S|
Smith|Brandy|B|
Titus|Gentry|G|
Holman|R W|RW|
Rodnick|Kenneth J|KJ|

nonenzymatic glycation (NEG)
Hb A
Amadori product
2,3-bisphosphoglycerate (2,3-BPG)
water
conjugate acid of Schiff base


Esophageal cancer in a family with hamartomatous tumors and germline PTEN frameshift and SMAD7 missense mutations.

Abstract: Germline mutations in the PTEN tumor-suppressor gene cause autosomal-dominant conditions such as Cowden and Bannayan-Riley-Ruvalcaba syndromes with variable presentations, including hamartomatous gastrointestinal tumors, dermatologic abnormalities, neurologic symptoms, and elevated cancer risk. We describe a father and son with extensive hamartomatous gastrointestinal polyposis who both developed early-onset esophageal cancer. Exome sequencing identified a novel germline PTEN frameshift mutation (c.568_569insC, p.V191Sfs*11). In addition, a missense mutation of SMAD7 (c.115G>A, p.G39R) with an allele frequency of 0.3% in the Exome Variant Server was detected in both affected individuals. Fluorescence in situ hybridization for PTEN in the resected esophageal cancer specimen demonstrated no PTEN copy loss in malignant cells; however, results of an immunohistochemical analysis demonstrated a loss of PTEN protein expression. While the risks of many cancers are elevated in the PTEN hamartoma tumor syndromes, association between esophageal adenocarcinoma and these syndromes has not been previously reported. Esophageal adenocarcinoma and extensive polyposis/ganglioneuromatosis could represent less common features of these syndromes, potentially correlating with this novel PTEN frameshift and early protein termination genotype. Alternatively, because simultaneous disruption of both the PTEN and TGF-β/SMAD4 pathways is associated with development of esophageal cancer in a mouse model and because SMAD4 mutations cause gastrointestinal hamartomas in juvenile polyposis syndrome, the SMAD7 mutation may represent an additional modifier of these individuals' PTEN-mutant phenotype.

Sherman|Scott K|SK|
Maxwell|Jessica E|JE|
Qian|Qining|Q|
Bellizzi|Andrew M|AM|
Braun|Terry A|TA|
Iannettoni|Mark D|MD|
Darbro|Benjamin W|BW|
Howe|James R|JR|

D017404:In Situ Hybridization, Fluorescence

esophageal cancer
PTEN
SMAD7
PTEN hamartoma tumor syndrome
Cowden syndrome


Anti-glioma activity and the mechanism of cellular uptake of asiatic acid-loaded solid lipid nanoparticles.

Abstract: Asiatic acid (AA), a pentacyclic triterpene found in Centella Asiatica, has shown neuroprotective and anti-cancer activity against glioma. However, owing to its poor aqueous solubility, effective delivery and absorption across biological barriers, in particular the blood brain barrier (BBB), are challenging. Solid lipid nanoparticles (SLNs) have shown a promising potential as a drug delivery system to carry lipophilic drugs across the BBB, a major obstacle in brain cancer therapy. Nevertheless, limited information is available about the cytotoxic mechanisms of nano-lipidic carriers with AA on normal and glioma cells. This study assessed the anti-cancer efficacy of AA-loaded SLNs against glioblastoma and their cellular uptake mechanism in comparison with SVG P12 (human foetal glial) cells. SLNs were systematically investigated for three different solid lipids; glyceryl monostearate (MS), glyceryl distearate (DS) and glyceryl tristearate (TS). The non-drug containing MS-SLNs (E-MS-SLNs) did not show any apparent toxicity towards normal SVG P12 cells, whilst the AA-loaded MS-SLNs (AA-MS-SLNs) displayed a more favourable drug release profile and higher cytotoxicity towards U87 MG cells. Therefore, MS-SLNs were chosen for further in vitro studies. Cytotoxicity studies of SLNs (± AA) were performed using MTT assay where AA-SLNs showed significantly higher cytotoxicity towards U87 MG cells than SVG P12 normal cells, as confirmed by flow cell cytometry. Cellular uptake of SLNs also appeared to be preferentially facilitated by energy-dependent endocytosis as evidenced by fluorescence imaging and flow cell cytometry. Using the Annexin V-PI double staining technique, it was found that these AA-MS-SLNs displayed concentration-dependent apoptotic activity on glioma cells, which further confirms the potential of exploiting these AA-loaded MS-SLNs for brain cancer therapy.

Garanti|Tanem|T|
Stasik|Aneta|A|
Burrow|Andrea Julie|AJ|
Alhnan|Mohamed A|MA|
Wan|Ka-Wai|KW|

Centella Asiatica
Apoptosis
Asiaticoside
Brain delivery
Glyceride
Tristearin
Triterpenoid


Elective neck dissection in adenoid cystic carcinoma of head and neck: yes or no? A systematic review.

Abstract:
PURPOSE
Adenoid cystic carcinoma of head and neck (AdCCHN) is salivary gland malignancy known for its slow progression accompanied with perineural invasion, rare lymphatic spread to the neck, high rate of local recurrence and delayed onset of distant metastases. While local recurrence and distant metastases are most common patterns of relapse and cause of death in AdCCHN, it has been debated whether lymph node involvement affects the course of the disease. The aim of this systematic review was to address this important issue and to recommend guidelines on clinically node-negative neck management in patients with AdCCHN.

METHODS
A systematic review of the published literature on cases of elective neck dissection (END) among patients with AdCCHN was performed.

RESULTS
This analysis included a total of 5767 AdCCHN patients with 2450 ENDs, ranging from 10 to 1190. Elective lymphadenectomy was employed in 42.5% of patients with AdCCHN (range 9.2-100%). The overall rate of occult neck metastases in patients with AdCCHN was reported to range between 0 and 43.7%, the average being 13.9%.

CONCLUSIONS
If performed, END should be limited to levels I-III of the ipsilateral neck since occult metastases are exclusively located within these neck regions. Although END is associated with a prolonged regional recurrence-free period, it influence on final outcome or survival is still controversial. This review strongly supports conduction of prospective trials on indications, prognostic significance and extent of END in AdCCHN.

