Effects of sodium-glucose cotransporter 2 inhibitors on serum uric acid in patients with type 2 diabetes mellitus: A systematic review and network meta-analysis.

Abstract:
AIMS
The present study aims to determine the effects of sodium-glucose cotransporter 2 (SGLT-2) inhibitors on the serum uric acid (SUA) levels of patients with type 2 diabetes mellitus (T2DM) in Asia.

METHODS
PubMed, CENTRAL, Embase and Cochrane Library databases were searched for randomized controlled trials of SGLT-2 inhibitors in patients with T2DM up to 15 July 2021, without language or date restrictions.

RESULTS
In total, 19 high-quality studies (4218 participants) were included in the present network meta-analysis. All of the included SGLT-2 inhibitors (empagliflozin, dapagliflozin, canagliflozin, ipragliflozin, luseogliflozin and tofogliflozin) significantly decreased SUA levels compared with those of the control [total standard mean difference -0.965, 95% CI (-1.029, -0.901), p = .000, I2  = 98.7%] in patients with T2DM. Subgroup analysis and meta-regression showed that the combined analysis of different inhibitors might lead to heterogeneity of the results. Therefore, among the SGLT-2 inhibitors, the results of the subsequent network meta-analysis revealed that luseogliflozin and dapagliflozin ranked the highest in terms of lowering SUA levels among the SGLT-2 inhibitors. Moreover, the network meta-analysis declared that luseogliflozin (1 and 10 mg) and dapagliflozin (5 mg) led to a superior reduction in SUA in patients with T2DM.

CONCLUSIONS
SGLT-2 inhibitors could significantly reduce SUA levels in patients with T2DM, particularly luseogliflozin (1 and 10 mg) and dapagliflozin (5 mg) possess the best effects. Therefore, SGLT-2 inhibitors look extremely promising as an antidiabetes treatment option in patients with T2DM with high SUA.

serum uric acid
network meta-analysis
T2DM
SGLT-2 inhibitor


Uses of Arterial Stiffness in Clinical Practice.

Abstract: As far back as the ancient Egyptians and Greeks, physicians have observed and interpreted the arterial pulse to diagnose disease. In the last 20 years, advances in modern engineering have rendered quantitative pulse wave analysis widely available, reliable, and reproducible. To date, measurement of arterial stiffness has remained almost exclusively a research activity. However, ongoing technological improvements coupled with already strong and growing evidence of clinical value should facilitate integration of arterial stiffness measures into clinical practice in the near future. This brief review will highlight clinical areas where arterial stiffness measures are likely to be the most informative in clinical practice.

Wilkinson|Ian B|IB|
Mäki-Petäjä|Kaisa M|KM|
Mitchell|Gary F|GF|

D001158:Arteries
D002318:Cardiovascular Diseases
D006801:Humans
D011237:Predictive Value of Tests
D011379:Prognosis
D063177:Pulse Wave Analysis
D015203:Reproducibility of Results
D018570:Risk Assessment
D012307:Risk Factors
D059289:Vascular Stiffness

pulse wave analysis
technology
vascular stiffness


Risk factors for transmission of Ebola or Marburg virus disease: a systematic review and meta-analysis.

Abstract:
BACKGROUND
The Ebola virus disease outbreak that started in Western Africa in 2013 was unprecedented because it spread within densely populated urban environments and affected many thousands of people. As a result, previous advice and guidelines need to be critically reviewed, especially with regard to transmission risks in different contexts.

METHODS
Scientific and grey literature were searched for articles about any African filovirus. Articles were screened for information about transmission (prevalence or odds ratios especially). Data were extracted from eligible articles and summarized narratively with partial meta-analysis. Study quality was also evaluated.

RESULTS
A total of 31 reports were selected from 6552 found in the initial search. Eight papers gave numerical odds for contracting filovirus illness; 23 further articles provided supporting anecdotal observations about how transmission probably occurred for individuals. Many forms of contact (conversation, sharing a meal, sharing a bed, direct or indirect touching) were unlikely to result in disease transmission during incubation or early illness. Among household contacts who reported directly touching a case, the attack rate was 32% [95% confidence interval (CI) 26-38%]. Risk of disease transmission between household members without direct contact was low (1%; 95% CI 0-5%). Caring for a case in the community, especially until death, and participation in traditional funeral rites were strongly associated with acquiring disease, probably due to a high degree of direct physical contact with case or cadaver.

CONCLUSIONS
Transmission of filovirus is unlikely except through close contact, especially during the most severe stages of acute illness. More data are needed about the context, intimacy and timing of contact required to raise the odds of disease transmission. Risk factors specific to urban settings may need to be determined.

Brainard|Julii|J|
Hooper|Lee|L|
Pond|Katherine|K|
Edmunds|Kelly|K|
Hunter|Paul R|PR|

D000818:Animals
D003710:Demography
D004196:Disease Outbreaks
D019142:Hemorrhagic Fever, Ebola
D049674:History, 21st Century
D006801:Humans
D008379:Marburg Virus Disease
D016017:Odds Ratio
D012307:Risk Factors

risk factors
Marburg virus
systematic review
Ebola virus disease
bodily fluids


(4+3) Cycloaddition Reactions of N-Alkyl Oxidopyridinium Ions.

Abstract: N-Methylation of methyl 5-hydroxynicotinate followed by reaction with a diene in the presence of triethylamine afforded (4+3) cycloadducts in good to excellent yields. High regioselectivity was observed with 1-substituted and 1,2-disubstituted butadienes. Density functional theory calculations indicate that the cycloaddition involves concerted addition of the diene onto the oxidopyridinium ion. The process provides rapid access to bicyclic nitrogenous structures resembling natural alkaloids.

(4+3) cycloaddition
dienes
alkaloids
pyridinium ions


X-ray spectra and doses.

Abstract: Using the Monte Carlo method the x-ray spectrum produced by 150keV electrons colliding with W, Rh and Mo targets were calculated. The x-ray spectra were calculated to 20, 50, and 100cm from the focal point. In order to analyze the effect of the filter, calculations were carried out with and without filter. The spectra were used to estimate the Kerma in air, the Ambient dose equivalent, and the Personal dose equivalent. The spectra were integrated in energy to obtain the total photon fluences. Calculated spectra depend on the type of target having the continuous spectrum due to bremsstrahlung and the characteristics x-rays. The Al filter eliminates the low-energy photons; however no effect is noticed when the photon energy is larger than 40keV. The largest effect of dose reduction due to the filter was noticed to 20cm for the Kerma in air.

Rodriguez-Ibarra|Johanna Lizbeth|JL|
Hernandez-Adame|Pablo Luis|PL|
Vega-Carrillo|Hector Rene|HR|
Rivera|Teodoro|T|

X-ray
Monte Carlo
Spectrum
Kerma
Ambient dose equivalent
Personal dose equivalent


Opinions of hearing parents about the causes of hearing impairment of their children with biallelic GJB2 mutations.

Abstract: Hereditary hearing impairment (HI) caused by recessive GJB2 mutations is a frequent sensory disorder. The results of the molecular-based studies of HI are widely used in various genetic test systems. However, the ethical aspects are less described than the genetic aspects. The concerns expressed by individuals from groups with genetic risks must be included in the counseling of patients and their families. For evaluation of subjective opinions of hearing parents about the presumed causes of HI of their children, we analyze the cohort of parents having children with confirmed hereditary HI caused by biallelic recessive GJB2 mutations (in a homozygous or a compound heterozygous state). This study included 70 deaf children with HI due to mutations in the GJB2 gene and 91 questionnaires about the presumed causes of their deafness filled by their parents. Most of the parents at 78% (CI 68.4-85.4%) attributed their children's HI to "non-hereditary" causes and 22% (CI 14.7-31.6%) to "hereditary" causes (p < 0.05). Therefore, the prior opinions of the parents did not correspond to positive GJB2 genetic testing results. The subjective opinions of parents are probably partly based on family history, since respondents with deaf relatives in their pedigree more likely supposed hereditary causes for HI in their children than the respondents without deaf relatives (p < 0.001).

Solovyev|Aisen V|AV|
Dzhemileva|Lilya U|LU|
Posukh|Olga L|OL|
Barashkov|Nikolay A|NA|
Bady-Khoo|Marita S|MS|
Lobov|Semen L|SL|
Popova|Natalya Yu|NY|
Romanov|Georgii P|GP|
Sazonov|Nikolay N|NN|
Bondar|Alexander A|AA|
Morozov|Igor V|IV|
Tomsky|Mikhail I|MI|
Fedorova|Sardana A|SA|
Khusnutdinova|Elza K|EK|

Hereditary hearing impairment
Genetic testing
GJB2 gene
Opinions of the parents


Diffusion Kurtosis Imaging of Microstructural Changes in Gray Matter Nucleus in Parkinson Disease.

Abstract: Objective: To explore the microstructural damage of extrapyramidal system gray matter nuclei in Parkinson disease (PD) using diffusion kurtosis imaging (DKI). Materials and Methods: We enrolled 35 clinically confirmed PD patients and 23 healthy volunteers. All patients underwent MR examination with conventional MRI scan sequences and an additional DKI sequence. We subsequently reconstructed the DKI raw images and analyzed the data. A radiologist in our hospital collected the Mini-Mental State Examination (MMSE) score of all subjects. Results: In the PD group, the mean kurtosis and axial kurtosis level decreased in the red nucleus (RN) and thalamus; the radial kurtosis increased in the substantia nigra (SN) and globus pallidus (GP). Fractional anisotropy decreased in the putamen. The largest area under the ROC curve of mean diffusion in GP was 0.811. Most kurtosis parameters demonstrated a positive correlation with the MMSE score, while several diffusion parameters showed a negative correlation with the same. Conclusion: DKI can qualitatively distinguish PD from healthy controls; furthermore, DKI-derived parameters can quantitatively evaluate the modifications of microstructures in extrapyramidal system gray matter nucleus in PD.

Bingbing|Gao|G| Yujing|Zhou|Z| Yanwei|Miao|M| Chunbo|Dong|D| Weiwei|Wang|W| Shiyun|Tian|T| Yangyingqiu|Liu|L| Jin|Shang|S| Qingwei|Song|S| Ailian|Liu|L| Lizhi|Xie|X|

gray matter
parkinson disease
diffusion magnetic resonance imaging
extrapyramidal tracts
neurodegenerative diseases


BRG1 regulates lipid metabolism in hepatocellular carcinoma through the PIK3AP1/PI3K/AKT pathway by mediating GLMP expression.

Abstract:
BACKGROUND
Brahma-related gene 1 (BRG1) is essential for embryogenesis and cellular metabolism. A deficiency of BRG1 in vivo decreases lipid droplets, but the molecular mechanism underlying its role in lipid metabolism associated with hepatocellular carcinoma (HCC) remains unknown.

AIMS
We aimed to determine the role of BRG1 in lipid metabolism in HCC.

METHODS
We assessed the differential expression of BRG1 in HCC and adjacent non-tumorous tissues using tissue microarrays. We stained lipid droplets in HCC cells with Bodipy fluorescence and Oil Red O, and verified BRG1 binding to the promoter region of glycosylated lysosomal membrane protein (GLMP) using chromatin immunoprecipitation.

