The development of a mutation in the precore region of the hepatitis B virus in a chronically infected individual.
Over a 15-year period, a white American woman was observed to have progressive hepatitis B that underwent hepatitis Be antigen (HBeAg) positivity to anti-HBe positivity with development of cirrhosis. This patient was found to have a non-sense mutation in the second codon of the pre-C region of the hepatitis B virus genome after her anti-HBe seroconversion but not in her serum when she was HBeAg+. As controls, serial blood specimens were analyzed from 12 other American patients who spontaneously converted from HBeAg to anti-HBe, who underwent an interferon alfa-associated HBeAg to anti-HBe seroconversion, and who did not seroconvert with interferon alfa therapy. No mutations in the pre-C region were observed to arise in these individuals. In conclusion, non-sense mutations that occur in the pre-C region in locations other than the 28th codon can be associated with HBeAg negative progressive liver disease. This report of a non-sense mutation occurring over time is unusual in that it occurred in a white American patient.


Structure of β-adrenergic receptors.
β-Adrenergic receptors (βARs) control key physiological functions by transducing signals encoded in catecholamine hormones and neurotransmitters to activate intracellular signaling pathways. As members of the large family of G protein-coupled receptors (GPCRs), βARs have a seven-transmembrane helix topology and signal via G protein- and arrestin-dependent pathways. Until 2007, three-dimensional structural information of GPCRs activated by diffusible ligands, including βARs, was limited to homology models that used the related photoreceptor rhodopsin as a template. Over many years, several labs have developed strategies that have finally allowed the structures of the turkey β(1)AR and the human β(2)AR to be determined experimentally. The challenges to overcome included heterologous receptor overexpression, design of stabilized and crystallizable modified receptor constructs, ligand-affinity purification of active receptor and the development of novel techniques in crystallization and microcrystallography. The structures of βARs in complex with inverse agonists, antagonists, and agonists have revealed the binding mode of ligands with different efficacies, have allowed to obtain insights into ligand selectivity, and have provided better templates for drug design. Also, the structures of β(2)AR in complex with a G protein and a G protein-mimicking nanobody have provided important insights into the mechanism of receptor activation and G protein coupling. This chapter summarizes the strategies and methods that have been successfully applied to the structural studies of βARs. These are exemplified with detailed protocols toward the structure determination of stabilized turkey β(1)AR-ligand complexes. We also discuss the spectacular insights into adrenergic receptor function that were obtained from the structures.


Acute ischemic syndromes. Early response.
The optimal treatment of patients with AIS depends on a well-run, integrated system of care involving patients and teams of health care professionals. It begins with patient education and extends to a method for accessing an efficient and effective EMS system. Medics must be well equipped and well trained to evaluate and begin initial treatment during prompt transport to an appropriate hospital. The role of out-of-hospital 12-lead ECGs and thrombolysis is reviewed and may be appropriate for some EMS systems. The initial evaluation and treatment in the ED goes on simultaneously and is a dynamic process. Prompt treatment with oxygen, nitroglycerin, morphine, and aspirin is indicated. Initial risk stratification is based on the first ECG, cardiac biomarkers, and the clinical history and physical exam. Disposition and further evaluation is individualized according to the initial work-up and risk assessment.


Chromosome aberrations in peripheral lymphocytes of male homosexuals.
Karyotypes of peripheral lymphocytes of 19 male homosexuals showed increased hypodiploidy. Chromosomes #19 and #20 were most frequently lost. Also, structural chromosome aberrations frequently occurred consisting chiefly of translocations and simple chromosome breaks. Terminal deletions, inversions, and isochromosomes occurred less commonly. In three of the cases, 100% of the cells were involved in a pericentric inversion of a chromosome #9. Chromosomes #3 in p21.1 and 1 in p32.3 were repeatedly affected. Structural aberrations were seen less frequently in men with acquired immunodeficiency syndrome(AIDS) and AIDS-related complex than in asymptomatic homosexuals. The hypodiploidy with preferential loss of chromosomes was constantly present. The marker chromosomes and simple breaks at repeated sites are another manifestation of damage to the immune system in these male homosexuals from Greenwich Village in New York City. The chromosomal damage was potentially the result of exposure to amyl and butyl nitrites, viral infections, or immunologic reactions to sperm, which crossreact with lymphocytes.


15-year aeroallergen records. Their usefulness in Athens Olympics, 2004.
About 5-25% of 16 000 athletes involved in preparation for the Athens 2004 Olympics may encounter respiratory allergy (asthma and rhinoconjunctivitis) triggered by exposure to aeroallergens (pollen and fungi spores). Provide information about circulating aeroallergens in three Olympic cities and ensure safety for the allergic athletes who will visit Greece from January to September 2004. Aeroallergens were recorded using a Burkard volumetric trap. The most frequently implicated pollen (cypress, hazel, wall pellitory, plane, olive, grasses, goosefoot and mugwort) and fungi spores (Alternaria spp., Cladosporium spp.) are presented. These data derive from a 15-year database created by the Pulmonary Department, Thessaloniki, a 2-year database (University of Heraklion-Crete) and a 6-year database by the Pediatric Department, Athens. The above data and the current aeroallergen counts will be continuously announced by the mass media and Internet during the Athens 2004 Olympics. Are expressed as: (A) Presentation (Graphs, Tables) of the fluctuation of mean daily values of pollen grains or fungi spores/m3. (B) Presentation (Tables) of the start, peak and end time of aeroallergen circulation. Peak pollen concentrations were observed between March and May (athletes preparation time). During the 2004 Olympics (August-September) relatively high concentrations of goosefoot, mugwort, Alternaria and Cladosporium will be observed. Aeroallergens circulate in Athens 10-15 days earlier than in Thessaloniki and 10 days later than in Heraklion. The data presented in the study are expected to help allergic Olympic athletes achieve peak performance under prophylactic measures.


Persistent subretinal indocyanine green induces retinal pigment epithelium atrophy.
To describe a case of a patient with macular hole with subretinal indocyanine green (ICG) during vitrectomy. Interventional case report. A 66-year-old woman with macular hole underwent a vitrectomy with ICG. After application of ICG into the vitreous, ICG was introduced in the subretinal space. Indocyanine green was found to be present for more than 6 months. Retinal pigment epithelium atrophy appeared at the site of the lesion. Although ICG may be a useful tool for distinguishing the internal limiting membrane and other tissues careful application is required to prevent side effects.


Light traps fail to estimate reliable malaria mosquito biting rates on Bioko Island, Equatorial Guinea.
The human biting rate (HBR), an important parameter for assessing malaria transmission and evaluating vector control interventions, is commonly estimated by human landing collections (HLC). Although intense efforts have been made to find alternative non-exposure mosquito collection methods, HLC remains the standard for providing reliable and consistent HBRs. The aim of this study was to assess the relationship between human landing and light trap collections (LTC), in an attempt to estimate operationally feasible conversion factors between the two. The study was conducted as part of the operational research component of the Bioko Island Malaria Control Project (BIMCP), Equatorial Guinea. Malaria mosquitoes were collected indoors and outdoors by HLCs and LTCs in three villages on Bioko Island, Equatorial Guinea during five bimonthly collections in 2009. Indoor light traps were suspended adjacent to occupied long-lasting, insecticide-treated bed nets. Outdoor light traps were placed close to the outer wall under the roof of the collection house. Collected specimens were subjected to DNA extraction and diagnostic PCR to identify species within the Anopheles gambiae complex. Data were analysed by simple regression of log-transformed values and by Bayesian regression analysis. There was a poor correlation between the two collection methods. Results varied by location, venue, month, house, but also by the statistical method used. The more robust Bayesian analyses indicated non-linear relationships and relative sampling efficiencies being density dependent for the indoor collections, implying that straight-forward and simple conversion factors could not be calculated for any of the locations. Outdoor LTC:HLC relationships were weak, but could be estimated at 0.10 and 0.07 for each of two locations. Light trap collections in combination with bed nets are not recommended as a reliable method to assess human biting rates on Bioko Island. Different statistical analyses methods give variable and inconsistent results. Substantial variation in collection methods prevents the determination of reliable and operationally feasible conversion factors for both indoor and outdoor data. Until improved mosquito collection methods are developed that can provide reliable and unbiased HBR estimates, HLCs should continue to serve as the reference method for HBR estimation.


The association between three major physiological stress systems and oxidative DNA and lipid damage.
Increased activity of the three major physiological stress systems (immune-inflammatory system, hypothalamic-pituitary-adrenal-axis [HPA-axis], and autonomic nervous system [ANS]) is part of the pathophysiology of various somatic and psychiatric diseases. Oxidative damage is a key mechanism in both ageing and disease. Elucidating the relationship between these stress systems and oxidative damage would contribute to the understanding of the role of physiological stress in disease. This study therefore investigates associations between various measures of physiological stress and oxidative DNA (8-hydroxy-2'-deoxyguanosine, 8-OHdG) and lipid (F2-isoprostanes) damage. Plasma 8-OHdG and F2-isoprostanes were measured using LC-MS/MS in 2858 subjects (aged 18-65). Plasma inflammation markers, salivary cortisol and ANS markers (three for each stress system) were determined. Linear regression analyses were adjusted for sociodemographics, sampling factors and medication. 8-OHdG was positively associated with all inflammation markers (β=0.047-0.050, p<0.01), evening cortisol (β=0.073, p<0.001), and unexpectedly with low respiratory sinus arrhythmia (RSA) reflecting low ANS stress (β=0.073, p<0.001). F2-isoprostanes were associated with higher C-reactive protein (β=0.072, p<0.001), high ANS stress reflected in heart rate (β=0.064, p<0.001) and RSA (β=-0.076, p=0.001), but not with cortisol. Analyses investigating the cumulative impact of the stress systems demonstrated that the number of systems with ≥1 marker in the high risk quartile showed a positive linear trend with both 8-OHdG (p=0.030) and F2-isoprostanes (p=0.009). This large-scale study showed that markers of inflammation, the HPA-axis and ANS are associated with oxidative DNA damage. Oxidative lipid damage is associated with inflammation and the ANS. Increased physiological stress across systems is associated with increasing oxidative damage in a dose-response fashion.


