Effect of Rifampin on the Single-Dose Pharmacokinetics of Oral Cabotegravir in Healthy Subjects.
Drug-drug interactions between antiretroviral medications and rifampin complicate the treatment of HIV and tuberculosis coinfection. This study evaluated the effect of rifampin on the pharmacokinetics of oral cabotegravir, an integrase strand transfer inhibitor being investigated for long-acting treatment and prevention of HIV-1 infection. This was a phase I, single-center, open-label, fixed-sequence crossover study in healthy adults. The objective was to evaluate the effect of steady-state rifampin on the single-dose plasma pharmacokinetics of cabotegravir. Subjects received a single oral dose of cabotegravir (30 mg) on day 1 followed by plasma sampling on days 1 to 8. Treatment with once-daily oral rifampin (600 mg) occurred on days 8 to 28. Subjects received a second dose of 30 mg cabotegravir on day 21 followed by pharmacokinetic sampling on days 21 to 28. Fifteen subjects were enrolled and completed the study. Rifampin decreased the cabotegravir area under the concentration-time curve from 0 h to infinity and the half-life by 59% and 57%, respectively, whereas oral clearance was increased 2.4-fold. The maximum concentration of cabotegravir in plasma was unaffected by coadministration with rifampin. All adverse events were mild in severity, with chromaturia attributed to rifampin observed in all subjects. Rifampin induction of cabotegravir metabolism resulted in increased cabotegravir oral clearance and significantly decreased cabotegravir exposures. Rifampin is expected to increase cabotegravir clearance following long-acting injectable administration. Concomitant administration of rifampin with oral and long-acting formulations of cabotegravir is not recommended currently without further study. (This study has been registered at ClinicalTrials.gov under registration no. NCT02411435.).


Association Between Renal Function and Troponin T Over Time in Stable Chronic Kidney Disease Patients.
Background People with reduced glomerular filtration rate (GFR) often have elevated cardiac troponin T (cTnT) levels. It remains unclear how cTnT levels develop over time in those with chronic kidney disease (CKD). The aim of this study was to prospectively study the association between cTnT and GFR over time in older advanced-stage CKD patients not on dialysis. Methods and Results The EQUAL (European Quality Study) study is an observational prospective cohort study in stage 4 to 5 CKD patients aged ≥65 years not on dialysis (incident estimated GFR, <20 mL/min/1.73 m²). The EQUAL cohort used for the purpose of this study includes 171 patients followed in Sweden between April 2012 and December 2018. We used linear mixed models, adjusted for important groups of confounders, to investigate the effect of both measured GFR and estimated GFR on high-sensitivity cTnT (hs-cTnT) trajectory over 4 years. Almost all patients had at least 1 hs-cTnT measurement elevated above the 99th percentile of the general reference population (≤14 ng/L). On average, hs-cTnT increased by 16%/year (95% CI, 13-19; P<0.0001). Each 15 mL/min/1.73 m2 lower mean estimated GFR was associated with a 23% (95% CI, 14-31; P<0.0001) higher baseline hs-cTnT and 9% (95% CI, 5-13%; P<0.0001) steeper increase in hs-cTnT. The effect of estimated GFR on hs-cTnT trajectory was somewhat lower than a previous myocardial infarction (15%), but higher than presence of diabetes mellitus (4%) and male sex (5%). Conclusions In CKD patients, hs-cTnT increases over time as renal function decreases. Lower CKD stage (each 15 mL/min/1.73 m2 lower) is independently associated with a steeper hs-cTnT increase over time in the same range as other established cardiovascular risk factors.


Ictal unilateral eye blinking and contralateral blink inhibition - A video-EEG study and review of the literature.
There is limited information on ictal unilateral eye blinking (UEB) as a lateralizing sign in focal seizures. We identified two patients with UEB and propose a novel mechanism of UEB based on a review of the literature. We report on two patients with intractable focal epilepsy showing UEB among 269 consecutive patients undergoing noninvasive video-EEG monitoring from October 2011 to May 2013. Unilateral eye blinking was observed in 0.7% (two of 269) of our patients. Patient one had four focal seizures. Semiological signs in all of her seizures were impaired consciousness, bilateral eye blinking (BEB), and UEB on the right. During one seizure, BEB recurred after UEB with a higher blink frequency on the right. Patient two had ten focal seizures. Among them were one electrographic seizure and nine focal seizures with BEB (in 3/10) and UEB on the left (in 1/10 seizures, respectively). Both patients did not display any clonic activity of the face. In seizures with UEB, ictal EEG onset was observed over the ipsilateral frontotemporal region in both of the patients (over F8 in 2/4, Fp2-F8 in 1/4, Sp2-T2 in 1/4, and F7 in 1/1 seizures, respectively). Ictal pattern during UEB showed bilateral ictal activity (in 4/4) and ictal discharges over the ipsilateral frontal region (maximum over F3 in 1/1 seizure). Interictal EEG showed sharp waves over the same regions. Unilateral eye blinking was ipsilateral to the frontotemporal ictal EEG pattern in both patients. The asymmetric blink frequency during BEB in patient one leads to the hypothesis that ictal UEB is caused by contralateral blink inhibition due to activation in frontotemporal cortical areas and mediated by trigeminal fibers.


Reinforcement mechanism of dentin mechanical properties by intracanal medicaments.
The reinforcement mechanism of dentin mechanical properties by intracanal medicaments was investigated. The dumbbell-shaped specimens were prepared from a collagen sheet, demineralized dentin and organic dissolved dentin. After immersing the specimens in intracanal medicaments (eugenol and formocresol), the tensile test was carried out in 37 degrees C water and the Vickers hardness test was performed. The tensile strengths increased after eugenol and formocresol immersion, especially collagen and organic dissolved dentin after formocresol immersion and demineralized dentin after eugenol immersion. Thus, formocresol immersion might have reinforced the dentin tensile strength by protein coagulation, while eugenol immersion might have reinforced the dentin tensile strength by not only protein coagulation but also chelation with hydroxyapatite. However, the hardness values did not significantly change after intracanal medicament immersion.


A Systematic Review Summarizing the State of Evidence on Bullying in Childhood Cancer Patients/Survivors [Formula: see text].
One in four school-aged children is bullied. However, the risk may be greater for childhood cancer patients/survivors (diagnosed <18 years), because of symptoms of the disease and treatment that may prejudice peers. While the serious consequences of bullying are well documented in the general population, bullying may have even greater impact in children with cancer due to the myriad of challenges associated with treatment and prolonged school absence. To summarize the state of evidence on bullying in childhood cancer patients/survivors; specifically, the rate and types of bullying experienced and the associated factors. We searched five electronic databases from inception to February 2018 for original research articles reporting on bullying in childhood cancer patients/survivors. We identified 29 eligible articles, representing 1,078 patients/survivors ( M = 14.35 years). Self-reports from patients/survivors revealed a considerably higher rate of bullying (32.2%) compared with the general population (25%). Our review identified little information on the factors associated with bullying in patients/survivors. However, the bullying described tended to be verbal and was often related to the physical side effects of treatment, indicating that differences in appearance may prejudice peers. It was further suggested that educating the child's classmates about cancer may prevent bullying. Our findings confirm that bullying is a significant challenge for many childhood cancer patients/survivors. Additional studies are needed to identify factors that may influence the risk of bullying, which will inform the development of evidence-based interventions and guidelines to prevent bullying in childhood cancer patients/survivors.


Null test for a highly paraboloidal mirror.
A circular null computer-generated hologram (CGH) was used to test a highly paraboloidal mirror (diameter, 90 mm; f number, 0.76). To verify the null CGH test a classic autocollimation test with a flat mirror was performed. Comparing the results, we show that the results of the null CGH test show good agreement with results of the autocollimation test.