Elective neck dissection
Adenoid cystic carcinoma
Recurrence
Survival
Head neck
Occult neck metastasis


Virulence and Antibiotic Resistance of Vibrio parahaemolyticus Isolates from Seafood from Three Developing Countries and of Worldwide Environmental, Seafood, and Clinical Isolates from 2000 to 2017.

Abstract: Vibrio parahaemolyticus is a leading cause of seafood-associated illness. This study investigated the prevalence, virulence, and antibiotic resistance of V. parahaemolyticus in three low- and middle-income countries. Freshly caught fish samples (n = 330) imported to Jordan from Yemen, India, and Egypt were tested. The overall prevalence of V. parahaemolyticus was 15% (95% confidence interval: 11 to 19%). Three isolates (6%) were positive for the thermostable direct hemolysin-related (trh) gene, and all isolates was negative for the thermostable direct hemolysin (tdh) gene. All isolates were resistant to colistin sulfate, neomycin, and kanamycin, and 51 and 43% of isolates were resistant to tetracycline and ampicillin, respectively. Only 4% of the isolates were resistant to cefotaxime and chloramphenicol, and no isolates were resistant to sulfamethoxazole-trimethoprim, streptomycin, gentamicin, ciprofloxacin, and nalidixic acid. All isolates were resistant to two classes of antibiotics, and 86% were multidrug resistant (resistant to at least one drug in three or more classes of antibiotics). A literature review of clinical, seafood, and environmental V. parahaemolyticus isolates worldwide revealed high rates of gentamicin and ampicillin resistance, emerging resistance to third-generation cephalosporins, and limited resistance to sulfamethoxazole-trimethoprim, ciprofloxacin, nalidixic acid, and chloramphenicol. Thus, last-resort antibiotics could be ineffective for treating V. parahaemolyticus infections. Several global reports also documented illness outbreaks in humans caused by trh- and tdh-negative V. parahaemolyticus strains. More research is needed to determine whether the presence of these genes is sufficient to classify the strains as virulent.

Obaidat|Mohammad M|MM|
Salman|Alaa E Bani|AEB|
Roess|Amira A|AA|

Virulence
Antimicrobials
Contamination
Exported fish
Pathogens
Trade


Coexistence of Multiple Endemic and Pandemic Lineages of the Rice Blast Pathogen.

Abstract: The rice blast fungus Magnaporthe oryzae (syn., Pyricularia oryzae) is both a threat to global food security and a model for plant pathology. Molecular pathologists need an accurate understanding of the origins and line of descent of M. oryzae populations in order to identify the genetic and functional bases of pathogen adaptation and to guide the development of more effective control strategies. We used a whole-genome sequence analysis of samples from different times and places to infer details about the genetic makeup of M. oryzae from a global collection of isolates. Analyses of population structure identified six lineages within M. oryzae, including two pandemic on japonica and indica rice, respectively, and four lineages with more restricted distributions. Tip-dating calibration indicated that M. oryzae lineages separated about a millennium ago, long after the initial domestication of rice. The major lineage endemic to continental Southeast Asia displayed signatures of sexual recombination and evidence of DNA acquisition from multiple lineages. Tests for weak natural selection revealed that the pandemic spread of clonal lineages entailed an evolutionary "cost," in terms of the accumulation of deleterious mutations. Our findings reveal the coexistence of multiple endemic and pandemic lineages with contrasting population and genetic characteristics within a widely distributed pathogen.IMPORTANCE The rice blast fungus Magnaporthe oryzae (syn., Pyricularia oryzae) is a textbook example of a rapidly adapting pathogen, and it is responsible for one of the most damaging diseases of rice. Improvements in our understanding of Magnaporthe oryzae's diversity and evolution are required to guide the development of more effective control strategies. We used genome sequencing data for samples from around the world to infer the evolutionary history of M. oryzae We found that M. oryzae diversified about 1,000 years ago, separating into six main lineages: two pandemic on japonica and indica rice, respectively, and four with more restricted distributions. We also found that a lineage endemic to continental Southeast Asia displayed signatures of sexual recombination and the acquisition of genetic material from multiple lineages. This work provides a population-level genomic framework for defining molecular markers for the control of rice blast and investigations of the molecular basis of differences in pathogenicity between M. oryzae lineages.

rice blast
population structure
indica rice
tip-dating calibration
recombination
clonality
deleterious mutations
introgression
japonica rice
population genomics


Qualitative study of women's experiences of safe childbirth in maternity care.

Abstract: Few studies have focused on women's childbirth experiences in relation to patient safety. The aim of this study was to explore the meaning of safety as a process phenomenon by outlining women's positive and negative experiences of safety in childbirth. A descriptive explorative design was chosen and 16 interviews were conducted. Qualitative content analysis was used. One main theme emerged: safe childbirth through involvement and guidance, based on four subthemes. The characteristics of women's experiences of safe childbirth included the need to be informed and involved by sharing and receiving trustworthy information. Women's experiences of unsafe childbirth included lack of meaningful and trustworthy information that resulted in feelings of being misled or lulled into a false sense of security. Not being involved evoked feelings of being ignored. In conclusion, this study highlights issues of importance for safe maternity care. The perspectives of childbearing women can contribute to an understanding of how to achieve meaningful improvements to provide safer maternity care.

women's experience
safe childbirth
childbirth
maternity care
qualitative content analysis


Possible Role of Myopia as a Risk Factor for Mechanical Neck Pain in Medical Students : A Pilot Study.

Abstract:
Background
Mechanical neck pain (MNP) is a common health concern. Some studies suggested a relationship between neck pain and visual activity. We assessed the role of myopia as a contributing factor in the development of chronic MNP.