Interventional bleeding, hematoma and scar-formation after vacuum-biopsy under stereotactic guidance: Mammotome(®)-system 11 g/8 g vs. ATEC(®)-system 12 g/9 g.
To evaluate prospectively the correlation of scar-formations after vacuum-assisted biopsy with different systems and needle-sizes and interventional bleeding/post-interventional hematoma. Between 01/2008 and 12/2009, 479 patients underwent vacuum-assisted biopsy under stereotactic-guidance, using the Mammotome(®)-system with 11/8-gauge and ATEC(®)-system with 12/9-gauge, whereas in 178 cases with representative benign histology no surgical-biopsy after vacuum-assisted biopsy was performed and at least a 2-plane-follow-up-mammogram after 6 month post-vacuum-assisted biopsy was available. Bleeding during intervention, hematoma post-intervention and scar-tissue was scored as minimal and moderate/severe. Statistical analysis included Chi-Square-trend-test, p-value <0.05 was considered to be significant. Significantly more bleedings and post-interventional hematomas for 8-gauge-Mammotome(®)-system vs. 11-gauge-Mammotome(®)-system (41.9% vs. 8.4%, p<0.001/35.5% vs. 16.7%, p=0.029), no significant-differences for the ATEC(®)-systems 9-gauge vs. 12-gauge (26.9% vs. 29.7%, p=0.799/42.3% vs. 43.2%, p=0.596). 11-gauge-Mammotome(®)-system vs. ATEC(®)-12-gauge-system revealed significantly less bleedings/hematomas (8.4% vs. 29.7%, p=0.015/16.7% vs. 43.2%, p=0.001), no significant differences for the large-systems (p=0.135/p=0.352). Follow-up of Mammotome(®)-11/8-gauge-system system has shown 13.1/16.1% minimal scar-formation and 1.2/3.2% moderate/severe scars, whereas ATEC(®)-12/9-gauge-system has shown 10.8/3.8% minimal scar-formation and 0/11.5% moderate/severe scars, no significant differences. No significant difference was found when comparing Mammotome(®)-11/8-g-systems vs. ATEC(®)-12/9-g-systems (p=0.609/p=0.823). There was also no correlation between risk of scar-formation after occurrence of bleeding or hematoma with any examined VAB-system or any needle size in this study (p=0.800). Using larger needle-sizes significantly (Mammotome(®))/not significant for ATEC(®)) more interventional bleedings and post-interventional hematomas were detected, only a tendency concerning scar-formation.


Recovery of muscle from tetrodotoxin-induced disuse and the influence of daily exercise. 1. Contractile properties.
The extent of recovery in rat gastrocnemius muscles which have undergone atrophic changes due to 4 weeks of inactivity caused by sciatic nerve superfusion of tetrodotoxin, was investigated. Control and tetrodotoxin-treated female Sprague-Dawley rats were subjected to either a daily program of grid-climbing or swim-training for 4 weeks, or benefited from cage activity only. In situ contractile properties of the gastrocnemius were then measured. Twenty-eight days of recovery was insufficient to allow a complete reversal of the changes produced by 28 days of inactivity. The gastrocnemius remained atrophied (25%) and tetanically weaker than normal in the recovered animals. The maximal rate of rise of the twitch was partially recovered whereas that developed during a maximal contraction was normal. Maximal rate of rise expressed relative to the tension output was elevated, however, for both twitch (%Pt/ms) and maximal contraction (%Po/ms). Swimming did not influence the recovery of muscle size or strength. Grid-climbing, on the other hand, produced heavier and stronger muscles and a faster recovery of %Pt/ms. This study clearly illustrates the importance of muscle load in regulating muscle size and strength.


Is attention needed for word identification? Evidence from the Stroop paradigm.
One of the most robust findings in attention research is that the time to name a color is lengthened markedly in the presence of an irrelevant word that spells a different color name: the Stroop effect. The Stroop effect is found even when the word is physically separated from the color, apparently indicating that words can be read outside the focus of spatial attention. The present study critically evaluated this claim. We employed several stringent measures within a Stroop paradigm to prevent participants from attending to the irrelevant words (e.g., limiting exposure duration to prevent attention capture). Nonetheless, residual Stroop effects were obtained for both color words and semantic associates (e.g., sky to blue). These data suggest that lexical processing can sometimes occur outside the focus of spatial attention.


Mapping the cerebral blood vessels with high-field MRI: technical and anatomic review.
The technical background and quality of images obtained upon studying the cerebral circulation with high-field MRI are reviewed. Fifty studies were selected as representative of normal cerebral blood vessels to illustrate the anatomic information derived from the review. MRI appears to be a safe, easy, and reliable method of imaging the cerebral circulation noninvasively.


Does failure to mask T1 cause lag-1 sparing in the attentional blink?
The attentional blink (AB) effect demonstrates that when participants are instructed to report two targets presented in a rapid visual stimuli stream, the second target (T2) is often unable to be reported correctly if presented 200-500 msec after the onset of the first target (T1). However, if T2 is presented immediately after T1, in the conventional lag-1 position (100-msec stimulus onset asynchrony; SOA), little or no performance deficit occurs. The present experiments add to the growing literature relating the "lag-1 sparing" effect to T1 masking. Using a canonical AB paradigm, our results demonstrate that T2 performance at lag 1 is significantly reduced in the presence of T1 masking. The implications of this outcome are discussed in relation to theories of the AB.


Retraction Note: Downregulated poly-C binding protein-1 is a novel predictor associated with poor prognosis in acute myeloid leukemia.
This article [1] is retracted at request of the Editor.


Ring melanoma of the ciliary body: clinical and ultrasound biomicroscopic characteristics.
Diagnosis of ring melanoma is clinically difficult since the mass can remain hidden with standard slit-lamp biomicroscopy. The aim of this study was to evaluate the utility of ultrasound biomicroscopy (UBM) as a diagnostic tool for ring melanoma of the ciliary body. This was a retrospective study of 6 eyes of 6 patients at Princess Margaret Hospital, Toronto, Ont., with a diagnosis of ring melanoma of the ciliary body. The tumor extension was measured clinically, gonioscopically, ultrasonographically (by UBM), and pathologically. Since 2000, 6 cases of ring melanoma have been diagnosed at Princess Margaret Hospital: 2 women and 4 men, median age 57 years. Five patients presented as uncontrolled hyperchromic glaucoma (83%). Ciliary body involvement on slit-lamp examination ranged from 60 to 180 degrees. Ciliary body involvement as assessed by UBM ranged from 180 to 300 degrees. Tumor extension according to pathological examination ranged from 210 to 360 degrees. With these measures, the ring melanoma clinical criteria were not filled by 5 patients. UBM is an important tool in determining the extent of ciliary body involvement and classifying these lesions.


Membrane topology of the Mep/Amt family of ammonium transporters.
The Mep/Amt proteins constitute a new family of transport proteins that are ubiquitous in nature. Members from bacteria, yeast and plants have been identified experimentally as high-affinity ammonium transporters. We have determined the topology of AmtB, a Mep/Amt protein from Escherichia coli, as a representative protein for the complete family. This was established using a minimal set of AmtB-PhoA fusion proteins with a complementary set of AmtB-LacZ fusions. These data, accompanied by an in silico analysis, indicate that the majority of the Mep/Amt proteins contain 11 membrane-spanning helices, with the N-terminus on the exterior face of the membrane and the C-terminus on the interior. A small subset, including E. coli AmtB, probably have an additional twelfth membrane-spanning region at the N-terminus. Addition of PhoA or LacZ alpha-peptide to the C-terminus of E. coli AmtB resulted in complete loss of transport activity, as judged by measurements of [14C]-methylammonium uptake. This C-terminal region, along with four membrane-spanning helices, contains multiple residues that are conserved within the Mep/Amt protein family. Structural modelling of the E. coli AmtB protein suggests a number of secondary structural features that might contribute to function, including a putative ammonium binding site on the periplasmic face of the membrane at residue Asp-182. The implications of these results are discussed in relation to the structure and function of the related human Rhesus proteins.


[Importance of early retinal fluorescein angiography in candidiasis in drug addicts].
Three cases of Candida albicans endophthalmia in drug addicts are reported. Three important signs suggestive of a fungal etiology for choroiditis are discussed: location of the granuloma at the end of a macular arteriole, early leak of fluorescein to the vitreous body, and solitary papillitis.


A nomogram for predicting the optimal oral dosage of tacrolimus in liver transplant recipients with small-for-size grafts.
No optimal tacrolimus dosage regimen suitable for clinical use in liver transplant recipients has yet been established. The purpose of this study was to determine the factors affecting the optimal dosage and pharmacokinetics of tacrolimus in living donor liver transplantation, and a nomogram for optimal tacrolimus dosage in the immediate postoperative period for recipients with small-for-size grafts was constructed. Twenty-four liver transplant patients (nine males and 15 females) and 24 donors (10 males and 14 females) were enrolled in this study. Two studies were performed. In study 1, the effect of the actual ratio of graft volume to standard liver volume (GV/SV ratio) on the elimination half-life (T1/2) of tacrolimus in the immediate postoperative period was analysed, and a nomogram for estimating the optimal oral dose of tacrolimus required to reach a target concentration was established. In study 2, the effect of donor age on the recovery of hepatic function with ability of the graft to eliminate tacrolimus was analysed. In the immediate postoperative period, T1/2 of tacrolimus showed great variability between patients, with values ranging from 16.3 to 110.9 h. Graft size (GV/SV ratio) is important and could influence intraindividual variations in the optimal dosage and T1/2 of tacrolimus. The recovered T1/2 ratio (T1/2 ratio=T1/2 1-10 d/T1/2 30-40 d), this ratio being related to the recovery of hepatic function with ability of the graft to eliminate tacrolimus, showed great variability between patients, with values ranging from 1.08 to 4.21 (mean+/-SD, 1.95+/-0.81). Age of the donor is a major factor affecting the recovered ratio of the graft to metabolize tacrolimus. The nomogram that we have constructed, based on graft size (GV/SV ratio), will easily provide optimal dose for each patient with small-for-size graft in the early postoperative period.


An evaluation of the therapeutic effects and dosage equivalence of glyburide and glipizide.
Nineteen noninsulin-dependent diabetic patients [ten women, nine men, aged 36-80 years (mean +/- SE 56.8 +/- 2.7 years)] were randomized to receive either glyburide or glipizide for 16 weeks, in a double-blind crossover fashion. A 2-week washout period preceded each treatment period. The patients measured blood glucose concentrations 16 times weekly using Chemstrip-bG. The medication dosages were titrated to achieve fasting blood glucose concentrations of less than or equal to 6.2 mM and preprandial and postprandial concentrations of less than or equal to 9.0 mM, or to a total daily dose of 20 mg for glyburide and 40 mg for glipizide. Glyburide therapy resulted in a significant decline in fasting, preprandial, postprandial and bedtime blood glucose levels, while glipizide treatment led to a significant lowering of postprandial and bedtime blood glucose. Furthermore, fasting, preprandial and postprandial blood glucose concentrations were significantly lower during glyburide as compared to glipizide treatment phase. Glycosylated hemoglobin levels were decreased only with glyburide. Serum C-peptide and insulin concentrations were not altered over the entire study. The mean final daily dose of glyburide (15.4 +/- 1.6 mg) was markedly lower than that of glipizide (29.7 +/- 3.1 mg). Thus, in this patient population, glyburide was twice as potent on a weight basis than glipizide.


