Plasma proenkephalin A 119-159 on intensive care unit admission is a predictor of organ failure and 30-day mortality.

Abstract:
BACKGROUND
Proenkephalin A 119-159 (penKid) has been suggested as a marker of renal failure and poor outcome. We aimed to investigate the association of penKid on ICU admission with organ dysfunction and mortality in a mixed ICU population. In this retrospective, observational study, admission penKid levels from prospectively collected blood samples of consecutive patients admitted to four Swedish ICUs were analysed. The association of penKid with day-two sequential organ failure assessment (SOFA) scores and 30-day mortality was investigated using (ordinal) logistic regression. The predictive power of penKid for 30-day mortality and dialysis was assessed using the area under the receiver operating characteristic curve (AUC).

RESULTS
Of 1978 included patients, 632 fulfilled the sepsis 3-criteria, 190 had a cardiac arrest, and 157 had experienced trauma. Admission penKid was positively associated with 30-day mortality with an odds ratio of 1.95 (95% confidence interval 1.75-2.18, p < 0.001), and predicted 30-day mortality in the entire ICU population with an AUC of 0.71 (95% confidence interval 0.68-0.73) as well as in the sepsis, cardiac arrest and trauma subgroups (AUCs of 0.61-0.84). Correction for admission plasma creatinine revealed that penKid correlated with neurological dysfunction.

CONCLUSION
Plasma penKid on ICU admission is associated with day-two organ dysfunction and predictive of 30-day mortality in a mixed ICU-population, as well as in sepsis, cardiac arrest and trauma subgroups. In addition to being a marker of renal dysfunction, plasma penKid is associated with neurologic dysfunction in the entire ICU population, and cardiovascular dysfunction in sepsis.

Proenkephalin
Intensive care
Mortality
Organ dysfunction
Biomarker


Construct Validity of an Obesity Risk Screening Tool in Two Age Groups.

Abstract: Home environment influences child health, but the impact varies as children move into adolescence. The Family Nutrition and Physical Activity (FNPA) screening tool has been used to evaluate home environments, but studies have not compared the utility of the tool in different age groups. The purpose of this study was to examine the efficacy of the FNPA tool in first and tenth grade samples. Parents of first grade (n = 250) and tenth grade (n = 99) students completed the FNPA and results were linked to body mass index (BMI) data. FNPA scores were examined by gender, income, race, and school-level socioeconomic status (SES). Correlations examined associations between FNPA scores and several BMI indicators. Logistic and linear regression analyses evaluated the construct validity of the FNPA in both groups. Mean FNPA score differed by age group, by SES in both age groups, and by race in the first grade sample only. Correlations between FNPA score and BMI indicators were higher in the first grade sample, but SES was significantly associated with BMI only in tenth graders. The FNPA has stronger utility in younger children, while school SES is a stronger predictor of adolescent weight status.

Family Nutrition and Physical Activity screening tool


Bioengineered ethosomes encapsulating AgNPs and Tasar silk sericin proteins for non melanoma skin carcinoma (NMSC) as an alternative therapeutics.

Abstract: Rising cases of Non melanoma skin carcinoma (NMSC) and escalating levels of ultraviolet radiations have underlined a profound correlation with the elevating levels of environmental detoriation and increasing health issues. However, the availability of therapeutics has not aided in controlling the recurrence rates of skin carcinoma. Frequent administration of therapeutics with higher chances of facial deformity escalates the patient's treatment expenses. Thus, this study initiates a low cost effective and biodegradable therapy by exploring four formulations with combinations of silver nanoparticles (AgNPs), sericin (isolated from cocoons of Antherea mylitta) and chitosan. Subsequently, various ethosomal formulations were evaluated as a platform for transdermal delivery vehicle for efficient skin intervention therapeutics. Characterization using UV visible spectroscopy, Dynamic light scattering, Fourier Infrared spectroscopy, X-ray dispersion, Transmission electron microscopy, Fluorescence assisted cell sorting and in vitro studies were done and it was inferenced that equal combination of AgNPs and sericin facilitated to combat the morphological and cellular deformation of the epidermoid A431skin carcinoma cells. The overproduction of superoxide (O2.) and nitric oxide (NO) radicals consequently depolarized the mitochondrial membrane potential triggering apoptosis and necrosis. The in vivo experiments exhibited the stimulation of IgM secretion with T cell-mediated immune response. Therefore, this study proposes a novel approach for treatment of NMSC using biocompatible formulations delivered through ethosomes.

Nayak|Debasis|D|
Thathapudi|Neethi C|NC|
Ashe|Sarbani|S|
Nayak|Bismita|B|

Ethosomes
Sericin
Silver nanoparticles
Reactive oxygen species
Skin cancer


In the rat pancreas, somatostatin tonically inhibits glucagon secretion and is required for glucose-induced inhibition of glucagon secretion.

Abstract:
AIM
It is debated whether the inhibition of glucagon secretion by glucose results from direct effects of glucose on the α-cell (intrinsic regulation) or by paracrine effects exerted by beta- or delta-cell products.

METHODS
To study this in a more physiological model than isolated islets, we perfused isolated rat pancreases and measured glucagon, insulin and somatostatin secretion in response to graded increases in perfusate glucose concentration (from 3.5 to 4, 5, 6, 7, 8, 10, 12 mmol/L) as well as glucagon responses to blockage/activation of insulin/GABA/somatostatin signalling with or without addition of glucose.

RESULTS
Glucagon secretion was reduced by about 50% (compared to baseline secretion at 3.5 mmol/L) within minutes after increasing glucose from 4 to 5 mmol/L (P < .01, n = 13). Insulin secretion was increased minimally, but significantly, compared to baseline (3.5 mmol/L) at 4 mmol/L, whereas somatostatin secretion was not significantly increased from baseline until 7 mmol/L. Hereafter secretion of both increased gradually up to 12 mmol/L glucose. Neither recombinant insulin (1 µmol/L), GABA (300 µmol/L) or the insulin-receptor antagonist S961 (at 1 µmol/L) affected basal (3.5 mmol/L) or glucose-induced (5.0 mmol/L) attenuation of glucagon secretion (n = 7-8). Somatostatin-14 attenuated glucagon secretion by ~ 95%, and blockage of somatostatin-receptor (SSTR)-2 or combined blockage of SSTR-2, -3 and -5 by specific antagonists increased glucagon output (at 3.5 mmol/L glucose) and prevented glucose-induced (from 3.5 to 5.0 mmol/L) suppression of secretion.

CONCLUSION
Somatostatin is a powerful and tonic inhibitor of glucagon secretion from the rat pancreas and is required for glucose to inhibit glucagon secretion.

somatostatin
glucagon secretion
intrinsic regulation
insulin
GABA
isolated perfused rat pancreas
paracrine regulation


In vitro assays on the susceptibility of four species of nematophagous fungi to anthelmintics and chemical fungicides/antifungal drug.

Abstract: Using nematophagous fungi for the biological control of animal parasitic nematodes will become one of the most promising strategies in the search for alternative chemical drugs. The purpose of this study was to check the in vitro activity of four anthelmintics, four chemical fungicides and two antifungal drugs on the spore germination of nematophagous fungi: Duddingtonia flagrans (SF170), Arthrobotrys oligospora (447), Arthrobotrys superba (435) and Arthrobotrys sp. (PS011). A modified 24-well cell culture plate assay was conducted to evaluate the susceptibility of nematophagous fungi against drugs tested by calculating the effective middle concentrations (EC50 ) of each tested drug to inhibit the germination of fungal spores. EC50 ranged between 0·7 and 47·2 μg ml-1 for fenbendazole, thiabendazole and ivermectin, except levamisole (546·5-4057·8 μg ml-1 ). EC50 of tested fungicides was 0·6-2·3 μg ml-1 for carbendazim, 55·9-247·4 μg ml-1 for metalaxyl, 24·4-45·2 μg ml-1 for difenoconazole, and 555·9-1438·3 μg ml-1 for pentachloronitrobenzene (PCNB). EC50 of two antifungal drugs was 0·03-3·4 μg ml-1 for amphotericin B and 0·3-10·9 μg ml-1 for ketoconazole. The results showed that 10 tested drugs, except for levamisole and PCNB, had in vitro inhibitory effects on nematophagous fungi. The chlamydospores of D. flagrans had the highest sensitivity to nine tested drugs, except for ketoconazole.

nematophagous fungi
ivermectin
levamisole
amphotericin B
ketoconazole
benzimidazoles


Prolonged Exposure to Alcohol Vapor Causes Change in Cardiovascular Function in Female but not in Male Rats.

Abstract:
BACKGROUND
Alcohol abuse is a health concern worldwide. Studies have associated alcohol abuse with cardiovascular impairments. In this study, we investigated differences in the effects of chronic alcohol vapor exposure on cardiovascular function between male and female rats by using the alcohol vapor chamber method to induce alcohol addiction-like behaviors in rats.

METHODS
We exposed male and female Long-Evans rats to alcohol vapor for 14 hours, followed by ethanol withdrawal for 10 hours, for 30 consecutive days or room air (control groups). The animals underwent preparation for the surgical implantation of cannulas into femoral vessels, for allowing the assessment of the basal arterial pressure and heart rate values, baroreflex function, and autonomic activity.

RESULTS
Female control rats showed higher basal heart rate compared to male control rats. Chronic alcohol vapor inhalation reduced basal heart rate in females, but not in males; this effect was followed by an increase in the parasympathetic tone of the heart. Further, female rats subjected to alcohol vapor showed an increase in the baroreflex activity.

CONCLUSIONS
These findings suggest that females are more sensitive to chronic alcohol vapor exposure than males because they had a reduction in basal heart rate and changes in the baroreflex activity.

D002492:Central Nervous System Depressants

Alcohol
Cardiovascular
Baroreflex
Blood Pressure
Sex


Transbiliary intravascular ultrasound-guided diagnostic biopsy of an inaccessible pancreatic head mass.

Abstract: Percutaneous image-guided biopsies of pancreatic malignancies may prove challenging and nondiagnostic due to a variety of anatomic considerations. For patients with complex post-surgical anatomy, such as a Roux-en-Y gastric bypass, diagnosis via endoscopic ultrasound with fine-needle aspiration may not be possible because of an inability to reach the proximal duodenum. This report describes the first diagnostic case of transbiliary intravascular ultrasound-guided biopsy of a pancreatic head mass in a patient with prior Roux-en-Y gastric bypass for which a diagnosis could not be achieved via percutaneous and endoscopic approaches. Transbiliary intravascular ultrasound-guided biopsy resulted in a diagnosis of pancreatic adenocarcinoma, allowing the initiation of chemotherapy.

Chick|Jeffrey Forris Beecham|JFB|
Roush|Benjamin B|BB|
Khaja|Minhaj S|MS|
Prohaska|Dennis|D|
Cooper|Kyle J|KJ|
Saad|Wael E|WE|
Srinivasa|Ravi N|RN|

Transbiliary
Pancreatic malignancy
Intravascular ultrasound-guided biopsy
Interventional radiology
Pancreatic cancer
Pancreatic mass
Transhepatic


Role of SMURF1 ubiquitin ligase in BMP receptor trafficking and signaling.