Materials and Methods
All medical students at Shiraz University School of Medicine, who were 18 to 22 years old, were invited to participate in this retrospective case-control study from March 2016 to March 2017. Numeric Pain Rating Scale (NPRS) was used to assess the average neck pain severity over the past 6 months in order to enroll participants as the case (≥3) or control (<3) groups. Demographic data and medical profile were obtained. After identifying eligible cases, we assigned age- and sex-matched controls, who also met the study criteria. Subsequently, participants completed the Neck Disability Index (NDI) and Neck Pain and Disability Scale (NPDS) questionnaires and were evaluated for myopia severity. Variables were compared between the case and control groups as well as within the case group. P-value<0.05 was considered statistically significant.

Results
From over 700 medical students, around 150 cooperated. Eventually, 31 eligible cases (and 31 controls) were studied. NDI and NPDS were significantly higher in the case group (P<0.001). However, no significant differences were noticed between the groups regarding the severity (P=0.123) and the duration (P=0.417) of myopia. Also, the correlation of myopia severity with NDPS (ρ=0.159, P=0.216) and NDI (ρ=0.201, P=0.116) was non-significant within the case group.

Conclusion
Our findings have not supported the influential role of myopia in the development of chronic MNP.

Myopia
Neck Pain
Pain Measurement
Refractive Errors
Visual Acuity


Enhanced Stability of MFI Zeolite Membranes for Separation of Ethanol/Water by Eliminating Surface Si-OH Groups.

Abstract: The practical application of pure-silica MFI zeolite membranes for ethanol/water separation by pervaporation is limited by its poor stability. Herein, we present the Si-OH eliminated MFI membranes by a simple dopamine modification, which can effectively prevent the chemical reaction between Si-OH groups and components, endowing the long-term pervaporation stability.

stability
MFI zeolite membrane
ethanol/water separation
pervaporation
dopamine modification


Accuracy of Patient Perception of Supine Sleep.

Abstract:
STUDY OBJECTIVES
For clinicians involved in investigating and treating sleep disorders, understanding the accuracy of patient recall of supine sleep would allow informed comparisons between polysomnography (PSG) and patient-reported sleep in patients with supine-predominant obstructive sleep apnea. This study aims to assess the accuracy of patient perception of supine sleep.

METHODS
Prospective observational cohort study, assessing patient perception of total sleep and supine sleep, including duration. Data were analyzed utilizing descriptive statistics, bias-plot (Bland-Altman) analysis, and Spearman correlation (rs) to analyze relationships among continuous data.

RESULTS
Total number of patients who underwent PSG was 518, with data from 368 of these patients analyzed. Most of these patients underwent diagnostic PSG (49.2%). Patients were excluded because of missing or incomplete data (n = 133) or immobility (n = 17). Some patients (n = 97, 26%) did not perceive supine sleep, with 34 (35% of those with unperceived supine sleep or 9% of whole group) of these having more than 60 minutes of PSG supine sleep (range 0-305.5 minutes). All "unsure" patients (n = 8, 2.2%) had significant supine sleep recorded (31.5-257.5 minutes). For the presence of any PSG supine sleep, questioning had a sensitivity of 77.9%, specificity 72.7% with positive predictive value of 96.7% and negative predictive value of 24.5%. There was a significant correlation (rs = 0.63, P < .0001) between perceived and PSG supine sleep, but wide limits of agreement (-246.9 to 194.2 minutes).

CONCLUSIONS
In patients undergoing in-laboratory PSG, the perception of supine sleep predicts the presence of PSG supine sleep. However, questioning patients has a poor negative predictive value and patient estimates of supine sleep duration are inaccurate.

Wallbridge|Peter D|PD|
Churchward|Thomas J|TJ|
Worsnop|Christopher J|CJ|

accuracy
patient perception
obstructive sleep apnea
agreement
sleep position
sleep-disordered breathing


Impact of tranexamic acid on blood loss and transfusion rate in children with cerebral palsy undergoing hip reconstruction with two or more osteotomies.

Abstract:
PURPOSE
Tranexamic acid (TXA), a synthetic lysine analogue, has been used in orthopedic procedures to limit blood loss and prevent allogeneic blood transfusions. However, data are scarce on its use in hip reconstruction of patients with cerebral palsy (CP). This study examines the effect of TXA on patients with CP undergoing hip reconstruction with at least two osteotomies.

METHODS
This is a single-center, retrospective study of patients with CP who underwent hip reconstruction with two or more osteotomies from January 2013 to April 2019. There were 43 patients, with a mean age of 9.9 years. Age, procedure, preoperative and postoperative hemoglobin/hematocrit, estimated blood loss (EBL), transfusions and length of stay were recorded. The patients were split into the following two groups: 24 patients who had received intraoperative TXA and 19 who had not.

RESULTS
Age, EBL, mean preoperative and postoperative hemoglobin or hematocrit, preoperative to postoperative hematocrit drop, and length of stay were similar for the two groups (p > 0.05). The risk for intraoperative transfusion (21 vs. 17%), postoperative transfusion (26 vs. 8%), and any transfusion (42 vs. 21%) appeared to be greater in the group that did not receive TXA, but this difference did not achieve statistical significance.

CONCLUSION
This pilot study shows patients with CP undergoing hip reconstruction with two or more osteotomies; the use of TXA, while not statistically significant, shows a trend toward a decreased need for allogeneic blood transfusion.

Masrouha|Karim Z|KZ|
Shabin|Zabrina M|ZM|
Bhutada|Kiran|K|
Sala|Debra A|DA|
Godfried|David H|DH|
Karamitopoulos|Mara S|MS|

Tranexamic acid
Transfusion
Cerebral palsy
Hip
Osteotomy


Does mental fatigue impair physical performance? A replication study.