In vitro growth characteristics and heterogeneity of mouse hepatitis virus type 3.
The in vitro virus yield of MHV3 reached 10(7) PFU/ml in mouse DBT cells infected with a virus suspension in HEPES-buffered medium containing DEAE-dextran. The virus titer was 10(6) PFU/ml in the presence of 10 micrograms actinomycin D/ml MHV3 growth in DBT cells gave three peaks of density (1.10--1.14 g/cm3, 1.18--1.20 g/cm3, and 1.25--1.31 g/cm3) in sucrose gradients. All these peaks retained infectivity.


Impact of Genetic Variant Reassessment on the Diagnosis of Arrhythmogenic Right Ventricular Cardiomyopathy Based on the 2010 Task Force Criteria.
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy, which is associated with life-threatening ventricular arrhythmias. Approximately 60% of patients carry a putative disease-causing genetic variant, but interpretation of genetic test results can be challenging. The aims of this study were to systematically reclassify genetic variants in patients with ARVC and to assess the impact on ARVC diagnosis. This study included patients from the Multicenter Zurich ARVC Registry who hosted a genetic variant deemed to be associated with the disease. Reclassification of pathogenicity was performed according to the modified 2015 American College of Medical Genetics criteria. ARVC diagnosis (categories: definite, borderline, possible) based on the 2010 Task Force Criteria was reclassified after genetic readjudication. In 79 patients bearing 80 unique genetic variants, n=47 (58.8%) genetic variants were reclassified, and reclassification was judged to be clinically relevant in n=33 (41.3%). Variants in plakophilin-2 (PKP2) were shown to reclassify less frequently as compared with other genes (PKP2, n=1, 8.3%; desmosomal non-PKP2, n=20, 66.7%; nondesmosomal, n=26, 68.4%; P=0.001for overall comparison; PKP2 versus desmosomal non-PKP2, P=0.001; PKP2 versus nondesmosomal, P<0.001). Genetic reclassification impacted ARVC diagnosis. Eight patients (10.1%) were downgraded from definite to borderline/possible disease at the time of initial genetic testing as well as last follow-up, respectively. Separate genetic reclassification in family members led to downgrading of n=5 (38.5%) variants. Given that approximately half of genetic variants were reclassified, with 10.1% of patients losing their definite disease status, accurate determination of variant pathogenicity is of utmost importance in the diagnosis of ARVC.


Central and peripheral injection of quaternary antagonist, SR58002C, reduces drinking.
Earlier research has demonstrated that opioid involvement in drinking is primarily mediated centrally [8,10]. Drinking is attenuated by the centrally and peripherally active opioid antagonists naloxone and naltrexone in doses as low as 1.0 mg/kg, but not by the quaternary forms of these antagonists [4]. Peripherally administered quaternary forms of these antagonists fail to suppress drinking in doses as high as 10 mg/kg. We generated dose-response curves for centrally and peripherally administered SR58002C, a "newer" quaternary opioid antagonist purported to have high peripheral selectivity, on drinking in 23.5 hr water deprived rats. SR58002C was administered both intracerebroventricularly (ICV, 0, 10, 40 and 80 micrograms/rat) and intraperitoneally (IP, 0, 10, 40 and 80 mg/kg). Doses of SR58002C above 10 mg/kg IP or 10 micrograms ICV significantly reduced drinking in comparison to controls. However, SR58002C appears to be less potent than quaternary naltrexone in suppressing drinking after ICV administration.


Erratum: Triple therapy with salmeterol/fluticasone propionate 50/250 plus tiotropium bromide improve lung function versus individual treatments in moderate-to-severe Japanese COPD patients: a randomized controlled trial - Evaluation of Airway sGaw after treatment with tripLE [Corrigendum].
[This corrects the article on p. 2393 in vol. 10, PMID: 26604737.].


Post-dialysis fatigue: Comparison of bicarbonate hemodialysis and online hemodiafiltration.
The present cross-sectional study aimed to compare the prevalence, the characteristics of post-dialysis fatigue and the length of recovery time after hemodialysis in prevalent end-stage renal disease patients (ESRD) receiving bicarbonate hemodialysis (HD) or hemodiafiltration (HDF). Patients were suffering from post-dialysis fatigue if they spontaneously offered this complaint when asked the open-ended question: "Do you feel fatigued after dialysis?". Moreover, each patient was invited to rate the intensity, duration, and frequency of post-dialysis fatigue from 1 to 5. In order to assess RECOVERY TIME AFTER DIALYSIS, patients were invited to answer to the following single open-ended question: "How long does it take you to recover from a dialysis session?" We included 335 patients: 252 received HD and 83 received HDF. Post-dialysis fatigue was present in 204 patients (60.9%). Prevalence of post-dialysis fatigue did not differ significantly between patients on HD (62.3%) and on HDF (56.6%; p = 0.430). Median recovery time after dialysis was 180 min [180-240] and did not differ significantly between the two subgroups (180 min [130-240] and 240 min [120-332] p = 0.671, respectively). Median post-dialysis fatigue intensity, duration, and frequency were 3 [1-5], 3 [1-5], and 4 [1-5] and did not differ significantly between patients on HD and on HDF. At the multivariate analysis, age, ADL and hemoglobin levels were the independent predictors of the HDF treatment. Prevalence and characteristics of post-dialysis fatigue do not differ significantly between patients receiving bicarbonate HD or HDF.


Observations on thermostable subpopulations of the unconventional agents that cause transmissible degenerative encephalopathies.
When scrapie agent is exposed to partially inactivating autoclave cycles, the fraction of infectivity that survives remains thermostable during relatively long periods of autoclaving. This resistant subpopulation can also be differentiated from the main population by its prolonged incubation periods in assay animals, compared with control material. Stabilisation of this subpopulation may occur through the smearing and drying of infected tissue that can occur prior to autoclaving, in which the disease-specific form of PrP protein (PrP(Sc)) could become rapidly heat-fixed. This may paradoxically be what protects this fraction of PrP(Sc) from further inactivation during autoclaving. Data are presented showing that the thermostability acquired by the resistant subpopulation is a stable characteristic; autoclaving for a second time results in very little further loss of infectivity. These observations suggest that inactivation procedures that do not involve rapid and effective fixation of PrP(Sc) may be better candidates for dealing effectively with scrapie-like agents.


Cost-Effectiveness Analyses on Various Models of The Red Light, Purple Light Self-Regulation Intervention for Young Children.
Early childhood interventions can improve self-regulation, but there are few economic evaluations of such interventions. This study analyzed the cost-effectiveness of an early childhood self-regulation intervention (Red Light Purple Light!; RLPL), comparing three different models of implementation across stages of intervention development: (Model 1) trained research assistants (RAs; graduate students) directly delivered the RLPL intervention to children; (Model 2) RAs trained trainers (e.g., program coaches), who then trained teachers to implement RLPL with children (e.g., train-the-trainer); and (Model 3) program faculty trained teachers to deliver the RLPL intervention to children. We implemented a cost-effectiveness analysis by calculating the incremental cost-effectiveness ratio. We also conducted a series of sensitivity analyses to adjust for parameter uncertainty. Our base-case analysis suggests that Model 2 was the most cost-effective strategy, in that a cost of $23 per child was associated with a one-unit increase of effect size on self-regulation scores. The "train-the-trainer" model remained the optimal strategy across scenarios in our sensitivity analysis. This study fills an important gap in cost-effectiveness analyses on early childhood self-regulation interventions. Our process and results can serve as a model for future cost-effectiveness analyses of early childhood intervention programs and may ultimately inform decisions related to intervention adoption that optimize resource allocation and improve program design.


Microplastic Pollution Focused on Sources, Distribution, Contaminant Interactions, Analytical Methods, and Wastewater Removal Strategies: A Review.
Plastics have been one of the most useful materials in the world, due to their distinguishing characteristics: light weight, strength, flexibility, and good durability. In recent years, the growing consumption of plastics in industries and domestic applications has revealed a serious problem in plastic waste treatments. Pollution by microplastics has been recognized as a serious threat since it may contaminate all ecosystems, including oceans, terrestrial compartments, and the atmosphere. This micropollutant is spread in all types of environments and is serving as a "minor but efficient" vector for carrier contaminants such as pesticides, pharmaceuticals, metals, polychlorinated biphenyls (PCBs), and polycyclic aromatic hydrocarbons (PAHs). The need to deeply study and update the evolution of microplastic sources, toxicology, extraction and analysis, and behavior is imperative. This review presents an actual state of microplastics, addressing their presence in the environment, the toxicological effects and the need to understand their extent, their interactions with toxic pollutants, the problems that arise in the definition of analytical methods, and the possible alternatives of treatments.


A tough, healable, and recyclable conductive polyurethane/carbon nanotube composite.
Recently, conductive composites have been used in flexible electronic devices and have attracted attention. The integration of self-healing, high sensitivity, large tensile strength, environmental stability, and easy recyclability into conductive composites is very desirable yet challenging. Hence, a conductive composite as a flexible strain sensor with a self-healing and recyclability is facilely developed, with a polyurethane (PU) elastomer bearing dynamic boronic ester as the polymer matrix and carbon nanotubes (CNTs) as a conductive filler. Due to the dynamic boronic ester bond and hydrogen bond, the prepared polyurethane conductive composite has good self-healing and mechanical properties. It not only has a high healing efficiency of 78 % but also has a tensile strength of 15.4 MPa and an elongation at break of 420 %. In addition, the prepared conductive composite has high conductivity (0.57 mS/cm) and sensitivity. As a wearable sensor, it can identify human activities in all directions, such as elbow and finger bending, speaking, and facial changes. Consequently, the polyurethane conductive composite prepared in this study exhibited wonderful application potential in wearable electronic devices such as self-healing strain sensors.


Musculoskeletal changes in children prenatally exposed to polychlorinated biphenyls and related compounds (Yu-Cheng children).
Fifty-five Yu-Cheng (oil-disease) children born between 1978 and 1985 to mothers who ate PCB-contaminated rice oil in 1978-1979 were studied and compared to age- and sex-matched control subjects in 1991. The children's growth profiles, bone mineral density and soft tissue composition, joint laxity, and serum parathyroid hormone, vitamin D, calcium, alkaline phosphatase, and phosphate were compared. The Yu-Cheng children were 3.1 cm (p < .05) smaller and had less total lean mass and soft tissue mass as compared to the matched control subjects. All other parameters studied were similar in both groups. The shorter height and decreased total lean mass and soft tissue content were only seen in the Yu-Cheng children who were the first born after the ingestion, but not in subsequent children. This was most likely due to decreased body burdens of the PCBs and related contaminants over time in the mothers.