Hepatitis B-Related Concerns and Anxieties Among People With Chronic Hepatitis B in Australia.
The psychological wellbeing of people with chronic hepatitis B (CHB) may be negatively affected due to the chronic and transmissible nature of the disease, and possible serious complications (e.g. cirrhosis and liver cancer). There are limited data investigating concerns and anxieties among people living with CHB. This study examined feelings about having hepatitis B among people with CHB, including hepatitis B-related concerns and anxieties. Using convenience sampling, people with CHB attending four public liver clinics and one general practice in three Australian jurisdictions between April and September 2013 completed a self-administered questionnaire about their feelings about having hepatitis B. Ninety-three people completed the survey. Mean age was 45 years, 57% were men, and 93% were born overseas (75% from Asia). Seventy-six percent of participants reported having hepatitis B-related concerns and anxieties. The most common concerns were of developing liver cancer (57%), and infecting other people (53%). Thirty-five percent of participants were unwilling to talk to anyone about their hepatitis B while 25% changed how they lived as a result of having hepatitis B. Lower educational level was associated with feeling scared of hepatitis B (adjusted Odds Ratio [OR]: 4.04; 95%CI: 1.09, 14.90; P = 0.04), and an unwillingness to talk to anyone about hepatitis B (adjusted OR: 4.41; 95%CI: 1.09, 17.83; P = 0.04). Very good English proficiency was associated with a higher likelihood of participants changing how they lived (adjusted OR: 12.66; 95%CI: 2.21, 72.42; P < 0.01), and seeing life differently as a result of having hepatitis B (adjusted OR: 21.10; 95%CI: 3.70, 120.19; P < 0.01). Health professionals were the key person for 34% of participants in helping them cope with having hepatitis B, while 18% reported that no one supported them. Hepatitis B-related concerns and anxieties are prevalent among people with CHB. Clinical management of people with CHB must address their psychological support needs as an essential component of comprehensive care.


The Tissue-Sparing Effect of Spatially Fractionated X-rays for Maintaining Spermatogenesis: A Radiobiological Approach for the Preservation of Male Fertility after Radiotherapy.
Radiotherapy can result in temporary or permanent gonadal toxicity in male cancer patients despite the high precision and accuracy of modern radiation treatment techniques. Previous radiobiological studies have shown an effective tissue-sparing response in various tissue types and species following exposure to spatially fractionated radiation. In the present study, we used an ex vivo mouse testicular tissue culture model and a conventional X-ray irradiation device to evaluate the tissue-sparing effect (TSE) of spatially fractionated X-rays for the protection of male fertility from radiotherapy-related adverse effects. We revealed a significant TSE for maintaining spermatogenesis in the ex vivo testes model following spatially fractionated X-ray irradiation. Moreover, we experimentally propose a possible mechanism by which the migration of spermatogonial cells, from the non-irradiated areas to the irradiated ones, in irradiated testicular tissue, is essential for the TSE and maintaining spermatogenesis. Therefore, our findings demonstrate that the control of TSE following spatially fractionated X-rays in the testes has a considerable potential for clinical application. Interdisciplinary research will be essential for further expanding the applicability of this method as an approach for the preservation of male fertility during or after radiotherapy.


Pain situations among working adults and the educational needs identified: an exploratory survey via WeChat.
The aim of this study is to 1) investigate the pain situation among working adults in China; 2) explore the self-initiate pain reliving strategies applied by working adults; and 3) collect people's interests and suggestions to the topics of the online pain education program. This is an exploratory survey through WeChat. The study was conducted from May 2018 to December 2018. Participants were recruited following the snowball sampling. In total of 664 people were recruited and 502 satisfied the criteria. SPSS was used for data analysis. Descriptive statistical analysis were used to present the utilization of pain treatments and suggested topics. Chi-square test, independent multiple logistic regression and Spearman's correlation were used to analysis the data. The overall incidence of pain among the participants is 45% and higher among female (63%) than male (37%). Neck (68.72%, 4.10 ± 2.31), shoulder (62.56%, 3.78 ± 2.41) and head (49.34%, 4.23 ± 2.52) are reported as the most common and severe pain sites. Working is affected by pain and the results show that there is a negative correlation between pain intensity and work (rs = - 0.194) among the working population. Non-pharmacological treatments (55.77%) were chosen more by pain suffers. Totally 63.39% of participants show interests in the online pain education program and physical and psychological impact of pain is the most suggested topic (22.51%). The pain prevalence is high among working adults in China. Impact of pain on work is a significant problem for the working adults. It is important to identify people at risk and deliver timely intervention to reduce pain. People showed their willingness in joining the online program. Therefore, future online pain education program can be developed.


Tracking Early Sentence-Building Progress in Graphic Symbol Communication.
Purpose As is the case with children who rely on spoken language, speech-language pathologists must support and track the expressive language development of children with complex communication needs who use graphic symbols to communicate. This research note presents a framework of the progression of expressive English sentence development using graphic symbols and introduces possible approaches for measuring and analyzing graphic symbol use. Method Current issues in measuring graphic symbol utterances are explored, and a range of measures designed to analyze individual graphic symbol utterances as well as larger samples of utterances are presented. Results Both the Graphic Symbol Utterance and Sentence Development Framework and suggested measures are based on years of graphic symbol intervention research, including two large ongoing research studies of preschoolers with severe speech impairments. Our framework adapts the work of Hadley (2014) to depict expressive language progression from early symbol combinations to childlike and adultlike sentences and highlights developmental patterns unique to graphic symbol productions. Adaptations of existing measures (such as mean length of utterance) as well as measures unique to graphic symbol analyses are presented and discussed. Conclusion To accurately track changes in early graphic symbol utterance growth and complexity, a multidimensional approach, which includes analyses such as symbol relevance, word class diversity, and lexical diversity, is recommended.


Sinonasal carcinoma associated with inverted papilloma: a report of 16 cases.
To analyse the characteristics and outcome of patients with carcinoma associated with inverted papilloma, and find predictors of associated malignancy. The medical records of 228 patients who were diagnosed with IP between January 1990 and December 2010 were retrospectively reviewed. Out of 228 patients, 16 were also diagnosed with carcinoma. We evaluated their clinical characteristics, treatment modalities, and survival outcomes. The incidence of carcinoma associated with IP was 7.0%. Fourteen were synchronous carcinomas and two were metachronous. Tumours arising inside the frontal sinus or the frontoethmoidal recess were more likely to be associated with carcinoma. Patients who had a stage of T2 or less had a much better outcome than those who had a stage of T3 or greater (disease-free period, 84.8 months vs. 5.7 months, p<0.001). Tumours originating in the frontal sinus or frontoethmoidal recess have a tendency to be associated with carcinoma. As most (87.5%) of the carcinomas were diagnosed at the same time as the inverted papilloma, complete histological examination of the whole excised tumour is warranted because early diagnosis and treatment is essential as T2 and lower stage carcinomas had a strikingly better prognosis than T3 and higher stage carcinomas.


Defining urban diffuse pollution loadings and receiving water hazard.
The use of unit area loading approaches to address the requirements of the US Clean Water Act (CWA) and the EU Water Framework Directive (WFD) to identify and manage diffuse urban pollution sources is outlined. Issues relating to traditional volume-concentration probabilistic modelling are highlighted and the robustness of total maximum daily load (TMDL) approaches is discussed. A hazard assessment methodology for catchment scale identification of source area pollutant loadings and receiving water ecological impacts is developed based on urban land use activities.


Responsibility of the obstetrician to the fetus. II. Influence of prepregnancy weight and pregnancy weight gain on birthweight.
The diet of pregnant women has been restricted in various ways since earliest history. Dietary restriction may have severely deleterious effects on the fetus. Our study revealed a positive correlation of prepregnancy weight and pregnancy weight gain to term infant birthweight. Their influences are independent and additive. It is of the utmost importance to the fetus and the future of the human race that the diet of pregnant women contain the caloric value and essential nutrients recommended by the National Research Council.