Abstract: The aim of this study is to replicate the hypothesis that mental fatigue impairs physical performance in a pre-registered (https://osf.io/wqkap/) within-subjects experiment. 30 recreationally active adults completed a time-to-exhaustion test (TTE) at 80% VO2max in two separate sessions, after completing a mental fatigue task or watching a documentary for 90 min. We measured power output, heart rate, (session) rating of perceived exertion (RPE) and subjective mental fatigue. Bayes factor analyses revealed extreme evidence supporting the alternative hypothesis that the mental fatigue task was more mentally fatiguing than the control task, BF01 = 0.009. However, we found moderate-to-strong evidence for the null hypothesis (i.e., no evidence of reduced performance) for average time in TTE (BF01 = 9.762) and anecdotal evidence for the null hypothesis in (session) RPE (BF01 = 2.902) and heart rate (BF01 = 2.587). Our data seem to challenge the idea that mental fatigue has a negative influence on exercise performance. Although we did succeed at manipulating subjective mental fatigue, this did not impair physical performance. However, we cannot discard the possibility that mental fatigue may have a negative influence under conditions not explored here, e.g., individualizing mentally fatiguing tasks. In sum, further research is warranted to determine the role of mental fatigue on exercise and sport performance.

fatigue Cognition endurance neuroscience psychology


The consumption of seaweed as a protective factor in the etiology of breast cancer: proof of principle.

Abstract: Daily consumption of seaweed has been proposed as a factor in explaining lower postmenopausal breast cancer (BC) incidence and mortality rates in Japan. This clinical trial assessed the impact of introducing seaweed- to non-seaweed-consuming American postmenopausal women. Fifteen healthy postmenopausal women were recruited for a 3-month single-blinded placebo controlled clinical trial; five had no history of BC (controls) and ten were BC survivors. Participants ingested ten capsules daily (5 g day-1) of placebo for 4 weeks, seaweed (Undaria) for 4 weeks, then placebo for another 4 weeks. Blood and urine samples were collected after each treatment period. Urinary human urokinase-type plasminogen activator receptor concentrations (uPAR) were analyzed by ELISA, and urine and serum were analyzed for protein expression using surface-enhanced laser desorption/ionization-time-of-flight mass spectrometry (SELDI-TOF-MS). Urinary creatinine standardized uPAR (in pg mL μg-1 creatinine) changed significantly between groups, decreasing by about half following seaweed supplementation (placebo 1, 1.5 (95 % CI, 0.9-2.1) and seaweed, 0.9 (95 % CI, 0.6-1.1) while placebo 2 returned to pre-seaweed concentration (1.7 (95 % CI, 1.2-2.2); p = 0.01, ANOVA). One SELDI-TOF-MS-identified urinary protein (m/z 9,776) showed a similar reversible decrease with seaweed and is reported to be associated with cell attachment. One serum protein (m/z 8,928) reversibly increased with seaweed and may be the immunostimulatory complement activation C3a des-arginine. uPAR is higher among postmenopausal women generally, and for BC patients, it is associated with unfavorable BC prognosis. By lowering uPAR, dietary seaweed may help explain lower BC incidence and mortality among postmenopausal women in Japan.

Teas|Jane|J|
Vena|Sylvia|S|
Cone|D Lindsie|DL|
Irhimeh|Mohammad|M|

Human urokinase-type plasminogen activator receptor (uPAR)

Surface-enhanced laser desorption/ionization–time-of-flight mass spectrometry (SELDI-TOF-MS)


Effect of perfluorooctane sulfonate on viability, maturation and gap junctional intercellular communication of porcine oocytes in vitro.

Abstract: Perfluorooctane sulfonate (PFOS) is a broadly used man-made surfactant whose long half-life has led to bioaccumulation. This perfluorinated compound is ubiquitous in human body fluids. PFOS concentrations as high as 26μM in plasma have been reported in occupationally exposed populations, and high levels of PFOS in human follicular fluid have been associated with subfertility. However, the effect of PFOS on the maturation of oocytes in mammals has not been reported to date. The aim of this study was to determine the effects of PFOS during oocyte maturation. Results indicate that PFOS inhibits oocyte viability (Lethal Concentration50=32μM) and maturation (inhibition of maturation50=22μM) at physiologically relevant concentrations. In order to evaluate the mechanisms of oocyte maturation inhibition by PFOS, gap junctional intercellular communication (GJIC) between oocytes and granulosa cells was assessed. GJIC between granulosa cells and the oocyte was significantly affected during the first 8h of maturation. However, the inhibitory effect of PFOS on GJIC was not due to an alteration on the expression of connexin genes Cx43, Cx45 and Cx60. These findings suggest that occupationally exposed populations could be at risk, and that PFOS might affect oocyte maturation by interfering the GJIC in the cumulus-oocyte complexes during the first hours of maturation.

Domínguez|A|A| Salazar|Z|Z| Arenas|E|E| Betancourt|M|M| Ducolomb|Y|Y| González-Márquez|H|H| Casas|E|E| Teteltitla|M|M| Bonilla|E|E|

Gap junction
PFOS
Oocyte maturation
Connexin


Health-related quality of life in children with PFAPA syndrome.

Abstract:
BACKGROUND
Conventionally, PFAPA syndrome is considered as a benign disease compared to other recurrent fevers because it completely passes before adulthood. However, in our clinical practice, fever episodes have a huge impact on daily activities.

METHODS
Observational cohort study using the Pediatric Quality of Life Inventory (PedsQL™ 4.0) Generic Core and Fatigue Scales. PedsQL™ uses a modular approach to measure the HRQOL in children with acute and chronic health conditions. We used pediatric FMF patients as the control group.

RESULTS
We included 33 children with PFAPA and compared them to 27 FMF patients matched for age: preschool-age children (2 to 7 years) and school-age children and youths (8 to18 years). PedsQL™ self-reported scores of children with PFAPA were systematically lower than those of FMF peers for general quality of life and physical and psychosocial functioning (significant only in the preschool-age group). PedsQL™ self-reported fatigue scores of children with PFAPA were significantly lower than those of FMF peers for both preschoolers and school-age children and youths. Parent proxy-reports were not significantly different, even though scores were systematically lower for the parents of PFAPA children.

CONCLUSION
Our study demonstrates, for the first time, that the wellbeing of PFAPA children is poor, with a major impact on psychosocial functioning and increased fatigue. The quality of life of PFAPA children appears to be even lower than that of FMF patients, for whom a lower than normal HRQOL has already been demonstrated.