High performance data compression method with pattern matching for biomedical ECG and arterial pulse waveforms.
Biomedical waveforms, such as electrocardiogram (ECG) and arterial pulse, always possess a lot of important clinical information in medicine and are usually recorded in a long period of time in the application of telemedicine. Due to the huge amount of data, to compress the biomedical waveform data is vital. By recognizing the strong similarity and correlation between successive beat patterns in biomedical waveform sequences, an efficient data compression scheme mainly based on pattern matching is introduced in this paper. The waveform codec consists mainly of four units: beat segmentation, beat normalization, two-stage pattern matching and template updating and residual beat coding. Three different residual beat coding methods, such as Huffman/run-length coding, Huffman/run-length coding in discrete cosine transform domain, and vector quantization, are employed. The simulation results show that our compression algorithms achieve a very significant improvement in the performances of compression ratio and error measurement for both ECG and pulse, as compared with some other compression methods.


Improved automated kinetic determination of uric acid in serum by use of uricase/catalase/aldehyde dehydrogenase.
The enzymatic determination of serum uric acid by use of uricase, catalase, and aldehyde dehydrogenase according to Haeckel [J. Clin. Chem. Clin Biochem. 14, 101 (1976)] showed interferences from ethanol-converting enzymes, which are present in some patients' sera. We have identified these enzymes as alcohol dehydrogenase isoenzymes. Among other substances, a mixture of pyrazole and oxalate can be used to eliminate these interferences. This inhibitor system gives good results when used in the automated kinetic uric acid determination, as is shown by a comparison with the manual assay for uric acid according to Kageyama [Clin. Chim. Acta 31, 421 (1971)].


Multiple drug-resistance in Shigella flexneri isolated from a patient with human immunodeficiency virus.
Persistent shigellosis, due to Shigella flexneri resistant to multiple antibiotics, developed in a 40-yr-old homosexual man with human immunodeficiency virus infection. The Shigella strain demonstrated resistance to ampicillin, tetracycline, and trimethoprim-sulfamethoxazole. Although Shigella flexneri isolates resistant to trimethoprim-sulfamethoxazole are uncommon in the United States, laboratories should monitor resistance patterns through routine in vitro susceptibility testing.


Emerging Entities in Renal Neoplasia.
This article reviews emerging entities in renal epithelial neoplasia, including tubulocystic carcinoma, clear-cell-papillary renal cell carcinoma (RCC), thyroid-like follicular RCC, ALK-related RCC, translocation RCC, acquired cystic disease-related RCC, succinate dehydrogenase-deficient RCC, and hereditary leiomyomatosis-RCC syndrome-associated RCC. Many of these rarer subtypes of RCC were recently studied in more depth and are included in the upcoming version of the World Health Organization classification of tumors. Emphasis is placed on common gross and morphologic features, differential diagnoses, use of ancillary studies for making accurate diagnoses, molecular alterations, and predicted biologic behavior based on previous studies.


State and trait anxiety levels of adolescents in a changing society, Kirikkale city, Turkey.
Adolescents face rapidly changing challenges. Psychosocial health problems during adolescence are relatively common in all cultures. This study was designed to evaluate the state and trait anxiety status and influencing sociodemographic and other factors, thought to pertain to youth, on anxiety among school children in Kirikkale. It was carried out at three public primary and two high schools representative of two different socioeconomic statuses. 430 Turkish school children (246 girls, 184 boys) were asked voluntarily to answer a set of questionnaires in their classrooms at the beginning of a training programme. Then the State and Trait Anxiety Inventory for Children was administered. Mean age of the students was 14.16 ± 1.87 years. The mean total STAI-CS and STAI-CT scores were 40.24 ± 11.64, and 44.71 ± 9.64, respectively. There were no differences in STAI-CS and STAI-CT scores between boys and girls in both schools and in all age groups. Among girls, a positive body image had a significant effect on state anxiety scores. There was a positive correlation between age and anxiety scores (r = .17, F:12.176, p < .001). Students identifying their families SES as bad and/or moderate scored significantly higher in comparison to the other groups (p < .05). STAI-CS scores were higher for lower educational grade, higher body weight and sleep problems. In Kirikkale, a city faced with substantial changes in cultural and traditional norms, adolescents could be expected to be under stress and appear to be responding to stress with anxiety.


Defined core-shell particles as the key to complex interfacial self-assembly.
The two-dimensional self-assembly of colloidal particles serves as a model system for fundamental studies of structure formation and as a powerful tool to fabricate functional materials and surfaces. However, the prevalence of hexagonal symmetries in such self-assembling systems limits its structural versatility. More than two decades ago, Jagla demonstrated that core-shell particles with two interaction length scales can form complex, nonhexagonal minimum energy configurations. Based on such Jagla potentials, a wide variety of phases including cluster lattices, chains, and quasicrystals have been theoretically discovered. Despite the elegance of this approach, its experimental realization has remained largely elusive. Here, we capitalize on the distinct interfacial morphology of soft particles to design two-dimensional assemblies with structural complexity. We find that core-shell particles consisting of a silica core surface functionalized with a noncrosslinked polymer shell efficiently spread at a liquid interface to form a two-dimensional polymer corona surrounding the core. We controllably grow such shells by iniferter-type controlled radical polymerization. Upon interfacial compression, the resulting core-shell particles arrange in well-defined dimer, trimer, and tetramer lattices before transitioning into complex chain and cluster phases. The experimental phase behavior is accurately reproduced by Monte Carlo simulations and minimum energy calculations, suggesting that the interfacial assembly interacts via a pairwise-additive Jagla-type potential. By comparing theory, simulation, and experiment, we narrow the Jagla g-parameter of the system to between 0.9 and 2. The possibility to control the interaction potential via the interfacial morphology provides a framework to realize structural features with unprecedented complexity from a simple, one-component system.


Fractionation and bioavailability of metals and their impacts on microbial properties in sewage irrigated soil.
A study was conducted to evaluate the effect of long-term irrigation of sewage contaminated with heavy metals like Cd, Cr, Cu and Pb on microbial and biochemical parameters of soils of West Bengal, India. The microbial parameters included microbial biomass carbon (MBC), microbial metabolic quotient; the biochemical parameters included fluorescein diacetate hydrolyzing activity, beta-glucosidase, urease, phosphatase, and aryl sulphatase activities. A sequential extraction technique was used to quantify water soluble, exchangeable, carbonate bound, Fe/Mn-oxide bound, organically bound, and residual metal fractions. Metal concentrations in the two most labile fractions (i.e., water soluble and exchangeable fractions) were generally low. Total metal concentrations at each site seemed to be associated with soil amorphous Fe and Al minerals. The MBC and the enzymes studied were significantly and negatively correlated with water soluble and exchangeable metals but not significantly correlated with other forms, indicating that water soluble and exchangeable forms exerted a strong inhibitory effect on the soil microbial and biochemical parameters. It was concluded that irrigating soils with metal contaminated sewage seemed to damage soil quality in the long term.


Pharmacokinetics of Morphine Sulfate Orodispersible Tablets and Bioequivalence with Immediate-Release Oral Morphine Sulfate Formulations in Healthy Adult Subjects Under Fasting Conditions: Single-Dose Comparative Bioavailability Studies.
An orodispersible tablet (ODT) formulation of morphine sulfate has been developed to provide a novel alternative for patients with severe pain requiring opioids. This formulation has been developed in a range of doses (1-30 mg), enabling relief from severe pain to be achieved and maintained with the lowest possible morphine dose for each patient. The ODT formulation is particularly suitable for patients with swallowing difficulties. The aim of this study was to compare the pharmacokinetics and bioequivalence of the ODTs with reference formulations of morphine sulfate. Three randomized, single-dose, laboratory-blinded, phase I, crossover studies were conducted in adult healthy volunteers under fasting conditions. The pharmacokinetics of a 30 mg morphine sulfate ODT were compared with those of equivalent doses of currently marketed oral immediate-release formulations: tablets (Sevredol®), capsules (Actiskenan®), and a solution (Oramorph®). The bioequivalence of 30 mg and 10 mg doses of the ODTs and tablets was then assessed in two further studies. Subjects were asked to complete a product appreciation questionnaire for two morphine formulations (ODT and solution). A total of 104 subjects were included across the three studies. The pharmacokinetics of the ODTs were assessed in 100 subjects and were found to be similar to those of the reference formulations. The time to maximum plasma concentration (Tmax) for the ODTs was 0.8 h, within the range observed for the reference formulations (0.75-1.25 h). Maximum plasma concentrations (Cmax) for the ODTs were 7.7 ± 2.7 ng/mL for the 10 mg dose and 26.1 ± 10.0 ng/mL for the 30 mg dose. These values were similar to those obtained for the 10 mg and 30 mg tablets (8.0 ± 2.9 ng/mL and 28.5 ± 11.9 ng/mL, respectively), and for the 30 mg capsule (29.9 ± 13.0 ng/mL). A higher Cmax was observed for the solution (37.9 ± 16.5 ng/mL). Plasma exposure to morphine (area under the plasma drug concentration-time curve [AUC]) after ODT administration was similar to that observed for the reference formulations: 39.8 ± 14.8 ng·h/mL and 115.5 ± 34.6 ng·h/mL for the 10 mg and 30 mg ODTs, versus 40.7 ± 13.5 ng·h/mL and 117.4 ± 31.5 ng·h/mL for the 10 mg and 30 mg tablets, and 121.8 ± 32.0 ng·h/mL and 121.0 ± 35.7 ng·h/mL for the 30 mg solution and capsule, respectively. Bioequivalence of the 30 mg and 10 mg ODTs and tablets, assessed in 83 patients across two studies, was demonstrated for both the Cmax and AUC from time zero to time t (AUC0-t). No serious or unexpected drug-related events were reported. A product appreciation questionnaire concluded that both ODTs and oral solution products were considered pleasant by most of the subjects. The ODTs were safe, well tolerated, and showed similar pharmacokinetics to those of the reference formulations. The development of a range of doses of morphine sulfate ODTs may provide a new alternative for the oral administration of immediate-release morphine for pain management in pediatric, geriatric and adult populations with swallowing problems.


Beta-amyloid peptide interacts specifically with the carboxy-terminal domain of human apolipoprotein E: relevance to Alzheimer's disease.
Growing evidence indicates the involvement of apolipoprotein E (apoE) in the development of late-onset and sporadic forms of Alzheimer's disease, although its exact role remains unclear. We previously demonstrated that beta-amyloid peptide (Abeta) displays membrane-destabilizing properties and that only apoE2 and E3 isoforms inhibit these properties. In this study, we clearly demonstrate that the carboxy-terminal lipid-binding domain of apoE (e.g., residues 200-299) is responsible for the Abeta-binding activity of apoE and that this interaction involves pairs of apoE amphipathic alpha-helices. We further demonstrate that Abeta is able to inhibit the association of the C-terminal domain of apoE with lipids due to the formation of Abeta/apoE complexes resistant to sodium dodecyl sulfate-polyacrylamide gel electrophoresis. On the contrary, the amino-terminal receptor-binding domain of apoE (e.g., residues 129-169) is not able to form stable complexes with Abeta. These data extend our understanding of human apoE-dependent binding of Abeta by involving the C-terminal domain of apoE in the efficient formation of apoE/Abeta complex.