Abstract: Heterozygous germline mutations in the bone morphogenetic protein type II receptor gene (BMPRII) are associated with hereditary pulmonary arterial hypertension (HPAH). Missense mutations, both in the extracellular ligand-binding and cytoplasmic kinase domains, mostly involve substitution of conserved Cys residues. Singular substitution at any of those Cys residues causes cytoplasmic, perinuclear localization of BMPR with reduced cell surface expression and BMP signaling. The present study examined the effect of Cys residue substitution on BMPR endocytic trafficking and lysosome degradation. We demonstrate that endocytosis/lysosomal degradation of BMPR occurs by two distinct pathways. SMURF1 ubiquitin ligase induces lysosomal degradation of BMPR, while ligase-inactive SMURF1 maintains BMPR protein level and cell surface expression. Substitution of BMPR Cys residues increases lysosomal degradation which is blocked by ligase-inactive SMURF1, elevating protein levels of Cys-substituted BMPRs. Expression of Cys-substituted BMPR suppresses basal BMP signaling activity which is also up-regulated by ligase-inactive SMURF1. Cys-residue substitution thus appears to cause BMPR endocytosis to lysosomes in a SMURF1 ubiquitin ligase-associated pathway. Kinase-activated BMPR undergoes endocytic/lysosomal degradation by a pathway with certain unique properties. Therefore, our results describe a novel mechanism whereby SMURF1 ubiquitin ligase regulates constitutive endocytosis of BMPR which may be mediated by its conserved Cys residues.

D052006:Bone Morphogenetic Protein Receptors, Type II

Hereditary pulmonary arterial hypertension

Conserved cysteine residues of BMP receptor


LL-37 peptide enhancement of signal transduction by Toll-like receptor 3 is regulated by pH: identification of a peptide antagonist of LL-37.

Abstract: LL-37 is a peptide secreted by human epithelial cells that can lyse bacteria, suppress signaling by Toll-like receptor 4 (TLR4), and enhance signaling to double-stranded RNA (dsRNA) by TLR3. How LL-37 interacts with dsRNA to affect signal transduction by TLR3 is not completely understood. We determined that LL-37 binds dsRNA and traffics to endosomes and releases the dsRNA in a pH-dependent manner. Using dynamic light scattering spectroscopy and cell-based FRET experiments, LL-37 was found to form higher order complexes independent of dsRNA binding. Upon acidification LL-37 will dissociate from a larger complex. In cells, LL-37 has a half-live of ∼ 1 h. LL-37 half-life was increased by inhibiting endosome acidification or inhibiting cathepsins, which include proteases whose activity are activated by endosome acidification. Residues in LL-37 that contact poly(I:C) and facilitate oligomerization in vitro were mapped. Peptide LL-29, which contains the oligomerization region of LL-37, inhibited LL-37 enhancement of TLR3 signal transduction. LL-29 prevented LL-37 · poly(I:C) co-localization to endosomes containing TLR3. These results shed light on the requirements for LL-37 enhancement of TLR3 signaling.

Singh|Divyendu|D|
Vaughan|Robert|R|
Kao|C Cheng|CC|

D000595:Amino Acid Sequence
D023181:Antimicrobial Cationic Peptides
D001665:Binding Sites
D011992:Endosomes
D006801:Humans
D006863:Hydrogen-Ion Concentration
D008969:Molecular Sequence Data
D010455:Peptides
D012330:RNA, Double-Stranded
D015398:Signal Transduction
D051196:Toll-Like Receptor 3
D015854:Up-Regulation

pH
Endosome
Innate Immunity
RNA-binding Protein
Toll-like Receptor (TLR)
pH Regulation


Synthesis, spectral characterization, DNA interaction, anticancer and molecular docking studies on some transition metal complexes with bidentate ligand.

Abstract: The ligand, N(2),N(3)-bis(3-nitrophenyl)quinoxaline-2.3-diamine was prepared by the condensation of quinoxaline-2.3(1,4H)-dione with 3-nitroaniline. It was treated with Co(II), Ni(II), Cu(II) and Zn(II) acetates to form the metal complexes. These were characterized by elemental analysis, molar conductance, magnetic moment, UV-Vis., IR, (1)H NMR, ESR and mass spectral data. Octahedral geometry has been assigned to Co(II), Ni(II) and Zn(II) complexes, whereas Cu(II) complex has distorted octahedral geometry. From the powder XRD data, crystallite size and unit cell parameters were calculated. The surface morphology of the synthesized compounds were determined using SEM analysis. The antimicrobial activity of the compounds against some bacterial species viz. Escherichiacoli, Klebsiella pneumoniae, Pseudomonas aeuruginosa and Staphylococcus aureus; also the fungal species, Aspergillus niger, and Candida albicans were done by disc diffusion method. DNA binding, cleavage and super oxide anion scavenging activities were also evaluated. The DNA binding activity of the compounds were identified using electronic absorption titrations and DNA cleavage was determined using gel electrophoresis. The anticancer activities of the compounds against HeLa cell line were determined using MTT assay. The highly potent compound among the five against HeLa cell line is subjected to molecular docking study against human papilloma virus receptor molecule and ATP binding site of telomerase.

Dhanaraj|C Justin|CJ|
Hassan|Israr Ul|IU|
Johnson|Jijo|J|
Joseph|J|J|
Joseyphus|R Selwin|RS|

DNA
Anticancer
Molecular docking
Antimicrobial
Quinoxaline


Conversion messages and attitude change: Strong arguments, not costly signals.

Abstract: A conversion narrative recounts the process that led the speaker to reject one belief for a different, usually incompatible, alternative. However, researchers know little about whether, when, and, if so, how such messages affect audience attitudes about controversial science. Using a general US population-sample experiment, we assessed the attitudinal impact of three versions of a statement by Mark Lynas, an environmental activist who converted from opposing to championing genetically modified crops. Participants were exposed to (1) a one-sided pro-genetically modified message by Lynas, (2) a two-sided pro-genetically modified message in which Lynas indicates but does not detail his conversion, or (3) a two-sided pro-genetically modified message in which Lynas explains the process that prompted his conversion. We find that his conversion messages influenced attitudes by way of perceived argument strength, but not speaker credibility. This finding implies such messages induce greater elaboration, which may lead to durable attitudes that predict behavior.

Lyons|Benjamin A|BA|0000-0001-7096-900X
Hasell|Ariel|A|0000-0002-1166-4318
Tallapragada|Meghnaa|M|
Jamieson|Kathleen Hall|KH|

conversion message
argument strength
credibility
costly talk
persuasion


Mutation screening in candidate genes in four Chinese brachydactyly families.

Abstract: Autosomal dominant brachydactyly (BD) is a skeletal disorder with several subtypes, including brachydactyly type A1 (BDA1) and brachydactyly type B1 (BDB1). Mutations in Indian hedgehog (IHH) are usually associated with BDA1, whereas heterozygous mutations in receptor tyrosine kinase-like orphan receptor 2 (ROR2) are mainly responsible for BDB1. On the basis of the clinical phenotype identification, we screened IHH and ROR2 by the candidate gene approach using PCR direct sequencing. We found three known mutations of IHH (c.283_285delGAG, p.E95del; c.298 G>A, p.D100N; c.300C>G, p.D100E) in three Chinese families with BDA1, and a novel heterozygous nonsense mutation of ROR2 (c.2273C>A, p.S758X) in a BDB1 family. It was noted that c.300C>G mutation was a new nucleotide substitution compared to the reported c.300C>A, which led to the same amino acid change (p.D100E). The novel nonsense mutation p.S758X was verified by absence in the unaffected family members and the 100 randomly-selected controls. In this paper, we report three recurrent mutations with a new nucleotide substitution of IHH in three Chinese families with BDA1 and a novel nonsense mutation in BDB1 pedigree. We therefore recommend the approach of candidate gene screening as the first choice for genetic testing for BD.

Dong|Sufang|S| Wang|Yinghui|Y| Tao|Shengxiang|S| Zheng|Fang|F|

D020022:Genetic Predisposition to Disease


Central Extracorporeal Membrane Oxygenation Support for Blastomycosis-Induced Septic Shock.

Abstract: Blastomyces dermatitidis, a rare fungus endemic to the central North America, has the potential to cause respiratory dysfunction in both immunocompromised and immunocompetent hosts. Blastomycosis infections can progress to severe respiratory failure and multisystem organ failure. Extracorporeal membrane oxygenation (ECMO) can be used as a temporary support device to allow time for a patient's organs to recover. Central ECMO has proven to be a successful treatment option for high-output septic shock. This case report describes a 12-year-old girl, erroneously diagnosed with juvenile idiopathic arthritis and treated with immunosuppressives, afflicted with blastomycosis-induced septic shock. High-flow central ECMO was used to reverse her lactic acidosis by increasing oxygen delivery. Unfortunately, continued lung deterioration secondary to the B. dermatitidis infection caused irreversible damage to the lung parenchyma. This is the second pediatric ECMO case report for severe respiratory failure related to blastomycosis and the first case report on central ECMO support for high-output septic shock from blastomycosis.

Watson|J Brandon|JB|
McDonald|Mark|M|
Schikler|Kenneth|K|

central extracorporeal membrane oxygenation


Proton Pump Inhibitors: Are They a Real Threat to the Patient?

Abstract:
Background
Proton pump inhibitors are among the most frequently prescribed drugs in the world and are generally considered safe. However, there is growing concern regarding their safety.

Summary
A nonsystematic review of the current literature was performed regarding proton pump inhibitors and their adverse effects. Proton pump inhibitors seem to be associated with fundic gland polyp development (without clinical relevance) and Clostridium difficile infection. Also, in cirrhotic patients, their prescription should be carefully reviewed. Regarding their association with other enteric infections, micronutrient deficiency, dementia, and chronic kidney disease, current evidence is still of low quality, and further studies are needed.

Key Messages
Considering the current evidence, most patients with a clear clinical indication for proton pump inhibitor treatment should probably benefit from the maintenance of their treatment without significant adverse effects. However, higher-quality studies are needed to confirm or dismiss most of the proposed adverse effects.

Proton pump inhibitors
Safety
Adverse effects


Impactful publishing: the Journal of Neurosurgery and its diamond anniversary (1944-2019).

Abstract: With this landmark issue of the Journal of Neurosurgery (JNS), we celebrate the 75th anniversary of continuous publication of articles in neurosurgery. It is likely not a coincidence that the diamond anniversary of the JNS coincides precisely with the 150th anniversary of the birth of Harvey Cushing. It is possible that some events in life are inextricably and cosmically tied together, such as the birth of the founding father of our specialty, the society named after him that ultimately became the American Association of Neurological Surgeons (AANS), and the journal of this organization-the JNS.

D000846:Anniversaries and Special Events

AANS = American Association of Neurological Surgeons

ASPN = American Society of Pediatric Neurosurgeons

JNSPG = Journal of Neurosurgery Publishing Group

PEDS = Journal of Neurosurgery: Pediatrics


Usefulness of feature analysis of breast-specific gamma imaging for predicting malignancy.

Abstract:
OBJECTIVES
The purpose of this study was to investigate which feature of the breast-specific gamma imaging (BSGI) uptake in women who were recently diagnosed with breast cancer was associated with malignancy.

METHODS
Data on 231 newly diagnosed breast cancer patients who underwent preoperative BSGI were retrospectively reviewed. Feature analysis was done by classifying BSGI uptake into mass, non-mass, or focus/foci. Descriptors for mass, non-mass, or focus/foci were shape, distribution, number, and intensity. BSGI features of known malignancies and lesions that were additionally found by BSGI were correlated with mammographic breast density, histology, hormonal status, and clinical follow-up data obtained over at least 2 years.