Grimwood|Claire|C| Kone-Paut|Isabelle|I| Piram|Maryam|M| Rossi-Semerano|Linda|L| Hentgen|Véronique|V|

Quality of life
PFAPA
Fatigue
Child
Familial Mediterranean fever
Hereditary auto inflammatory diseases
Preschool child


Case of endobronchial metastasis from breast cancer accompanied with Cunninghamella bertholletiae tracheobronchial mycetoma.

Abstract: Cunninghamella is a member of the class Zygomycetes. Cunninghamella species include ubiquitous filamentous fungi; infections caused by Cunninghamella species are less frequent but have higher mortality rates than infections caused by Mucorales group members such as Rhizopus and Mucor. Herein, we reported a rare fatal case of endobronchial metastasis from breast cancer accompanied with Cunninghamella bertholletiae tracheobronchial mycetoma. A 73-year-old female with a history of right-sided breast cancer who had undergone mastectomy 11 years previously and had no recurrence presented to our emergency department with a 1-week history of left-sided back pain. Chest X-ray revealed left lung atelectasis; bronchoscopy revealed an endobronchial mass lesion in the left main bronchus. Pathological examination revealed fungal mycetoma but malignant lesions were not detected. Endobronchial and lung mycetoma caused by Cunninghamella bertholletiae were initially diagnosed; liposomal amphotericin B was administered, but her condition deteriorated. Rigid endoscopy showed growth of hemorrhagic tissue occupying the left main bronchus just under the carina. Pathological examination of the shaved lesion revealed metastasis from breast cancer covered with abundant necrotic tissue. No mold was observed in the necrotic tissue; this was probably due to liposomal amphotericin B treatment. To our knowledge, this is the first case of endobronchial metastasis from breast cancer accompanied with Cunninghamella bertholletiae mycetoma. Distinguishing endobronchial metastases from breast cancer and atypical presentations of Cunninghamella endobronchial mycetomas can be very difficult. Repeated bronchoscopies maybe helpful in establishing an accurate diagnosis when clinical prognosis does not match the initial diagnosis.

Uno|Kenji|K| Hishiya|Naokuni|N| Matsuda|Masayuki|M| Kai|Yoshiro|Y| Amano|Masayuki|M| Nakamura|Atsuhiro|A| Tohjyo|Takashi|T| Kawaguchi|Takeshi|T| Nakano|Ryuichi|R| Yano|Hisakazu|H| Kasahara|Kei|K| Mikasa|Keiichi|K|

Endobronchial metastasis
Breast cancer
Cunninghamella bertholletiae
Tracheobronchial mycetoma
Liposomal amphotericin B


Hydro(deoxygenation) Reaction Network of Lignocellulosic Oxygenates.

Abstract: Hydrodeoxygenation (HDO) is a key transformation step to convert lignocellulosic oxygenates into drop-in and functional high-value hydrocarbons through controlled oxygen removal. Nevertheless, the mechanistic insights of HDO chemistry have been scarcely investigated as opposed to a significant extent of hydrodesulfurization chemistry. Current requirements emphasize certain underexplored events of HDO of oxygenates, which include 1) interactions of oxygenates of varied molecular size with active sites of the catalysts, 2) determining the conformation of oxygenates on the active site at the point of interaction, and 3) effects of oxygen contents of oxygenates on the reaction rate of HDO. It is realized that the molecular interactions of oxygenates with the surface of the catalyst dominates the degree and nature of deoxygenation to derive products with desired selectivity by overcoming complex separation processes in a biorefinery. Those oxygenates with high carbon numbers (>C10), multiple furan rings, and branched architectures are even more complex to understand. This article aims to focus on concise mechanistic analysis of biorefinery oxygenates (C10-35 ) for their deoxygenation processes, with a special emphasis on their interactions with active sites in a complex chemical environment. This article also addresses differentiation of the mode of interactions based on the molecular size of oxygenates. Deoxygenation processes coupled with or without ring opening of furan-based oxygenates and site-substrate cooperativity dictate the formation of diverse value-added products. Oxygen removal has been the key step for microbial deoxygenation by the use of oxygen-removing decarbonylase enzymes. However, challenges to obtain branched and long-chain hydrocarbons remain, which require special attention, including the invention of newer techniques to upgrade the process for combined depolymerization-HDO from real biomass.

hydrodeoxygenation
hydrocarbons
biomass
reaction mechanisms
supported catalysts


Pancreatic head cancer: Open or minimally invasive pancreaticoduodenectomy?

Abstract: Pancreatic head cancer still represents an insurmountable barrier for patients and pancreatic surgeons. Pancreaticoduodenectomy (PD) continues to be the operative standard of care and potentially curative procedure for pancreatic head cancer. Despite the rapid development of minimally invasive techniques, whether the efficacy of minimally invasive pancreaticoduodenectomy (MIPD) is noninferior or superior to open pancreaticoduodenectomy (OPD) remains unclear. In this review, we summarized the history of OPD and MIPD and the latest staging and classification information for pancreatic head cancer as well as the proposed recommendations for MIPD indications for patients with pancreatic head cancer. By reviewing the MIPD- vs. OPD-related literature, we found that MIPD shows noninferiority or superiority to OPD in terms of safety, feasibility, enhanced recovery after surgery (ERAS) and several short-term and long-term outcomes. In addition, we analyzed and summarized the different MIPD outcomes in the USA, Europe and China. Certain debates over MIPD have continued, however, selection bias, the large number of low-volume centers, the steep MIPD learning curve, high conversion rate and administration of neoadjuvant therapy may limit the application of MIPD for pancreatic head cancer.

Feng|Mengyu|M| Cao|Zhe|Z| Sun|Zhiwei|Z| Zhang|Taiping|T| Zhao|Yupei|Y|


The carboxy-terminal insert in the Q-loop is needed for functionality of Escherichia coli cytochrome bd-I.