Special considerations in pediatric electromyography.
This article reviews the unique physiologic and clinical characteristics that affect electrodiagnosis in children. The impact of peripheral neurodevelopment is discussed. A variety of pediatric neuromuscular diseases are highlighted.


Altered arachidonic acid metabolism during differentiation of the human monoblastoid cell line U937.
The human cell line U937 was used as a model for differentiation along the mononuclear phagocyte lineage. Following treatment with the phorbol ester TPA, PGE2 and TxB2 secretion was induced 50-100-fold, and both PGF2 alpha and PGI2 levels became detectable in the supernatant of TPA-differentiated U937 cells. The content of the prostaglandin precursor, arachidonic acid, remained unchanged in the cellular phospholipids of undifferentiated and TPA-differentiated U937 cells. Of the enzymes involved in the availability and metabolism of arachidonic acid, phospholipase A2 activity was increased 2-fold in the membranes of TPA-differentiated U937 cells, whereas lysophosphatide acyltransferase activity remained unaltered. Cyclooxygenase activity, however, was enhanced 5-10-fold, which was due to enhanced expression of the enzyme as demonstrated by dot-blot analysis. The data suggest that the capacity to secrete prostaglandins is acquired during differentiation with TPA and results mainly from an increased cyclooxygenase activity. Despite the capacity of TPA-differentiated U937 cells to synthesize prostaglandins, none of the known monocytic stimuli further stimulated prostaglandin secretion in TPA-differentiated U937 cells. Generation of leukotrienes appears to represent a later state in the differentiation along the monocyte-macrophage lineage, since neither LTB4 nor cysteinyl-leukotrienes were detectable in the supernatants of either undifferentiated or TPA-differentiated U937 cells.


Development of a model meat system and investigation of the growth characteristics and genetic stability of Escherichia coli O157:H7, in the absence of meat microflora.
Model meat systems were produced using both aseptically procured and irradiated raw minced beef to initially compare the growth characteristics of a three-strain mixture of Escherichia coli O157:H7 in each medium. A multiplex PCR assay (detecting VT1, VT2 and eae genes) was used to determine the proportion of individual strains recovered at each sampling time by virtue of the different combinations of these virulence factors encoded by each strain, and to investigate their genetic stability. No differences in the growth characteristics of the pathogen (P>0.05) were recorded in the meat matrices, irrespective of the preparation method, thus validating the use of irradiation to sterilise (42 kGy, in vacuo at <-5 degrees C) minced meat in the production of control meat matrices for application to further research investigations. A novel plating method, incorporating a period of catalase-induced resuscitation, was found to give significantly higher recovery of the pathogen (P<0.05) from these meat matrices when compared to conventional spread-plating on Trypticase Soy Agar (TSA). A proportion of the recovered populations, however, was found to be failing to produce an amplicon relating to a Verotoxin (VT) gene. A further investigation demonstrated that O157:H7 strain E 90197 (VT2 and eae positive) was displaying genetic instability during growth in and recovery from meat matrices with the apparent loss of the VT2 gene. An alternative VT2 and eae positive strain (ATCC 43889) demonstrated no such genetic instability, demonstrating inter-strain variation for this phenomenon. Thus, it should be considered that an essential pre-requisite to studies relying upon the maintenance of the pathogenic potential of E. coli O157:H7 should be an evaluation of the genetic stability of proposed strains of this serotype.


Sexual response in spinal cord injured adults: a review of the literature.
The literature on sexual response in spinal cord injured (SCI) adults is reviewed and criticized. Principal characteristics of spinal cord injury are reviewed, and variables usually taken into account in studying sexual behavior in the SCI population are specified. Target behaviors of erection, ejaculation, attempts at intercourse, and male and female orgasm are isolated, and relevant data are reported. Attention is given to conceptual and methodological shortcomings of past research. Literature relevant to remediation of sexual problems in the SCI population is reported, and outcomes are noted. Future directions for research are indicated with particular emphasis placed on the appropriate utilization of psychophysiological techniques.


Chronopharmacology.
The time of day that drugs are given can have a profound effect upon both their pharmacodynamics, i.e. their effectiveness and toxicity, and their pharmacokinetics, i.e. the way they themselves behave in the body. The chronopharmacokinetics of relatively few drugs have been investigated and are mostly those used for the treatment of cancer. We have shown that the toxicity and chronopharmacokinetics of drugs can be altered by pretreatment with steroids or melatonin.


Measurement of the humoral immune response against Streptococcus pneumoniae type 3 capsular polysaccharide and oligosaccharide containing antigens by ELISA and ELISPOT techniques.
A sensitive ELISA has been developed to study immune responses in mice against Streptococcus pneumoniae type 3 capsular polysaccharide (S3PS) and hexasaccharide (HS)-protein conjugates derived therefrom. An advantage of the described system is that the same microtiter plates can be used for both ELISA and ELISPOT tests with a standardized washing procedure and diluent composition. S3PS induced predominantly IgM antibodies and minute amounts of IgG as measured by ELISA in serum. This was accompanied by large numbers (greater than 14000) of IgM spot-forming cells in the spleen. A shift towards IgG production was achieved by addition of lipid A. HS-protein conjugates induced predominantly IgG antibodies after booster immunization(s). Furthermore these conjugates induced large numbers (greater than 40000) of IgG spot-forming cells (SFC) in the spleen. ELISA and ELISPOT assays on microtiter plates are both reliable and highly reproducible assays for the evaluation of immune responses to S. pneumoniae antigens.


Hydrological isolation affected the chemo-diversity of dissolved organic matter in a large river-connected lake (Poyang Lake, China).
The transportation processes during aquatic systems regulate the ultimate chemistry of dissolved organic matter (DOM), and in recent years, climate changes and human activities have altered the hydrological patterns of many rivers and lakes, which generated some severe issues, such as hydrological isolation. However, how hydrological isolation affects variations of DOM chemistry in large lake systems is still poorly understood. Here, optical properties and molecular compositions of DOM samples derived from a large river-connected lake (Poyang Lake, China) and its nearby seasonal sub-lakes (formed by hydrological isolation) were characterized using Fourier transform ion cyclotron resonance mass spectrometry (FT ICR MS) and ultraviolet-visible (UV-Vis) spectroscopy. The results revealed more abundance of organic matter in sub-lakes than that in the main lake according to high dissolved organic carbon (DOC) concentrations and absorption coefficients (a254 and a280). Large proportions of CHOS formulas were identified by FT ICR MS in sub-lakes DOM, which were produced through Kraft reactions (sulfide/bisulfide + lignin CHO → CHOS) in the interface of sediment/water, and greatly contributed to aliphatic compounds. In addition, obvious variations of compounds (such as polyphenols, highly unsaturated and aliphatic compounds) and lability of DOM were observed between sub-lakes and main lakes, which were mainly caused by the different degradation pathways of DOM (photodegradation in sub-lakes while biodegradation in the main lake). Our results demonstrated that hydrological isolation has significant impacts on DOM chemistry, and provides an improved understanding of the DOM biogeochemistry process in Poyang Lake and supports the management of the large lake systems.


Enhanced Raman signals from switchable nanoparticle probes.
We demonstrate here a DNA-based conformationally switchable nanodumbell structure that modulates the interparticle distance between two gold-silver core-shell nanoparticles to induce significant changes in the SERS signal.


The effect of etodolac on experimental temporomandibular joint osteoarthritis in dogs.
The purpose of this study was to test the effect of etodolac on a dog model of osteoarthritic temporomandibular joints (TMJ). Ten adult beagle dogs underwent surgery to induce osteoarthritis in the right TMJ, and were then randomly divided into two groups each of 5 dogs. From 2 to 6 weeks after surgery, the dogs in group 1 (control group) were given an empty gelatin capsule daily, and the dogs in group 2 (study group) were given 15 mg/kg of etodolac daily. All joints were examined radiologically and histologically 8 weeks postoperatively. In group 1, the operated right joints showed severe osteoarthritic changes in the condyle and severe morphological differences in comparison with the unoperated (left joint). Group 2 showed fewer morphological differences between the unoperated control (left) and the operated (right) TMJ. Osteoarthritic changes in the TMJ were significantly less severe in group 2 (etodolac) than in group 1. Oral administration of etodolac at a dose of 15 mg/kg minimized the continuation of experimentally induced osteoarthritic changes in the canine TMJ, when compared with the placebo. Thus, etodolac may play a role in preventing progression of human TMJ osteoarthritis.


Bioelectrochemical stability improvement by Ce-N modified carbon-based cathode in high-salt stress and mechanism research.
Although microbial fuel cells (MFCs) have potential for high-salt wastewater treatment, their application is limited by poor salt tolerance, deactivation and unstable catalytic performance. This study designed Ce-C, N-C, and Ce-N modified activated carbon (Ce-N-C) based on the catalytic mechanism and salt tolerance performance of Ce and N elements to address these limitations. With activated carbon (AC) as the control, this study analyzed the stability of the four cathodes under different salinity environments using norfloxacin (NOR) as a probe to assess the effect of cathodes and salinity on MFC degradation performance. After three months, comparing with other three cathodes, the Ce-N-C cathode demonstrated superior and stable electrochemical and power generation performance. In particular, the advantages of Ce-N-C in high-salt (600 mM NaCl) environment is more significant than no-salt or low-salt. The potential of Ce-N-C-End at current density of 0 was 14.0% higher than AC-End, and the power density of the MFC with Ce-N-C cathode was 105.7 mW/m2, which was 3.1 times higher than AC. Also, the stability of NOR removal under the function of Ce-N-C improved with the increase of NaCl concentration or operation time. The CeO2(111) crystal form, N-Ce-O bond and pyridine N might be the key factors in improving the catalytic performance and salt tolerance of the Ce-N modified carbon-based cathode using XPS and XRD analysis.