Posttranscriptional regulation of cyclooxygenase-2 in rat intestinal epithelial cells.
Modulation of cyclooxygenase-2 (COX-2) mRNA stability plays an important role in the regulation of its expression by oncogenic Ras. Here, we evaluate COX-2 mRNA stability in response to treatment with two known endogenous promoters of gastrointestinal cancer, the bile acid (chenodeoxycholate; CD) and ceramide. Treatment with CD and ceramide resulted in a 10-fold increase in the level of COX-2 protein and a four-fold lengthening of the half-life of COX-2 mRNA. COX-2 mRNA stability was assessed by Northern blot analysis and by evaluating the AU-rich element located in the COX-2 3'-UTR. A known inhibitor of mitogen-activated protein (MAP)/extracellular signal-regulated kinase (ERK) kinase (MEK), PD98059, reversed the effects of CD or ceramide to stabilize COX-2 mRNA. Overexpression of a dominant-negative ERK-1 or ERK-2 protein also led to destabilization of COX-2 mRNA. Treatment with a p38 MAPK inhibitor, PD169316, or transfection with a dominant-negative p38 MAPK construct reversed the effect of CD or ceramide to stabilize COX-2 mRNA. Expression of a dominant-negative c-Jun N-terminal kinase (JNK) had no effect on COX-2 mRNA stability in cells treated with CD or ceramide. We conclude that posttranscriptional mechanisms play an important role in the regulation of COX-2 expression during carcinogenesis.


The Reproducibility of Racial Differences in Ambulatory Blood Pressure Phenotypes and Measurements.
We examined the reproducibility of differences in ambulatory blood pressure (BP) monitoring (ABPM) phenotypes and other parameters (sustained hypertension, masked hypertension, nocturnal hypertension, and nondipping) between African Americans and Whites. A total of 420 participants untreated for hypertension attended 2 research visits 1 week apart during which traditional office BP averages and ABPM session averages were determined. We computed percent agreement in ABPM phenotypes across the 2 visits stratified by race and associated kappa statistics with 95% confidence intervals. Whites on average were older, more likely to be male, and had a higher body mass index. There was no significant difference in sleep quality as defined by sleep diary between the 2 races. There were also no significant differences between races in the proportions of participants with sustained hypertension, sustained normotension, or masked hypertension at either testing session. The prevalence of nocturnal hypertension was 59% vs. 75% (P = 0.012) at session 1 and 59% vs. 73% (P = 0.024) at session 2 for Whites and African Americans, respectively, with moderate reproducibility for both (kappas 0.45 and 0.44). Nocturnal BP nondipping had a prevalence 29% vs. 53% (P < 0.001) at session 1 and 29% vs. 47% (P = 0.004) at session 2 for Whites and African Americans, respectively, with fair reproducibility (kappas 0.28 and 0.29). Our findings support that African Americans indeed exhibit a greater preponderance of abnormal nocturnal BP patterns than Whites. Our work is some of the first to demonstrate that these abnormal patterns are modestly reproducible.


AXIN2 polymorphism and its association with astrocytoma in a Turkish population.
The product of AXIN2, a component of Wnt signalling, plays a role in tumorigenesis and is dysregulated in cancer cells. In order to determine whether the AXIN2 polymorphism is a risk factor for astrocytoma, we analysed eight polymorphic regions of this gene in 100 astrocytoma patients compared to 100 healthy controls in a Turkish population using PCR-RFLP methods. For the Exon1-148 T/C, Exon1-432 C/T, Exon5-1365 G/A, Intron5-1712+19G/T, Exon7-2062 C/T and Intron7-2141+73 G/A SNPs of AXIN2, no significant association between controls and astrocytoma patients was found. For the Exon5-1386 C/T SNP, a statistically significant association between controls and patients was found (p<0.05). For this astrocytoma, patients with the TT genotype showed an increased risk with an OR of 2.92 (adjusted for age, gender and smoking status) (95% CI 1.14-7.47) as compared to the controls with the CC genotype. Our results suggest that AXIN2 SNPs may be associated with astrocytoma.


Cytological techniques to analyze meiosis in Arabidopsis arenosa for investigating adaptation to polyploidy.
Arabidopsis arenosa is a close relative of the model plant A. thaliana, and exists in nature as stable diploid and autotetraploid populations. Natural tetraploids have adapted to whole genome duplication and do not commonly show meiotic errors such as multivalent and univalent formation, which can lead to chromosome non-disjunction and reduced fertility. A genome scan for genes strongly differentiated between diploid and autotetraploid A. arenosa identified a subset of meiotic genes that may be responsible for adaptation to polyploid meiosis. To investigate the mechanisms by which A. arenosa adapted to its polyploid state, and the functionality of the identified potentially adaptive polymorphisms, a thorough cytological analysis is required. Therefore, in this chapter we describe methods and techniques to analyze male meiosis in A. arenosa, including optimum plant growth conditions, and immunocytological and cytological approaches developed with the specific purpose of understanding meiotic adaptation in an autotetraploid. In addition we present a meiotic cytological atlas to be used as a reference for particular stages and discuss observations arising from a comparison of meiosis between diploid and autotetraploid A. arenosa.


Homogenization of three-dimensional metamaterial objects and validation by a fast surface-integral equation solver.
A homogenization model is applied to describe the wave interaction with finite three-dimensional metamaterial objects composed of periodic arrays of magnetodielectric spheres and is validated with full-wave numerical simulations. The homogenization is based on a dipolar model of the inclusions, which is shown to hold even in the case of densely packed arrays once weak forms of spatial dispersion and the full dynamic array coupling are taken into account. The numerical simulations are based on a fast surface-integral equation solver that enables the analysis of scattering from complex piecewise homogeneous objects. We validate the homogenization model by considering electrically large disk- and cube-shaped arrays and quantify the accuracy of the transition from an array of spheres to a homogeneous object as a function of the array size. Simulation results show that the fields scattered from large arrays with up to one thousand spheres and equivalent homogeneous objects agree well, not only far away from the arrays but also near them.


CCR9+ macrophages are required for acute liver inflammation in mouse models of hepatitis.
Antigen-presenting cells (APCs) are involved in the induction of liver inflammation. We investigated the roles of specific APCs in the pathogenesis of acute liver injury in mice. We used concanavalin A (con A) or carbon tetrachloride to induce acute liver inflammation in mice and studied the roles of macrophages that express CCR9. After injection of con A, we detected CCR9(+)CD11b(+)CD11c(-) macrophages that express tumor necrosis factor (TNF)-α in livers of mice, whereas CCR9(+)Siglec-H(+)CD11b(-)CD11c(low) plasmacytoid DCs (pDCs), which are abundant in normal livers, disappeared. The CCR9(+) macrophages were also detected in the livers of RAG-2(-/-) mice, which lack lymphocytes and natural killer T cells, after injection of con A. Under inflammatory conditions, CCR9(+) macrophages induced naive CD4(+) T cells to become interferon gamma-producing Th1 cells in vivo and in vitro. CCR9(-/-) mice injected with con A did not develop hepatitis unless they also received CCR9(+) macrophages from mice that received con A; more CCR9(+) macrophages accumulated in their inflamed livers than CCR9(+) pDCs, CCR9(-) pDCs, or CCR9(-) macrophages isolated from mice that had received injections of con A. Levels of CCL25 messenger RNA increased in livers after injection of con A; neutralizing antibodies against CCL25 reduced the induction of hepatitis by con A by blocking the migration of CCR9(+) macrophages and their production of TNF-α. Peripheral blood samples from patients with acute hepatitis had greater numbers of TNF-α-producing CCR9(+)CD14(+)CD16(high) monocytes than controls. CCR9(+) macrophages contribute to the induction of acute liver inflammation in mouse models of hepatitis.


Clinical Usefulness of Endoscopy, Barium Fluoroscopy, and Chest Computed Tomography for the Correct Diagnosis of Achalasia.
Objective The definite diagnosis of esophageal achalasia is established using manometry, which is performed in patients with suspected achalasia based on the findings of screening examinations, such as upper gastrointestinal endoscopy, chest computed tomography (CT), or a barium swallow test. However, the exact values of test characteristics in these supportive diagnostic examinations remain unclear. Methods We estimated the sensitivity and specificity of characteristic findings in the supportive diagnostic examinations for achalasia by comparing the data of a large number of achalasia patients and others with digestive symptoms. Patients Achalasia patients (n=119) and non-achalasia patients with suspected achalasia and repeated feelings of chest discomfort (n=37) who were treated in a single university hospital. Results Characteristic findings on chest CT (i.e., dilated esophagus, air-fluid level formation) and barium swallow tests were observed in more than 80% of achalasia patients but in less than 10% of non-achalasia patients. In contrast, conventional characteristic findings of upper gastrointestinal endoscopy (i.e., intra-esophageal food debris, feeling of resistance at the esophagogastric junction) were seen in only 40-70% of achalasia patients. In particular, the feeling of resistance at the esophagogastric junction was observed by the examiner in only 30-50% of patients. Conclusion Intra-esophageal food debris or resistance at the esophagogastric junction on upper gastrointestinal endoscopy will be positive in only about half of patients with achalasia. Other supportive diagnostic examinations, such as chest CT or barium fluoroscopy, should therefore be included in order to avoid overlooking the disease.