RESULTS
The expression of GLMP, a potential lipid metabolism regulator, was suppressed by BRG1 via transcriptional activity. Knockdown of BRG1 decreased lipid droplets, increased GLMP expression and altered the phosphoinositide-3-kinase adaptor protein 1 (PIK3AP1)/phosphatidylinositol-3 kinase (PI3K)/protein kinase B (AKT) pathway in HCC, which further GLMP knockdown partially restored. Thus, GLMP knockdown increased lipid droplets and differentially altered the PI3K/AKT pathway.

CONCLUSIONS
Downregulating BRG1 decreased lipid droplet deposition in HCC cells by upregulating GLMP and altering the PI3K/AKT pathway. Both BRG1 and GLMP might serve as therapeutic targets for disorders associated with dysregulated lipid metabolism, such as NAFLD and NAFLD-associated HCC.

Liu|Gao|G| Sun|Bao-Ye|BY| Sun|Jian|J| Zhou|Pei-Yun|PY| Guan|Ruo-Yu|RY| Zhou|Cheng|C| Yang|Zhang-Fu|ZF| Wang|Zhu-Tao|ZT| Zhou|Jian|J| Fan|Jia|J| Yi|Yong|Y| Qiu|Shuang-Jian|SJ|


Dual plating for fixation of humeral shaft fractures: A mechanical comparison of various combinations of plate lengths.

Abstract:
OBJECTIVE
The role of plate configuration was found inconclusive on the biomechanical effects of the plate size and hole number for dual plate constructions in humeral shaft fractures. The purpose of this study was to test the biomechanical stability of various dual plate constructions.

METHODS
Twenty-four left humeri (4th Generation Composite Humerus, Sawbones, Malmö, Sweden) with comminuted midshaft humeral fracture were used. Four groups of plate constructs were tested: laterally fixed 8-hole locking plate and screws were combined with anteriorly locking plates containing 0, 4, 6, or 8 holes in groups I, II, III, and IV, respectively. The alterations in axial, bending, and torsional angles were recorded.

RESULTS
There were no fixation failures during axial, bending, or torsional stiffness testing within the elastic behavior limits. Axial stiffness was highest in Group IV. Torsional stiffness, posterior-to-anterior bending stiffness, lateral-to-medial bending stiffness, and medial-to-lateral bending stiffness were lowest in Group I.

CONCLUSION
The similar stiffness values for the 8-to-4 hole and 8-to-6 hole plate constructions indicate that the 8-to-4 hole construction is an option in young adults, while the stiffest 8-to-8 hole combination may be an option for osteoporotic patients.

Karakasli|Ahmet|A| Basci|Onur|O| Ertem|Fatih|F| Sekik|Eyad|E| Havitcioglu|Hasan|H|

D001696:Biomechanical Phenomena
D001860:Bone Plates
D001863:Bone Screws
D005593:Fracture Fixation, Internal
D018460:Fractures, Comminuted
D006801:Humans
D006810:Humeral Fractures
D008422:Materials Testing
D011474:Prosthesis Design
D013314:Stress, Mechanical
D013548:Sweden

Dual plate
Fixation
Humeral shaft fractures


Response to dietary carbohydrates in European seabass (Dicentrarchus labrax) muscle tissue as revealed by NMR-based metabolomics.

Abstract:
INTRODUCTION
Feed optimization is a key step to the environmental and economic sustainability of aquaculture, especially for carnivorous species. Plant-derived ingredients can contribute to reduce costs and nitrogenous effluents while sparing wild fish stocks. However, the metabolic use of carbohydrates from vegetable sources by carnivorous fish is still not completely understood.

OBJECTIVES
We aimed to study the effects of diets with carbohydrates of different digestibilities, gelatinized starch (DS) and raw starch (RS), in the muscle metabolome of European seabass (Dicentrarchus labrax).

METHODS
We followed an NMR-metabolomics approach, using two sample preparation procedures, the intact muscle (HRMAS) and the aqueous muscle extracts (1H NMR), to compare the variations in muscle metabolome between the two diets.

RESULTS
In muscle, multivariate analysis revealed similar metabolome shifts for DS and RS diets, when compared with the control diet. HRMAS of intact muscle, which included both hydrophobic and hydrophilic metabolites, showed increased lipid in DS-fed fish by univariate analysis. Regardless of the nature of the starch, increased glycine and phenylalanine, and decreased proline were observed when compared to the Ctr diet. Combined univariate analysis of intact muscle and aqueous extracts indicated specific diet related changes in lipid and amino acid metabolism, consistent with increased dietary carbohydrate supplementation.

CONCLUSIONS
Due to differential sample processing, outputs differ in detail but provide complementary information. After tracing nutritional alterations by profiling fillet components, DS seems to be the most promising alternative to fishmeal-based diets in aquaculture. This approach should be reproducible for other farmed fish species and provide valuable information on nutritional and organoleptic properties of the final product.

Jarak|Ivana|I|
Tavares|Ludgero|L|
Palma|Mariana|M|
Rito|João|J|
Carvalho|Rui A|RA|
Viegas|Ivan|I|0000-0003-2589-2212

D066244:Proton Magnetic Resonance Spectroscopy

Aquaculture
Fish
Metabolism
Diet optimization
Digestible starch
Tissue extracts


Pharmacokinetics of a Sustained Release Formulation of Buprenorphine After Intramuscular and Subcutaneous Administration to American Kestrels ( Falco sparverius ).

Abstract: Previous studies have validated the clinical use of opioids with μ-receptor affinities for pain management in raptors. Buprenorphine appears to have a longer duration of action and minimal adverse effects when compared to other opioids in American kestrels ( Falco sparverius ). To determine the pharmacokinetics of a sustained release formulation of buprenorphine in kestrels, we administered a commercially available product (Buprenorphine SR-LAB; Wildlife Pharmaceuticals, Windsor, CO, USA) intramuscularly and subcutaneously to adult kestrels in a partial-crossover experimental design study. A total of 12 birds (6 males and 6 females) were assigned randomly to 3 groups of 4 birds each. A single dose of Buprenorphine SR-LAB (1.8 mg/kg) was administered intramuscularly (IM), and blood samples were collected at 0.25, 3, and 24 hours (n = 4); 1, 6, and 48 hours (n = 4); and 2, 12, and 72 hours (n = 4) after drug administration. Plasma buprenorphine concentrations were measured by tandem liquid chromatography-mass spectrometry. Pharmacokinetic parameters were determined by use of least squares linear regression and noncompartmental analysis of naïve pooled data. After 1 year, the same dose of buprenorphine was administered subcutaneously (SC) to 12 birds divided into 3 groups as previously, and blood samples were collected at the same times after drug administration. Maximum plasma buprenorphine concentration was measured at 15 minutes after IM and SC administration. Mean plasma buprenorphine concentrations were >1 ng/mL for 48 hours after IM and SC administration. The elimination half-life was 13.5 and 11.1 hours for IM and SC administration, respectively. Depending on the severity and type of pain, adjunctive therapy, and the individual response, Buprenorphine SR-LAB administered at 1.8 mg/kg IM or SC to American kestrels would require administration every 12 to 72 hours to manage pain. Further pharmacodynamic and clinical evaluations are warranted in kestrels and other raptors to establish accurate dosing recommendations.

Guzman|David Sanchez-Migallon|DS|
Knych|Heather K|HK|
Olsen|Glenn H|GH|
Paul-Murphy|Joanne R|JR|

pharmacokinetics
sustained release
buprenorphine
American kestrels
Falco sparverius
opioids
raptor
analgesia
avian


Novel serine/threonine-O-glycosylation with N-acetylneuraminic acid and 3-deoxy-D-manno-octulosonic acid by bacterial flagellin glycosyltransferases.

Abstract: Some bacterial flagellins are O-glycosylated on surface-exposed serine/threonine residues with nonulosonic acids such as pseudaminic acid, legionaminic acid and their derivatives by flagellin nonulosonic acid glycosyltransferases, also called motility-associated factors (Maf). We report here two new glycosidic linkages previously unknown in any organism, serine/threonine-O-linked N-acetylneuraminic acid (Ser/Thr-O-Neu5Ac) and serine/threonine-O-linked 3-deoxy-D-manno-octulosonic acid or keto-deoxyoctulosonate (Ser/Thr-O-KDO), both catalyzed by Geobacillus kaustophilus Maf and Clostridium botulinum Maf. We identified these novel glycosidic linkages in recombinant G. kaustophilus and C. botulinum flagellins that were coexpressed with their cognate recombinant Maf protein in Escherichia coli strains producing the appropriate nucleotide sugar glycosyl donor. Our finding that both G. kaustophilus Maf (putative flagellin sialyltransferase) and C. botulinum Maf (putative flagellin legionaminic acid transferase) catalyzed Neu5Ac and KDO transfer on to flagellin indicates that Maf glycosyltransferases display donor substrate promiscuity. Maf glycosyltransferases have the potential to radically expand the scope of neoglycopeptide synthesis and posttranslational protein engineering.

Khairnar|Aasawari|A|
Sunsunwal|Sonali|S|
Babu|Ponnusamy|P|
Ramya|T N C|TNC|

flagellin O-glycosylation Maf Neu5Ac KDO


Fibular Strut Graft for Revisional Tibiotalocalcaneal Arthrodesis.

Abstract:
Tibiotalocalcaneal arthrodesis with an intramedullary nail is a procedure reserved for patients who have conditions affecting the ankle joint and subtalar joint. The most common complications include nonunion, malunion, delayed union, infection, periprosthetic fracture, hardware failure, lateral plantar nerve injury, and wound healing. Significant bone void may result if the hardware requires removal secondary to one of these complications. The purpose of this article is to report on 2 cases of infected intramedullary nails, which were revised with fibular inlay strut grafts. Both cases were augmented with either internal or external fixation.

LEVELS OF EVIDENCE
Therapeutic, Level IV: Case report.

Monaco|Spencer J|SJ|
Lowery|Nick|N|
Crim|Brandon|B|

bone
bone healing
diagnostic and therapeutic techniques
orthobiologics
osteomyelitis
reconstructive foot and ankle surgery


Exploring symptom meaning: perspectives of palliative care physicians.

Abstract:
CONTEXT
Understanding patients' symptom experiences is essential to providing effective clinical care. The discussion between patients and physicians of symptom meaning and its significance, however, is ill understood.

OBJECTIVES
To investigate palliative care physicians' understanding of symptom meaning, and their experiences of and attitudes towards the discussion of symptom meaning with patients.

METHODS
Semi-structured interviews were conducted (N = 17) across Sydney, Australia. Transcripts were analysed using framework analysis.

RESULTS
Six key themes were identified: (1) definitions of symptom meaning (causal meanings, functional impact, existential impact, and cascade of meanings); (2) meanings are personal (demographic, culture, spiritual, and family differences); (3) eliciting meanings requires subtlety and trust (following the patient's cues); discussing meaning can be (4) hard (for the patient and health professional); (5) therapeutic (assuaging fears, feeling listened to and valued, increased sense of control, and reduced symptom distress); and (6) enhances clinicians' practice and work satisfaction (provision of more tailored care, reassurance through the provision of information, and strengthening of doctor-patient relationship).

CONCLUSIONS
Exploring symptom meaning can serve to provide information, alleviate anxiety, and facilitate individualised care, but only when patients present cues or are open to discuss symptom-related concerns. However, various barriers hinder such dialogue in consultations. Greater awareness of symptom meaning and its influence may facilitate physicians exploring symptom meaning more with patients in the future.

Symptom meaning
Palliative care
Symptom experience
Health professionals
Advanced cancer
Qualitative research


ENSO effects on the transpiration of eastern Amazon trees.