Interactions between the mixotrophic dinoflagellate Takayama helix and common heterotrophic protists.
The phototrophic dinoflagellate Takayama helix that is known to be harmful to abalone larvae has recently been revealed to be mixotrophic. Although mixotrophy elevates the growth rate of T. helix by 79%-185%, its absolute growth rate is still as low as 0.3d-1. Thus, if the mortality rate of T. helix due to predation is high, this dinoflagellate may not easily prevail. To investigate potential effective protistan grazers on T. helix, feeding by diverse heterotrophic dinoflagellates such as engulfment-feeding Oxyrrhis marina, Gyrodinium dominans, Gyrodinium moestrupii, Polykrikos kofoidii, and Noctiluca scintillans, peduncle-feeding Aduncodinium glandula, Gyrodiniellum shiwhaense, Luciella masanensis, and Pfiesteria piscicida, pallium-feeding Oblea rotunda and Protoperidinium pellucidum, and the naked ciliates Pelagostrobilidium sp. (ca. 40μm in cell length) and Strombidinopsis sp. (ca. 150μm in cell length) on T. helix was explored. Among the tested heterotrophic protists, O. marina, G. dominans, G. moestrupii, A. glandula, L. masanensis, P. kofoidii, P. piscicida, and Strombidinopsis sp. were able to feed on T. helix. The growth rates of all these predators except Strombidinopsis sp. with T. helix prey were lower than those without the prey. The growth rate of Strombidinopsis sp. on T. helix was almost zero although the growth rate of Strombidinopsis sp. with T. helix prey was higher than those without the prey. Moreover, T. helix fed on O. marina and P. pellucidum and lysed the cells of P. kofoidii and G. shiwhaense. With increasing the concentrations of T. helix, the growth rates of O. marina and P. kofoidii decreased, but those of G. dominans and L. masanensis largely did not change. Therefore, reciprocal predation, lysis, no feeding, and the low ingestion rates of the common protists preying on T. helix may result in a low mortality rate due to predation, thereby compensating for this species' low growth rate.


Vibrational and ab initio studies of 3-acetyl-6-bromocoumarin and 3-acetyl-6-methylcoumarin.
Infrared absorption and Raman spectra (3500-50 cm(-1)) of 3-acetyl-6-bromocoumarin and 3-acetyl-6-methylcoumarin have been measured and interpreted, aided by electronic structure calculations at RHF and B3LYP using 6-31(d, p) basis set. It has been determined that the rotation of the acetyl group with respect to the coumarin ring results in three conformers--two trans and one cis--for each molecule, with one trans conformer being the most stable in both cases. There are significant changes in the vibrational structure as characterized by positions and intensities of certain modes in going from 3-acetyl-6-bromocoumarin to 3-acetyl-6-methylcoumarin. The carbonyl stretching mode of the pyrone ring is stable in both molecules whereas the same mode in acetyl groups is not. Ring stretching vibrations are coupled to C-H in-plane bending vibrations. Down-shifting of frequencies of methyl vibrations in acetyl group occurs vis-à-vis methyl vibrations in 3-acetyl-6-methylcoumarin. A strong Raman band at 126 cm(-1) in both molecules is structure-independent non-genuine mode, correlated to lattice vibrations in the solid phase.


Prophylactic antibiotics are not indicated in clean general surgery cases.
In assigning risk of infection, the traditional wound classification system has been replaced by the National Nosocomial Infection Surveillance (NNIS) system. NNIS classification is determined by procedure length, wound cleanliness, and ASA status. To date, no prophylactic antibiotic guidelines have been proposed for the NNIS system. Clean general surgery cases were retrospectively reviewed in our hospital for infection and prophylactic antibiotic use. These cases were then stratified per the NNIS system. One thousand twenty-three clean general surgery cases had 16 (1%) surgical site infections. The infection rate in NNIS class 0, 1, and 2 cases not given prophylactic antibiotics was 1.21%, 3.03%, and 0%, respectively. The infection rate in NNIS class 0, 1, and 2 cases given prophylactic antibiotics was 0.94%, 2.44%, and 6.67%, respectively. No statistically significant decrease in infection rate was demonstrated by us using prophylactic antibiotics, regardless of the NNIS classification in clean general surgery cases.


Phase II study of intensive chemotherapy with carboplatin, ifosfamide and etoposide plus recombinant human granulocyte colony-stimulating factor and sequential radiotherapy in locally advanced, unresectable non-small-cell lung cancer.
From June 1991 to August 1994, 61 patients with stage III unresectable non-small-cell lung cancer (NSCLC; 16 cases of stage IIIA with N2 bulky disease and 45 cases of stage IIIB) were treated with ifosfamide given i.v. at 3 g/m2 on day 1, carboplatin given i.v. at 200 mg/m2 on days 1 and 2, etoposide given i.v. at 120 mg/m2 on days 1-3 (ICE) and recombinant human granulocyte colony-stimulating factor (rhG-CSF) given s.c. at 5 micrograms/kg on days 4-13. Chemotherapy was given every 3 weeks for up to three cycles and, unless the disease progressed, was followed by thoracic radiotherapy on the tumor volume (total dose 60 Gy) and mediastinum (40 Gy). All patients had measurable or evaluable unresectable disease and a performance status (Eastern Cooperative Oncology Group) of 0-1. Only 61% of the enrolled patients received the full program of chemoradiotherapy according to the study design. At the end of sequential chemo-radiotherapeutic treatment, 41% of the patients had an objective response (24 partial responses and 1 complete response), 31% showed no change and 28% had progressive disease. The response rate noted for patients in stage IIIA with N2 bulky disease and that recorded for patients in stage IIIB did not differ significantly. The median time to progression was 5.4 months and the median survival was 8.2 months, with the 1-year survival rate being 31%. Sites of progression were mostly intrathoracic. Haematological toxicity was the main side effect, with grade III-IV thrombocytopenia being reported in 24% of the 165 courses of intensive ICE chemotherapy given. Febrile neutropenia was described in six courses (three patients). Non-haematological toxicities and radiotherapy-related side effects were generally mild and easily manageable. In conclusion, in unresectable stage III NSCLC a short program of moderately intensified ICE chemotherapy with rhG-CSF protection followed by sequential radiotherapy failed to increase the percentage of objective responses and reached a median survival comparable with that previously achieved with standard doses.


Possible involvement of interleukin-1 in cyclooxygenase-2 induction after spinal cord injury in rats.
A standardized compression injury of rat spinal cord brought about a time-dependent biphasic production of thromboxane A2 (detected as thromboxane B2) and prostaglandin I2 (detected as 6-ketoprostaglandin F1alpha). Thromboxane B2 was predominant during the first 1 h, whereas the 6-ketoprostaglandin F1alpha level exceeded that of thromboxane B2 at 8 h postinjury. As examined by inhibitor experiments and northern blotting, cyclooxygenase-1 was responsible for the first phase, and cyclooxygenase-2 was involved in the second phase. On compression injury the levels of interleukin-1alpha and -1beta detected as mRNA and protein increased and peaked at 2-4 h. Injection of exogenous interleukin-1alpha into the spinal cord resulted in an increase of cyclooxygenase-2 mRNA content and a predominant production of 6-ketoprostaglandin F1alpha resembling the second phase of eicosanoid production. Concomitantly, extravascular migration of polymorphonuclear leukocytes was enhanced after the interleukin-1alpha injection. These cells together with vascular endothelial cells and glial cells were stained positively with an anti-cyclooxygenase-2 antibody. The results suggest that the immediate eicosanoid synthesis after spinal cord injury was due to the constitutive cyclooxygenase-1 and the delayed synthesis of eicosanoids was attributable to the induction of cyclooxygenase-2 mediated by interleukin-1alpha.


A meta-analysis comparing tenotomy or tenodesis for lesions of the long head of the biceps tendon with concomitant reparable rotator cuff tears.
The best treatment for lesions of the long head of the biceps tendon (LHBT) with concomitant reparable rotator cuff tears is still controversial. The purpose of the meta-analysis was to compare clinical outcomes of biceps tenotomy and tenodesis for LHBT lesions. A literature retrieval was conducted in MEDLINE, Embase, and Cochrane Library from 1979 to March 2018. Comparative studies (level of evidence I or II) comparing tenotomy and tenodesis for LHBT lesions with concomitant reparable rotator cuff tears were included. Risk of bias for all included studies was assessed using the Cochrane Collaboration's risk of bias tool. Clinical outcomes compared were Popeye sign, Constant score, VAS pain score, cramping pain, elbow flexion and forearm supination strength, and re-tear of the rotator cuff. Two randomized controlled trials (RCTs) and five prospective cohort studies (PCS) with 288 biceps tenotomy patients and 303 biceps tenodesis patients were included in this review. Tenotomy resulted in significantly greater rates of Popeye sign (RR, 2.70 [95% CI, 1.80 to 4.04]; P < 0.01) and a less favorable Constant score (MD, - 1.09 [95% CI, - 1.90 to - 0.28]; P < 0.01) compared to tenodesis. No significant heterogeneity was found between the two groups across all parameters except forearm supination strength. The current evidence indicates that biceps tenodesis for LHBT lesions with concomitant reparable rotator cuff tears results in decreased rate of Popeye sign and improved Constant score compared to biceps tenotomy. PROSPERO, CRD42018105504. Registered on 13 August 2018.


Interaction Induced High Catalytic Activities of CoO Nanoparticles Grown on Nitrogen-Doped Hollow Graphene Microspheres for Oxygen Reduction and Evolution Reactions.
Nitrogen doped graphene hollow microspheres (NGHSs) have been used as the supports for the growth of the CoO nanoparticles. The nitrogen doped structure favors the nucleation and growth of the CoO nanoparticles and the CoO nanoparticles are mostly anchored on the quaternary nitrogen doped sites of the NGHSs with good monodispersity since the higher electron density of the quaternary nitrogen favors the nucleation and growth of the CoO nanoparticles through its coordination and electrostatic interactions with the Co(2+) ions. The resulting NGHSs supported CoO nanoparticles (CoO/NGHSs) are highly active for the oxygen reduction reaction (ORR) with activity and stability higher than the Pt/C and for the oxygen evolution reaction (OER) with activity and stability comparable to the most efficient catalysts reported to date. This indicates that the CoO/NGHSs could be used as efficient bi-functional catalysts for ORR and OER. Systematic analysis shows that the superior catalytic activities of the CoO/NGHSs for ORR and OER mainly originate from the nitrogen doped structure of the NGHSs, the small size of the CoO nanoparticles, the higher specific and electroactive surface area of the CoO/NGHSs, the good electric conductivity of the CoO/NGHSs, the strong interaction between the CoO nanoparticles and the NGHSs, etc.


An investigation of the effects of saccharides on the memory performance of middle-aged adults.
To investigate the effects of glucose, or a combination of saccharides, or a placebo on the memory performance of middle-aged adults. A double-blind, placebo controlled design was used. A population-based sample of 45 men and women (aged 40-63 years) completed a series of memory tasks following administration of a single dose of either glucose, a combination of saccharides or placebo. Memory tasks included immediate and delayed recall, recognition, short-term memory, working memory, and a test of general cognitive ability. There were no statistically significant effects of treatments on any of the outcome measures. The pattern of means in the combination of saccharides group suggests potential enhancement effects of memory performance in middle-aged adults that deserves further investigation.