Control of Ambipolar Transport in SnO Thin-Film Transistors by Back-Channel Surface Passivation for High Performance Complementary-like Inverters.
For ultrathin semiconductor channels, the surface and interface nature are vital and often dominate the bulk properties to govern the field-effect behaviors. High-performance thin-film transistors (TFTs) rely on the well-defined interface between the channel and gate dielectric, featuring negligible charge trap states and high-speed carrier transport with minimum carrier scattering characters. The passivation process on the back-channel surface of the bottom-gate TFTs is indispensable for suppressing the surface states and blocking the interactions between the semiconductor channel and the surrounding atmosphere. We report a dielectric layer for passivation of the back-channel surface of 20 nm thick tin monoxide (SnO) TFTs to achieve ambipolar operation and complementary metal oxide semiconductor (CMOS) like logic devices. This chemical passivation reduces the subgap states of the ultrathin channel, which offers an opportunity to facilitate the Fermi level shifting upward upon changing the polarity of the gate voltage. With the advent of n-type inversion along with the pristine p-type conduction, it is now possible to realize ambipolar operation using only one channel layer. The CMOS-like logic inverters based on ambipolar SnO TFTs were also demonstrated. Large inverter voltage gains (>100) in combination with wide noise margins are achieved due to high and balanced electron and hole mobilities. The passivation also improves the long-term stability of the devices. The ability to simultaneously achieve field-effect inversion, electrical stability, and logic function in those devices can open up possibilities for the conventional back-channel surface passivation in the CMOS-like electronics.


Isomeric Separation of α2,3/α2,6-Linked 2-Aminobenzamide (2AB)-Labeled Sialoglycopeptides by C18-LC-MS/MS.
Determination of the relative expression levels of the α2,3/α2,6-sialic acid linkage isomers on glycoproteins is critical to the analysis of various human diseases such as cancer, inflammation, and viral infection. However, it remains a challenge to separate and differentiate site-specific linkage isomers at the glycopeptide level. Some derivatization methods on the carboxyl group of sialic acid have been developed to generate mass differences between linkage isomers. In this study, we utilized chemical derivatization that occurred on the vicinal diol of sialic acid to separate linkage isomers on a reverse-phase column using a relatively short time. 2-Aminobenzamide (2AB) labeling derivatization, including periodate oxidation and reductive amination, took only ∼3 h and achieved high labeling efficiency (>90%). Within a 66 min gradient, the sialic acid linkage isomers of 2AB-labeled glycopeptides from model glycoproteins can be efficiently resolved compared to native glycopeptides. Two different methods, neuraminidase digestion and higher-energy collision dissociation tandem mass spectrometry (HCD-MS2) fragmentation, were utilized to differentiate those isomeric peaks. By calculating the diagnostic oxonium ion ratio of Gal2ABNeuAc and 2ABNeuAc fragments, significant differences in chromatographic retention times and in mass spectral peak abundances were observed between linkage isomers. Their corresponding MS2 PCA plots also helped to elucidate the linkage information. This method was successfully applied to human blood serum. A total of 514 2AB-labeled glycopeptide structures, including 152 sets of isomers, were identified, proving the applicability of this method in linkage-specific structural characterization and relative quantification of sialic acid isomers.


Diagnostic work-up for food-dependent, exercise-induced anaphylaxis.
Fourteen patients with suspected food-dependent, exercise-induced anaphylaxis (EIAn) were subjected to prick tests with commercial food extracts and common airborne allergens, prick + prick tests with fresh foods, determination of total IgE levels, and specific IgE for 31 foods (CAP System FEIA RAST). All were positive for two or more foods; 10 presented hypersensitivity to 11 or more foods. On the basis of these findings, history data, and responses to food-exercise challenges (treadmill stress tests 90 min after meals containing none of the suspected foods and none associated with skin-test and/or RAST positivity) and suspected food-exercise challenges (SFECs - administered after meals containing the suspected food), three patients were diagnosed as having specific food-dependent EIAn (for wheat in two cases, tomato in one). In nine others, the presence of specific IgE for numerous foods (including those suspected on the basis of histories and utilized in the SFECs) suggests involvement of specific food hypersensitivity, although SFEC confirmation could not be obtained. Avoidance of all foods associated with test positivity 4 h before exercise has prevented all further EIAn episodes in these 12 patients. In two others, the reactions did not appear to be related to IgE directed against specific food allergens, and these subjects have eliminated further reactions by avoiding all meals for the 4 h preceding exercise. These findings emphasize the importance of allergologic testing with a wide panel of food allergens (including foods used for seasoning, such as garlic or parsley) in all patients with suspected food-dependent EIAn. Prick + prick tests with fresh foods and the CAP System RAST disclosed numerous hypersensitivities.


Allelotype of renal cell carcinoma.
Several recent studies based on restriction fragment length polymorphism analysis have supported the concept that the accumulation of multiple genetic alterations converts a normal cell to a malignant cell. Activation of oncogenes and/or inactivation of tumor suppressor genes have been observed during tumor progression in colorectal cancer, lung cancer, and breast cancer. To investigate the possibility that multiple genes are altered during the progression of renal cell carcinoma, we have used restriction fragment length polymorphism markers throughout the genome to test for loss of heterozygosity in 38 renal cell carcinomas. Nearly 64% of the tumors had lost heterozygosity on the short arm of chromosome 3. We also observed loss of heterozygosity averaging about 30% at informative loci on six other chromosomal arms (chromosomes 5q, 6q, 10q, 11q, 17p, and 19p). These results lead us to suspect the existence of several tumor suppressor genes associated with carcinogenesis of renal cell carcinoma.


A comprehensive vowel space for whispered speech.
Whispered speech is a relatively common form of communications, used primarily to selectively exclude or include potential listeners from hearing a spoken message. Despite the everyday nature of whispering, and its undoubted usefulness in vocal communications, whispers have received relatively little research effort to date, apart from some studies analyzing the main whispered vowels and some quite general estimations of whispered speech characteristics. In particular, a classic vowel space determination has been lacking for whispers. For voiced speech, this type of information has played an important role in the development and testing of recognition and processing theories over the past few decades and can be expected to be equally useful for whisper-mode communications and recognition systems. This article aims to redress the shortfall by presenting a vowel formant space for whispered speech and comparing the results with corresponding phonated samples. In addition, because the study was conducted using speakers from Birmingham, the analysis extends to discuss the effect of the common British West Midlands accent in comparison with Standard English (Received Pronunciation). Thus, the article presents the analysis of formant data showing differences between normal and whispered speech while also considering an accentual effect on whispered speech.


Extra-articular scapular fractures: comparison of theoretical and actual treatment.
Discrete radiographic thresholds of scapular fracture deformity proposed as a guide for when to utilize operative treatment are a matter of debate. The purpose of the present study was to determine how many patients would have received operative treatment according to these criteria and how many actually received operative treatment. Three hundred and thirty patients with an extra-articular fracture of the scapula at two level 1 trauma centers were retrospectively analyzed. Glenopolar angle, translation, angulation and medial/lateral displacement were measured on computed tomogaphy scans or radiographs to determine the theoretical operative treatment recommendation according to Cole's criteria. Sixty-two patients (19%) had one or more radiographic indications for operative treatment, half of them had more than 20 mm of lateral displacement, and one fourth of them had substantial translation. No patients had operative treatment of the scapular body. Two patients had operative treatment of an acromion fracture, neither of which met radiographic criteria for surgery. At least in our centres, there is a striking discrepancy between theoretical and actual recommendations for surgery. There is clearly a need for more research to determine whether patients are being undertreated or whether the guidelines are too stringent.