RESULTS
Among 372 breast lesions from 231 patients, 241 malignancies had been pathologically confirmed prior to BSGI and 131 additional lesions were found on BSGI. Irregular shape was more predictive of malignancy than oval shape (p=0.004) in mass uptake. Linear/ductal distribution was more predictive of malignancy than focal, regional, and segmental distribution (p<0.05) in non-mass uptake. Mammographic breast density was not associated with BSGI features. The lesion to normal ratio (LNR) was higher in the postmenopausal patients than that in the premenopausal patients (p=0.003).

CONCLUSIONS
The feature analysis of radiotracer uptake in BSGI is useful in predicting whether breast lesions are malignant or benign.

KEY POINTS
• The feature analysis of BSGI uptake is useful in predicting malignancy. • Irregular shape was predictive of malignancy in mass uptake. • Linear/ductal distribution was predictive of malignancy in non-mass uptake.

Choi|Eun Kyoung|EK|
Im|Jooyeon Jamie|JJ|
Park|Chang Suk|CS|
Chung|Yong-An|YA|
Kim|Kijun|K|
Oh|Jin Kyoung|JK|

Breast Neoplasms
Diagnostic Imaging
Molecular Imaging
Radionuclide Imaging
Technetium Tc 99m Sestamibi


Inhibitory effect of Morus australis leaf extract and its component iminosugars on intestinal carbohydrate-digesting enzymes.

Abstract: α-Amylase and α-glucosidase are central enzymes involved in the digestion of carbohydrates. α-Glucosidase includes maltase-glucoamylase and sucrase-isomaltase. We have previously performed the kinetic analysis of the inhibitory effects of powdered or roasted Morus australis leaf extract and its component iminosugars, such as 1-deoxynojirimycin (1-DNJ), fagomine, and 2-O-α-d-galactopyranosyl deoxynojirimycin (GAL-DNJ) on the activity of maltase. In this study, we analyzed the inhibitory effects of the aforementioned compounds against α-amylase, glucoamylase, sucrase, and isomaltase. At pH 6.0 and 37 °C, each leaf extract sample inhibited glucoamylase, sucrase, and isomaltase but not α-amylase. 1-DNJ and fagomine showed weak α-amylase inhibitory activity while GAL-DNJ exhibited none. 1-DNJ showed a strong glucoamylase, sucrase, and isomaltase inhibitory potential. The inhibitory potential against these three enzymes was 18-500 and 1500-3000-fold higher in the case of 1-DNJ than that observed in the case of fagomine and GAL-DNJ, respectively. We also observed that the indigestible dextrin could considerably inhibit α-amylase. When the powdered M. australis leaf extract was blended with indigestible dextrin, the mixture inhibited α-amylase, as well as maltase, glucoamylase, sucrase, and isomaltase. These results suggest that the ingestion of the leaf extract blended with indigestible dextrin might have the potential to efficiently suppress the postprandial blood glucose level increase.

Qiao|Ying|Y| Ito|Masaaki|M| Kimura|Toshiyuki|T| Ikeuchi|Takeaki|T| Takita|Teisuke|T| Yasukawa|Kiyoshi|K|

Morus australis
Iminosugar
α-Amylase
α-Glucosidase
Indigestible dextrin


A Grounded Theory of Music-Video Use in an Exercise Facility.

Abstract: Purpose: Despite considerable interest in the effects of music in an exercise context, there is a dearth of research examining the use of music-videos. This is surprising given the ubiquity of this medium in exercise facilities. The present study sought to examine the impact of a music-video channel on the social process of exercising in a public exercise facility. Method: A grounded theory approach underpinned by pragmatism and symbolic interactionism was employed. Thirteen exercisers completed reflective diaries following each attendance at the facility over a 4-week period. Subsequently, 11 exercisers were interviewed regarding the impact of the music-video channel on the social process of exercising at the facility. Staff members' perspectives were deemed important throughout the iterative process of data collection and analysis. Accordingly, four staff members were interviewed with reference to the social process of managing an exercise facility that featured a music-video channel. Data were analyzed using open, axial, and selective coding. Results: The results provide support for a three-stage substantive theory that commences with the content of the music-video channel. The second stage depicts a series of moderators (e.g., exercise factors, temporal factors) that revolve around the core category, appraisal of the appropriateness of channel content. Lastly, a range of effects pertaining to exercisers and facility staff are predicted, and relevant social processes are expounded. Conclusion: Given the prevalence of music-video channels in contemporary exercise and health facilities, the substantive theory bears relevance to exercisers, health/performance practitioners, and researchers.

D003258:Consumer Behavior
D015444:Exercise
D066296:Grounded Theory
D015438:Health Behavior
D006801:Humans
D007398:Interpersonal Relations
D009146:Music
D036301:Qualitative Research
D012931:Social Environment
D014741:Video Recording

Audiovisual stimuli
exercise psychology
physical activity
qualitative research


Bringing context to balance: development of a reactive balance test within the injury prevention and return to sport domain.

Abstract:
Background
Balance tests are commonly used in clinical practice with applicability in injury prevention and return to sport decisions. While most sports injuries occur in a changing environment where reacting to a non-planned stimulus is of great importance, these balance tests only evaluate pre-planned movements without taking these dynamics environmental aspects into account. Therefore, the goal of this paper was to develop a clinician-friendly test that respects these contextual interactions and to describe the test protocol of an adapted Y-balance test that includes environmental perception and decision-making.

Methods
Within the theoretical construct of balance and adaptability, balance errors were selected as outcome measures for balance ability and, visuomotor reaction time and accuracy are selected as outcome measures for adaptability. A reactive balance task was developed and described using the Y-balance test for the balance component, while the FitLight training systemTM was chosen for the environmental perception and decision-making component of the test.

Results
This paper describes the test protocol of a reactive balance test as an adapted Y-balance test. The LED-lights of the FitLight training systemTM are placed at 80% of the maximal reach distance for each axis along the Y-Balance test kitTM. To induce cognitive load within the visuomotor task, colours were fixed to a corresponding axis, and both the order of the visual stimuli as the interstimulus time were randomised to integrate environmental perception and decision-making.

Conclusion
The reactive balance test is a functional test that allows clinicians to score balance ability and athlete adaptability easily.

Verschueren|Jo|J|
Tassignon|Bruno|B|
Pluym|Bert|B|
Van Cutsem|Jeroen|J|
Verhagen|Evert|E|
Meeusen|Romain|R|

Balance
Injury prevention
Return to sport
Adaptability
Visuomotor reaction time
Stability


Local Differential Privacy in the Medical Domain to Protect Sensitive Information: Algorithm Development and Real-World Validation.

Abstract:
BACKGROUND
Privacy is of increasing interest in the present big data era, particularly the privacy of medical data. Specifically, differential privacy has emerged as the standard method for preservation of privacy during data analysis and publishing.

OBJECTIVE
Using machine learning techniques, we applied differential privacy to medical data with diverse parameters and checked the feasibility of our algorithms with synthetic data as well as the balance between data privacy and utility.

METHODS
All data were normalized to a range between -1 and 1, and the bounded Laplacian method was applied to prevent the generation of out-of-bound values after applying the differential privacy algorithm. To preserve the cardinality of the categorical variables, we performed postprocessing via discretization. The algorithm was evaluated using both synthetic and real-world data (from the eICU Collaborative Research Database). We evaluated the difference between the original data and the perturbated data using misclassification rates and the mean squared error for categorical data and continuous data, respectively. Further, we compared the performance of classification models that predict in-hospital mortality using real-world data.

RESULTS
The misclassification rate of categorical variables ranged between 0.49 and 0.85 when the value of ε was 0.1, and it converged to 0 as ε increased. When ε was between 102 and 103, the misclassification rate rapidly dropped to 0. Similarly, the mean squared error of the continuous variables decreased as ε increased. The performance of the model developed from perturbed data converged to that of the model developed from original data as ε increased. In particular, the accuracy of a random forest model developed from the original data was 0.801, and this value ranged from 0.757 to 0.81 when ε was 10-1 and 104, respectively.

CONCLUSIONS
We applied local differential privacy to medical domain data, which are diverse and high dimensional. Higher noise may offer enhanced privacy, but it simultaneously hinders utility. We should choose an appropriate degree of noise for data perturbation to balance privacy and utility depending on specific situations.

differential privacy
privacy
algorithm
development
validation
big data
medical data
machine learning
feasibility
synthetic data
electronic health record
medical informatics
privacy-preserving


Longitudinal assessment of hippocampus structure in children with type 1 diabetes.

Abstract: The extant literature finds that children with type 1 diabetes mellitus (T1D) experience mild cognitive alterations compared to healthy age-matched controls. The neural basis of these cognitive differences is unclear but may relate in part to the effects of dysglycemia on the developing brain. We investigated longitudinal changes in hippocampus volume in young children with early-onset T1D. Structural magnetic resonance imaging data were acquired from 142 children with T1D and 65 age-matched control subjects (4-10 years of age at study entry) at 2 time points, 18 months apart. The effects of diabetes and glycemic exposure on hippocampal volume and growth were examined. Results indicated that although longitudinal hippocampus growth did not differ between children with T1D and healthy control children, slower growth of the hippocampus was associated with both increased exposure to hyperglycemia (interval HbA1c) and greater glycemic variability (MAGE) in T1D. These observations indicate that the current practice of tolerating some hyperglycemia to minimize the risk of hypoglycemia in young children with T1D may not be optimal for the developing brain. Efforts that continue to assess the factors influencing neural and cognitive development in children with T1D will be critical in minimizing the deleterious effects of diabetes.

hippocampus
type 1 diabetes mellitus
brain
hyperglycemia
blood glucose


Botulinum Toxin Type A Injection for Cervical Dystonia in Adults with Dyskinetic Cerebral Palsy.

Abstract: We aimed to evaluate the efficacy and safety of injecting botulinum toxin A (BoNT-A) into the neck muscles to treat cervical dystonia (CD) in patients with dyskinetic cerebral palsy (CP). This was a randomized, double-blinded, placebo-controlled trial with cross-over design. We prospectively enrolled adults with dyskinetic CP who were over 20 years old and had been clinically diagnosed with CD for more than one year. The primary outcome measure was the change in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) at four weeks from the baseline TWSTRS. Seventeen patients were initially enrolled, but one patient was excluded after the final evaluation because of a violation of the study protocol. At four weeks, the BoNT-A injections showed significant improvement in TWSTRS total scores compared to the saline injections (p = 0.0286 for ANCOVA). At 12 weeks, the BoNT-A injections resulted in greater improvements in TWSTRS total scores than the saline injections without statistical significance (p = 0.0783 for ANCOVA). Dysphagia occurred in three out of 16 patients: two after BoNT-A and one after saline. The dysphagia was transient and improved naturally within two weeks without any special treatment. BoNT-A injection for CD in adults with dyskinetic CP is relatively safe and improves pain and disability.

botulinum toxin
cervical dystonia
dyskinetic cerebral palsy
clinical trials randomized controlled


Designing an Interactive Field Epidemiology Case Study Training for Public Health Practitioners.

Abstract: Globally, public health practitioners are called upon to respond quickly and capably to mitigate a variety of immediate and incipient threats to the health of their communities, which often requires additional training in new or updated methodologies or epidemiologic phenomena. Competing public health priorities and limited training resources can present challenges in developed and developing countries alike. Training provided to front-line public health workers by ministries of health, donors and/or partner organizations should be delivered in a way that is effective, adaptable to local conditions and culture, and should be an experience perceived as a job benefit. In this review, we share methods for interactive case-study training methodologies, including the use of problem-based scenarios, role-play activities, and other small-group focused efforts that encourage the learner to discuss and synthesize the concepts taught. We have fine-tuned these methods through years of carrying out training of all levels of public health practitioners in dozens of countries worldwide.