Abstract: Tree transpiration is important in the recycling of precipitation in the Amazon and might be negatively affected by El Niño-Southern Oscillation (ENSO)-induced droughts. To investigate the relative importance of soil moisture deficits versus increasing atmospheric demand (VPD) and determine if these drivers exert different controls over tree transpiration during the wet season versus the dry season (DS), we conducted sap flow measurements in a primary lowland tropical forest in eastern Amazon during the most extreme ENSO-induced drought (2015/2016) recorded in the Amazon. We also assessed whether trees occupying different canopy strata contribute equally to the overall stand transpiration (T stand). Canopy trees were the primary source of T stand However, subcanopy trees are still important as they transpired an amount similar to other biomes around the globe. Tree water use was higher during the DS, indicating that during extreme drought trees did not reduce transpiration in response to low soil moisture. Photosynthetically active radiation and VPD exerted an overriding effect on water use patterns relative to soil moisture during extreme drought, indicating that light and atmospheric constraints play a critical role in controlling ecosystem fluxes of water. Our study highlights the importance of canopy and subcanopy trees to the regional water balance and highlights the resilience to droughts that these trees show during an extreme ENSO event.This article is part of a discussion meeting issue 'The impact of the 2015/2016 El Niño on the terrestrial tropical carbon cycle: patterns, mechanisms and implications'.

Brum|Mauro|M|0000-0002-9790-254X
Gutiérrez López|Jose|J|
Asbjornsen|Heidi|H|
Licata|Julian|J|
Pypker|Thomas|T|
Sanchez|Gilson|G|
Oiveira|Rafael S|RS|

drought
sap flow
El Niño
hysteresis
vapour pressure deficit


Preparation of poly(N-vinylpyrrolidone)-stabilized ZnO colloid nanoparticles.

Abstract: We propose a method for the synthesis of a colloidal ZnO solution with poly(N-vinylpyrrolidone) (PVP) as stabilizer. Stable colloidal solutions with good luminescence properties are obtained by using PVP as stabilizer in the synthesis of ZnO nanoparticles by a sol-gel method assisted by ultrasound. Nanoparticles with sizes of 30-40 nm in a PVP matrix are produced as a solid product. The colloidal ZnO/PVP/methanol solution, apart from the most intense PL band at 356 nm coming from the PVP, exhibits a strong PL band at 376 nm (3.30 eV) which corresponds to the emission of the free exciton recombination in ZnO nanoparticles.

Gutul|Tatyana|T| Rusu|Emil|E| Condur|Nadejda|N| Ursaki|Veaceslav|V| Goncearenco|Evgenii|E| Vlazan|Paulina|P|

poly(N-vinylpyrrolidone)
colloidal solutions
nanocomposite
sol–gel
zinc oxide


Intravital imaging reveals cell cycle-dependent myogenic cell migration during muscle regeneration.

Abstract: During muscle regeneration, extracellular signal-regulated kinase (ERK) promotes both proliferation and migration. However, the relationship between proliferation and migration is poorly understood in this context. To elucidate this complex relationship on a physiological level, we established an intravital imaging system for measuring ERK activity, migration speed, and cell-cycle phases in mouse muscle satellite cell-derived myogenic cells. We found that in vivo, ERK is maximally activated in myogenic cells two days after injury, and this is then followed by increases in cell number and motility. With limited effects of ERK activity on migration on an acute timescale, we hypothesized that ERK increases migration speed in the later phase by promoting cell-cycle progression. Our cell-cycle analysis further revealed that in myogenic cells, ERK activity is critical for G1/S transition, and cells migrate more rapidly in S/G2 phase 3 days after injury. Finally, migration speed of myogenic cells was suppressed after CDK1/2-but not CDK1-inhibitor treatment, demonstrating a critical role of CDK2 in myogenic cell migration. Overall, our study demonstrates that in myogenic cells, the ERK-CDK2 axis promotes not only G1/S transition but also migration, thus providing a novel mechanism for efficient muscle regeneration.

intravital imaging
cell migration
ERK
CDK
Skeletal muscle regeneration
cell cycle


Integration of Computational and Experimental Approaches to Elucidate Mechanisms of First-Pass Lymphatic Drug Sequestration and Long-Acting Pharmacokinetics of the Injectable Triple-HIV Drug Combination TLC-ART 101.

Abstract: TLC-ART101 is a long-acting triple-HIV drug combination of lopinavir-ritonavir-tenofovir in one nanosuspension intended for subcutaneous injection. After a single TLC-ART 101 administration in nonhuman primates, drug concentrations in both plasma and HIV-target lymph node mononuclear cells were sustained for 2 weeks. Nevertheless, the mechanisms leading to the targeted long-acting pharmacokinetics remain elusive. Therefore, an intravenous study of TLC-ART 101 in nonhuman primates was conducted to elucidate the degree of association of drugs in vivo, estimate subcutaneous bioavailability, and refine a mechanism-based pharmacokinetic (MBPK2) model. The MBPK2 model considers TLC-ART 101 systemic drug clearances, nanoparticle-associated/dissociated species, more detailed mechanisms of lymphatic first-pass retention of associated-drugs after subcutaneous administrations, and the prediction of drug concentration time-courses in lymph node mononuclear cells. For all 3 drugs, we found a high association with the nanoparticles in plasma (>87% lopinavir-ritonavir, 97% tenofovir), and an incomplete subcutaneous bioavailability (<29% lopinavir-ritonavir, 85% tenofovir). As hypothesized by the MBPK2 model, the incomplete SC bioavailability observed is due to sequestration into a lymphatic node depot after subcutaneous absorption (unlike most intramuscular nanodrug products having near-to-injection depots), which contributes to long-acting profiles detected in plasma and target cells. This combined experimental and modeling approach may be applicable for the clinical development of other long-acting drug-combination injectables.

Perazzolo|Simone|S|
Shireman|Laura M|LM|
McConnachie|Lisa A|LA|
Koehn|Josefin|J|
Kinman|Loren|L|
Lee|Wonsok|W|
Lane|Sarah|S|
Collier|Ann C|AC|
Shen|Danny D|DD|
Ho|Rodney J Y|RJY|

1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) (PubChem CID: 94190)

1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (ammonium salt) (DSPE-mPEG(2000)) (PubChem CID: 406952)


Exploring perceived barriers, drivers, impacts and the need for evaluation of public involvement in health and social care research: a modified Delphi study.

Abstract:
OBJECTIVE
To explore areas of consensus and conflict in relation to perceived public involvement (PI) barriers and drivers, perceived impacts of PI and ways of evaluating PI approaches in health and social care research.

BACKGROUND
Internationally and within the UK the recognition of potential benefits of PI in health and social care research is gathering momentum and PI is increasingly identified by organisations as a prerequisite for funding. However, there is relatively little examination of the impacts of PI and how those impacts might be measured.

DESIGN
Mixed method, three-phase, modified Delphi technique, conducted as part of a larger MRC multiphase project.

SAMPLE
Clinical and non-clinical academics, members of the public, research managers, commissioners and funders.

FINDINGS
This study found high levels of consensus about the most important barriers and drivers to PI. There was acknowledgement that tokenism was common in relation to PI; and strong support for the view that demonstrating the impacts and value of PI was made more difficult by tokenistic practice. PI was seen as having intrinsic value; nonetheless, there was clear support for the importance of evaluating its impact. Research team cohesion and appropriate resources were considered essential to effective PI implementation. Panellists agreed that PI can be challenging, but can be facilitated by clear guidance, together with models of good practice and measurable standards.

CONCLUSIONS
This study is the first to present empirical evidence of the opinions voiced by key stakeholders on areas of consensus and conflict in relation to perceived PI barriers and drivers, perceived impacts of PI and the need to evaluate PI. As such it further contributes to debate around best practice in PI, the potential for tokenism and how best to evaluate the impacts of PI. These findings have been used in the development of the Public Involvement Impact Assessment Framework (PiiAF), an online resource which offers guidance to researchers and members of the public involved in the PI process.

Snape|D|D| Kirkham|J|J| Britten|N|N| Froggatt|K|K| Gradinger|F|F| Lobban|F|F| Popay|Jennie|J| Wyatt|K|K| Jacoby|Ann|A|

Impacts
Evaluation
Public Involvement
Consensus
Conflict
Barriers and Drivers


Association between height and hypercholesterolemia in adults: a nationwide population-based study in Korea.

Abstract:
BACKGROUND
Previous studies reported that stature is inversely related to the risk of cardiovascular disease. However, there is limited evidence on the association between height and lipid profiles. We aimed to examine the association of height with total cholesterol and hypercholesterolemia based on the nationally representative dataset of Korean adults.

METHODS
The data of 13,701 adults aged ≥19 years who participated in the Korea National Health and Nutrition Examination Survey (2013-2015) were used in this nationwide population-based cross-sectional study. Hypercholesterolemia was defined as a serum total cholesterol level ≥ 240 mg/dL or use of lipid-lowering medications. Multivariable linear regression and logistic regression analyses were used to examine the association of height with mean total cholesterol level and odds ratios (ORs) of hypercholesterolemia.

RESULTS
Approximately 17% of participants had hypercholesterolemia. Mean total cholesterol levels decreased in the higher quartile (Q) groups of height after adjusting for confounding variables including age, sex, body mass index, smoking status, alcohol consumption, physical activity, income, educational level, hypertension, and diabetes mellitus (P for trend = 0.035). After adjusting for these potential confounding variables, the adjusted ORs of hypercholesterolemia were significantly lower in the Q3 and Q4 groups than in the Q1 group; ORs decreased in the higher quartile groups of height (OR: 0.83, 95% confidence interval: 0.71-0.99 in Q3; 0.81, 0.69-0.95 in Q4, P for trend = 0.007). The association between height (Q4 vs. Q1-Q3) and hypercholesterolemia was stronger in men or individuals without hypertension or diabetes than in women or individuals with such diseases.

CONCLUSIONS
Height is inversely associated with total cholesterol level and odds of hypercholesterolemia among Korean adults. Childhood environment related to short stature may be associated with hypercholesterolemia and cardiovascular health in adulthood.

Height
Hypercholesterolemia
Adults
Total cholesterol


Physiological Processes Modulated by the Chloride-Sensitive WNK-SPAK/OSR1 Kinase Signaling Pathway and the Cation-Coupled Chloride Cotransporters.

Abstract: The role of Cl- as an intracellular signaling ion has been increasingly recognized in recent years. One of the currently best described roles of Cl- in signaling is the modulation of the With-No-Lysine (K) (WNK) - STE20-Proline Alanine rich Kinase (SPAK)/Oxidative Stress Responsive Kinase 1 (OSR1) - Cation-Coupled Cl- Cotransporters (CCCs) cascade. Binding of a Cl- anion to the active site of WNK kinases directly modulates their activity, promoting their inhibition. WNK activation due to Cl- release from the binding site leads to phosphorylation and activation of SPAK/OSR1, which in turn phosphorylate the CCCs. Phosphorylation by WNKs-SPAK/OSR1 of the Na+-driven CCCs (mediating ions influx) promote their activation, whereas that of the K+-driven CCCs (mediating ions efflux) promote their inhibition. This results in net Cl- influx and feedback inhibition of WNK kinases. A wide variety of alterations to this pathway have been recognized as the cause of several human diseases, with manifestations in different systems. The understanding of WNK kinases as Cl- sensitive proteins has allowed us to better understand the mechanistic details of regulatory processes involved in diverse physiological phenomena that are reviewed here. These include cell volume regulation, potassium sensing and intracellular signaling in the renal distal convoluted tubule, and regulation of the neuronal response to the neurotransmitter GABA.