Salivary gland tumors in Turkey: demographic features and histopathological distribution of 510 patients.
The aim of this study was to evaluate the demographic and clinicopathologic data of salivary gland tumors managed at a tertiary referral medical center in Turkey. The data of 510 patients with salivary gland tumors managed during the period of January 1984 to May 2012, were reviewed. Only primary neoplasms derived from salivary glands were included. Out of 510 neoplasms, 352 (69.0 %) were classified as benign and 158 (31.0 %) were classified as malignant. There was a male predominance and male:female ratio was 1.23 (281/229). The most common location was parotid gland (372/510, 72.9 %) followed by minor salivary glands (97/510, 19.0 %) and submandibular gland (40/510, 7.9 %). The malignancy rates were 21.5, 40.0, and 56.7 % in parotid, submandibular, and minor salivary glands locations, respectively. The most common location for minor salivary gland neoplasms was oral cavity (61/97, 62.9 %). Pleomorphic adenoma (PA) was the most common histopathological type (45.3 %) in the whole study group and also among pediatric patients. The most common malignant neoplasms were adenoid cystic carcinoma (39/510, 7.6 %) and mucoepidermoid carcinoma (5.7 %). Salivary gland tumors are more common in men. The malignancy rate is almost three times higher in neoplasms derived from minor glands when compared to parotid gland. PA is the most common histopathological tumor type in all locations and in all age groups.


Novel symmetrical and unsymmetrical fluorine-containing metallophthalocyanines: synthesis, characterization and investigation of their biological properties.
In this study, a new fluorinated phthalonitrile compound namely 5-bis[4-(trifluoromethoxy)-thiophenyl] phthalonitrile was synthesized. In addition, peripherally substituted symmetric metallated phthalocyanine derivatives [M = Co (2) and M = Zn (3)] and unsymmetrically substituted zinc phthalocyanine (ZnPc) complex (4) were synthesized by cyclotetramerization of this phthalonitrile compound. Characterization of all new compounds was carried out using FT-IR, NMR, UV-Vis, and mass spectroscopy. Additionally, antioxidant activity, DNA cleavage activity, antimicrobial activity, biofilm inhibition activity, and bacterial viability inhibition test of the compounds (1-4) were investigated. The antioxidant activities of the new phthalocyanine complexes were studied by performing two different methods. The results indicated that the highest DPPH (1,1-diphenyl-2-picrylhydrazyl) free radical scavenging activity was determined to be 67.85% for 2 and also 3 showed the highest activity with 31.65% for chelating activity at 200 mg L-1 concentration. Phthalocyanine compounds demonstrated effective DNA cleavage and antimicrobial activities. The highest percentage of cell vitality inhibition was found for compound 4, 56.92%. Also, test compounds exhibited good biofilm inhibition activity.


Primary aldosteronism: adrenal venous sampling.
In primary aldosteronism, high-resolution adrenal computed tomography (CT) increasingly identifies subtle anatomic abnormalities. To interpret the functional significance of adrenal micronodular changes on CT scan, we have reevaluated selective adrenal venous sampling. Thirty-four patients with primary aldosteronism were selected prospectively for adrenal venous sampling on the basis of CT findings: normal findings or minimal thickening of an adrenal limb (n = 15), unilateral microadenoma (n = 6), bilateral adrenal nodules (n = 9), or atypical unilateral adrenal macroadenoma (n = 4). Both adrenal veins were catheterized in 33 of 34 patients. Six (40%) of 15 patients with normal or minimal adrenal limb thickening had a unilateral source of aldosterone. Six patients with apparent unilateral microadenoma had ipsilateral aldosterone-producing adenomas. Four (44%) of nine patients with bilateral adrenal masses had a unilateral source of aldosterone secretion. Three of four patients with unilateral atypical adrenal macroadenomas had ipsilateral aldosterone-producing adenomas. A unilateral source of aldosterone excess may be found in selected patients with adrenal glands that appear normal or show a minimally expanded adrenal limb on CT scan. Findings on adrenal venous sampling are crucial in determining the source of aldosterone excess in patients with bilateral adrenal masses or atypical-appearing macroadenomas.


[Endoscopic application of surgical lasers in persistent obstructions in laryngopharynx, larynx and trachea in children].
CO2, YAG-Nd and copper lasers were applied for elimination of persistent obstruction of the laryngopharynx, larynx and trachea in 331 patients aged 23 days to 15 years. Scar stenosis, vascular tumors, cysts, nonspecific granulemas were diagnosed in 271, 29, 8 and 23 patients, respectively. Current and newly-developed techniques reducing thermal damage to the adjacent to laser-exposed tissues and principles of laser treatment choice for different obstructions are analysed.


Manganese superoxide dismutase (MnSOD) gene polymorphism, interactions with carotenoid levels and prostate cancer risk.
The manganese superoxide dismutase (MnSOD) gene encodes an antioxidant enzyme (SOD2) that may protect cells from oxidative damage. The MnSOD allele with Val as amino acid 16 encodes a protein that has 30-40% lower activity compared with the MnSOD Ala variant, hence possibly increasing susceptibility to oxidative stress. On the other hand, some epidemiologic studies suggest that the Ala allele is associated with a higher risk of cancer, including prostate cancer. We conducted a nested case-control study in the Health Professionals Follow-up Study with 612 incident prostate cancer cases and 612 matched controls to investigate the role of the MnSOD gene Ala16Val polymorphism and its joint association with plasma carotenoid concentrations in relation to risk of total prostate cancer and aggressive prostate cancer (advanced stage or Gleason sum > or =7). The allele frequencies in the controls were 49.8% for Ala and 50.2% for Val. No association was found between the MnSOD genotype and risk of total and aggressive prostate cancer. Furthermore, no statistically significant interaction was observed between the MnSOD genotype and any of the plasma carotenoids in relation to risk of total and aggressive prostate cancer. In analyses in which we combined data from plasma and dietary carotenoids and created a quintile score to reflect long-term carotenoid status, a 3-fold [95% confidence interval: 1.37-7.02] increased risk of aggressive prostate cancer was observed among men with the Ala/Ala genotype in the presence of low long-term lycopene status (P-value, test for interaction = 0.02) as compared with men with the Ala/Val+Val/Val genotypes with low long-term lycopene status. In this cohort of mainly white men, the MnSOD gene Ala16Val polymorphism was not associated with total or aggressive prostate cancer risk. However, men with the MnSOD Ala/Ala genotype who had low long-term lycopene status had a higher risk of aggressive prostate cancer compared with individuals with the other genotypes. These results are consistent with findings from earlier studies that reported when antioxidant status is low, the MnSOD Ala/Ala genotype may be associated with an increased risk of aggressive prostate cancer.


PRMT5 silencing selectively affects MTAP-deleted mesothelioma: In vitro evidence of a novel promising approach.
Malignant mesothelioma (MM) is an aggressive asbestos-related cancer of the serous membranes. Despite intensive treatment regimens, MM is still a fatal disease, mainly due to the intrinsic resistance to current therapies and the lack of predictive markers and new valuable molecular targets. Protein arginine methyltransferase 5 (PRMT5) inhibition has recently emerged as a potential therapy against methylthioadenosine phosphorylase (MTAP)-deficient cancers, in which the accumulation of the substrate 5'-methylthioadenosine (MTA) inhibits PRMT5 activity, thus sensitizing the cells to further PRMT5 inhibition. Considering that the MTAP gene is frequently codeleted with the adjacent cyclin-dependent kinase inhibitor 2A (CDKN2A) locus in MM, we assessed whether PRMT5 could represent a therapeutic target also for this cancer type. We evaluated PRMT5 expression, the MTAP status and MTA content in normal mesothelial and MM cell lines. We found that both administration of exogenous MTA and stable PRMT5 knock-down, by short hairpin RNAs (shRNAs), selectively reduced the growth of MTAP-deleted MM cells. We also observed that PRMT5 knock-down in MTAP-deficient MM cells reduced the expression of E2F1 target genes involved in cell cycle progression and of factors implicated in epithelial-to-mesenchymal transition. Therefore, PRMT5 targeting could represent a promising new therapeutic strategy against MTAP-deleted MMs.