Nelson|Amy L|AL|
Bradley|Lauren|L|
MacDonald|Pia D M|PDM|

epidemiology
case study
training
public health
workforce development


Evidences for reduced metal-uptake and membrane injury upon application of nitric oxide donor in cadmium stressed rice seedlings.

Abstract: Heavy metal Cadmium (Cd) contaminates the environment through various anthropogenic sources. Cadmium-induced productions of free radicals lead to oxidative stress and H2O2 formation in plants. Endogenous Nitric oxide (NO) acts as signal molecules in plant stress response and play a significant role in key regulatory pathways of plant development. This study investigates the effect of 50 μM exogenous sodium nitroprusside (SNP, NO donor), on roots and shoots of rice cv. HUR 3022 grown under 50 μM Cd-stress at 7 days of growth. Plants treated with Cd alone showed stunted growth, decreased length and weight, lower cell viability and less chlorophyll. An elevated lipid peroxidation complemented with more electrolyte leakage was noted. Levels of hydrogen peroxide and superoxide anion increased in Cd-exposed plants with corresponding increase in activity of antioxidant enzymes catalase and superoxide dismutase. Lower chlorophyll levels paralleled with more uptake of cadmium in Cd-treatments as compared to controls. Application of equimolar amount of SNP to cadmium-stressed rice in the growth medium inhibited Cd-uptake and reversed the Cd-induced toxic effects by restoring membrane integrity. The levels of H2O2 and O2(-) were considerably recovered due to SNP treatment. The results indicate that exogenous NO diminishes the deleterious effects of Cd in rice plants.

Cadmium
Rice
Sodium nitroprusside
Lipid peroxides
Electrolyte leakage


Epidemiology of Functioning Pituitary Adenomas.

Abstract: Pituitary adenomas (PAs) are defined as benign monoclonal tumors in the pituitary gland that cause symptoms due to either hormonal hypersecretion or a space-occupying effect, and are classified as functioning or non-functioning. Because of their rarity and slow-growing with symptomless nature in most cases, it has been challenging to investigate the epidemiology of PAs. Considering their public health impact and association with increased morbidity and mortality, however, it is essential to understand the prevalence and incidence of PAs in order to improve patient outcomes and to minimize the resultant burden on the health care system. Fortunately, developments in imaging modalities and easier access to large-scale population data have enabled investigators to analyze the epidemiology of PAs more accurately. This review summarizes previously reported epidemiologic data on functioning PAs in Korea and other countries.


Circulating microRNAs in esophageal squamous cell carcinoma: association with locoregional staging and survival.

Abstract: Locoregional staging and prognostic information play a critical role in esophageal squamous cell carcinoma (ESCC) treatment strategies. Although microRNA (miRNA) is a promising marker for cancer detection, the relationship between circulating plasma miRNAs and ESCC remains unclear. Our study aims to investigate the association between circulating plasma miRNAs and tumor diagnosis or prognosis in ESCC patients. Plasma levels of miR-16, miR-21, miR-22, miR-126, miR-148b, miR-185, miR-221, miR-223, and miR-375 were evaluated by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) assays from 38 ESCC patients prior to treatment and 19 healthy subjects. Differences in selected miRNAs and their diagnostic and prognostic value were examined. Levels of four of the selected miRNAs were found to be significantly higher in ESCC patients than in controls; namely, miR-16, miR-21, miR-185, and miR-375 (P < 0.050). In addition, the area under the receiver operating characteristic (ROC) curve (AUC) for miR-375 was 0.921 (95% confidence interval [CI] 0.817-0.976). Moreover, the expression levels of miR-16 were higher in patients with T3-4 tumors than in patients with T1-2 tumors (P = 0.020). Kaplan-Meier survival analysis showed that high expression levels of miR-16 and miR-21 in the plasma correlated significantly with shortened progression-free survival (PFS; P = 0.031 and P = 0.038, respectively) and overall survival (OS; P = 0.022 and P = 0.041, respectively) in ESCC patients. Four plasma miRNAs were identified that could potentially serve as novel diagnostic biomarkers for ESCC. Moreover, specific miRNAs, such as miR-16 and miR-21, can predict poor survival in ESCC.

Li|Bing-Xin|BX| Yu|Qi|Q| Shi|Ze-Liang|ZL| Li|Ping|P| Fu|Shen|S|

MicroRNA
esophageal squamous cell carcinoma
locoregional staging
prognosis


Antibody-dependent CD56+ T cell responses are functionally impaired in long-term HIV-1 infection.

Abstract:
BACKGROUND
Antibody-dependent cellular cytotoxicity (ADCC), which mainly mediated by natural killer (NK) cells, may play a critical role in slowing human immunodeficiency virus type-1 (HIV-1) disease progression and protecting from HIV-1 infection. Besides classic NK cells, CD56+ T cells also have some NK cell-like properties, such as the large granular lymphocyte morphology and the capacity to destroy NK-sensitive target cells. However, little is known about the potentials of antibody-dependent CD56+ T cell responses and the association between antibody-dependent CD56+ T cell responses and HIV-1 disease progression.

RESULTS
In the present study, we showed evidences that, in addition to NK cells, CD56+ T cells could generate degranulation upon CD16 cross-linking. Ex vivo study showed that FcγRIII (CD16)-mediated CD56+ T cell responses were distinctly induced by IgG antibody-bound P815 cells. Comparatively, CD56- T cells and invariant NKT (CD3+ 6B11+) failed to induce antibody-dependent activation. Antibody-dependent CD56+ T cell responses were mainly ascribed to CD4/CD8 double negative subset and were functionally impaired in long-term HIV-1-infected former plasma donors, regardless of hepatitis C virus (HCV) coinfection status. Also, CD56+ T cell-mediated HIV-1-specific antibody-dependent responses were declined in men who have sex with men with HIV-1 infection over 3 years. Finally, we showed that matrix metalloprotease (MMP) inhibitor GM6001 could partially restored antibody-dependent CD56+ T cell responses of chronic HIV-1-infected subjects.

CONCLUSIONS
Our results suggested that CD56+ T cells could mediate ADCC responses and the responses were impaired in chronic HIV-1 infection.

Fan|Xueying|X| Zhu|Liyan|L| Liang|Hua|H| Xie|Zhe|Z| Huang|Xiangbo|X| Wang|Shuo|S| Shen|Tao|T|

CD56+ T
ADCC
CD16 cross-linking
Chronic HIV infection
MMP inhibitor
iNKT


Association of GWAS-supported noncoding area loci rs404860, rs3117098, and rs7775228 with asthma in Chinese Zhuang population.

Abstract:
BACKGROUND
Asthma is a complicated and polygenic inheritance disease, and its prevalence increases worldwide. Recent genome-wide association studies (GWASs) identified a significant association of single nucleotide polymorphism with asthma in the Japanese population. This study aimed to examine the association of GWAS-supported noncoding area loci, namely rs404860, rs3117098, and rs7775228, with asthma in Chinese Zhuang population.

METHODS
A case-control study involving 223 individuals, comprising 123 patients with asthma and 100 healthy controls, was conducted. Genotypes were determined by polymerase chain reaction (PCR)/ligase detection reaction assay. The association between gene polymorphisms and asthma risk was calculated by logistic regression analysis using different genetic models through comparisons of alleles (A vs a), homozygote genotypes (AA vs aa), heterozygote genotypes (Aa vs aa), dominant models (AA+Aa vs aa), and recessive models (AA vs. Aa+aa).

RESULTS
The distribution of the genotype frequency of rs3117098 was statistically different between the case and control groups. For rs3117098, significant associations were observed through comparisons of alleles (OR: 1.832, 95% CI: 1.048-3.204, P = .034) and dominant models (OR: 2.065, 95% CI: 1.001-4.260, P = .050). The statistical analysis showed no significant difference for loci rs404860 and rs7775228 between patients with asthma and controls.

CONCLUSION
rs3117098 may be the risk factor for asthma in Chinese Zhuang population.

GWAS-supported
noncoding area loci
asthma
Zhuang population


The weakly electric fish, Apteronotus albifrons, actively avoids experimentally induced hypoxia.

Abstract: Anthropogenic environmental degradation has led to an increase in the frequency and prevalence of aquatic hypoxia (low dissolved oxygen concentration, DO), which may affect habitat quality for water-breathing fishes. The weakly electric black ghost knifefish, Apteronotus albifrons, is typically found in well-oxygenated freshwater habitats in South America. Using a shuttle-box design, we exposed juvenile A. albifrons to a stepwise decline in DO from normoxia (> 95% air saturation) to extreme hypoxia (10% air saturation) in one compartment and chronic normoxia in the other. On average, A. albifrons actively avoided the hypoxic compartment below 22% air saturation. Hypoxia avoidance was correlated with upregulated swimming activity. Following avoidance, fish regularly ventured back briefly into deep hypoxia. Hypoxia did not affect the frequency of their electric organ discharges. Our results show that A. albifrons is able to sense hypoxia at non-lethal levels and uses active avoidance to mitigate its adverse effects.

Dissolved oxygen
Electric organ discharge
Active sensing
Gymnotiform
Shuttle-box choice chamber


Iterative reconstruction of radially-sampled 31P bSSFP data using prior information from 1H MRI.

Abstract: The purpose of this study is to improve direct phosphorus (31P) MR imaging. Therefore, 3D density-adapted radially-sampled balanced steady-state free precession (bSSFP) sequences were developed and an iterative approach exploiting additional anatomical information from hydrogen (1H) data was evaluated. Three healthy volunteers were examined at B0=7T in order to obtain the spatial distribution of the phosphocreatine (PCr) intensities in the human calf muscle with a nominal isotropic resolution of 10mm in an acquisition time of 10min. Three different bSSFP gradient schemes were investigated. The highest signal-to-noise ratio (SNR) was obtained for a scheme with two point-reflected density-adapted gradients. Furthermore, the conventional reconstruction based on a gridding algorithm was compared to an iterative method using an 1H MRI constraint in terms of a segmented binary mask, which comprises prior knowledge. The parameters of the iterative approach were optimized and evaluated by simulations featuring 31P MRI parameters. Thereby, partial volume effects as well as Gibbs ringing artifacts could be reduced. In conclusion, the iterative reconstruction of 31P bSSFP data using an 1H MRI constraint is appropriate for investigating regions where sharp tissue boundaries occur and leads to images that represent the real PCr distributions better than conventionally reconstructed images.

Rink|Kristian|K|
Benkhedah|Nadia|N|
Berger|Moritz C|MC|
Gnahm|Christine|C|
Behl|Nicolas G R|NG|
Lommen|Jonathan M|JM|
Stahl|Vanessa|V|
Bachert|Peter|P|
Ladd|Mark E|ME|
Nagel|Armin M|AM|

Iterative reconstruction
Prior knowledge
(31)P MRI
High-energy phosphate metabolism
Radially-sampled bSSFP


First zoeal stage of the snapping shrimps Alpheus formosus Gibbes, 1850 and Alpheus malleator Dana, 1852 (Caridea: Alpheidae), with new characters to the genus.