Murillo-de-Ozores|Adrián Rafael|AR|
Chávez-Canales|María|M|
de Los Heros|Paola|P|
Gamba|Gerardo|G|
Castañeda-Bueno|María|M|

cell volume regulation
potassium
distal convoluted tubule
GABAergic activity
arterial blood pressure
intracellular chloride concentration


Laparoscopic repair of parahiatal hernia after esophagectomy: a case report.

Abstract:
BACKGROUND
Diaphragmatic hernia is a potential complication of esophagectomy, which usually occurs as a hiatal hernia and more frequently after minimally invasive esophagectomy. Parahiatal hernia is a rare form of diaphragmatic hernia, and to the best of our knowledge, parahiatal hernia after esophagectomy has not been previously reported. Here, we report a case of parahiatal hernia after esophagectomy that was successfully managed laparoscopically.

CASE PRESENTATION
A 73-year-old man underwent thoracoscopic esophagectomy for esophageal cancer with gastric tube reconstruction via the posterior mediastinum. Postoperative morbidity was ileus, which required conservative treatment, and intestinal obstruction for which operation with laparotomy was necessary. He was admitted with abdominal pain and vomiting at 15 months after esophagectomy. Abdominal X-ray revealed colon gas in the intrathoracic space. A barium enema examination showed a transverse colon incarcerated in the intrathoracic space. The patient was preoperatively diagnosed with hiatal hernia after esophagectomy, and laparoscopic hernia repair was performed. During the surgery, the hiatus was found to be intact, and the defect was clearly separated from the left crus of the diaphragm. Parahiatal hernia was the operative diagnosis. The incarcerated colon was repositioned in the abdominal cavity, and the defect was repaired using a composite mesh.

CONCLUSIONS
Laparoscopic surgery was found to be effective for the diagnosis and repair of parahiatal hernia.

Akiyama|Yuji|Y| Iwaya|Takeshi|T| Endo|Fumitaka|F| Chiba|Takehiro|T| Takahara|Takeshi|T| Otsuka|Koki|K| Nitta|Hiroyuki|H| Koeda|Keisuke|K| Mizuno|Masaru|M| Kimura|Yusuke|Y| Sasaki|Akira|A|

Laparoscopic repair
Parahiatal hernia
Esophagectomy
Mesh repair


Chronic inflammation confers to the metabolic reprogramming associated with tumorigenesis of colorectal cancer.

Abstract: It's well known that microenvironment inflammatory signals could promote cancer development and progression. In colorectal cancer (CRC), chronic inflammation is a major driving mechanism for the development of CRC in patients having long-standing inflammatory bowel disease (IBD). Though it has been addressed that cancer cells ferment much of their glucose supply into lactate regardless of the presence of oxygen, it is unclear whether cell metabolism has been reprogramed during the process from IBD to CRC. Herein, with dextran sulfate sodium (DSS)-induced mouse colitis model, we found that inflammation upregulated key glycolytic enzymes expression via activation of STAT3/c-Myc signaling pathway. Interestingly, during the whole phase of chronic inflammation, the key metabolic enzymes demonstrated increased expression constantly, indicating the metabolic reprogramming was induced by long-term inflammatory signal. Moreover, either the inhibition of STAT3 signaling or c-Myc activity could block the glycolytic enzymes expression induced by interleukin 6 (IL-6). Thus, we presented the view that inflammation could induce the metabolic reprogramming and promote the progression from chronic colitis to colorectal cancer.

Qu|Dingding|D| Shen|Liangliang|L| Liu|Shaoqing|S| Li|Huichen|H| Ma|Yongzheng|Y| Zhang|Ruohan|R| Wu|Kaichun|K| Yao|Libo|L| Li|Jipeng|J| Zhang|Jian|J|


The Predicted Cross Value for Genetic Introgression of Multiple Alleles.

Abstract: We consider the plant genetic improvement challenge of introgressing multiple alleles from a homozygous donor to a recipient. First, we frame the project as an algorithmic process that can be mathematically formulated. We then introduce a novel metric for selecting breeding parents that we refer to as the predicted cross value (PCV). Unlike estimated breeding values, which represent predictions of general combining ability, the PCV predicts specific combining ability. The PCV takes estimates of recombination frequencies as an input vector and calculates the probability that a pair of parents will produce a gamete with desirable alleles at all specified loci. We compared the PCV approach with existing estimated-breeding-value approaches in two simulation experiments, in which 7 and 20 desirable alleles were to be introgressed from a donor line into a recipient line. Results suggest that the PCV is more efficient and effective for multi-allelic trait introgression. We also discuss how operations research can be used for other crop genetic improvement projects and suggest several future research directions.

Han|Ye|Y|
Cameron|John N|JN|
Wang|Lizhi|L|
Beavis|William D|WD|

D000465:Algorithms
D000483:Alleles
D018556:Crops, Agricultural
D056426:Genetic Loci
D006824:Hybridization, Genetic
D008957:Models, Genetic
D000069600:Plant Breeding
D011995:Recombination, Genetic
D012641:Selection, Genetic

predicted cross value
trait introgression
operations research
gene stacking
parental selection


Epidemiological assessment of distress during chemotherapy: who is affected?

Abstract:
Objectives
Following the rise in the incidence of cancer, the need for chemotherapy has escalated, as have its side effects. Psychological distress is one of the known side effects of chemotherapy; however, it has not received adequate attention. The purpose of this study was to measure psychological distress in patients receiving chemotherapy, making comparisons on the basis of age, gender, marital status, and chemotherapy dose, and to assess the patients' willingness to continue with treatment.

Methodology
A descriptive cross-sectional study was performed on outpatients receiving chemotherapy beyond the first dose at the Radiation & Isotopes Centre Khartoum (Rick). Data were collected via a face-to-face interview with the patients using the Hospital Anxiety and Depression Scale.

Results
Among patients undergoing chemotherapy, 55 (25.5%) experienced anxiety and depression. Of the 216 patients recruited, the majority were middle-aged (30-50 years old) married women. Development of psychological distress followed a U-shaped curve in relation to the number of chemotherapy doses received. Patients who received 1-5 and >10 doses experienced more psychological distress than those who received 6-10 chemotherapy doses. As many as 212 (98%) patients were willing to continue with chemotherapy.

Conclusion
In our study, psychological distress burdened a quarter of the patients receiving chemotherapy. Psychological distress plays a role in cancer recurrence and recovery; thus, there is a need for a holistic approach to the management of patients with cancer, including psychological evaluation to identify those at risk.

El Kheir|Dalia Y M|DYM|
Ibrahim|Arwa H M|AHM|

Chemotherapy
Cancer
Psychological distress
Anxiety and depression
Psychological evaluation


Key factor cutoffs and interval reference values for stratified fall risk assessment in community-dwelling older adults: the role of physical fitness, body composition, physical activity, health condition, and environmental hazards.

Abstract:
BACKGROUND
Fall risk assessment and determination of older adults' individual risk profiles are crucial elements in fall prevention. As such, it is essential to establish cutoffs and reference values for high and low risk according to key risk factor outcomes. This study main objective was to determine the key physical fitness, body composition, physical activity, health condition and environmental hazard risk outcome cutoffs and interval reference values for stratified fall risk assessment in community-dwelling older adults.

METHODS
Five-hundred community-dwelling Portuguese older adults (72.2 ± 5.4 years) were assessed for falls, physical fitness, body composition, physical (in) activity, number of health conditions and environmental hazards, and sociodemographic characteristics.

RESULTS
The established key outcomes and respective cutoffs and reference values used for fall risk stratification were multidimensional balance (low risk: score > 33, moderate risk: score 32-33, high risk: score 30-31, and very high: score < 30); lean body mass (low risk: > 44 kg, moderate risk: 42-44 kg, high risk: 39-41 kg, and very high: < 39 kg); fat body mass (low risk: < 37%, moderate risk: 37-38%, high risk: 39-42%, and very high: > 42%); total physical activity (low risk: > 2800 Met-min/wk., moderate risk: 2300-2800 Met-min/wk., high risk: 1900-2300 Met-min/wk., and very high: < 1900 Met-min/wk); rest period weekdays (low risk: < 4 h/day, moderate risk: 4-4.4 h/day, high risk: 4.5-5 h/day, and very high: > 5 h/day); health conditions (low risk: n < 3, moderate risk: n = 3, high risk: n = 4-5, and very high: n > 5); and environmental hazards (low risk: n < 5, moderate risk: n = 5, high risk: n = 6-8, and very high: n > 8).

CONCLUSIONS
Assessment of community-dwelling older adults' fall risk should focus on the above outcomes to establish individual older adults' fall risk profiles. Moreover, the design of fall prevention interventions should manage a person's identified risks and take into account the determined cutoffs and respective interval values for fall risk stratification.

Pereira|Catarina|C|0000-0001-8111-1455
Veiga|Guida|G|
Almeida|Gabriela|G|
Matias|Ana Rita|AR|
Cruz-Ferreira|Ana|A|
Mendes|Felismina|F|
Bravo|Jorge|J|

Cutoffs
Falling
Risk assessment
Risk stratification
Elderly


Bidirectional relationships of psychiatric symptoms with internet addiction in college students: A prospective study.

Abstract:
BACKGROUND/PURPOSE
This prospective study evaluated the predictive ability of psychiatric symptoms at initial consultation for the occurrence and remission of Internet addiction during a 1-year follow-up period among college students. Furthermore, it evaluated the predictive ability of changes in psychiatric symptoms for Internet addiction at the initial consultation during the 1-year follow-up period among college students.

METHODS
Five hundred college students (262 women and 238 men) were recruited. The baseline and follow-up consultations measured the levels of Internet addiction and psychiatric symptoms using the Chen Internet Addiction Scale and Symptom Checklist-90 Revised, respectively.

RESULTS
The results indicated that severe interpersonal sensitivity and paranoia symptoms might predict the incidence of Internet addiction at 1-year follow-up. The college students with internet addiction did not have significant improvement in the severities of psychopathology, whereas those without internet addiction had significant improvement in obsession-compulsion, interpersonal sensitivity, paranoid and psychoticism during the same period.

CONCLUSION
Psychiatric symptoms and Internet addiction exhibited bidirectional relationships in college students during the 1-year follow-up period.

Lin|Yen-Ju|YJ|
Hsiao|Ray C|RC|
Liu|Tai-Ling|TL|
Yen|Cheng-Fang|CF|

Psychiatric symptoms
Internet addiction
College student


A Collaborative Family Planning Program in Rural Uganda Utilizing Community Health Workers.

Abstract: In 2015, a household survey was conducted in rural eastern Ugandan villages to determine fertility rate, prevalence of childbirth in the hospital setting, use of and unmet need for modern contraception. There remains a high fertility rate as well as high unmet need for contraception in the surveyed villages. However, Uganda Village Project's community health worker-based family planning program has shown promise to address these concerns.

D003150:Community Health Workers
D003267:Contraception
D003695:Delivery of Health Care
D005193:Family Planning Services
D019538:Health Care Surveys
D006801:Humans
D000070516:Intersectoral Collaboration
D015397:Program Evaluation
D012424:Rural Population
D014454:Uganda

family planning
Uganda
community health workers
reproductive health


The Development and Psychometric Evaluation of a New Mating Effort Questionnaire.