The role of inferior frontal junction in controlling the spatially global effect of feature-based attention in human visual areas.
Feature-based attention has a spatially global effect, i.e., responses to stimuli that share features with an attended stimulus are enhanced not only at the attended location but throughout the visual field. However, how feature-based attention modulates cortical neural responses at unattended locations remains unclear. Here we used functional magnetic resonance imaging (fMRI) to examine this issue as human participants performed motion- (Experiment 1) and color- (Experiment 2) based attention tasks. Results indicated that, in both experiments, the respective visual processing areas (middle temporal area [MT+] for motion and V4 for color) as well as early visual, parietal, and prefrontal areas all showed the classic feature-based attention effect, with neural responses to the unattended stimulus significantly elevated when it shared the same feature with the attended stimulus. Effective connectivity analysis using dynamic causal modeling (DCM) showed that this spatially global effect in the respective visual processing areas (MT+ for motion and V4 for color), intraparietal sulcus (IPS), frontal eye field (FEF), medial frontal gyrus (mFG), and primary visual cortex (V1) was derived by feedback from the inferior frontal junction (IFJ). Complementary effective connectivity analysis using Granger causality modeling (GCM) confirmed that, in both experiments, the node with the highest outflow and netflow degree was IFJ, which was thus considered to be the source of the network. These results indicate a source for the spatially global effect of feature-based attention in the human prefrontal cortex.


Molecular determinants of the ATP hydrolysis asymmetry of the CCT chaperonin complex.
The eukaryotic cytosolic chaperonin CCT is a molecular machine involved in assisting the folding of proteins involved in important cellular processes. Like other chaperonins, CCT is formed by a double-ring structure but, unlike all of them, each ring is composed of eight different, albeit homologous subunits. This complexity has probably to do with the specificity in substrate interaction and with the mechanism of protein folding that takes place during the chaperonin functional cycle, but its detailed molecular basis remains unknown. We have analyzed the known proteomes in search of residues that are differentially conserved in the eight subunits, as predictors of functional specificity (specificity-determining positions; SDPs). We have found that most of these SDPs are located near the ATP binding site, and that they define four CCT clusters, corresponding to subunits CCT3, CCT6, CCT8 and CCT1/2/4/5/7. Our results point to a spatial organisation of the CCT subunits in two opposite areas of the ring and provide a molecular explanation for the previously described asymmetry in the hydrolysis of ATP.


Aneuploidy Enables Cross-Adaptation to Unrelated Drugs.
Aneuploidy is common both in tumor cells responding to chemotherapeutic agents and in fungal cells adapting to antifungal drugs. Because aneuploidy simultaneously affects many genes, it has the potential to confer multiple phenotypes to the same cells. Here, we analyzed the mechanisms by which Candida albicans, the most prevalent human fungal pathogen, acquires the ability to survive both chemotherapeutic agents and antifungal drugs. Strikingly, adaptation to both types of drugs was accompanied by the acquisition of specific whole-chromosome aneuploidies, with some aneuploid karyotypes recovered independently and repeatedly from very different drug conditions. Specifically, strains selected for survival in hydroxyurea, an anticancer drug, acquired cross-adaptation to caspofungin, a first-line antifungal drug, and both acquired traits were attributable to trisomy of the same chromosome: loss of trisomy was accompanied by loss of adaptation to both drugs. Mechanistically, aneuploidy simultaneously altered the copy number of most genes on chromosome 2, yet survival in hydroxyurea or caspofungin required different genes and stress response pathways. Similarly, chromosome 5 monosomy conferred increased tolerance to both fluconazole and to caspofungin, antifungals with different mechanisms of action. Thus, the potential for cross-adaptation is not a feature of aneuploidy per se; rather, it is dependent on specific genes harbored on given aneuploid chromosomes. Furthermore, pre-exposure to hydroxyurea increased the frequency of appearance of caspofungin survivors, and hydroxyurea-adapted C. albicans cells were refractory to antifungal drug treatment in a mouse model of systemic candidiasis. This highlights the potential clinical consequences for the management of cancer chemotherapy patients at risk of fungal infections.


Tumor Necrosis Factor Inhibitors and the Risk of Cancer among Older Americans with Rheumatoid Arthritis.
TNF inhibitors (TNFi) effectively treat rheumatoid arthritis but may increase patient risk of some malignancies, particularly lymphomas or skin cancers. We used Surveillance, Epidemiology, and End Results (SEER)-Medicare data to conduct a case-control study in patients with rheumatoid arthritis (2007-2015). Cases were individuals with a first cancer diagnosed in SEER registries (ages 66-99, 22 cancer sites, N = 10,263). Skin cancer cases [nonmelanoma skin cancer (NMSC, N = 501), basal cell carcinoma (BCC, N = 161), squamous cell carcinoma (SCC, N = 150)] and cancer-free controls (N = 30,475) were selected from Medicare beneficiaries residing in SEER areas. Cases and controls had prior Medicare claims-based evidence for rheumatoid arthritis, and TNFi exposure was ascertained from part B and part D claims. Logistic regression was used to estimate adjusted odds ratios (aOR). TNFi exposure was present in 16.2% of controls and 12.8% to 33.7% of cancer cases, varying by site. TNFi use was associated with increased risk of NMSC overall (aOR 1.32, 95% confidence interval 1.06-1.63), non-Hodgkin lymphoma (NHL) overall (1.28, 1.06-1.56) and, specifically, follicular lymphoma (2.63, 1.63-4.24). TNFi exposure was not associated with other SEER cancer sites, BCC or SCC specifically, or other common NHL subtypes. Among older adults with rheumatoid arthritis, TNFi exposure was associated with elevated risk of NMSC and NHL, driven specifically by follicular lymphoma. Exposure was not associated with increased risk for other cancer sites. Our results support a role for TNF in lymphomagenesis. Given the association with NMSC, patients initiating TNFi therapy may benefit from skin cancer screening and sun protection measures.


Central inhibition of IKKβ/NF-κB signaling attenuates high-fat diet-induced obesity and glucose intolerance.
Metabolic inflammation in the central nervous system might be causative for the development of overnutrition-induced metabolic syndrome and related disorders, such as obesity, leptin and insulin resistance, and type 2 diabetes. Here we investigated whether nutritive and genetic inhibition of the central IκB kinase β (IKKβ)/nuclear factor-κB (NF-κB) pathway in diet-induced obese (DIO) and leptin-deficient mice improves these metabolic impairments. A known prominent inhibitor of IKKβ/NF-κB signaling is the dietary flavonoid butein. We initially determined that oral, intraperitoneal, and intracerebroventricular administration of this flavonoid improved glucose tolerance and hypothalamic insulin signaling. The dose-dependent glucose-lowering capacity was profound regardless of whether obesity was caused by leptin deficiency or high-fat diet (HFD). To confirm the apparent central role of IKKβ/NF-κB signaling in the control of glucose and energy homeostasis, we genetically inhibited this pathway in neurons of the arcuate nucleus, one key center for control of energy homeostasis, via specific adeno-associated virus serotype 2-mediated overexpression of IκBα, which inhibits NF-κB nuclear translocation. This treatment attenuated HFD-induced body weight gain, body fat mass accumulation, increased energy expenditure, and reduced arcuate suppressor of cytokine signaling 3 expression, indicative for enhanced leptin signaling. These results reinforce a specific role of central proinflammatory IKKβ/NF-κB signaling in the development and potential treatment of DIO-induced comorbidities.


Lectin binding in the ovary of the chick embryo and newborn.
The content, distribution and changes of the glycoconjugates sugar residues in the ovaries of chick embryos, from the 8th day of incubation to hatching and in 1-day old chick, were investigated. For this purpose, a battery of seven HRP-conjugated lectins was used (DBA, SBA, PNA, ConA, WGA, LTA and UEA I). Our data showed that SBA was a marker of the most immature oogonia in the ovarian cortex and medulla. The reactivity with ConA appeared to characterize the cells immediately prior to as well as during the meiotic division, as demonstrated by the presence of alpha-D-mannose at the "Balbiani bodies" in the oogonia of the ovarian cortex. The detection of Con A and SBA reactivity corresponded to maturative stages of the early oogonia in different cortical zones of the chick ovary. Our data also revealed that PNA seemed to be a marker of the degenerating oogonia located in the ovarian medulla. Moreover, PNA binding was a characteristic finding in the endothelial cells of the vessels located in the compact portion of the medulla in the left ovary, from the 8th to the 21st day of incubation and after hatching; PNA reactivity was only seen from the 16th day onwards in the endothelial cells of the cortex. During the whole considered period of incubation and after hatching, reactivity with UEAI, LTA and DBA was never detected.