Abstract: Cytochrome bd, a component of the prokaryotic respiratory chain, is important under physiological stress and during pathogenicity. Electrons from quinol substrates are passed on via heme groups in the CydA subunit and used to reduce molecular oxygen. Close to the quinol binding site, CydA displays a periplasmic hydrophilic loop called Q-loop that is essential for quinol oxidation. In the carboxy-terminal part of this loop, CydA from Escherichia coli and other proteobacteria harbors an insert of ~60 residues with unknown function. In the current work, we demonstrate that growth of the multiple-deletion strain E. coli MB43∆cydA (∆cydA∆cydB∆appB∆cyoB∆nuoB) can be enhanced by transformation with E. coli cytochrome bd-I and we utilize this system for assessment of Q-loop mutants. Deletion of the cytochrome bd-I Q-loop insert abolished MB43∆cydA growth recovery. Swapping the cytochrome bd-I Q-loop for the Q-loop from Geobacillus thermodenitrificans or Mycobacterium tuberculosis CydA, which lack the insert, did not enhance the growth of MB43∆cydA, whereas swapping for the Q-loop from E. coli cytochrome bd-II recovered growth. Alanine scanning experiments identified the cytochrome bd-I Q-loop insert regions Ile318-Met322, Gln338-Asp342, Tyr353-Leu357, and Thr368-Ile372 as important for enzyme functionality. Those mutants that completely failed to recover growth of MB43∆cydA also lacked oxygen consumption activity and heme absorption peaks. Moreover, we were not able to isolate cytochrome bd-I from these inactive mutants. The results indicate that the cytochrome bd Q-loop exhibits low plasticity and that the Q-loop insert in E. coli is needed for complete, stable, assembly of cytochrome bd-I.

Goojani|Hojjat Ghasemi|HG|
Konings|Julia|J|
Hakvoort|Henk|H|
Hong|Sangjin|S|
Gennis|Robert B|RB|
Sakamoto|Junshi|J|
Lill|Holger|H|
Bald|Dirk|D|

D045222:Electron Transport Chain Complex Proteins

Q-loop
Cytochrome bd
Biochemistry
Mutagenesis
Terminal oxidase


Differences in Functional Outcome Across Subtypes with Spetzler-Martin Grade II Arteriovenous Malformations.

Abstract:
BACKGROUND
The Spetzler-Martin grading system for brain arteriovenous malformations (AVMs) is based on size (S), eloquence (E), and deep venous drainage (V). However, variation exists due to subgroup heterogeneity. While previous studies have demonstrated variations in outcomes within grade III AVMs, no studies have focused on grade II AVM subtypes.

OBJECTIVE
We aim to delineate how functional outcomes differ among patients with subtypes of grade II AVMs.

METHODS
We retrospectively reviewed patients with AVMs evaluated at our institution from 1990 to 2013. Grade II AVMs were divided into 3 subtypes: group 1 (S2V0E0), group 2 (S1V0E1), and group 3 (S1V1E0). Baseline characteristics were compared, and functional status was assessed using the modified Rankin Scale (mRS) at pretreatment and last follow-up. Differences in mRS between the 2 time points were compared.

RESULTS
A total of 208 grade II patients (34.0%) were retrieved from 611 graded patients. After accounting for missing data, our cohort consisted of 137 patients. Mean age of all patients was 37.2 years, with 74 females (54.0%). No significant difference was observed across subgroups for pretreatment mRS ( P = .096), treatment modalities ( P = .943), follow-up durations ( P = .125), and mRS at last follow-up ( P = .716). In a subgroup analysis between group 1 and group 3, more patients with worsened mRS were observed in group 3 ( P = .039). This distinction was further confirmed in surgically treated patients ( P = .049), but not in patients treated with radiosurgery ( P = .863).

CONCLUSION
Subtypes of grade II AVMs portend different posttreatment gains in functional outcome. Group 1 (S2V0E0) patients had the best functional outcome gain from treatment, while group 3 (S1V1E0) patients fared less well, particularly with surgical treatment.

Hung|Alice L|AL|
Yang|Wuyang|W|
Westbroek|Erick M|EM|
Garzon-Muvdi|Tomas|T|
Caplan|Justin M|JM|
Braileanu|Maria|M|
Wang|Joanna Y|JY|
Colby|Geoffrey P|GP|
Coon|Alexander L|AL|
Tamargo|Rafael J|RJ|
Huang|Judy|J|

Arteriovenous malformations
Spetzler-Martin grading system
Grade II AVMs


Asthma and pulmonary tuberculosis: misdiagnosis or coexistence.

Abstract: Asthma and pulmonary tuberculosis (PTB) are disease entities with different pathogenesis. However, endobronchial tuberculosis (EBTB), a peculiar form of PTB, can mimic the symptoms of asthma. Although uncommon, the coexistence of asthma and PTB can appear. We report three cases of PTB. The first two cases with EBTB were misdiagnosed as asthma and the third case with asthma developed PTB four months after high-dose inhaled corticosteroid (ICS) therapy. The first two cases presented with chronic cough up mucopurulent/purulent sputum and localized wheezing which revealed diagnostic clues. The third case presented with dry cough and showed a positive bronchodilator response and the right pulmonary apical fibrosis which could be associated with quiescent tuberculous infection. EBTB should be included in the differential diagnosis of asthma. Although rare, physicians should be aware that PTB can also be developed during the treatment course of asthma.

Asthma
endobronchial tuberculosis
inhaled corticosteroid
wheezing


Titanium Dioxide Nanoparticles and Cetylpyridinium Chloride Enriched Glass-Ionomer Restorative Cement: A Comparative Study Assessing Compressive Strength and Antibacterial Activity.

Abstract:
OBJECTIVE
To evaluate the addition of titanium dioxide (TiO2) nanoparticles and cetylpyridinium chloride (CPC) on the compressive strength and antibacterial activity of conventional glass-ionomer cement (GIC).

STUDY DESIGN
TiO2 nanoparticles enriched GIC was prepared by adding 3% TiO2 nanoparticles (w/w) into the powder component of conventional GIC. CPC containing GIC was developed by incorporating 1% CPC (w/w) into conventional GIC powder. Samples were segregated into three groups: GIC with 3% TiO2 nanoparticles, GIC with 1% CPC and unmodified conventional GIC. Compressive strength was assessed using the universal testing machine on cylindrical specimens made from each material. Antibacterial activity was assessed by measuring inhibition zones on Mitis Salivarius Bacitracin (MSB) agar inoculated with pure strain of Streptococcus mutans (S. mutans).