Abstract: In this study, we review the psychometric literature on mating effort and find that extant instruments (1) have not been adequately evaluated in terms of internal structure and measurement invariance, and (2) disproportionately focus on mate retention and intrasexual competition tactics designed to repel competitors, relative to attraction and investment effort. To address these gaps in the literature, we carried out two studies to develop and validate a new Mating Effort Questionnaire (MEQ). In Study 1, we report a pilot study in which participants' responses to an item pool were submitted to exploratory factor analysis. In Study 2, we replicated the structure found in Study 1 using confirmatory factor analysis in an independent sample. A three-factor solution yielded the best fit. The three factors reflected respondents' allocation of energy to attracting high mate value partners when already mated, seeking out romantic partners when single, and investing in their current romantic partner and relationships. Strong partial measurement invariance held across the sexes, implying that observed scores may be used to compare them. We also found evidence of concurrent validity via associations between the MEQ and constructs such as sociosexual orientation, K-factor, mate retention behaviors, and respondents' sexual behavior. These findings suggest that the MEQ is a valid and novel measure of individual differences in mating effort which is well suited to complement existing mating effort measures.

Albert|Graham|G|0000-0002-5866-7479
Richardson|George B|GB|
Arnocky|Steven|S|
Senveli|Zeynep|Z|
Hodges-Simeon|Carolyn R|CR|

Mating effort
Measurement
Human mating
Life history


Modeling the oxygen uptake kinetics during exercise testing of patients with chronic obstructive pulmonary diseases using nonlinear mixed models.

Abstract:
BACKGROUND
The six-minute walk test (6MWT) is commonly used to quantify exercise capacity in patients with several cardio-pulmonary diseases. Oxygen uptake ([Formula: see text]O2) kinetics during 6MWT typically follow 3 distinct phases (rest, exercise, recovery) that can be modeled by nonlinear regression. Simultaneous modeling of multiple kinetics requires nonlinear mixed models methodology. To the best of our knowledge, no such curve-fitting approach has been used to analyze multiple [Formula: see text]O2 kinetics in both research and clinical practice so far.

METHODS
In the present study, we describe functionality of the R package medrc that extends the framework of the commonly used packages drc and nlme and allows fitting nonlinear mixed effects models for automated nonlinear regression modeling. The methodology was applied to a data set including 6MWT [Formula: see text]O2 kinetics from 61 patients with chronic obstructive pulmonary disease (disease severity stage II to IV). The mixed effects approach was compared to a traditional curve-by-curve approach.

RESULTS
A six-parameter nonlinear regression model was jointly fitted to the set of [Formula: see text]O2 kinetics. Significant differences between disease stages were found regarding steady state [Formula: see text]O2 during exercise, [Formula: see text]O2 level after recovery and [Formula: see text]O2 inflection point in the recovery phase. Estimates obtained by the mixed effects approach showed standard errors that were consistently lower as compared to the curve-by-curve approach.

CONCLUSIONS
Hereby we demonstrate the novelty and usefulness of this methodology in the context of physiological exercise testing.

Baty|Florent|F|
Ritz|Christian|C|
van Gestel|Arnoldus|A|
Brutsche|Martin|M|
Gerhard|Daniel|D|

D029424:Pulmonary Disease, Chronic Obstructive

Modeling
Exercise testing
Chronic obstructive pulmonary disease
Nonlinear mixed effects
Oxygen kinetics


Concurrent intracranial and extracranial artery stenosis and the prognosis of transient ischaemic symptoms or imaging-negative ischaemic stroke.

Abstract:
BACKGROUND AND PURPOSE
Transient ischaemic attack (TIA), transient symptoms with infarction (TSI) and diffusion-weighted imaging (DWI)-negative acute ischaemic stroke (AIS) share similar aetiologies but are considered to have a rather benign prognosis. We intended to investigate the association between intracranial atherosclerotic stenosis (ICAS), extracranial atherosclerotic stenosis (ECAS) and the prognosis of patients with TIA, TSI and DWI-negative AIS.

METHODS
Clinical and imaging data of eligible participants were derived from the Chinese Intracranial Atherosclerosis study, according to symptom duration, acute infarction on DWI and discharge diagnosis. Based on the severity and location of arterial atherosclerosis, we categorised the study population into four groups: no or <50% ICAS and no ECAS; ≥50% ICAS but no ECAS; no or <50% ICAS with ECAS; and concurrent ≥50% ICAS and ECAS. Using multivariable Cox regression models, we analysed the relationship between the severity and distribution of large artery atherosclerosis and the prognosis of TIA, TSI and DWI-negative AIS.

RESULTS
A total of 806 patients were included, 67.3% of whom were male. The median age of the study participants was 63 years. Patients in the concurrent ≥50% ICAS and ECAS subgroup had both a significantly higher 1-year recurrence rate (adjusted HR 3.4 (95% CI 1.15 to 10.04), p=0.027) and a higher risk of composite vascular events (adjusted HR 3.82 (95% CI 1.50 to 9.72), p=0.005).

CONCLUSIONS
Concurrent ICAS and ECAS is associated with a higher possibility of 1-year recurrent stroke or composite vascular events. Large artery evaluation is necessary to assess patients with transient ischaemic symptoms or DWI-negative AIS. Progress in shortening the time interval between symptom onset and large vessel evaluation is needed.


Profile of drug-resistant-conferring mutations among new and previously treated pulmonary tuberculosis cases from Aligarh region of Northern India.

Abstract:
Background
The prevalence of multidrug-resistant-tuberculosis (MDR-TB) among new and previously treated cases is increasing worldwide as well as in India. Rapid detection of MDR-TB allows the establishment of an effective treatment regimen; minimizes the risk of further resistance, and limits the spread of drug-resistant strains. Early diagnosis of MDR-TB is the need of the hour in high-TB burden countries like India, and GenotypeMTBDRplus is quite sensitive and specific in determining the molecular resistance in drugs such as rifampicin and isoniazid.

Methods
The present study was done for molecular detection of rifampicin and isoniazid resistance and resistance patterns among MDR-TB suspects and comparison of resistance patterns among new and previously treated cases by GenoType® MTBDRplus Line Probe Assay. A total of 1268 sputum samples of MDR-TB suspects were subjected to fluorescent microscopy. Fluorescent microscopy positive samples were subjected to GenoType® MTBDRplus (HAIN Lifescience) assay.

Results
MDR-TB was detected 11.02%, 20.03% in new and previously treated cases. Among MDR-TB patients S531 L was the most common mutation detected in rpoB gene; 71.43% in new, and 72.17% in previously treated cases. S315T1 was the most common mutation noted in katG gene; 100% in new and 81.74% in previously treated. While in hA gene, it was C15T (7.8%) among previously treated cases.

Conclusion
MDR-TB has high prevalence in the western part of Uttar Pradesh, India. Previously treated cases have even more high rate of MDR-TB than new TB cases. The most dominant gene mutations associated with resistance to INH and RIF were observed in codon 315 of the katG gene and codon 531 of the rpoB gene. While comparing the mutation patterns by Genotype MTBDRplus assay, previously treated cases showed more diversity of mutations and had greater number of unknown mutations.

Ahmed|Shariq|S|
Shukla|Indu|I|
Fatima|Nazish|N|
Varshney|Sumit K|SK|
Shameem|Mohammad|M|
Tayyaba|Uzma|U|

D024901:Drug Resistance, Multiple, Bacterial

rpoB gene
katG gene
inhA gene
multi-drug resistant tuberculosis


Leukemic Non-nodal Mantle Cell Lymphoma: Diagnosis and Treatment.

Abstract: Mantle cell lymphoma (MCL) encompasses nearly 6% of all the non-Hodgkin lymphomas. It is considered an incurable neoplastic process arising from B cells. The cytogenetic abnormality t(11;14) (q13; q32) leading to cyclin D1 overexpression is the sentinel genetic event and provides an exceptional marker for diagnosis. MCL is generally considered to have an aggressive course as compared with other indolent lymphomas with traditionally reported median survival of 3-5 years. According to the 2016 WHO classification, there are two major known variants of MCL: classical which affects the lymph nodes and extra nodal sites and leukemic non-nodal MCL (L-NN-MCL) which characteristically involves the bone marrow, peripheral blood, and the spleen. It is important to distinguish between classical and leukemic non-nodal MCL since the latter variant of MCL follows a rather indolent course with a wait and watch approach in order to avoid overtreatment. However, a subset of patients with L-NN-MCL can transform into a more aggressive course requiring treatment. Current evidence suggests those patients with alteration in TP53 gene do not respond to standard chemotherapy agents and may need targeted therapy. In this review, we describe the characteristics of L-NN-MCL, its diagnosis, and management.

Jain|Akriti Gupta|AG|
Chang|Chung-Che|CC|
Ahmad|Sarfraz|S|
Mori|Shahram|S|

D003131:Combined Modality Therapy
D003937:Diagnosis, Differential
D019468:Disease Management
D018450:Disease Progression
D004198:Disease Susceptibility
D006801:Humans
D020522:Lymphoma, Mantle-Cell
D060787:Neoplasm Grading
D009367:Neoplasm Staging
D016896:Treatment Outcome

Leukemic
Non-nodal
Mantle cell lymphoma
Diagnosis
Treatment
P53 gene mutation


Proteomic study reveals a co-occurrence of gallic acid-induced apoptosis and glycolysis in B16F10 melanoma cells.

Abstract: Gallic acid (GA) has long been associated with a wide range of biological activities. In this study, its antitumor effect against B16F10 melanoma cells was demonstrated by MTT assay, cell migration assay, wound-healing assay, and flow cytometric analysis. GA with a concentration >200 μM shows apoptotic activity toward B16F10 cells. According to Western blotting data, overexpressions of cleaved forms of caspase-9, caspase-3, and PARP-1 and pro-apoptotic Bax and Bad, accompanied by underexpressed anti-apoptotic Bcl-2 and Bcl-xL indicate that GA induces B16F10 cell apoptosis via mitochondrial pathway. The 2-DE based comparative proteomics was further employed in B16F10 cells with and without GA treatment for a large-scale protein expression profiling. A total of 41 differential protein spots were quantified, and their identities were characterized using LC-MS/MS analysis and database matching. In addition to some regulated proteins that were associated with apoptosis, interestingly, some identified proteins involved in glycolysis such as glucokinase, α-enolase, aldolase, pyruvate kinase, and GAPDH were simultaneously up-regulated, which reveals that the GA-induced cellular apoptosis in B16 melanoma cells is associated with metabolic glycolysis.

Liu|Cheng|C| Lin|Jen-Jie|JJ| Yang|Zih-Yan|ZY| Tsai|Chi-Chu|CC| Hsu|Jue-Liang|JL| Wu|Yu-Jen|YJ|

proteomics
apoptosis
glycolysis
gallic acid
2-DE
mitochondrial dysfunction


Corneal endothelial cell dysfunction: etiologies and management.