Genetic effects on sperm design in the zebra finch.
Sperm design and function are important determinants of male reproductive success and are expected to be under strong selection. The way that spermatozoa phenotypes evolve is poorly understood, because there have been few studies of the quantitative genetics of sperm. Here we show, in the zebra finch Taeniopygia guttata, an extraordinary degree of inter-male variation in sperm design that is independent of sperm swimming velocity. A quantitative genetics study using data from over 900 zebra finches in a complex breeding experiment showed that sperm head, mid-piece and flagellum length are heritable, that negative genetic correlations exist between sperm traits, and that significant indirect (maternal) genetic effects exist. Selection on the zebra finch sperm phenotype may be low because sperm competition is infrequent in this species, and this, in combination with negative genetic correlations and maternal genetic effects, may account for the variation in sperm phenotype between males. These results have important implications for the evolution of sperm in other taxa.


Wave energy technology in China.
This paper traces the research stages of China's study of wave energy technology, summarizing the findings and deficiencies of each stage from oscillating water column, through onshore oscillating buoy to floating Duck. It also highlights the major innovations in China's new floating Duck device.


Periprosthetic sepsis.
The diagnosis of septic implant failure can be difficult to make, yet is imperative for optimal patient outcomes in revision total hip arthroplasty. In most cases, a thorough history and physical examination combined with preoperative laboratory tests and an intraoperative frozen section are sufficient to differentiate septic from aseptic failure. If preoperative laboratory test values are elevated, preoperative aspiration of the hip can be used in selected patients to confirm or exclude the diagnosis of infection. Nuclear medicine studies comprise a second-line investigation to evaluate patients with a painful total hip arthroplasty in whom revision surgery otherwise is not indicated. Intraoperative tissue appearance in combination with intraoperative Gram stains are unreliable for detecting periprosthetic sepsis, and neither is adequate when considered alone for ruling out infection at the time of revision total hip arthroplasty. It is imperative that the surgeon doing revision total hip arthroplasty thoroughly understands the relative utility of preoperative and intraoperative tests used to diagnose periprosthetic sepsis.


An investigation of the diet, exercise, sleep, BMI, and health outcomes of autistic adults.
Studies of autistic children suggest that restricted eating, reduced physical activity, and sleep disorders are common; however, no studies attempt to broadly describe the diet, exercise, and sleep patterns of autistic adults or consider relationships between lifestyle behaviors and the widely reported increased risks of obesity and chronic conditions. To address this, the authors developed the largest study of lifestyle patterns of autistic adults and assessed their relationships to body mass index, health outcomes, and family history. We administered an anonymized, online survey to n = 2386 adults (n = 1183 autistic) aged 16-90 years of age. We employed Fisher's exact tests and binomial logistic regression to describe diet, exercise, and sleep patterns; mediation of seizure disorders on sleep; body mass index (BMI); relationships of lifestyle factors to BMI, cardiovascular conditions, and diabetic conditions; and sex differences among autistic adults. Autistic adults, and particularly autistic females, exhibit unhealthy diet, exercise, and sleep patterns; they are also more likely to be underweight or obese. Limited sleep duration and high rates of sleep disturbances cannot be accounted for by epilepsy or seizure disorders. Lifestyle factors are positively related to higher risk of cardiovascular conditions among autistic males, even more than family history. Our sample may not be representative of all autistic and non-autistic people, as it primarily comprised individuals who are white, female, have a high school education or higher, and reside in the UK. Our sampling methods may also exclude some individuals on the autism spectrum, and particularly those with moderate to severe intellectual disability. This is a cross-sectional sample that can test for relationships between factors (e.g., lifestyle factors and health outcomes) but cannot assess the direction of these relationships. Autistic adults are less likely to meet minimal health recommendations for diet, exercise, and sleep-and these unhealthy behaviors may relate to excess risk of cardiovascular conditions. Although the present study can only provide preliminary, correlational evidence, our findings suggest that diet, exercise, and sleep should be considered and further investigated as key targets for reducing the now widely reported and dramatically increased risks of health comorbidity and premature death among autistic individuals compared to others. Physicians should work cooperatively with patients to provide health education and develop individualized strategies for how to better manage challenges with diet, exercise, and sleep.


Reconstitution of active transport in proteoliposomes containing cytochrome o oxidase and lac carrier protein purified from Escherichia coli.
Most active transport across the bacterial cell membrane is driven by a proton electrochemical gradient (delta-muH+, interior negative and alkaline) generated via electron transfer through a membrane-bound respiratory chain. This phenomenon is now reproduced in vitro with proteoliposomes containing only two proteins purified from the membrane of Escherichia coli. An o-type cytochrome oxidase was extracted from membranes of a cytochrome d terminal oxidase mutant with octyl beta-D-glucopyranoside after sequential treatment with urea and cholate and was purified to homogeneity by ion-exchange chromatography. The purified oxidase contains four polypeptides (MrS 66,000, 35,000, 22,000, and 17,000), two b-type cytochromes (b558 and b563), and 16-17 nmol of heme b per mg of protein, and it catalyzes the oxidation of ubiquinol and other electron donors with specific activities 20- to 30-fold higher than crude membranes. The lac carrier protein was purified as described. Proteoliposomes were formed in the presence of the oxidase and lac carrier protein by detergent dilution, followed by freeze-thaw/sonication. The system generates a delta-muH+ (interior negative and alkaline) with ubiquinol as electron donor and the magnitude of delta-muH+ is dependent on the concentration of cytochrome o in the proteoliposomes. Furthermore, the proteoliposomes transport lactose against a concentration gradient to an extent that is commensurate with the magnitude of delta-muH+ generated. The results provide powerful additional support for the "chemiosmotic hypothesis" and demonstrate that purified lac carrier protein retains the ability to function in a physiological manner.


Pre-deployment risk factors for PTSD in active-duty personnel deployed to Afghanistan: a machine-learning approach for analyzing multivariate predictors.
Active-duty Army personnel can be exposed to traumatic warzone events and are at increased risk for developing post-traumatic stress disorder (PTSD) compared with the general population. PTSD is associated with high individual and societal costs, but identification of predictive markers to determine deployment readiness and risk mitigation strategies is not well understood. This prospective longitudinal naturalistic cohort study-the Fort Campbell Cohort study-examined the value of using a large multidimensional dataset collected from soldiers prior to deployment to Afghanistan for predicting post-deployment PTSD status. The dataset consisted of polygenic, epigenetic, metabolomic, endocrine, inflammatory and routine clinical lab markers, computerized neurocognitive testing, and symptom self-reports. The analysis was computed on active-duty Army personnel (N = 473) of the 101st Airborne at Fort Campbell, Kentucky. Machine-learning models predicted provisional PTSD diagnosis 90-180 days post deployment (random forest: AUC = 0.78, 95% CI = 0.67-0.89, sensitivity = 0.78, specificity = 0.71; SVM: AUC = 0.88, 95% CI = 0.78-0.98, sensitivity = 0.89, specificity = 0.79) and longitudinal PTSD symptom trajectories identified with latent growth mixture modeling (random forest: AUC = 0.85, 95% CI = 0.75-0.96, sensitivity = 0.88, specificity = 0.69; SVM: AUC = 0.87, 95% CI = 0.79-0.96, sensitivity = 0.80, specificity = 0.85). Among the highest-ranked predictive features were pre-deployment sleep quality, anxiety, depression, sustained attention, and cognitive flexibility. Blood-based biomarkers including metabolites, epigenomic, immune, inflammatory, and liver function markers complemented the most important predictors. The clinical prediction of post-deployment symptom trajectories and provisional PTSD diagnosis based on pre-deployment data achieved high discriminatory power. The predictive models may be used to determine deployment readiness and to determine novel pre-deployment interventions to mitigate the risk for deployment-related PTSD.