Abstract: The first zoeae of Alpheus formosus Gibbes, 1850 and Alpheus malleator Dana, 1852 are described and illustrated for the first time, based on laboratory-hatched larvae from parental females sampled in Vitória Island, Ubatuba, Brazil. Both species shared many characters with other species of genus Alpheus Fabricius, 1798, but they also have some exclusive characters as 10 setae on the basis of the maxilla, first maxilliped with endopod 2-segmented and exopod 4-segmented, second maxilliped with exopod 4-segmented, presence of bud only of the first pereopod, presence of anal spine and simple dorsal setae on the pleon. The zoea I of both species, nevertheless, can be separated by segmentation in the exopod of the antenna (8 in A. formosus, 6 in A. malleator); segmentation in the endopod and exopod of the third maxilliped (5 in A. formosus and 4 in A. malleator); peduncle of antennule 3-segmented in A. formosus (unsegmented or 2-segmented in other species) and presence of a medial tubercle in the proximal segment in the exopod of the antenna of A. malleator (absent in A. formosus, not reported in all other species). In this study three new characters are proposed to be analyzed in zoea of the genus Alpheus: presence of anal spine in both species (absent in Alpheus saxidomus Holthuis, 1980, but not reported in other species) and for the first time reported, presence of a tubercle in the exopod of the antenna (present only in A. malleator) and presence of simple dorsal setae on the pleon (both species), here analyzed under light and scanning electron microscopy.

Pasinatto|Karmine|K|
Mantelatto|Fernando L|FL|
Terossi|Mariana|M|

Atlantic, Decapoda, larval morphology, SEM, zoea, Crustacea


Quantification of autofluorescence imaging can accurately and objectively assess the severity of ulcerative colitis.

Abstract:
BACKGROUND AND AIMS
No endoscopic examination has been able to evaluate severity of ulcerative colitis (UC) by quantification. This prospective study investigated the efficacy of quantifying autofluorescence imaging (AFI) to assess the severity of UC, which captures the fluorescence emitted from intestinal tissue and then quantifies the intensity using an image-analytical software program.

MATERIALS AND METHODS
Eleven endoscopists separately evaluated 135 images of conventional endoscopy (CE) and AFI from a same lesion. A CE image corresponding to Mayo endoscopic subscore 0 or 1 was defined as being inactive. The fluorescence intensities of AFI were quantified using an image-analytical software program (F index; FI). Active inflammation was defined when Matts' histological grade was 2 or more. A cut-off value of the FI for active inflammation was determined using a receiver operating characteristic (ROC) analysis. The inter-observer consistency was calculated by unweighted kappa statistics.

RESULTS
The correlation coefficient for the FI was inversely related to the histological severity (r = -0.558, p < 0.0001). The ROC analysis showed that the optimal cut-off value for the FI for active inflammation was 0.906. The average diagnostic accuracy of the FI was significantly higher than those of the CE (84.7 vs 78.5 %, p < 0.01). The kappa values for the inter-observer consistency of CE and the FI were 0.60 and 0.95 in all participants, 0.53 and 0.97 in the less-experienced endoscopists group and 0.67 and 0.93 in the expert group, respectively.

CONCLUSIONS
The quantified AFI is considered to be an accurate and objective indicator that can be used to assess the activity of ulcerative colitis, particularly for less-experienced endoscopists.

Moriichi|Kentaro|K| Fujiya|Mikihiro|M| Ijiri|Masami|M| Tanaka|Kazuyuki|K| Sakatani|Aki|A| Dokoshi|Tatsuya|T| Fujibayashi|Shugo|S| Ando|Katsuyoshi|K| Nomura|Yoshiki|Y| Ueno|Nobuhiro|N| Kashima|Shin|S| Gotoh|Takuma|T| Sasajima|Junpei|J| Inaba|Yuhei|Y| Ito|Takahiro|T| Tanabe|Hiroki|H| Saitoh|Yusuke|Y| Kohgo|Yutaka|Y|

D003093:Colitis, Ulcerative
D016099:Endoscopy, Gastrointestinal
D005260:Female
D006801:Humans
D008297:Male
D008875:Middle Aged
D015588:Observer Variation
D061848:Optical Imaging
D011446:Prospective Studies
D012720:Severity of Illness Index

Autofluorescence imaging
Ulcerative colitis
Endoscopy


Pulmonary Atresia With Ventriculocoronary Arterial Connections and a Large Conoventricular Septal Defect.

Abstract: Ventriculocoronary arterial connections are typically found in patients with pulmonary atresia with an intact ventricular septum. This report describes a case of ventriculocoronary arterial connections in a patient with pulmonary atresia with a ventricular septal defect. Our case supports recent data suggesting a primary coronary artery developmental anomaly in pulmonary atresia. (Level of Difficulty: Advanced.).

Jakamy|Réda|R|
Séguéla|Pierre-Emmanuel|PE|
Valdeolmillos|Estibaliz|E|
Mostefa Kara|Mansour|M|
Mouton|Jean-Baptiste|JB|
Iriart|Xavier|X|
Thambo|Jean-Benoit|JB|

PA-IVS, pulmonary atresia with intact ventricular septum

PA-VSD, pulmonary atresia with ventricular septal defect

VCAC, ventriculocoronary arterial connection


Population-level variation in neonicotinoid tolerance in nymphs of the Heptageniidae.

Abstract: Anthropogenic activities can have significant ecological and evolutionary consequences on populations and communities. In the United States, neonicotinoid insecticides are widespread across the agricultural Midwest and frequently detected in stream systems. Their effect on Heptageniidae mayflies is a major concern because they are highly sensitive to neonicotinoids and have some of the lowest reported tolerance values of any organism. Our objective was to evaluate population-level variation in neonicotinoid sensitivity. We did so by conducting 96 h half maximal effective concentration (EC5096-h) tests for the neonicotinoids clothianidin and thiamethoxam on populations of Stenacron, Stenonema, and Maccaffertium mayflies and testing for associations with agricultural landcover. Additionally, we collected water samples to assess temporal patterns of neonicotinoid presence in stream habitats. We found variation in neonicotinoid tolerance with EC50 values ranging from 4.9 μg/L to 32 μg/L and 19.8 μg/L to 86.5 μg/L for clothianidin and thiamethoxam, respectively. Agricultural landcover was associated with neonicotinoid tolerance for Stenacron and thiamethoxam but not for other comparisons. Moreover, water samples demonstrated that the amount of agricultural landcover was not a strong predictor of neonicotinoids presence in streams. Our data suggest that populations of Heptageniidae mayflies can vary substantially in neonicotinoid tolerance. Population-level variation should be considered in toxicity assessments and presents the potential for evolved tolerance.

Rackliffe|D Riley|DR|
Hoverman|Jason T|JT|

Neonicotinoid
Mayfly
EC50
Aquatic toxicity
Pesticide resistance


Economic burden of comorbid chronic kidney disease and diabetes.

Abstract:
OBJECTIVE
To estimate real-world healthcare utilization and expenditures across the spectrum of chronic kidney disease (CKD), as determined by estimated glomerular filtration rate (eGFR) categories in patients with diabetes.

METHODS
This study employed a retrospective cohort study design using the Truven Healthcare and Claims Dataset from 2009-2012. Index date was defined as the first eGFR value during a continuous enrollment period of 24 months. Cohorts of patients were stratified by Kidney Disease: Improving Global Outcomes CKD stage based on eGFR (stages 1: ≥90 mL/min/1.73 m2; 2: 60-89; 3A: 45-59; 3B: 30-44; 4: 15-29; 5: <15). Healthcare expenditures (total patient and payer paid claims) and utilization (number of claims or visits) were estimated 12-months post-index date using generalized linear modeling and negative binomial modeling, respectively, after adjusting for baseline characteristics.

RESULTS
Of 130,098 patients with an index eGFR value and 24-months continuous enrolment, 64,521 (49.59%) were in stage 1 CKD, 47,816 (36.75%) were in stage 2, 13,377 (10.28%) were in stage 3A, 3,217 (2.47%) were in stage 3B, 898 (0.69%) were in stage 4, and 269 (0.21%) were in stage 5. Patients in stages 3A, 3B, and 4 CKD had 1.32 (95% CI = 1.22-1.43), 1.59 (95% CI = 1.41-1.80), and 2.65 (95% CI = 2.23-3.14) times higher rates of diabetes-associated inpatient visits, respectively, compared with stage 1 CKD patients. Patients in stages 3A, 3B, and 4 CKD had increased incremental total annual healthcare expenditures of $1,732 (95% CI = $1,109-$2,356), $2,632 (95% CI = $1,647-$3,619), and $6,949 (95% CI = $5,466-$8,432), respectively, compared with stage 1 CKD patients.

LIMITATIONS
The claims data were generated for billing and reimbursement, not for research purposes.

CONCLUSIONS
These real-world data suggest an incremental and significant increase in economic burden in diabetes as kidney function declines, starting with moderate (stage 3A) CKD.

McQueen|R Brett|RB|
Farahbakhshian|Sepehr|S|
Bell|Kelly F|KF|
Nair|Kavita V|KV|
Saseen|Joseph J|JJ|

D000367:Age Factors
D000368:Aged
D003920:Diabetes Mellitus
D005260:Female
D005919:Glomerular Filtration Rate
D006442:Glycated Hemoglobin A
D005102:Health Expenditures
D006801:Humans
D007345:Insurance Claim Review
D008297:Male
D008875:Middle Aged
D017059:Models, Econometric
D051436:Renal Insufficiency, Chronic
D012189:Retrospective Studies
D012720:Severity of Illness Index
D012737:Sex Factors
D012959:Socioeconomic Factors

Economic burden
chronic kidney disease
diabetes


Incidence and spontaneous clearance of hepatitis C virus (HCV) in people who inject drugs at the Stockholm Needle Exchange-Importance for HCV elimination.

Abstract: The major transmission route for hepatitis C virus (HCV) is through sharing of unsterile injection equipment among people who inject drugs (PWID). The WHO strategy for HCV elimination by 2030 proposes increased efforts to treat PWID populations that drive the HCV epidemic. Among participants in the Stockholm needle exchange programme (NEP), the HCV prevalence is 60%. We aimed to study HCV incidence, spontaneous HCV clearance rate, and predictors associated with new HCV infections and reinfections in NEP participants. All 2320 patients enrolled in the programme between 8 April 2013 and 23 September 2016 were tested for HCV at baseline, and responded to a questionnaire regarding sociodemographic data and injection risk behaviour. Tests for HCV were repeated at an interval of 3-6 months. The anti-HCV prevalence in the NEP participants at baseline was 77%, and the prevalence of HCV RNA was 57%. 24% of the anti-HCV positive were HCV RNA negative with a spontaneously cleared HCV infection. The overall HCV incidence rate was 22/100 PY. The HCV incidence rate in the HCV naive group was 26/100 PY, and in the spontaneously cleared group 19/100. Although there were no significant differences in becoming HCV infected between the two groups (31% vs 29%), the rate of spontaneous HCV clearance was significantly lower in the HCV naive group, 20% vs 44%, (P < 0.05). A high HCV incidence rate was noted among the PWID indicating that treatment needs to be scaled up in conjunction with harm reduction measures to achieve HCV elimination goals set by WHO. This includes high coverage needle exchange programmes and effective addiction treatment for substance users, including opiate substitution treatment.

incidence
hepatitis C
PWID
needle exchange programmes
reinfection
harm reduction


Bacterial profiling in brine samples of the Emalahleni Water Reclamation Plant, South Africa, using 454-pyrosequencing method.