Abstract: A transparent cornea is essential for the formation of a clear image on the retina. The human cornea is arranged into well-organized layers, and each layer plays a significant role in maintaining the transparency and viability of the tissue. The endothelium has both barrier and pump functions, which are important for the maintenance of corneal clarity. Many etiologies, including Fuchs' endothelial corneal dystrophy, surgical trauma, and congenital hereditary endothelial dystrophy, lead to endothelial cell dysfunction. The main treatment for corneal decompensation is replacement of the abnormal corneal layers with normal donor tissue. Nowadays, the trend is to perform selective endothelial keratoplasty, including Descemet stripping automated endothelial keratoplasty and Descemet's membrane endothelial keratoplasty, to manage corneal endothelial dysfunction. This selective approach has several advantages over penetrating keratoplasty, including rapid recovery of visual acuity, less likelihood of graft rejection, and better patient satisfaction. However, the global limitation in the supply of donor corneas is becoming an increasing challenge, necessitating alternatives to reduce this demand. Consequently, in vitro expansion of human corneal endothelial cells is evolving as a sustainable choice. This method is intended to prepare corneal endothelial cells in vitro that can be transferred to the eye. Herein, we describe the etiologies and manifestations of human corneal endothelial cell dysfunction. We also summarize the available options for as well as recent developments in the management of corneal endothelial dysfunction.

etiologies
management
corneal endothelial dysfunction
human corneal endothelium


Boesenbergia rotunda extract accelerates human keratinocyte proliferation through activating ERK1/2 and PI3K/Akt kinases.

Abstract: Boesenbergia rotunda (BR) has long been used as tradition medicine. For its pharmacological effects on wound healing, previous studies in an animal model provided convincing results that the ethanolic extract from the rhizome of this plant can stimulate wound healing. However, the mechanism about how this plant promotes wound healing at the molecular level has not been elucidated. As a step towards the development of wound healing agents, our current study utilized a human keratinocyte cell line (HaCaT) as an in vitro model to define the potential molecular mechanisms of BR extract in enhancing wound-healing. Our HPLC results showed that BR extract contained kaempferol as one of its potential compounds. The extract strongly promoted wound healing of HaCaT cell monolayer. This effect was eventually defined to be regulated through the ability of BR extract to induce cell proliferation. At the signaling level, we discovered that BR extract rapidly activated ERK1/2 and Akt phosphorylation upon the addition of the extract. Additionally, our experiments where specific inhibitors of MEK (U0126) and PI3K (LY294002) were utilized verified that BR enhanced cell proliferation and wound healing through stimulating the MAPK and PI3K/Akt signal transduction pathways. Moreover, direct inhibition of keratinocyte DNA synthesis by mitomycin C (MMC) could completely block the proliferative effects of BR extract. Nevertheless, data from Transwell migration assay revealed that BR extract did not promote keratinocyte migration. Altogether, we provided more evidence that BR possesses its wound healing-promoting action through the activation of proliferation and survival pathways, and our study suggests that BR is an interesting candidate to be developed as a wound healing-promoting agent.

Ruttanapattanakul|Jirapak|J|
Wikan|Nitwara|N|
Okonogi|Siriporn|S|
Na Takuathung|Mingkwan|M|
Buacheen|Pensiri|P|
Pitchakarn|Pornsiri|P|
Potikanond|Saranyapin|S|
Nimlamool|Wutigri|W|

D019950:Mitogen-Activated Protein Kinase 1

D048052:Mitogen-Activated Protein Kinase 3

Boesenbergia rotunda
ERK1/2
PI3K/Akt
Wound healing
Dermatology
Human keratinocyte HaCaT cells
Regenerative medicine


Novel rhodamine derivate as high selective detection lead sensor.

Abstract: A novel rhodamine based sensor 1 has been synthesized and characterized by NMR, FT-IR and mass. The binding properties of sensor 1 were investigated in the presence of various metal ions by UV-Vis spectroscopy and fluorescence spectroscopy. Sensor 1 showed colorimetric and high emission intensity enhancement in the presence of Pb(2+) in chloroform-THF (7:3).

D017550:Spectroscopy, Fourier Transform Infrared


Overlooked guide wire: a multicomplicated Swiss Cheese Model example. Analysis of a case and review of the literature.

Abstract: Objectives: Central venous catheter (CVC) implementation is now usual in emergency department. The most common complications are misplacement, bleeding, pleural perforation, thrombosis and sepsis. Forgetting a guide wire in the patient's body after catheterization is an underestimated complication of this procedure; only 76 cases are described. Even if the majority of patients remained asymptomatic, severe complications can happened even years later. This article's aim is to identify the sequence of elements that led to the event occurrence and to suggest recommendations of good practice to minimize complications related to central catheter placement.Method: After reviewing all the complications related to central venous catheterization and their frequencies, we analyse from a case report and a review of the literature the sequence of elements that led to the medical error. We use an Ishikawa diagram to show our results and the links between them.Results: Our Ishikawa diagram shows that material, human resources, procedural and radiological involvement factors are the main elements on which we can act to reduce the complications rate after central venous catheterization. We advocate for the establishment of standardized procedures before, during and after the technical gesture.Conclusions: Because of human nature, errors will always be possible when taking care of a patient. However, we propose good practice recommendations to avoid the repetition of a forgetting guide wire after central venous catheterization.

D000328:Adult
D002405:Catheterization, Central Venous
D057189:Checklist
D005260:Female
D005547:Foreign Bodies
D015390:Gastric Bypass
D006801:Humans
D007084:Iliac Vein
D008103:Liver Cirrhosis
D019300:Medical Errors
D012308:Risk Management
D014682:Vena Cava, Inferior
D014683:Vena Cava, Superior
D020246:Venous Thrombosis

emergency department
Central catheter
checklist
human error
incident reporting
patient safety


Objectives and methodology of Romanian SEPHAR II Survey. Project for comparing the prevalence and control of cardiovascular risk factors in two East-European countries: Romania and Poland.

Abstract:
INTRODUCTION
Comparing results of representative surveys conducted in different East-European countries could contribute to a better understanding and management of cardiovascular risk factors, offering grounds for the development of health policies addressing the special needs of this high cardiovascular risk region of Europe. The aim of this paper was to describe the methodology on which the comparison between the Romanian survey SEPHAR II and the Polish survey NATPOL 2011 results is based.

MATERIAL AND METHODS
SEPHAR II, like NATPOL 2011, is a cross-sectional survey conducted on a representative sample of the adult Romanian population (18 to 80 years) and encompasses two visits with the following components: completing the study questionnaire, blood pressure and anthropometric measurements, and collection of blood and urine samples.

RESULTS
From a total of 2223 subjects found at 2860 visited addresses, 2044 subjects gave written consent but only 1975 subjects had eligible data for the analysis, accounting for a response rate of 69.06%. Additionally we excluded 11 subjects who were 80 years of age (NATPOL 2011 included adult subjects up to 79 years). Therefore, the sample size included in the statistical analysis is 1964. It has similar age groups and gender structure as the Romanian population aged 18-79 years from the last census available at the moment of conducting the survey (weight adjustments for epidemiological analyses range from 0.48 to 8.7).

CONCLUSIONS
Sharing many similarities, the results of SEPHAR II and NATPOL 2011 surveys can be compared by a proper statistical method offering crucial information regarding cardiovascular risk factors in a high-cardiovascular risk European region.

Dorobantu|Maria|M| Tautu|Oana-Florentina|OF| Darabont|Roxana|R| Ghiorghe|Silviu|S| Badila|Elisabeta|E| Dana|Minca|M| Dobreanu|Minodora|M| Baila|Ilarie|I| Rutkowski|Marcin|M| Zdrojewski|Tomasz|T|

epidemiology
cardiovascular disease
cross-sectional study
hypertension
metabolic disorders


Association of dentine hypersensitivity with different risk factors - a cross sectional study.

Abstract:
BACKGROUND
This study was done to assess the prevalence of Dentine hypersensitivity (DH) and its associated risk factors.

MATERIALS & METHODS
This epidemiological study was done among patients coming to dental college regarding prevalence of DH. A self structured questionnaire along with clinical examination was done for assessment. Descriptive statistics were obtained and frequency distribution was calculated using Chi square test at p value <0.05. Stepwise multiple linear regression was also done to access frequency of DH with different factors.

RESULTS
The study population was comprised of 655 participants with different age groups. Our study showed prevalence as 55% and it was more common among males. Similarly smokers and those who use hard tooth brush had more cases of DH. Step wise multiple linear regression showed that best predictor for DH was age followed by habit of smoking and type of tooth brush. Most aggravating factors were cold water (15.4%) and sweet foods (14.7%), whereas only 5% of the patients had it while brushing.

CONCLUSION
A high level of dental hypersensitivity has been in this study and more common among males. A linear finding was shown with age, smoking and type of tooth brush. How to cite this article: Vijaya V, Sanjay V, Varghese RK, Ravuri R, Agarwal A. Association of Dentine Hypersensitivity with Different Risk Factors - A Cross Sectional Study. J Int Oral Health 2013;5(6):88-92 .

Vijaya|V|V|
Sanjay|Venkataraam|V|
Varghese|Rana K|RK|
Ravuri|Rajyalakshmi|R|
Agarwal|Anil|A|

Dentine hypersensitivity
prevalence
tooth brush
smoking


Design and fabrication of in-situ N-doped paper-like carbon nanofiber film for thiophene removal from a liquid model fuel.

Abstract: The novel nitrogen-doped porous carbon nanofibers film (PAN-CNFs) had been successfully prepared by electrospinning with polyacrylonitrile as carbon precursor after calcination under N2 atmosphere. The structure and physical properties of PAN-CNFs were determined by a series of characterizations. The results showed that the PAN-CNFs-800 have the higher N content (10.02 wt.%), larger surface area (354.327 m2/g) and optional Vmic/VTotal (28.14 %). The adsorption desulphurization was examined by thiophene (TH) simulated oil. The experimental results demonstrated that the PAN-CNFs were the desirable adsorption materials as alternative candidate in present adsorption technique. Furthermore, the pseudo order kinetics and adsorption isotherm of the PAN-CNFs-800 was intensive studied, which exhibited good adsorptive capacity for thiophene (TH) reached 113.33 mg/L according to the Langmuir isotherm model and maintained promising recycling reusing performance. The adsorption mechanism was proposed by these models, which should be attributed to the cooperating effect of the proper pore structure and the π-π complexation interactions.

Carbon nanofibers
Thiophene
Nitrogen-doped
Electrospinning
Desulfurization


Prevalence of Smoking among Iranian Adults: Findings of the National STEPs Survey 2016.

Abstract:
BACKGROUND
Tobacco smoking is one of the most important avoidable causes of mortality from non-communicable diseases (NCDs). This study aimed to report the crude and standardized prevalence of current, ever, and secondhand smoking at national and provincial levels.

METHODS
This study was performed through an analysis of the results of the STEPs survey 2016, which was conducted as a cross-sectional national study. The samples were selected via multistage cluster sampling and they were representative of general population aged ≥18 years in all provinces of Iran. All the data were analyzed via survey analysis while considering population weights. Age-standardized prevalence was also calculated for the Iranian national population in 2016 and the World Health Organization (WHO) Population 2000-2025.

RESULTS
A total of 29963 subjects aged ≥18 years from all provinces of Iran, except for Qom, participated in this study. The age standardized prevalence of current tobacco smoking among adult males and females were 24.4% (95% CI: 23.6%-25.1%) and 3.8% (95% CI: 3.5%-4.1%), respectively. Among the participants, the majority of the current smokers were among those aged 45-54 years (14.5%; 95% CI: 13.6%-15.5%). With increase in age, the prevalence of secondhand smoking decreased to 34.8% (95% CI: 33.3%-36.7%) among people aged 18-24 years and to 22·6% (95% CI: 21.0%-24.3%) among subjects over 70 years.

CONCLUSION
The result of the study can be used to inform policy makers about the status of smoking and help them to design policies for setting rules on and limiting the import of cigarettes and their components to the country.