HDAC2 was involved in placental P-glycoprotein regulation both in vitro and vivo.
Placental P-glycoprotein (P-gp) plays a significant role in regulating drugs' transplacental transfer rates. Investigations on placental P-gp regulation could provide more therapeutic targets for individualized and safe pharmacotherapy during pregnancy. Currently, the epigenetic regulation of placental P-gp is rare. Our previous study has demonstrated that HDACs inhibition could up-regulate placental P-gp and HDAC1/2/3 might be involved in this process. The present study was carried out to further explore whether HDAC1/2/3 were indeed involved in the regulation of placental P-gp or not and screen out the subtype engaged in this process. BeWo and JAR cells were transfected with HDAC1/2/3 specific siRNA. After 48 h of transfection, cells were harvested for real-time quantitative PCR (qRT-PCR), Western blot, immunofluorescence and fluorescent dye efflux assay to evaluate P-gp expression, localization, and efflux activity, respectively. Hdac2 siRNA was intraperitoneally injected to pregnant mice every 48 h from E7.5 to E15.5 and digoxin was administered by gavages 1 h prior to euthanasia at E16.5. Placental Hdac1/2/3 and P-gp expression were determined by qRT-PCR and Western blot. Maternal plasma and fetal-unit digoxin concentrations were detected by enzyme-multiplied immunoassay. In vitro, HDAC2 inhibition could significantly elevate P-gp expression and reduce intracellular accumulation of P-gp substrates (DiOC2 (3) and Rh 123) both in BeWo and JAR, while knockdown of HDAC1/3 had no influence on P-gp expression and its efflux activity. Additionally, in vivo, Hdac2 silencing in pregnant mice also elevated placental P-gp expression and decreased digoxin transplacental transfer rate. HDAC2 inhibition could result in induction of placental P-gp expression and functionality both in vitro and in vivo.


p47phox-Nox2-dependent ROS Signaling Inhibits Early Bone Development in Mice but Protects against Skeletal Aging.
Bone remodeling is age-dependently regulated and changes dramatically during the course of development. Progressive accumulation of reactive oxygen species (ROS) has been suspected to be the leading cause of many inflammatory and degenerative diseases, as well as an important factor underlying many effects of aging. In contrast, how reduced ROS signaling regulates inflammation and remodeling in bone remains unknown. Here, we utilized a p47(phox) knock-out mouse model, in which an essential cytosolic co-activator of Nox2 is lost, to characterize bone metabolism at 6 weeks and 2 years of age. Compared with their age-matched wild type controls, loss of Nox2 function in p47(phox-/-) mice resulted in age-related switch of bone mass and strength. Differences in bone mass were associated with increased bone formation in 6-week-old p47(phox-/-) mice but decreased in 2-year-old p47(phox-/-) mice. Despite decreases in ROS generation in bone marrow cells and p47(phox)-Nox2 signaling in osteoblastic cells, 2-year-old p47(phox-/-) mice showed increased senescence-associated secretory phenotype in bone compared with their wild type controls. These in vivo findings were mechanistically recapitulated in ex vivo cell culture of primary fetal calvarial cells from p47(phox-/-) mice. These cells showed accelerated cell senescence pathway accompanied by increased inflammation. These data indicate that the observed age-related switch of bone mass in p47(phox)-deficient mice occurs through an increased inflammatory milieu in bone and that p47(phox)-Nox2-dependent physiological ROS signaling suppresses inflammation in aging.


Editorial: The Predictive Power of Preschool Irritability Comes Into Focus.
In recent decades, the search for early childhood markers of risk for later psychopathology has been vigorous. It has garnered escalating interest from multiple facets of developmental science, and has extended to periods as early as prenatal development. The principle that early identification of neurodevelopmental risk to target intervention during relatively higher neuroplastic periods offers a window of opportunity for larger effects and more enduring change is one key driver of this effort. Despite this intense interest and focus, the ability to test the predictive power of early markers requires time, persistence, and patience, with the later childhood and adolescent outcomes of some key longitudinal studies starting in early childhood only now becoming available. The Stony Brook Temperament Study is one such sample, from which Sorcher et al.1 report strong relationships between preschool irritability and a variety of outcomes in early adolescence, some of them surprisingly broad. Findings from this community sample demonstrate that irritability at age 3 years predicts later internalizing and externalizing outcomes as well as poor peer relations, global impairment, and health problems, even after controlling for other key established risk factors. These findings are some of the most convincing yet available to suggest that preschool irritability should be an intervention target to prevent poor long-term outcomes. However, in contrast to prior hypotheses, these data suggest that it may not be a specific marker of later affective disorders, although differences between youth and parent report were found along these lines. Surprisingly, only parent report suggested that early irritability had greater specificity to affective disorder outcomes, whereas youth self-report did not.


Hyaluronic acid-capped compact silica-supported mesoporous titania nanoparticles for ligand-directed delivery of doxorubicin.
Mesoporous titania nanoparticles (MTN), owing to their high surface area to volume ratio and tunable pore sizes, appear capable of delivering sizable amounts of drug payloads, and hence, show considerable promise as drug delivery candidates in cancer therapy. We designed silica-supported MTN (MTNst) coated with hyaluronic acid (HA) to effectively deliver doxorubicin (DOX) for breast cancer therapy. The HA coating served a dual purpose of stabilizing the payload in the carriers as well as actively targeting the nanodevices to CD44 receptors. The so-formed HA-coated MTNst carrying DOX (HA/DOX-MTNst) had spheroid particles with a considerable drug-loading capacity and showed significantly superior in vitro cytotoxicity against MDA-MB-231 cells as compared to free DOX. HA/DOX-MTNst markedly improved the cellular uptake of DOX in an apparently CD44 receptor-dependent manner, and increased the number of apoptotic cells as compared to free DOX. These nanoplatforms accumulated in large quantities in the tumors of MDA-MB-231 xenograft tumor-bearing mice, where they significantly enhanced the inhibition of tumor growth compared to that observed with free DOX with no signs of acute toxicity. Based on these excellent results, we deduced that HA/DOX-MTNst could be successfully used for targeted breast cancer therapy. STATEMENT OF SIGNIFICANCE: This is the first study to use silica-supported mesoporous titania nanoparticles (MTNst) for doxorubicin (DOX) delivery to treat breast cancer, which exhibited effective and enhanced in vitro and in vivo apoptosis and tumor growth inhibition. Solid silica was used to support the mesoporous TiO2 resulting in MTNst, which efficiently incorporated a high DOX payload. The hyaluronic acid (HA) coating over the MTNst surface served a dual purpose of first, stabilizing DOX inside the MTNst (capping agent), and second, directing the nanoplatform device to CD44 receptors that are highly expressed in MDA-MB-231 cells (targeting ligand). The NPs exhibited highly efficacious in vitro tumor-cell killing and excellent in vivo tumor regression, highlighting the enormous promise of this system for breast cancer therapy.


[Nutritional effect of bariatric surgery with Scopinaro operation. Analysis of 40 cases].
To analyze the influence of bariatric surgery over nutritional status in patients with morbid obesity after 1 year of following. To know the influence of specific factors as age, sex and common channel's length. Retrospective study from 1998-2001. All patients suffering from morbid obesity that had been operated during this period of time, 40 subjects: 28 women and 12 men with a mean age of 38 +/- 12 years old. Were studied. We analyzed the variations of weight and other anthropometric measures, biochemical parameters and the micronutrient (vitamins A, D, E, B12, folate, C, zinc, Calcium, Magnesium) status during 1 year of following after surgery. Percentage weight loss was 29.7 +/- 2.9% without sex differences. A significant (p < 0.005) descent of serum cholesterol, triglycerides, and uric acid level as well as liver function markers was observed. All the hyperglycemic disturbances were reverted. 97% and 48% of the patients developed hypovitaminosis A and D respectively, that was correlated to steatorrhea. Vitamin E deficiency was found in 72% of the patients, and zinc deficiency in 68% Our expected weight loss 1 year after bariatric surgery is 30%, irrespective of sex and age. This loss is accompanied by a significant improvement in metabolic parameters, but the high prevalence of micronutrients deficiency that was found makes an early supplementation and close follow-in of these patients very advisable.


Innovations in Care Delivery for Patients With Serious Mental Illness Among Accountable Care Organizations.
This study examined whether and how organizations participating in accountable care organization (ACO) contracts integrate primary care and treatment for patients with serious mental illness. This study used responses to the 2017–2018 National Survey of ACOs (55% response rate) to measure ACO-reported use of three integrated care strategies: care manager to address physical health treatment coordination or nonmedical needs (e.g., job support and housing), patient registries to track physical health conditions, and primary care clinician colocated in a specialty mental health setting. Logistic regression was used to determine associations between ACO characteristics and strategy use. Of 399 respondents who answered questions on integration, 303 (76%) reported using at least one integrated care strategy in at least one location. Use of care managers (defined by the respondent) was most common (N=281, 70%), followed by use of a patient registry (N=146, 37%) and colocation of a primary care clinician in a specialty mental health setting (N=118, 30%). Respondents reporting that their largest Medicaid contract or largest commercial contract included quality measures specific to serious mental illness (e.g., antipsychotic adherence) were more likely to use each integrated care delivery strategy. Self-reported use of three collaborative care strategies (care management, patient registry, or mental health consulting clinician) for treatment of depression or anxiety was associated with use of integrated primary care and treatment for serious mental illness. In a national survey of ACOs, few respondents reported using either patient registries or primary care colocation to integrate primary care and treatment for serious mental illness.


The Belmarsh Scheme. A prospective study of the transfer of mentally disordered remand prisoners from prison to psychiatric units.
Contracting in psychiatric services from the NHS into prisons has been advocated to improve the care of the mentally disordered in custody. The Belmarsh Scheme is such a service. A prospective study investigating the characteristics of a six-month cohort of remand prisoners requiring transfer to hospital and evaluating the service's effectiveness. Fifty-three (4.3%; 95% CL 3.2% to 5.6%) of the 1229 new remands required transfer to hospital; all were accepted. The transfer group contained a higher proportion of black men (51%) than all other remands (30%) (difference 21%; 95% CL 8% to 35%, P = 0.002). Transfer times were lower than those reported for a neighbouring prison. The Belmarsh Scheme secured in-patient psychiatric care rapidly for all those identified as needing it.