Abstract: A metagenomic approach was applied using 454-pyrosequencing data analysis for the profiling of bacterial communities in the brine samples of the water reclamation plant. Some physicochemical characteristics of brine samples were also determined using standard methods. Samples ranged from being lightly alkaline to highly alkaline (pH 7.40-10.91) throughout the various treatment stages, with the salinity ranging from 1.62 to 4.53 g L(-1) and dissolved oxygen concentrations ranging from 7.47 to 9.12 mg L(-1). Phenotypic switching was found to occur due to these physicochemical parameters. Microbial diversities increased from those present in Stage I reactor (six taxonomic groups) to those in Reverse Osmosis (RO) stage I (17 taxonomic groups), whereas in the second phase of the treatment, it increased in Stage II clarifier (14 taxonomic groups) followed by a decrease in RO stage II (seven taxonomic groups). Overall, seven phyla were detected, apart from many bacterial sequences that were unclassified at the phylum level. The most dominant phylum found was Proteobacteria accounting for 59% of the total sequences. A blastn sequence similarity search showed that the majority of the sequences (56%) were homologous to the uncultured bacterial species, underlining the vast untapped bacterial diversity.

Sekar|Sudharshan|S|
Zintchem|Armand A E A|AA|
Keshri|Jitendra|J|
Kamika|Ilunga|I|
Momba|Maggy N B|MN|

brine
acid mine drainage
halophilic bacteria


The desire for children among adult survivors of childhood cancer: Psychometric evaluation of a cancer-specific questionnaire and relations with sociodemographic and psychological characteristics.

Abstract:
OBJECTIVE
Long-term childhood cancer survivors (CCS) are less likely to become parents than their peers of the same age. Previous research has suggested that besides fertility, this outcome is shaped by psychosocial factors such as emotional motives toward having a child. Drawing from a sample of CCS with survival times >25 years, we present the validation of a questionnaire assessing cancer-specific reproductive motives and concerns.

METHODS
We evaluated the cancer-specific version of the Leipzig Questionnaire of Motives to have a Child (LKM-C) in a register-based sample of adult CCS (N = 632, 31% had children, 44.5% women). We conducted a confirmatory factor analysis and tested associations with sociodemographic characteristics and psychological symptoms (PHQ-9, GAD-2).

RESULTS
The questionnaire showed good item discrimination parameters and reliability (α = 0.86). The two-factorial structure was confirmed with the independent scales "return to normalcy" and "illness-related worries (child's/own health)." On average, CCS reported more motives in favor of a child than worries (P < .001; d = 1.12). Favorable attitudes were associated with the presence of a partnership and children, stronger current desire for a child, and fewer depressive symptoms. Worries were associated with an unfulfilled desire to have a child and elevated levels of depression and anxiety symptoms.

CONCLUSIONS
The LKM-C offers a brief measure of parenthood motivations in long-term CCS. Having a child signifies return to normalcy, health, fulfillment of life perspectives, and enrichment of the partnership. Less intense worries included illnesses of the child and concerns regarding one's own health. The questionnaire could inform follow-up care, psychotherapy, and fertility treatments.

Ernst|Mareike|M|0000-0003-4952-9717
Brähler|Elmar|E|
Wild|Philipp S|PS|
Faber|Jörg|J|
Merzenich|Hiltrud|H|
Beutel|Manfred E|ME|

desire for children
cancer
childhood cancer survivors
parenthood
family planning
oncology
survivorship


Activity of Different Antistaphylococcal Therapies, Alone or Combined, in a Rat Model of Methicillin-Resistant Staphylococcus epidermidis Osteitis without Implant.

Abstract: We developed a rat model of methicillin-resistant Staphylococcus epidermidis (MRSE) osteitis without implant to compare the efficacy of vancomycin, linezolid, daptomycin, ceftaroline, and rifampin either alone or in association with rifampin. A clinical strain of MRSE was inoculated into the proximal tibia. Following a 1-week infection period, rats received either no treatment or 3, 7, or 14 days of human-equivalent antibiotic regimen. Quantitative bone cultures were performed throughout the 14-day period. The mean ± SD quantity of staphylococci in the bone after a 1-week infection period was 4.5 ± 1.0 log10 CFU/g bone, with this bacterial load remaining stable after 3 weeks of infection (4.9 ± 1.4 log10 CFU/g bone). Vancomycin monotherapy was the most slowly bactericidal treatment, whereas ceftaroline monotherapy was the most rapidly bactericidal treatment. The addition of rifampin significantly increased the bacterial reduction for vancomycin, linezolid, and daptomycin. All tibias were sterilized after 2 weeks of treatment except for animals receiving vancomycin or daptomycin alone (66.6% and 50% of sterilization, respectively). These results show that ceftaroline and linezolid alone remain good options in the treatment of MRSE osteitis without implant. The combination with rifampin increases the antibiotic effect of vancomycin and daptomycin lines.

Albac|S|S| Labrousse|D|D| Hayez|D|D| Anzala|N|N| Bonnot|D|D| Chavanet|P|P| Aslangul|E|E| Croisier|D|D|0000-0002-8744-5832

osteitis
MRSE
preclinical drug studies
rifampin combination


Inconsistency in the strength testing of dental resin-based composites among researchers.

Abstract:
UNLABELLED
The aims of this paper were to review the current strength testing methods of the dental resin-based composites (RBCs) and to explore the inconsistencies with regard to strength testing among researchers. Data selection/extraction: An outline of the most relevant aspects of RBCs was created, and a subsequent literature search for articles published during last four decades (1970-2010) was conducted using the databases, namely PubMed, Science Direct and ISI Web of Knowledge.

CONCLUSION
The literature review highlighted a lack of consensus among researchers regarding the reliability of ISO recommended three-point flexure strength testing method. Several investigators have used Weibull statistics for the analysis of RBCs strength data, however their applicability might be questioned as many RBCs contain greater resin content and may exhibit sufficient viscous deformation prior to brittle failure. In addition, variability in the selection of cross-head speed and mould material for strength testing was evident which may lead to variation in the strength data and render the interpretation difficult among researchers.

Strength
Deformation rate
Mould variability
Resin composite
Weibull modulus


Microsurgical Resection of Hybrid Nerve Sheath Tumor Involving the Orbit and Lateral Wall of the Cavernous Sinus: 2-Dimensional Operative Video.

Abstract: Surgical removal of the tumor involving both the orbital and cavernous sinus remains challenging. Hybrid nerve sheath tumors (HNSTs) are defined as benign peripheral nerve sheath tumors with combined features of more than one type of benign peripheral nerve sheath tumors, including schwannoma, neurofibroma, and perineurinoma.1 They rarely arise from the orbit.1-3 This video shows the microsurgical resection of HNST involving both the orbit and lateral wall of the cavernous sinus. A 43-yr-old woman presented with 1-yr history of a slowly growing painless mass in her left medial eyelid. Neuroimaging examinations demonstrated a multilobulated and well-demarcated mass with a heterogeneous enhancement located in the extraconal region, just above the levator muscle, and extending from the eyelid to the middle fossa through the superior orbital fissure. Based on the neuroimaging features, we diagnosed it as trigeminal schwannoma involving the orbit and lateral wall of the cavernous sinus preoperatively. We performed left frontotemporal craniotomy with superolateral orbitotomy to gain access to the tumor. The tumor was grayish yellow and relatively firm. No intact nerve fibers of the frontal and ophthalmic nerves could be identified, making the diagnosis of the tumor originating from both nerves. Finally, we completely resected the tumor, which was confirmed by postoperative magnetic resonance images. Her postoperative course was uneventful, except for transient diplopia and expected left forehead hypesthesia. The pathology returned to HNST containing schwannoma and neurofibroma with no malignancy. The patient consented to the procedure prior to the surgery. And, the patient consented to the publication of their image.

Hybrid nerve sheath tumor
Orbit
Cavernous sinus
Orbitotomy
Pterional approach


What is the minimal dose of cognitive behavior therapy for psychosis? An approximation using repeated assessments over 45 sessions.

Abstract:
BACKGROUND
The general efficacy of cognitive behavior therapy for psychosis (CBTp) is well established. Although guidelines recommend that CBTp should be offered over a minimum of 16 sessions, the minimal number of sessions required to achieve significant changes in psychopathology has not been systematically investigated. Empirically informed knowledge of the minimal and optimal dose of CBTp is relevant in terms of dissemination and cost-effectiveness.

METHODS
We approached the question of what constitutes an appropriate dose by investigating the dose (duration of CBTp)×response (symptomatic improvement) relationship for positive symptoms, negative symptoms and depression. Patients with psychotic disorders (n=58) were assessed over the course of 45 sessions of CBTp in a clinical practice setting. At baseline and after session 5, 15, 25, and 45, general psychopathology, psychotic symptoms, symptom distress and coping were assessed with self-report questionnaires. Additionally, individually defined target symptoms and coping were assessed after each session.

RESULTS
Significant symptom improvement and reduction of symptom distress took place by session 15, and stayed fairly stable thereafter. The frequency of positive and negative symptoms reached a minimum by session 25.

CONCLUSIONS
Our findings support recommendations to provide CBTp over a minimum of 16 sessions and indicate that these recommendations are generalizable to clinical practice settings. However, the findings also imply that 25 sessions are the more appropriate dose. This study contributes to an empirically informed discussion on the minimal and optimal dose of CBTp. It also provides a basis for planning randomized trials comparing briefer and longer versions of CBTp.

Lincoln|T M|TM|
Jung|E|E|
Wiesjahn|M|M|
Schlier|B|B|

Dissemination
CBT
Effectiveness
Mechanisms of change
Treatment duration
Treatment guidelines


The effect of zinc supplementation on pregnancy outcome: a randomized controlled trial.

Abstract:
OBJECTIVES
This study aimed to evaluate the impact of prenatal zinc supplementation on pregnancy outcomes.

METHODS
A randomized controlled trial with equal randomization (1:1) was conducted on 540 pregnant women in Rasht, Iran from January 2010 to January 2012. Participants were randomly assigned to receive a daily supplement including 400-µg folic acid and 30-mg ferrous sulfate, with or without 15-mg zinc sulfate from the 16th week of gestation until delivery.

RESULTS
Mean difference of birth weight between the two groups was not significantly different (3262 ± 390 g in the zinc, 3272 ± 403 g in the no-zinc groups) (p = 0.780). There were no significant differences between the two groups in terms of means of head circumference (p = 0.999), length (p = 0.848), and gestational age at birth (p = 0.057) incidences of low birth weight (p = 0.863), macrosomia (p = 0.642), and the Apgar score >7 at 5 min (p = 0.999), incidences of preterm delivery (p = 0.999), pre-eclampsia (p = 0.835), premature rupture of membranes (p = 0.630), and spontaneous abortion (p = 0.772). Abruption of placenta, amnionitis, stillbirth, and intrauterine death were not observed.

CONCLUSION
Based on our findings, 15-mg zinc supplementation daily from 16 weeks of pregnancy until delivery cannot improve pregnancy outcomes.

Zahiri Sorouri|Ziba|Z|
Sadeghi|Hossein|H|
Pourmarzi|Davoud|D|

zinc supplementation
Birth weight
maternal outcome
neonatal outcome


Imaging Posture Veils Neural Signals.