Varmaghani|Mehdi|M| Sharifi|Farshad|F| Mehdipour|Parinaz|P| Sheidaei|Ali|A| Djalalinia|Shirin|S| Gohari|Kimiya|K| Modirian|Mitra|M| Pazhuheian|Forough|F| Peykari|Niloofar|N| Haghshenas|Rosa|R| Khajavi|Alireza|A| Zokaei|Hossein|H| Moradi|Ghobad|G| Mahdavihezaveh|Alireza|A| Farzadfar|Farshad|F|

Prevalence
Tobacco Smoking
Iran
Second hand smoke


Long-Term Effects of Ionizing Radiation on the Hippocampus: Linking Effects of the Sonic Hedgehog Pathway Activation with Radiation Response.

Abstract: Radiation therapy represents one of the primary treatment modalities for primary and metastatic brain tumors. Although recent advances in radiation techniques, that allow the delivery of higher radiation doses to the target volume, reduce the toxicity to normal tissues, long-term neurocognitive decline is still a detrimental factor significantly affecting quality of life, particularly in pediatric patients. This imposes the need for the development of prevention strategies. Based on recent evidence, showing that manipulation of the Shh pathway carries therapeutic potential for brain repair and functional recovery after injury, here we evaluate how radiation-induced hippocampal alterations are modulated by the constitutive activation of the Shh signaling pathway in Patched 1 heterozygous mice (Ptch1+/-). Our results show, for the first time, an overall protective effect of constitutive Shh pathway activation on hippocampal radiation injury. This activation, through modulation of the proneural gene network, leads to a long-term reduction of hippocampal deficits in the stem cell and new neuron compartments and to the mitigation of radio-induced astrogliosis, despite some behavioral alterations still being detected in Ptch1+/- mice. A better understanding of the pathogenic mechanisms responsible for the neural decline following irradiation is essential for identifying prevention measures to contain the harmful consequences of irradiation. Our data have important translational implications as they suggest a role for Shh pathway manipulation to provide the therapeutic possibility of improving brain repair and functional recovery after radio-induced injury.

ionizing radiation
astrocytes
cognitive effects
hippocampal neurogenesis


Phosphate Removal During Conventional Hemodialysis: a Decades-Old Misconception.

Abstract:
BACKGROUND/AIMS
Hyperphosphatemia is associated with high mortality rate in patients on dialysis. Conventional hemodialysis (HD) is a limit technique in removing phosphate (P). There is a widespread belief that P is removed mainly in the first hour of HD. The aim of this study was to certify the percentage of 1-hour removal of P as compared to the entire procedure.

METHODS
data from the first dialysis of the week of 21 patients (13 men, age 44±15 years), for 3 consecutive dialysis sessions were evaluated. Fresh dialysate samples were collected at 1 hour and at the end of the session from a partial spent dialysate collection method.

RESULTS
Pre dialysis serum P was 4.7±1.7 mg/dl. Reduction rate of serum P was 47.4 ± 14.3 and 45.1 ± 10.8% in 1- and 4-hour of HD, respectively (p=0.322). P removal was 194 (145, 242) mg in 1-hour (p<0.0001), which represents 25.0 ± 0.2% of the total removed during the entire HD. Patients with pre dialysis P ≥ 5.5mg/dl had higher P removal during HD than those with P < 5.5mg/dl [975 (587, 1354) vs. 776 (580, 784) mg, p=0.025], although the percentage of removal in 1 hour was not different from those with P < 5.5mg/d (24.9 ± 0.3 vs. 25.0 ± 0.1%, p=0.918). P removal during dialysis correlated with pre dialysis serum P (r=0.455, p=0.001), parathormone (r=0.264, p=0.037) and ultrafiltration volume (r=0.343, p=0.019).

CONCLUSION
despite the P serum concentration normalizing in the first hour of hemodialysis, the removal in the same period reaches only 25% of the entire session.

Elias|Rosilene M|RM|
Alvares|Valeria R C|VRC|
Moysés|Rosa M A|RMA|

Phosphate removal
Hemodialysis
Hyperphosphatemia
Dialysate


Fast nonclinical ventricular tachycardia inducible after ablation in patients with structural heart disease: Definition and clinical implications.

Abstract:
BACKGROUND
Noninducibility of ventricular tachycardia (VT) with an equal or longer cycle length (CL) than that of the clinical VT is considered the minimum ablation endpoint in patients with structural heart disease. Because their clinical relevance remains unclear, fast nonclinical VTs are often not targeted. However, an accepted definition for fast VT is lacking. The shortest possible CL of a monomorphic reentrant VT is determined by the ventricular refractory period (VRP).

OBJECTIVE
The purpose of this study was to propose a patient-specific definition for fast VT based on the individual VRP (fVTVRP) and assess the prognostic significance of persistent inducibility after ablation of fVTVRP for VT recurrence.

METHODS
Of 191 patients with previous myocardial infarction or with nonischemic cardiomyopathy undergoing VT ablation, 70 (age 63 ± 13 years; 64% ischemic) remained inducible for a nonclinical VT and composed the study population. FVTVRP was defined as any VT with CL ≤VRP400 + 30 ms. Patients were followed for VT recurrence.

RESULTS
After ablation, 30 patients (43%) remained inducible exclusively for fVTVRP and 40 (57%) for any slower VT. Patients with only fVTVRP had 3-year VT-free survival of 64% (95% confidence interval [CI] 46%-82%) compared to 27% (95% CI 14%-48%) for patients with any slower remaining VT (P = .013). Inducibility of only fVTVRP was independently associated with lower VT recurrence (hazard ratio 0.38; 95% CI 0.19-0.86; P = .019). Among 36 patients inducible for any fVTVRP, only 1 had recurrence with fVTVRP.

CONCLUSION
In patients with structural heart disease, inducibility of exclusively fVTVRP after ablation is associated with low VT recurrence.

Watanabe|Masaya|M|
de Riva|Marta|M|
Piers|Sebastiaan R D|SRD|
Dekkers|Olaf M|OM|
Ebert|Micaela|M|
Venlet|Jeroen|J|
Trines|Serge A|SA|
Schalij|Martin J|MJ|
Pijnappels|Daniël A|DA|
Zeppenfeld|Katja|K|

Ventricular tachycardia
Structural heart disease
Noninducibility
Refractory period
Catheter ablation


Safety of adjuvant gemcitabine plus cisplatin chemotherapy in a patient with bilateral ureteral cancer undergoing hemodialysis.

Abstract: An 80 year old Japanese man with bilateral ureteral cancer underwent laparoscopic bilateral nephroureterectomy and lymph-node dissection. The pathological stage of the left and right ureteral tumors was pT3pN0M0. He received two courses of adjuvant gemcitabine and cisplatin chemotherapy while undergoing hemodialysis. The standard dose of gemcitabine and 50% of the standard dose of cisplatin were administered on the same day. Hemodialysis was started 6 h after gemcitabine administration and 1 h after cisplatin administration. The side effects were evaluated according to the Common Terminology Criteria for Adverse Events v4.0. In the first course, Grade 4 side effects including leukopenia, neutropenia, and thrombocytopenia were observed. He was treated with granulocyte colony-stimulating factor and platelet transfusion. Because the second course was administered without reducing the doses, granulocyte colony-stimulating factor was administered prophylactically, and Grade 4 side effects were reduced to Grade 3. Gemcitabine plus cisplatin chemotherapy can be administered safely in a patient with advanced ureteral cancer undergoing hemodialysis by adequately managing adverse events.

Goto|Yumiko|Y|0000-0001-5133-755X Kanao|Kent|K| Matsumoto|Kazuhiro|K| Kobayashi|Ikuo|I| Kajikawa|Keishi|K| Onishi|Masafumi|M|

Gemcitabine plus cisplatin
Bilateral ureteral cancer
Hemodialysis
Adjuvant chemotherapy


New paradigms for the treatment of lysosomal storage diseases: targeting the endocannabinoid system as a therapeutic strategy.

Abstract: Over the past three decades the lysosomal storage diseases have served as model for rare disease treatment development. While these efforts have led to considerable success, important challenges remain. For example, no treatments are currently approved for nearly two thirds of all lysosomal diseases, and there is limited impact of the existing drugs on the central nervous system. In addition, the costs of these therapies are extremely high, in part due to the fact that drug development has focused on a "single hit" approach - i.e., one drug for one disease. To overcome these obstacles researchers have begun to focus on defining common disease mechanisms in the lysosomal diseases, particularly in the central nervous system, with the hope of identifying drugs that might be used in several lysosomal diseases rather than an individual disease. With this concept in mind, herein we review a new potential treatment approach for the lysosomal storage diseases that focuses on modulation of the endocannabinoid system. We provide a short introduction to lysosomal storage diseases and the endocannabinoid system, followed by a brief review of data supporting this concept.

D002490:Central Nervous System
D063388:Endocannabinoids
D056947:Enzyme Replacement Therapy
D015316:Genetic Therapy
D006801:Humans
D016464:Lysosomal Storage Diseases

Treatment
Lysosomal storage diseases
Endocannabinoids


The risk of HIV transmission at each step of the HIV care continuum among people who inject drugs: a modeling study.

Abstract:
BACKGROUND
People who inject drugs (PWID) are at continued risk for HIV in the U.S., and experience disparities across the HIV care continuum compared to other high-risk groups. Estimates of the risk of HIV transmission at each stage of the care continuum may assist in identifying public health priorities for averting incident infections among PWID, in addition to transmissions to sexual partners of PWID.

METHODS
We created an agent-based model simulating HIV transmission and the HIV care continuum for PWID in New York City (NYC) in 2012. To account for sexual transmission arising from PWID to non-PWID, the simulation included the entire adult NYC population. Using surveillance data and estimates from the National HIV Behavioral Surveillance system, we simulated a dynamic sexual and injecting network. We estimated the proportion of HIV transmission events attributable to PWID in the following categories, those: without an HIV diagnosis ('Undiagnosed'); diagnosed but not on antiretroviral therapy (ART) ('Diagnosed - not on ART'); those who initiated ART but were not virally suppressed ('Unsuppressed'); and, those who achieved viral suppression ('Suppressed').

RESULTS
We estimated HIV incidence among PWID to be 113 per 100,000 person-years in 2012, with an overall incidence rate for the entire adult NYC population of 33 per 100,000 person-years. Despite accounting for only 33% of the HIV-infected PWID population, the Undiagnosed were associated with 52.6% (95% simulation interval [95% SI]: 47.1-57.0%) of total transmission events. The Diagnosed - not on ART population contributed the second-largest proportion of HIV transmissions, with 36.6% (95% SI: 32.2-41.5%). The Unsuppressed population contributed 8.7% (95% SI: 5.6-11.8%), and Suppressed 2.1% (95% SI: 1.1-3.9%), relatively little of overall transmission.

CONCLUSIONS
Among PWID in NYC, more than half (53%) of transmissions were from those who were unaware of their infection status and more than 36% were due to PWID who knew their status, but were not on treatment. Our results indicate the importance of early diagnosis and interventions to engage diagnosed PWID on treatment to further suppress population-level HIV transmission. Future HIV prevention research should focus on the elimination of identified and potential barriers to the testing, diagnosis, and retention of PWID on HIV treatment.