RESULTS
GIC containing TiO2 nanoparticles exhibited significantly greater compressive strength as compared with CPC and conventional GIC groups (P < 0.01). However, there was no significant difference between the compressive strengths of CPC and conventional GIC group (P >0.05). Antibacterial activity was significantly greater for TiO2 group than conventional GIC (P <0.05). CPC increased the antibacterial activity of conventional GIC, though not significantly.

CONCLUSION
The addition of 3% TiO2 nanoparticles improves the compressive strength of GIC as well as its antibacterial activity against S. mutans.

Hamid|Nida|N|
Telgi|Ravishankar Lingesha|RL|
Tirth|Amit|A|
Tandon|Vaibhav|V|
Chandra|Smita|S|
Chaturvedi|Rupesh Kumar|RK|

D000900:Anti-Bacterial Agents
D002594:Cetylpyridinium
D019245:Compressive Strength
D003793:Dental Restoration, Permanent
D005899:Glass Ionomer Cements
D008422:Materials Testing
D053758:Nanoparticles
D013499:Surface Properties
D014025:Titanium

nanoparticles
cetylpyridinium chloride
compressive strength
antibacterial activity
CPC
Glass ionomer
TiO


High-Parameter Immune Profiling with CyTOF.

Abstract: Mass cytometry, or CyTOF, is a useful technology for high-parameter single-cell phenotyping, especially from suspension cells such as blood or PBMC. It is particularly appealing to monitor the systemic immune changes that could accompany cancer immunotherapy. Here we present a reference panel for identification of all major immune cell populations, with flexibility for addition of trial-specific markers. We also describe best-practice measures for minimizing and tracking batch variability. These include: sample barcoding, use of spiked-in reference cells, and lyophilization of the antibody cocktail. Our protocol assumes the use of cryopreserved PBMC, both for convenience of batching samples and for maximum comparability across patients and time points. Finally, we show an option for automated analysis using the Astrolabe platform (Astrolabe Diagnostics, Inc.).

Sahaf|Bita|B|
Rahman|Adeeb|A|
Maecker|Holden T|HT|
Bendall|Sean C|SC|

D000906:Antibodies
D001800:Blood Specimen Collection
D002469:Cell Separation
D005434:Flow Cytometry
D005612:Freeze Drying
D017408:Guidelines as Topic
D006801:Humans
D007963:Leukocytes, Mononuclear
D013058:Mass Spectrometry
D009369:Neoplasms
D040901:Proteomics
D059010:Single-Cell Analysis

Mass cytometry
Differential analysis
Multiplexed
Phenotypic markers
Subpopulation


New pyran derivative with antioxidant and anticancer properties isolated from the probiotic Lactobacillus plantarum H24 strain.

Abstract: This work was aimed to prepare, isolate and identify antioxidant and cytotoxic compound from the culture filtrate of a probiotic lactobacillus strain. New compound, plantarone (1), together with two known compounds, kojic acid (2) and methyl dodecanoate (3), were isolated from the ethyl acetate extract of the culture filtrate of probiotic Lactobacillus plantarum H24. Their structures were elucidated using spectroscopic methods including 2 D NMR, HRMS analyses. Isolated compounds were screened for antioxidant and cytotoxic activities against Caco-2 colon cancer cells. Compounds 1 and 2 showed lowers DPPH radical scavenging activities (p < 0.05) with IC50 values of 66.3 ± 0.34 μM and 50.2 ± 0.28 μM respectively, compared to standard butylated hydroxyanisole (BHA: IC50 = 44.2 ± 0.24 μM). Whereas only compound 1 showed a good cytotoxicity activity with inhibition value of 60.72 ± 3.55%. Accordingly, L. plantarum H24 could be used to prevent oxidative stress and its injuries, improving human health.

probiotics
Lactobacillus plantarum H24
plantarone
cytotoxic activity
Antioxidant activity
Spectroscopy


Medial Rectus Muscle Injuries after Functional Endoscopic Sinus Surgery.

Abstract: In recent years, functional endoscopic sinus surgery (FESS) has improved the treatment of sinus disorders. However, various orbital complications have been reported, including optic nerve damage, orbital hemorrhage, infection, lacrimal drainage system injury, and strabismus. Complications are rare but may cause severe morbidity. We describe two patients who underwent endoscopic sinus surgery procedures that resulted in trauma to the medial rectus muscle. The first patient had medial rectus paresia due to contusional trauma and showed spontaneous resolution in a month. The other patient had an orbital medial wall defect with medial rectus injury and he underwent orbitotomy. Medial rectus innervation returned at postoperative 8 months. Several extraocular muscles may be traumatized during FESS. Timing and method of treatment are based on the severity and type of injury and the number of muscles involved. Treatment strategies are dependent on accurate interpretation of magnetic resonance imaging scans.

Demirayak|Bengi|B| Altıntaş|Özgül|Ö| Ağır|Hakan|H| Alagöz|Şahin|Ş|

endoscopic sinus surgery
Strabismus
diplopia
extraocular muscle injury


Subcutaneous adipose tissue response to a non-invasive hyperthermic treatment using a 1,060 nm laser.

Abstract:
BACKGROUND
We postulated that a hyperthermic treatment using a 1,060 nm laser can cause a controlled adipocyte injury resulting in non-invasive fat reduction. This three-part study identified treatment parameters for a safe and tolerable treatment, demonstrated short- and long-term tissue response, and assessed the potential of this treatment for non-invasive fat reduction.