Abstract: Whereas modern brain imaging often demands holding body positions incongruent with everyday life, posture governs both neural activity and cognitive performance. Humans commonly perform while upright; yet, many neuroimaging methodologies require participants to remain motionless and adhere to non-ecological comportments within a confined space. This inconsistency between ecological postures and imaging constraints undermines the transferability and generalizability of many a neuroimaging assay. Here we highlight the influence of posture on brain function and behavior. Specifically, we challenge the tacit assumption that brain processes and cognitive performance are comparable across a spectrum of positions. We provide an integrative synthesis regarding the increasingly prominent influence of imaging postures on autonomic function, mental capacity, sensory thresholds, and neural activity. Arguing that neuroimagers and cognitive scientists could benefit from considering the influence posture wields on both general functioning and brain activity, we examine existing imaging technologies and the potential of portable and versatile imaging devices (e.g., functional near infrared spectroscopy). Finally, we discuss ways that accounting for posture may help unveil the complex brain processes of everyday cognition.

posture cognition upright neuroimaging EEG fMRI perception supine


Association of plasma levels of lipid and polychlorinated biphenyls in Iranian adult.

Abstract:
Background
Exposure to Polychlorinated biphenyls (PCBs) continues over the world through seafood consumption and indoor exposure to building materials containing PCB. This study aimed to assess the relationship between plasma level of PCB congeners and lipid profile and Body Mass Index (BMI) as well.

Methods
The study population consisted of 181 Iranian adults. Data on BMI, plasma concentration of PCB congeners and serum level of lipid profile including Triglyceride, low-density lipoproteins and high-density lipoproteins, recruited from database of a project entitled "Occupational and environmental exposure to PCBs in Iran". Multiple linear regression analysis of associations between different quartiles of PCB congeners and various lipid fractions and BMI have been conducted.

Results
A linear increase in average serum Triglyceride and low-density lipoproteins (LDL) levels of participants in first, second, third and fourth quartiles of some PCB congeners was obtained. Following adjustment for age, gender, diet and other variables, only the association between different quartiles of PCB 138, PCB 153, PCB 118 and PCB sum and TG remained statistically significant.

Conclusion
The study showed a significant positive relation between plasma PCBs concentrations and serum level of TG in the study population with normal PCBs levels.

Aminian|Omid|O| Moinfar|Zeinab|Z| Eftekhari|Sahar|S| Esser|André|A| Schettgen|Thomas|T| Felten|Michael|M| Kaifie|Andrea|A| Kraus|Thomas|T|

Polychlorinated biphenyls
Body mass index
Triglyceride
LDL
Biological sciences
Endocrinology
HDL
Health sciences
Public health
Serum lipid


Whole-exome sequencing identifies somatic mutations associated with lung cancer metastasis to the brain.

Abstract:
Background
Lung cancer is the most aggressive cancer, resulting in one-quarter of all cancer-related deaths, and its metastatic spread accounts for >70% of these deaths, especially metastasis to the brain. Metastasis-associated mutations are important biomarkers for metastasis prediction and outcome improvement.

Methods
In this study, we applied whole-exome sequencing (WES) to identify potential metastasis-related mutations in 12 paired lung cancer and brain metastasis samples.

Results
We identified 1,702 single nucleotide variants (SNVs) and 6,131 mutation events among 1,220 genes. Furthermore, we identified several lung cancer metastases associated genes (KMT2C, AHNAK2). A mean of 3.1 driver gene mutation events per tumor with the dN/dS (non-synonymous substitution rate/synonymous substitution rate) of 2.13 indicating a significant enrichment for cancer driver gene mutations. Mutation spectrum analysis found lung-brain metastasis samples have a more similar Ti/Tv (transition/transversion) profile with brain cancer in which C to T transitions are more frequent while lung cancer has more C to A transversion. We also found the most important tumor onset and metastasis pathways, such as chronic myeloid leukemia, ErbB signaling pathway, and glioma pathway. Finally, we identified a significant survival associated mutation gene ERF in both The Cancer Genome Atlas (TCGA) (P=0.01) and our dataset (P=0.012).

Conclusions
In summary, we conducted a pairwise lung-brain metastasis based exome-wide sequencing and identified some novel metastasis-related mutations which provided potential biomarkers for prognosis and targeted therapeutics.

Liu|Zhenghao|Z| Zheng|Meiguang|M| Lei|Bingxi|B| Zhou|Zhiwei|Z| Huang|Yutao|Y| Li|Wenpeng|W| Chen|Qinbiao|Q| Li|Pengcheng|P| Deng|Yuefei|Y|

somatic mutation
Whole-exome sequencing (WES)
brain metastasis
lung cancer (LC)


Maternal influences on oral and faecal microbiota maturation in neonatal calves in beef and dairy production systems.

Abstract:
BACKGROUND
The dam is considered an important source of microbes for the calf; consequently, the development of calf microbiota may vary with farming system due to differences between the contact the calf has with the dam. The objective of this study was to characterise the early changes in the composition of oral and faecal microbiota in beef and dairy calves (N = 10) using high-throughput sequencing of the 16S rRNA gene. The microbiota of calves was compared to selected anatomical niches on their dams which were likely to contribute to the vertical transfer of microbes.

RESULTS
A total of 14,125 amplicon sequence variants (ASVs) were identified and taxonomically assigned. The oral microbiota of calves and their dams were composed of more similar microbes after the first 4 weeks of life than immediately after calving. The faecal microbiota of four-week old calves was composed of microbes which were more similar to those found in the oral microbiota of calves and adult cows than the faecal microbiota of adult cows. Specific ASVs were identified in the oral microbiota of four-week old calves that were also present in cow niches at calving, whereas very few ASVs were present in the calf faecal microbiota at four-weeks of age were present in any adult cow niche at calving. These results were observed in both beef and dairy calves.

CONCLUSIONS
We did not observe any marked differences in the maturation of the oral and faecal microbiota between beef or dairy calves, despite dairy calves having very limited contact with their dam. This suggests the development of gastrointestinal microbiota in calves may not be affected by continued vertical transmission of microbes from the dam. Although the calf faecal microbiota changed over the first four-weeks of life, it was composed of microbes which were phylogenetically closer to those in the oral microbiota of calves and adult cows than the faeces of adult cows. There was little evidence of persistent microbial seeding of the calf faeces from anatomical niches on the cow at calving in either beef or dairy animals.

Microbiota
Neonates
Dairy calves
Beef calves
Gastrointestinal tract


The 1.9 Å crystal structure of the extracellular matrix protein Bap1 from Vibrio cholerae provides insights into bacterial biofilm adhesion.

Abstract: Growth of the cholera bacterium Vibrio cholerae in a biofilm community contributes to both its pathogenicity and survival in aquatic environmental niches. The major components of V. cholerae biofilms include  polysaccharide (VPS) and the extracellular matrix proteins RbmA, RbmC, and Bap1. To further elucidate the previously observed overlapping roles of Bap1 and RbmC in biofilm architecture and surface attachment, here we investigated the structural and functional properties of Bap1. Soluble expression of Bap1 was possible only after the removal of an internal 57-amino-acid-long hydrophobic insertion sequence. The crystal structure of Bap1 at 1.9 Å resolution revealed a two-domain assembly made up of an eight-bladed β-propeller interrupted by a β-prism domain. The structure also revealed metal-binding sites within canonical calcium blade motifs, which appear to have structural rather than functional roles. Contrary to results previously observed with RbmC, the Bap1 β-prism domain did not exhibit affinity for complex N-glycans, suggesting an altered role of this domain in biofilm-surface adhesion. Native polyacrylamide gel shift analysis did suggest that Bap1 exhibits lectin activity with a preference for anionic or linear polysaccharides. Our results suggest a model for V. cholerae biofilms in which Bap1 and RbmC play dominant but differing adhesive roles in biofilms, allowing bacterial attachment to diverse environmental or host surfaces.

Kaus|Katherine|K|0000-0001-9174-7588 Biester|Alison|A| Chupp|Ethan|E| Lu|Jianyi|J| Visudharomn|Charlie|C| Olson|Rich|R|0000-0002-5432-206X

D015964:Gene Expression Regulation, Bacterial

extracellular matrix protein
Vibrio cholerae
cholera
biofilm
lectin
X-ray crystallography
amyloid
glycobiology
microbial pathogenesis
virulence factor


Magnetically Guided Micromanipulation of Magnetic Microrobots for Accurate Creation of Artistic Patterns in Liquid Environment.

Abstract: In this paper, a magnetically guided micromanipulation method is proposed to accurately create artistic patterns with magnetic microrobots in a liquid environment for tissue engineering. A magnetically guided device is developed depend on symmetrical combination of square permanent magnets and array layout of soft magnetic wires, which changed the space distribution of magnetic field of conventional permanent magnet and generated powerful magnetic flux density and high magnetic field gradient. Furthermore, the morphological structure of the magnetic microrobot is flexibly adjusted via precise control of the volumetric flow rates inside the microfluidic device and the magnetic nanoparticles are taken along to enable its controllability by rapid magnetic response. And then, the spatial posture of the magnetic microrobot is contactless controlled by the magnetically guided manipulator and it is released under the influence of surface tension and gravity. Subsequently, the artistic fashions of the magnetic microrobots are precisely distributed via the dot-matrix magnetic flux density of the magnetically guided device. Finally, the experimental results herein demonstrate the accuracy and diversity of the pattern structures in the water and the developed method will be providing a new way for personalized functional scaffold construction.

micromanipulation
magnetic microrobot
tissue engineering
dot-matrix magnetic flux density
magnetic guidance


Manipulation of Subcortical and Deep Cortical Activity in the Primate Brain Using Transcranial Focused Ultrasound Stimulation.

Abstract: The causal role of an area within a neural network can be determined by interfering with its activity and measuring the impact. Many current reversible manipulation techniques have limitations preventing their application, particularly in deep areas of the primate brain. Here, we demonstrate that a focused transcranial ultrasound stimulation (TUS) protocol impacts activity even in deep brain areas: a subcortical brain structure, the amygdala (experiment 1), and a deep cortical region, the anterior cingulate cortex (ACC, experiment 2), in macaques. TUS neuromodulatory effects were measured by examining relationships between activity in each area and the rest of the brain using functional magnetic resonance imaging (fMRI). In control conditions without sonication, activity in a given area is related to activity in interconnected regions, but such relationships are reduced after sonication, specifically for the targeted areas. Dissociable and focal effects on neural activity could not be explained by auditory confounds.

Folloni|Davide|D|
Verhagen|Lennart|L|
Mars|Rogier B|RB|
Fouragnan|Elsa|E|
Constans|Charlotte|C|
Aubry|Jean-François|JF|
Rushworth|Matthew F S|MFS|
Sallet|Jérôme|J|

ultrasound
amygdala
cingulate cortex
functional connectivity
limbic
macaque monkey
neuromodulation
resting-state connectivity
transcranial stimulation


KLF5 mediates the hyper-proliferative phenotype of the intestinal epithelium in mice with intestine-specific endogenous K-RasG12D expression.