Intracranial volume conduction of cortical spikes and sleep potentials recorded with deep brain stimulating electrodes.
To examine interictal epileptiform and sleep potentials recorded intracranially from deep brain stimulation (DBS) electrodes in patients treated with DBS for epilepsy. Specifically, this study sought to determine whether the DBS-recorded potentials represent: (a) volume conduction from surface neocortical discharges or (b) transsynaptic propagation along cortical-subcortical pathways with local generation of the subcortical potentials near the DBS targets. Six patients with intractable epilepsy treated with thalamic DBS of the central median nucleus (CM; one patient) or anterior thalamus (5 patients) who had focal interictal spikes were studied. Sleep potentials were also studied in a 7th patient with Parkinson disease treated with DBS of the subthalamic nucleus (STN). Focal interictal cortical spikes recorded by scalp electroencephalography (EEG) were recorded synchronously, but with opposite polarity, from the DBS electrodes in CM as well as the more superficial anterior thalamic contacts situated in the anterior nucleus (AN) and dorsal medial nucleus (DM). In referential montages, the subcortical potentials were of highest amplitude ipsilateral to the focal cortical spikes, with a small but reproducible amplitude decrement present at each electrode contact more distant from the cortical source, irrespective of the specific DBS target. Subcortical sleep potentials (K-complexes and sleep spindles) were also recorded synchronously and with inverse polarity compared to the corresponding scalp potentials, and appeared in a similar fashion at all subcortical sites sampled by the DBS electrodes. Amplitude attenuation in the thalamus of intracranial volume conducted potentials with increasing distance from their cortical spike sources was measured at approximately 5-10 microV/mm. Recent reports on scalp-CM or scalp-STN EEG recordings in patients treated with DBS for epilepsy have interpreted the intracranial waveforms as evidence of transsynaptic cortical-subcortical transmission across neuroanatomical pathways presumed to be involved in the generation of sleep potentials (Clin. Neurophysiol. 113 (2002) 25) and epileptiform activity (Clin. Neurophysiol. 113 (2002) 1391). However, our results show that the intracranial spikes recorded from DBS electrodes in various regions of the thalamus (CM, AN and DM) represent subcortical volume conduction of the synchronous cortical spikes recorded with scalp EEG. The same is true for the intracranial reflections of scalp EEG sleep potentials recorded from DBS electrodes in CM, AN, DM and STN. These interictal DBS waveforms thus cannot be used to support hypotheses of specific cortical-subcortical pathways of neural propagation or subcortical generation of the DBS-recorded potentials associated with scalp EEG interictal spikes and sleep potentials. Detailed analysis of the intracranial potentials recorded from DBS electrodes in association with scalp EEG spikes and sleep discharges shows that the intracranial waveforms represent volume conduction from discharges generated in the neocortex and not, as has been suggested, locally generated activity resulting from cortical-subcortical neural propagation.


Promoting Adolescents' Social Responsibility through Parent-Adolescent Conversations about the COVID-19 Pandemic.
This longitudinal mixed-method study examined the content and qualities of parent-adolescent conversations about the COVID-19 pandemic, and whether discourse about social responsibility (i.e., care for others and health protective behaviors [HPBs]) within conversations predicted changes in adolescents' socially responsible behavior across the first year of the pandemic. Participants were 122 ethnically/racially diverse parent-adolescent dyads from Southern California. In spring 2020 (Time 1), adolescents completed an online survey measuring their engagement in HPBs (e.g., social distancing) and prosociality (both pandemic-specific and global). A few months following survey completion (Time 2), parent-adolescent dyads engaged in an audio-recorded conversation about the pandemic. In winter 2020 (Time 3), adolescents' engagement in HPBs and prosociality were reassessed via an online survey. Dyads spent 25% of conversational turns, on average, discussing social responsibility (4% and 21% of turns discussing care for others and HPBs, respectively). Internal state language reflecting emotion terms was positively correlated with the proportion of conversational turns spent discussing care for others and negatively associated with conversational turns spent discussing HPBs. Regression analyses revealed that both care for others and HPB conversation themes uniquely predicted increases in adolescents' engagement in HPBs over time; however, care for others was a stronger predictor (β = 0.24 vs. β = 0.16). Discussions about care for others (but not HPBs) predicted increases in pandemic-specific prosociality, but not global prosocial behavior. Parent-adolescent conversations may be rich ground for the socialization of adolescents' social responsibility during crises and can inform best practices for engaging adolescents in current and future community health initiatives.


Tobacco tax and price in the developed and developing countries in the World.
An ecologic study was conducted on 177 countries which the information of tobacco tax and price and also Human Development Index (HDI) was available in 2014. In this study, the relationship between HDI and four reported indexes by World Health Organization (WHO) was studied. These four indexes included: Tobacco affordability, Taxes as a percent of price of the most sold brand (total tax), Price of a 20 cigarette pack of the most sold brand international dollars at purchasing power parity (Price_ppp) and Price of a 20 cigarette pack of the most sold brand in US$ at official exchange rates (Price_US$). The data of HDI and tobacco were mined from WHO and United Nations Development Programme sites respectively. To study the correlation between HDI and the variables of this study, Pearson correlation coefficient was used and also Linear Regression Analysis was used to study the relationship between HDI and the variables of the study. According to the findings of the linear regression analysis, there was a significant relationship between HDI and total tax (B = 0.81, CI 95%: 0.63-0.99) and tobacco affordability (B = --0.35, CI 95%: --0.42 _ --0.28). There was also a significant relationship between HDI whit price-ppp (B = 9.44, CI 95%: 7.13-11.75) and price-US$ ;(B = 11.97, CI 95%: 9.71-14.23). According to the findings of this study, less developed countries devote less tax on tobacco. Due to the rising trend of the prevalence and also development of non-communicable diseases such as lung cancer in developing countries, policy makers of these countries are required to design stricter policies toward tobacco production and supply as well.


Synthesis and characterization of Schiff base containing bovine serum albumin-gum arabic aldehyde hybrid nanogels via inverse miniemulsion for delivery of anticancer drug.
The periodate modified gum arabic was used as a natural-based, non-toxic cross-linker to synthesize hybrid bovine serum albumin-gum arabic aldehyde (BSA-GAA) nanogels by Schiff base reaction through the inverse miniemulsion method for the first time. The synthesis process was performed in the absence of toxic organic solvents using fractionated coconut oil as the continuous phase. The particle size of the nanogels was managed by tweaking the concentration of the surfactants (Span 80/Tween 80) and the total volume of the aqueous phase. Based on the bicinchoninic acid method, the cross-linking efficiency of BSA and GAA was estimated at 98%. 5-fluorouracil (5-FU) was selected as the sample drug. The 5-FU-loaded hybrid nanogels showed a spherical morphology with an average diameter of 231.33 ±12.74 nm and a zeta potential of -31.6 mV. The encapsulation and loading efficiency of the nanogels were calculated at 42 ± 4.52% and 2.37 ± 0.59%, respectively. The properties of the hybrid nanogels were analyzed by dynamic light scattering (DLS), Fourier transform infrared microscopy (FTIR) analysis, field emission scanning electron microscopy (FE-SEM), and thermogravimetric analysis (TGA). The pH sensitivity of the hybrid nanogels was confirmed by the in vitro release profiles of 5-FU in different buffers. Hemolysis assay revealed the in vitro hemocompatibility of the hybrid nanogels which inhibited the growth of MCF-7 cells with an IC50 value of 16.21 μM. The present study suggested that these biobased hybrid nanogels could have a great potential in drug delivery and other biomedical applications.


Stroke is associated with coronary calcification as detected by electron-beam CT: the Rotterdam Coronary Calcification Study.
Coronary calcification as detected by electron-beam CT measures the atherosclerotic plaque burden and has been reported to predict coronary events. Because atherosclerosis is a generalized process, coronary calcification may also be associated with manifest atherosclerotic disease at other sites of the vascular tree. We examined whether coronary calcification as detected by electron-beam CT is related to the presence of stroke. From 1997 onward, subjects were invited to participate in the prospective Rotterdam Coronary Calcification Study and undergo electron-beam CT to detect coronary calcification. The study was embedded in the population-based Rotterdam Study. Calcifications were quantified in a calcium score according to Agatston's method. Calcium scores were available for 2013 subjects (mean age [SD], 71 [5.7] years). Fifty subjects had experienced stroke before scanning. Subjects were 2 times more likely to have experienced stroke when their calcium score was between 101 and 500 (odds ratio [OR], 2.1; 95% CI, 0.9 to 4.7) and 3 times more likely when their calcium score was above 500 (OR, 3.3; 95% CI, 1.5 to 7.2), compared with subjects in the lowest calcium score category (0 to 100). Additional adjustment for cardiovascular risk factors did not materially alter the risk estimates. In this population-based study, a markedly graded association was found between coronary calcification and stroke. The results suggest that coronary calcification as detected by electron-beam CT may be useful to identify subjects at high risk of stroke.


Cardiovascular disease risk in women with PCOS.
Cardiac disease is the number one killer in women. Adolescents and reproductive age women with PCOS have an increased prevalence of cardiovascular risk factors. These include obesity, impaired glucose tolerance, diabetes, hypertension, mood disorders and metabolic syndrome. There is sufficient evidence to confirm the presence of subclinical atherosclerosis in women with PCOS compared to age matched controls. There are, however, few prospective studies examining non-fatal and fatal cardiac events in women with well-defined PCOS. Future directions of research should include longitudinal studies in peri- and post-menopausal women with prospectively defined PCOS to better estimate the risk of cardiac morbidity and mortality in this high-risk population. In the meantime, regular screening for risk factors and timely early interventions are critical to reduce the overall risk burden.


Performance of iPad-based threshold perimetry in glaucoma and controls.
Independent validation of iPad visual field testing software Melbourne Rapid Fields (MRF). To examine the functionality of MRF and compare its performance with Humphrey SITA 24-2 (HVF). Prospective, cross-sectional validation study. Sixty glaucomas mean deviation (MD:-5.08±5.22); 17 pre-perimetric, 43 HVF field defects and 25 controls. The MRF was compared with HVF for scotoma detection, global indices, regional mean threshold values and sensitivity/specificity. Long-term test-retest variability was assessed after 6 months. Linear regression and Bland Altman analyses of global indices sensitivity/specificity using (ROC) curves, intraclass correlations. Using a cluster definition of three points at <1% or two at 0.5% to define a scotoma on HVF, MRF detected 39/54 abnormal hemifields with a similar threshold-based criteria. Global indices were highly correlated between MRF and HVF: MD r2 = 0.80, PSD r2 = 0.77, VFI r2 = 0.85 (all P < 0.0001). For manifest glaucoma patients, correlations of regional mean thresholds ranged from r2 = 0.45-0.78, despite differing array of tested points between devices. ROC analysis of global indices showed reasonable sensitivity/specificity with (AUC) values of MD:0.89, (PSD:0.85) and (VFI:0.88). MRF retest variability was low with (ICC) values at 0.95 (MD and VFI), 0.94 (PSD). However, individual test point variability for mid-range thresholds was higher. MRF perimetry, despite using a completely different test paradigm, shows good performance characteristics compared to HVF for detection of defects, correlation of global indices and regional mean threshold values. Reproducibility for individual points may limit application for monitoring change over time, and fixation monitoring needs improvement.