Escudero|Daniel J|DJ|
Lurie|Mark N|MN|
Mayer|Kenneth H|KH|
King|Maximilian|M|
Galea|Sandro|S|
Friedman|Samuel R|SR|
Marshall|Brandon D L|BDL|

HIV care continuum
People who inject drugs
ART
HAART
HIV care cascade


Needle decompression in a patient with vision-threatening orbital emphysema.

Abstract: Orbital emphysema is a condition resulting from trapping of air in loose subcutaneous or orbital tissues from the paranasal sinuses. This condition commonly seen in patients with a history of periorbital trauma or surgery, especially following sneezing or nose blowing. It usually has a benign and self-limited course. However, the entrapped orbital air can cause a substantial increase in pressure with restricted ocular motility or vascular compromise and become severe enough to cause visual impairment. We herein present the case of a patient who developed severe orbital emphysema after blunt trauma followed by sneezing and was successfully treated with needle decompression of intraorbital air. Emergency needle decompression resulted in an improvement in vision and intraocular pressure.

Lin|Che-Yu|CY| Tsai|Chieh-Chih|CC| Kao|Shu-Ching|SC| Kau|Hui-Chuan|HC| Lee|Fenq-Lih|FL|

needle decompression
orbital emphysema
trauma


Spinal Cord Involvement in MS and Other Demyelinating Diseases.

Abstract: Diagnostic accuracy is poor in demyelinating myelopathies, and therefore a challenge for neurologists in daily practice, mainly because of the multiple underlying pathophysiologic mechanisms involved in each subtype. A systematic diagnostic approach combining data from the clinical setting and presentation with magnetic resonance imaging (MRI) lesion patterns, cerebrospinal fluid (CSF) findings, and autoantibody markers can help to better distinguish between subtypes. In this review, we describe spinal cord involvement, and summarize clinical findings, MRI and diagnostic characteristics, as well as treatment options and prognostic implications in different demyelinating disorders including: multiple sclerosis (MS), neuromyelitis optica spectrum disorder, acute disseminated encephalomyelitis, anti-myelin oligodendrocyte glycoprotein antibody-associated disease, and glial fibrillary acidic protein IgG-associated disease. Thorough understanding of individual case etiology is crucial, not only to provide valuable prognostic information on whether the disorder is likely to relapse, but also to make therapeutic decision-making easier and reduce treatment failures which may lead to new relapses and long-term disability. Identifying patients with monophasic disease who may only require acute management, symptomatic treatment, and subsequent rehabilitation, rather than immunosuppression, is also important.

Marrodan|Mariano|M|0000-0002-4142-8375
Gaitán|María I|MI|
Correale|Jorge|J|

spinal cord
multiple sclerosis
neuromyelitis optica
acute disseminated encephalomyelitis
glial fibrillary acidic protein
myelin oligodendrocyte glycoprotein
myelitis


Increased risk for intracranial arterial stenosis in subjects with coronary artery calcification.

Abstract:
BACKGROUND AND PURPOSE
Intracranial arterial stenosis (ICAS) is considered an important cause of stroke in Asians. Coronary artery calcification (CAC) is a surrogate marker for subclinical atherosclerosis. We aimed to analyze the association of ICAS assessed by transcranial Doppler ultrasonography and CAC in middle-aged Korean population.

METHODS
This study included 10 550 participants (81.3% men, mean age 43 years) from a health screening program, in whom transcranial Doppler ultrasonography was used to detect >50% intracranial stenosis based on criteria modified from the stroke outcomes and neuroimaging of intracranial atherosclerosis trial. Multidetector computed tomography was used to assess coronary artery calcium score (CACS). CAC grade (0, 1-100, and >100) was defined by CACS.

RESULTS
The subjects with CAC showed significantly higher proportion of subjects with ICAS compared with those without CAC (4.4% versus 2.8%; P<0.01). Conversely, the subjects with ICAS showed significantly higher proportion of subjects with CAC (24.8% versus 17.1%; P<0.01). When logistic regression analysis was performed with ICAS as the dependent variable, the presence of CAC showed significantly increased risk for ICAS after adjustment for confounding variables (odds ratio, 1.439; 95% confidence interval, 1.095-1.891). When CACS grade was included in the model, the odds ratio for ICAS was the highest in subjects with CACS >400 compared with those with CACS=0 (odds ratio, 2.754; 95% confidence interval, 1.205-2.936).

CONCLUSIONS
The risk for ICAS was significantly increased in middle-aged Korean subjects with CAC compared with that in those without CAC. These findings suggest the possibility of a separate undetected atherosclerotic focus in subjects with 1 atherosclerotic event.

intracranial atherosclerosis
coronary artery disease
transcranial Doppler ultrasound
vascular calcification


Creation of the WHO Indicators of Infant and Young Child Development (IYCD): metadata synthesis across 10 countries.

Abstract:
Background
Renewed global commitment to the improvement of early child development outcomes, as evidenced by the focus of the United Nations Sustainable Development Goal 4, highlights an increased need for reliable and valid measures to evaluate preventive and interventional efforts designed to affect change. Our objective was to create a new tool, applicable across multicultures, to measure development from 0 to 3 years through metadata synthesis.

Methods
Fourteen cross-sectional data sets were contributed on 21 083 children from 10 low/middle-income countries (LMIC), assessed using seven different tools (caregiver reported or directly assessed). Item groups, measuring similar developmental skills, were identified by item mapping across tools. Logistic regression curves displayed developmental trajectories for item groups across countries and age. Following expert consensus to identify well-performing items across developmental domains, a second mapping exercise was conducted to fill any gaps across the age range. The first version of the tool was constructed. Item response analysis validated our approach by putting all data sets onto a common scale.

Results
789 individual items were identified across tools in the first mapping and 129 item groups selected for analysis. 70 item groups were then selected through consensus, based on statistical performance and perceived importance, with a further 50 items identified at second mapping. A tool comprising 120 items (23 fine motor, 23 gross motor, 20 receptive language, 24 expressive language, 30 socioemotional) was created. The linked data sets on a common scale showed a curvilinear trajectory of child development, highlighting the validity of our approach through excellent coverage by age and consistency of measurement across contributed tools, a novel finding in itself.

Conclusions
We have created the first version of a prototype tool for measuring children in the early years, developed using novel easy to apply methodology; now it needs to be feasibility tested and piloted across several LMICs.

indices of health and disease and standardisation of rates


The influence of few-layer graphene on the gas permeability of the high-free-volume polymer PIM-1.

Abstract: Gas permeability data are presented for mixed matrix membranes (MMMs) of few-layer graphene in the polymer of intrinsic microporosity PIM-1, and the results compared with previously reported data for two other nanofillers in PIM-1: multiwalled carbon nanotubes functionalized with poly(ethylene glycol) (f-MWCNTs) and fused silica. For few-layer graphene, a significant enhancement in permeability is observed at very low graphene content (0.05 vol.%), which may be attributed to the effect of the nanofiller on the packing of the polymer chains. At higher graphene content permeability decreases, as expected for the addition of an impermeable filler. Other nanofillers, reported in the literature, also give rise to enhancements in permeability, but at substantially higher loadings, the highest measured permeabilities being at 1 vol.% for f-MWCNTs and 24 vol.% for fused silica. These results are consistent with the hypothesis that packing of the polymer chains is influenced by the curvature of the nanofiller surface at the nanoscale, with an increasingly pronounced effect on moving from a more-or-less spherical nanoparticle morphology (fused silica) to a cylindrical morphology (f-MWCNT) to a planar morphology (graphene). While the permeability of a high-free-volume polymer such as PIM-1 decreases over time through physical ageing, for the PIM-1/graphene MMMs a significant permeability enhancement was retained after eight months storage.

graphene
mixed matrix membranes
polymers of intrinsic microporosity
gas permeation


Managing the COVID-19 pandemic in poor urban neighborhoods: The case of Accra and Johannesburg.

Abstract: Without a vaccine, practicing social distancing and protective hygiene are the most effective measures to curb the spread of COVID-19. In order to understand how the urban poor mitigate their risk of infection, we conducted a survey with more than 1,400 poor households in two of the African cities with the most COVID-19 infections, Accra and Greater Johannesburg, early in the pandemic, during lockdowns of public life. We find that many of the urban poor already engage in the appropriate hygienic behavior and follow social distancing rules. However, despite citywide lockdowns, about 25-40% of people still report attending large gatherings, 10-20% report receiving guests at home, and 30-35% report leaving the house more than once per week. Lack of cooperation with governmental regulations seems to be more related to a lack of infrastructure or poverty rather than unwillingness to engage in behavioral change. Interestingly, even with the stricter lockdown in South Africa, people are at least equally likely to deviate from social distancing rules. Our results indicate that more South African respondents perceive their government's actions as too extreme and underestimate COVID-19 cases in their country. About half of the sample in both countries report knowing (mainly through TV) about current COVID-19 case numbers. Most participants know that coughing is a symptom, but only half mention fever and difficulty breathing, and very few people mention tiredness. Ghanaians seem to be somewhat better informed. While lack of information is an issue, misinformation appears to be limited. We conclude that a costly shutdown of public life is only effective-and might even be prevented-with a well-informed population, who perceives their government's actions as appropriate and who has access to the infrastructure required to follow WHO safety regulations.

Durizzo|Kathrin|K|
Asiedu|Edward|E|
Van der Merwe|Antoinette|A|
Van Niekerk|Attie|A|
Günther|Isabel|I|

Covid-19
Urban poor
Lockdown
South Africa
Ghana
Mitigation measures


A Rapid Terrestrial Laser Scanning Method for Coastal Erosion Studies: A Case Study at Freeport, Texas, USA.

Abstract: Terrestrial laser scanning (TLS) has become a powerful data acquisition technique for high-resolution high-accuracy topographic and morphological studies. Conventional static TLS surveys require setting up numerous reflectors (tie points) in the field for point clouds registration and georeferencing. To reduce surveying time and simplify field operational tasks, we have developed a rapid TLS surveying method that requires only one reflector in the field. The method allows direct georeferencing of point clouds from individual scans to an East-North-Height (ENH) coordinate system tied to a stable geodetic reference frame. TLS datasets collected at a segment of the beach-dune-wetland area in Freeport, Texas, USA are used to evaluate the performance of the rapid surveying method by comparing with kinematic GPS measurements. The rapid surveying method uses two GPS units mounted on the scanner and a reflector for calculating the northing angle of the scanner's own coordinate system (SOCS). The Online Positioning User Service (OPUS) is recommended for GPS data processing. According to this study, OPUS Rapid-Static (OPUS-RS) solutions retain 1-2 cm root mean square (RMS) accuracy in the horizontal directions and 2-3 cm accuracy in the vertical direction for static observational sessions of approximately 30 min in the coastal region of Texas, USA. The rapid TLS surveys can achieve an elevation accuracy (RMS) of approximately 3-5 cm for georeferenced points and 2-3 cm for digital elevation models (DEMs). The elevation errors superimposed into the TLS surveying points roughly fit a normal distribution. The proposed TLS surveying method is particularly useful for morphological mapping over time in coastal regions, where strong wind and soft sand prohibit reflectors from remaining strictly stable for a long period. The theories and results presented in this paper are beneficial to researchers who frequently utilize TLS datasets in their research, but do not have opportunities to be involved in field data acquisition.

Xiong|Lin|L| Wang|Guoquan|G| Bao|Yan|Y| Zhou|Xin|X| Wang|Kuan|K| Liu|Hanlin|H| Sun|Xiaohan|X| Zhao|Ruibin|R|

coastal erosion
TLS
registration
georeferencing
GPS
OPUS
DEM
LiDAR