Abstract: Oncogenic K-Ras activation is a common mutational event in colorectal cancer. We previously showed that transcription factor, Krüppel-like factor 5 (KLF5), contributes to intestinal polyposis in mice with K-Ras activation. At 14 months of age, Villin-Cre/LSL-K-Ras mice developed small intestinal and colonic hyperplastic polyps while LSL-K-Ras had none. The intestinal crypts of Villin-Cre/LSL-K-Ras mice contained a higher number of mitotic figures and increased crypt heights compared to controls. The intestinal epithelium of Villin-Cre/LSL-K-Ras mice showed prolific KLF5 expression throughout and above the elongated crypts. In contrast, KLF5 expression was limited to the upper crypt region in the controls. The levels of K-Ras effectors were significantly increased in Villin-Cre/LSL-K-Ras as compared to controls. The Villin-Cre/LSL-K-Ras mice showed decreased survival upon treatment with azoxymethane (AOM) as compared to controls. Furthermore, loss of one of Klf5 alleles reduced levels of K-Ras effector proteins and prevented mortality of Villin-Cre/LSL-K-Ras mice upon AOM treatment. The Villin-Cre/LSL-K-Ras mice spontaneously develop hyperplastic intestinal polyps and display a hyper-proliferative intestinal phenotype with elongated crypts, increased numbers of mitotic figures, elevated expression of KLF5, and other pro-proliferative targets. Induction of colonic tumorigenesis with AOM is detrimental to Villin-Cre/LSL-K-Ras mice that is in part dependent of KLF5.

Nandan|Mandayam O|MO|
Bialkowska|Agnieszka B|AB|
Yang|Vincent W|VW|

KLF5
colonic tumorigenesis
KRAS
intestinal hyper-proliferation


Long term performance evaluation of small-diameter vascular grafts based on polyvinyl alcohol hydrogel and dextran and MSCs-based therapies using the ovine pre-clinical animal model.

Abstract: The functional and structural performance of a 5cm synthetic small diameter vascular graft (SDVG) produced by the copolymerization of polyvinyl alcohol hydrogel with low molecular weight dextran (PVA/Dx graft) associated to mesenchymal stem cells (MSCs)-based therapies and anticoagulant treatment with heparin, clopidogrel and warfarin was tested using the ovine model during the healing period of 24 weeks. The results were compared to the ones obtained with standard expanded polyetetrafluoroethylene grafts (ePTFE graft). Blood flow, vessel and graft diameter measurements, graft appearance and patency rate (PR), thrombus, stenosis and collateral vessel formation were evaluated by B-mode ultrasound, audio and color flow Doppler. Graft and regenerated vessels morphologic evaluation was performed by scanning electronic microscopy (SEM), histopathological and immunohistochemical analysis. All PVA/Dx grafts could maintain a similar or higher PR and systolic/diastolic laminar blood flow velocities were similar to ePTFE grafts. CD14 (macrophages) and α-actin (smooth muscle) staining presented similar results in PVA/Dx/MSCs and ePTFE graft groups. Fibrosis layer was lower and endothelial cells were only detected at graft-artery transitions where it was added the MSCs. In conclusion, PVA/Dx graft can be an excellent scaffold candidate for vascular reconstruction, including clinic mechanically challenging applications, such as SDVGs, especially when associated to MSCs-based therapies to promote higher endothelialization and lower fibrosis of the vascular prosthesis, but also higher PR values.

Alexandre|Nuno|N|
Amorim|Irina|I|
Caseiro|Ana Rita|AR|
Pereira|Tiago|T|
Alvites|Rui|R|
Rêma|Alexandra|A|
Gonçalves|Ana|A|
Valadares|Guilherme|G|
Costa|Elísio|E|
Santos-Silva|Alice|A|
Rodrigues|Miguel|M|
Lopes|Maria Ascensão|MA|
Almeida|André|A|
Santos|José Domingos|JD|
Maurício|Ana Colette|AC|
Luís|Ana Lúcia|AL|

Dextran
Synthetic small diameter vascular graft
PVA
Mesenchymal stem cells
Ovine model


Steroids in pediatric acute respiratory distress syndrome.

Abstract: Acute respiratory distress syndrome (ARDS) is a complex entity with high potential for harm and healthcare resource utilization. Despite multiple clinical advances in its ventilatory management, ARDS continues to be one of the most challenging disease processes for intensivists. It continues to lack a direct, proven and desperately needed effective therapeutic intervention. Given their biologic rationale, corticosteroids have been widely used by clinicians and considered useful by many in the management of ARDS since its first description. Adult data is abundant, yet contradictory. Controversy remains regarding the routine use of corticosteroids in ARDS. Therefore, widespread evidence-based recommendations for this heterogeneous disease process have not been made. In this article, our aim was to provide a summary of available evidence for the role of steroids in the treatment of ARDS, while giving special focus on pediatric ARDS (PARDS).

Monteverde-Fernández|Nicolás|N| Cristiani|Federico|F| McArthur|Jenniffer|J| González-Dambrauskas|Sebastián|S|

Acute lung injury, acute respiratory distress syndrome (ARDS)

pediatric acute respiratory distress syndrome (PARDS)


The sex ratio at birth in South Africa may be a sentinel health indicator.

Abstract:
INTRODUCTION
The sex ratio at birth is commonly expressed as M/T, denoting male births divided by total births. Males are almost invariably born slightly in excess. Stress and negative socioeconomic conditions lower M/T and this has been mooted as a possible reason for the observed low M/T for Black births worldwide. South Africa is experiencing a period of economic prosperity. This study was carried out in order to ascertain whether improving conditions in South Africa as measured by available health indicators, were associated with a rise in M/T in this country.

METHODS
Annual male and female births were obtained from Statistics South Africa along with key health indicators: total fertility rate, life expectancy, infant mortality and under 5year mortality, for 2003-2014.

RESULTS
There were a total of 12,409,437 births (M/T 0.5035, 95% CI 0.5032-0.5037). There was a rise in M/T over the initial period studied (2003-2010) with a plateau thereafter. The rise over the entire period studied was significant (Chi for linear trend=30.3, p<0.0001). M/T was significantly positively correlated with life expectancy and significantly negatively correlated with infant mortality, under 5year mortality and total fertility rate.

DISCUSSION
It has been mooted that the lower M/T observed in Blacks may be stress-related. The observed rise in M/T associated with health improvements in South Africa support this contention. Moreover, this study suggests that M/T may serve as a sentinel health indicator, and may not only highlight adverse conditions through its decline, but also improvements in overall conditions with its rise.

D003906:Developing Countries
D005260:Female
D006304:Health Status
D006801:Humans
D007231:Infant, Newborn
D008297:Male
D012744:Sex Ratio
D012959:Socioeconomic Factors
D013019:South Africa

Sex ratio
South Africa
Birth rate/*trends
Infant, newborn


Berberine ameliorates ovariectomy-induced anxiety-like behaviors by enrichment in equol generating gut microbiota.

Abstract: The gut microbiota is recognized as a promising therapeutic target for anxiety. Berberine (BBR) has shown efficacy in the treatment of diseases such as postmenopausal osteoporosis, obesity, and type 2 diabetes through regulating the gut microbiota. However, the effects of BBR on postmenopausal anxiety are still unclear. The purpose of the study is to test whether BBR ameliorates anxiety by modulating intestinal microbiota under estrogen-deficient conditions. Experimental anxiety was established in specific pathogen-free (SPF) ovariectomized (OVX) rats, which were then treated with BBR for 4 weeks before undergoing behavioral tests. Open field and elevated plus maze tests demonstrated that BBR treatment significantly ameliorated anxiety-like behaviors of OVX rats compared with vehicle-treated counterparts. Moreover, as demonstrated by 16S rRNA sequencing and liquid chromatography/mass spectrometry (LC/MS) analysis, BBR-treated OVX rats harbored a higher abundance of beneficial gut microbes, such as Bacteroides, Bifidobacterium, Lactobacillus, and Akkermansia, and exhibited increased equol generation. Notably, gavage feeding of BBR had no significant anti-anxiety effects on germ-free (GF) rats that underwent ovariectomy, whereas GF rats transplanted with fecal microbiota from SPF rats substantially phenocopied the donor rats in terms of anxiety-like symptoms and isoflavone levels. This study indicates that the gut microbiota is critical in the treatment of ovariectomy-aggravated anxiety, and that BBR modulation of the gut microbiota is a promising therapeutic strategy for treating postmenopausal symptoms of anxiety.

Fang|Yuan|Y| Zhang|Jindong|J| Zhu|Shiwei|S| He|Meibo|M| Ma|Shurong|S| Jia|Qiong|Q| Sun|Qinghua|Q| Song|Lijin|L| Wang|Yan|Y| Duan|Liping|L|

Demethyleneberberine (PubChem CID: 363209)


Catestatin is involved in neuropathic pain mediated by purinergic receptor P2X4 in the spinal microglia of rats.

Abstract: Neuropathic pain is defined as a type of chronic pathological pain that often results from nerve damage or disease. The purinergic receptor P2X4 is mainly expressed on the cell surface of spinal dorsal horn microglia and is known to be involved in neuropathic pain. Catestatin (CST) is an endogenous peptide derived from chromogranin A. Here, we attempted to identify how CST function in neuropathic pain. Rat model of chronic constriction injury (CCI) was used and experimental results indicated that mechanical and thermal pain sensitivities were significantly increased in CCI rats. The group of CCI rats that received intrathecal CST injection (CCI + CST) exhibited higher P2X4 mRNA and protein levels compared with the CCI group. Moreover, the phosphorylation level of extracellular signal-regulated kinase 1/2 (ERK1/2) in the CCI + CST group was higher than in the CCI group. This suggested that CST might aggravate neuropathic pain by enhancing P2X4 receptor expression in spinal microglia, and that the ERK1/2 pathway might be key in the development of neuropathic pain.

Deng|Zeyu|Z| Li|Congcong|C| Liu|Chenglong|C| Du|Errong|E| Xu|Changshui|C|

D019950:Mitogen-Activated Protein Kinase 1

D048052:Mitogen-Activated Protein Kinase 3

Extracellular signal-regulated kinase 1/2


Rhabdomyolysis after bariatric surgery: a multicenter, prospective study on incidence, risk factors, and therapeutic strategy in a cohort from South Italy.

Abstract:
BACKGROUND
At present, prospectively collected data on rhabdomyolysis (RML) after bariatric surgery are limited.

OBJECTIVES
To evaluate the incidence, risk factors, and therapeutic strategy of RML in different bariatric procedures.

SETTING
University hospitals, Italy.

METHODS
Obese patients were prospectively enrolled. Preoperative demographic characteristics and clinical data, as well as type of anesthesia and type and total duration of surgery, were recorded as potential risk factors for RML. RML was defined as postoperative creatine kinase (CK)>1000 U/L. Incidence, possible risk factors, and therapeutic outcome of RML were assessed and compared with comparative groups.

RESULTS
Four hundred eighty obese patients were included in the study. After surgery, RML was diagnosed in 62 (12.9%) patients. Muscular pain was present in 12 patients (19.3%). In RML patients, mean CK value was 1346±2132.5 U/L (range 1191-37,400). Only duration of surgery was identified as an independent risk factor for RML (P<.001). The best cutoff value of time as a predictor was 230 minutes. Aggressive therapy with fluids and diuretics started within 24 hours after surgery was more effective in relieving RML and muscle pain than a comparative retrospective group with a delayed diagnosis and therapy.

CONCLUSION
After bariatric surgery, the risk of RML increases, especially when the duration of surgery is>230 minutes. CK testing should be performed in all patients after bariatric surgery to make an early diagnosis and properly start fluids and diuretics.

Tolone|Salvatore|S| Pilone|Vincenzo|V| Musella|Mario|M| Rossetti|Gianluca|G| Milone|Marco|M| Fei|Landino|L| Forestieri|Pietro|P| Docimo|Ludovico|L|

Rhabdomyolysis
Bariatric Surgery
Obesity