METHODS
In vivo temperature measurements were conducted prior to abdominoplasty via a thermal camera (for surface readings) and thermocouple needle (for subcutaneous readings). Short- and long-term tissue response was evaluated on the abdomen immediately post to 6 months post a 1,060 nm laser treatment. Laser dosage was varied to identify safe and effective parameters for fat reduction. Tissue biopsies for hematoxylin/eosin (H&E) staining were taken at weeks 1 and 2, as well as at 1, 2, 3, and 6 months (if applicable). Additionally, six subjects received a hyperthermic laser treatment to the flanks; four patients receiving laser treatment to one flank and cryolipolysis on the other, and two patients receiving laser treatment on one side with the other side as an untreated control. Efficacy measurements included ultrasound measurement of fat thickness at baseline, 2, 3, and 6 months; Magnetic Resonance Imaging (MRI) to calculate fat volume at baseline, 3 and 6 months; and blinded photograph evaluation at baseline, 1, 2, 3, and 6 months.

RESULTS
In vivo temperature measurements demonstrated that the hyperthermic temperature target (42-47°C) can be achieved and maintained in subcutaneous adipose tissue via a 1,060 nm laser in conjunction with surface cooling. Short- and long-term tissue responses were evaluated by tissue histology up to 6 months following treatment. Histological changes included inflammation, followed by macrophage infiltration starting at approximately 2 weeks, with evacuation of cellular debris completed by approximately 6 months. Clinical results demonstrated average fat thickness reduction at 14%, 18%, and 18% at 2, 3, and 6 months, respectively. Average fat volume reduction measured by MRI at 3 and 6 months was 24% and 21%, respectively. Blinded photo evaluation showed improvement starting at 1-month post-treatment and was maintained at 6 months. Adverse events were rare and included mild tenderness that resolved by 1-week post-treatment.

CONCLUSION
Parameters were identified that selectively injure and reduce adipocytes in subcutaneous tissue using a 1,060 nm externally applied laser. The treatment had an excellent safety profile and was well tolerated. The clinical study demonstrated that a 1,060 nm hyperthermic laser treatment for non-invasive fat reduction can be safe and effective. Lasers Surg. Med. 49:480-489, 2017. © 2016 Wiley Periodicals, Inc.

Decorato|John W|JW|
Chen|Bo|B|
Sierra|Rafael|R|

non-invasive fat reduction
body contouring
laser fat reduction
non-invasive body contouring


Ocean Surface Drifting Buoy System Based on UAV-Enabled Wireless Powered Relay Network.

Abstract: We design an ocean surface drifting buoy system based on an unmanned aerial vehicle (UAV)-enabled wireless powered relay network in which the UAV acts as mobile hybrid access point that broadcasts energy to all buoys in the downlink and forwards information from the buoys to a ship signal tower (ST) in the uplink. In order to maximize the resource allocation efficiency of the system, due to the different initial energy reserve of the buoys, a novel communication mode selection strategy is proposed. In the direct transmission mode (DT mode), an energy-sufficient buoy transmits information directly to the ST, and in the relay transmission mode (RT mode), an energy-insufficient buoy relays information to the ST through the UAV. By applying the block coordinate descent and successive convex optimization, a joint UAV trajectory and resource allocation algorithm is proposed to maximize the minimum throughput of the buoys to work in the RT mode. Simulation results show that the proposed algorithm can significantly improve the minimum throughput of the ocean surface drifting buoys.

Chen|Haole|H|0000-0003-1851-4686 Yin|Feng|F| Huang|Wei|W| Liu|Mingliu|M| Li|Deshi|D|

resource allocation
buoy communication
maximize minimum throughput
unmanned aerial vehicle (UAV)
wireless powered communication networks


Mandatory pre-abortion counseling is a barrier to accessing safe abortion services.

Abstract: Empirical research showcases that pre-abortion counseling scarcely reverses the woman's decision either to terminate a pregnancy or not. Growing evidence regarding the high levels of decisional certainty among women seeking abortions renders a careful rethink of the place of mandatory pre-abortion counseling packages. Mandatory counseling packages, when inscribed in the laws, at times contain false information that can deter women from going in for safe abortions. Mandatory waiting times indirectly label opting for an abortion as not being the right thing to do. In areas where abortion stigma from health care providers and communities remains highly prevalent, women are forced to incur extra expenses by travelling to other countries. I argue that pre-abortion counseling on opting-in grounds is ethically sound (enhances the woman's reproductive autonomy), since most clients in need of abortions are certain on their decisions before the abortion care provider and do not regret these decisions after the process. Regrets are prone to be more prevalent in areas with high unsafe abortion practices, generally due to complications from excessive bleeding, pain, and post abortion infections. Allowing systematic mandatory pre-abortion counseling practice as the rule in a competent adult is unjustified ethically and empirically, is time consuming and presents the legality of abortions in most settings an oxymoron.

mandatory pre-abortion counseling access Abortion legal


A hybrid approach for chronic pancreatitis: combination of laparoscopic assisted distal pancreatectomy and open Frey procedure.

Abstract:
BACKGROUND
The treatment of chronic pancreatitis requires a surgical approach in patients who are refractory to medical therapy. During surgical treatment, ductal decompression is required, but a pancreatectomy is necessary for some patients, such as those with severe stenosis of the pancreatic duct. Indeed, suboptimal procedures lead to recurrent pancreatitis. We used a laparoscopic hybrid approach for patients with severe stenosis of the pancreatic duct. In this report, we present the feasibility and outcomes of our approach.

METHODS
We selected a laparoscopic approach for the distal pancreatectomy, which is relatively safe and the effect of reducing the length of the wound is substantial. We selected an open approach for the Frey procedure because complete ductal compression has a high risk for injury to the vessels posterior to the pancreas. We recorded the operative outcomes, postoperative complications, and recurrence of pancreatitis.

RESULTS
We performed the laparoscopic hybrid approach on 3patients between January and December 2018. There were no major intraoperative complications (Clavien-Dindo classification IIIa or more) and the postoperative course was uneventful in all patients. There were no recurrences of pancreatitis and no postoperative pain in all patients in > 2 years of follow-up.

CONCLUSION
Our hybrid method with a focus on complete ductal compression with safety and minimal invasiveness might be the optimal approach for the surgical treatment of chronic pancreatitis that requires a pancreatectomy with the Frey procedure.

Hybrid approach
Chronic pancreatitis
Frey procedure
Laparoscopic distal pancreatectomy