[Cognitive impairments in early restorative period of ischemic stroke].
The aim was to study prevalence and peculiarity of cognitive impairments in patients with ischemic stroke. 76 patients with stroke were examined in early restorative period of disease. Neurologic status of the patients was examined with NIHSS scale, Renkin scale was employed for measuring the degree of disability, MMSE and FAB was used to estimate cognitive functions. 24-hour, non-invasive ambulatory blood pressure (BP) monitoring was used to reveal arterial hypertension and impairment of circadian rhythm of ABP. Considerable prevalence of cognitive impairments was shown. 34.2% patients suffered from dementia. The most impaired cognitive functions were memory, calculation, repetition and writing. Risk factors of cognitive impairments in patients with ischemic stroke were advanced age, severe neurological impairments, increasing SBP, minimal DBP. Examination cognitive function after stroke is necessary to plan treatment, prevention and reablement.


Prevalence and potential risk factors of rhinitis and atopic eczema among schoolchildren in Vientiane capital, Lao PDR: ISAAC questionnaire.
In 1998, an epidemiological study on asthma and allergic diseases using ISAAC questionnaire in Laos was first conducted in the recommended schools located in Vientiane capital showing that the prevalence of rhinoconjunctivitis and atopic eczema were 23.7% and 7.1% among children aged 13-14 year-old, respectively. This study aimed to reassess the prevalence of rhinoconjunctivitis and atopic eczema using the same ISAAC questionnaire by employing random sampling method and to identify the potential risk factors for these rhinitis and atopic eczema. This school-based cross-sectional study was conducted in Vientiane capital from December 2006 to February 2007. Of 536 children, prevalence of rhinoconjunctivitis and atopic eczema among schoolchildren were 9.3% and 11.8%, respectively. Children with early respiratory infection (AOR = 4.06; p = 0.001), parasitic infestation especially by Opisthorchis viverrini (AOR = 3.41; p < 0.05) were more likely to have rhinitis. While history of measles (OR = 2.24; p < 0.01) and respiratory infection (OR = 1.96; p < 0.05), eating vegetables everyday (AOR = 2.96; p < 0.01) were associated with atopic eczema. The similarity of prevalence of rhinitis and rhinoconjunctivitis were also revealed between children aged 13-14 year-old in this study and 6-7 in the previous study in 1998. The validation study on ISAAC questionnaire in Lao language is needed in order to generalize this questionnaire in Lao.


Accessing distributions of exchange and dipolar couplings in stiff molecular rulers with Cu(II) centres.
Determining distributed exchange couplings is important for understanding the properties of synthetic magnetic molecules. Such distributions can be determined from pulsed dipolar spectroscopy (PDS) data, but this is challenging due to the similar influence of both exchange and dipolar couplings on such data. In this work we introduce two models that aim to identify these two contributions to the spin-spin couplings from frequency-domain PDS data of shape-persistent molecules having either two Cu(ii) ions, or a Cu(ii) ion and a nitroxide radical as the paramagnetic moieties. The first model assumes correlated Lorentzian or Gaussian exchange and dipole-dipole coupling distributions whose parameters are the model's unknowns. The second model relies on prior knowledge of the distance distribution and by performing Tikhonov regularization along the exchange coupling dimension yields the latter distribution model-free. Both models were able to differentiate between the absence and the presence of exchange interaction, to determine the coupling regime (ferro- or antiferromagnetic) and to estimate the distribution shape. In contrast, calculations within the exchange resilient model of the neural network analysis implemented in DeerAnalysis2018 were not able for our data to identify exchange couplings and return correct distance distributions. However, the generic model was able to identify and separate the strongly curved intermolecular background in the relaxation-induced dipolar modulation enhancement (RIDME) experiments. Our analysis revealed that in such systems exchange coupling may be present up to at least 3.3 nm in π-conjugated systems involving Cu(ii)-PyMTA, while it is negligible for distances r ≥ 4.5 nm between Cu(ii) ions and r ≥ 3.8 nm between a Cu(ii) ion and an unpaired electron of a nitroxide radical. Disruption of the π-conjugation between the ligand of the Cu(ii) complex and the nitroxide leads to negligible exchange coupling at distances r ≥ 2.6 nm in the corresponding [Cu(ii)-TAHA]-nitroxide ruler. Overall, for cases with known distance distributions, the presented analysis techniques allow to determine distributions of exchange couplings from PDS data.


Chlorhexidine--pharmaco-biological activity and application.
Chlorhexidine (CHX) is one of the most widely used antiseptic, especially in dentistry. At low concentrations CHX is bacteriostatic and at high concentrations acts bactericidal causing cell death by cytolysis. In this study, we performed a systematic review of pharmaco-biological activity and application of CHX. Articles for inclusion in this review were retrieved from online databases PubMed/Medline. The selected papers were included in the present manuscript according to their relevance for the topic. Totally 75 papers were enrolled in this research. CHX has strong biocidal activity against Gram-positive bacteria and weaker activity against Gram-negative bacteria. It is also active against yeasts, some dermatophytes and some lipophilic viruses. The most widely application CHX has found in dentistry and antisepsis. Numerous studies have confirmed the beneficial effects of CHX in reducing of plaque accumulation, in tooth caries, gingivitis, periodontitis and in alveolar osteitis. Unfortunately, CHX exhibits cytotoxic activity on human cells, can cause colorization of teeth and fillings, and its activity depends on the pH of the environment and the presence of organic substances. CHX play a valuable role in the dentistry and antisepsis. However, it can also cause side effects, limiting its application time.


Urinary o-cresol in toluene exposure.
The determination of urinary o-cresol in varying exposure to toluene vapor showed a linear relationship between the metabolite and the inhaled solvent. The analytical method involves acid hydrolysis of 20 ml of urine with subsequent extraction of the phenolic compounds in dichloromethane, followed by gas chromatographic analysis. The lowest limit of detection lies at 0.5 micromol/l, whereas the practical limit as an exposure test is at 2.5 micromol/l [corresponding to 0.2 micromol/l (5 ppm) of toluene vapor]. The test may also have indirect toxicologic significance, as the underlying initial arene oxides which produce the cresolic compounds are involved in toluene toxicity.


Significance of enzymatically catalyzed exchange reactions in chemotherapy.
1) 3-Acetyl pyridine has been found to be quite toxic when administered to mice. Simultaneous administration of nicotinamide or DPN protects against the toxicity of acetyl pyridine. Nicotinic acid and tryptophan do not protect animals from the lethal effects of the compound. 2) Nicotinamide inhibits the formation of the 3-acetyl pyridine analog of DPN from acetyl pyridine and DPN in mouse brain homogenates. Nicotinic acid has no inhibitory effect on analog synthesis. 3) Administration of acetyl pyridine results in a fourfold increase in the DPN level of the lever. No acetyl pyridine analog of DPN is found in the liver after injection of the antimetabolite. 4) Injection of acetyl pyridine into tumor mice results in the formation of the acetyl pyridine analog of DPN in the neoplastic tissues. A decrease in DPN concentration is associated with the analog synthesis. The DPN analog has been isolated from tumor tissue and identified. 5) The results are discussed with respect to the significance of enzymatically catalyzed exchange reactions in chemotherapy.


Direct Determination of Ca, K, and Mg in Soy Leaf Samples Using Laser-Induced Breakdown Spectroscopy.
This study was dedicated to developing analytical methods for determining macronutrients (Ca, K, and Mg) in soy leaf samples with and without petioles. The study's primary purpose was to present Laser-induced breakdown spectroscopy (LIBS) as a viable alternative for directly analyzing leaf samples using chemometric tools to interpret the data obtained. The instrumental condition chosen for LIBS was 70 mJ of laser pulse energy, 1.0 µs of delay time, and 100 µm of spot size, which was applied to 896 samples: 305 of soy without petioles and 591 of soy with petioles. The reference values of the analytes for the proposition of calibration models were obtained using inductively coupled plasma optical emission spectroscopy (ICP-OES) technique. Twelve normalization modes and two calibration strategies were tested to minimize signal variations and sample matrix microheterogeneity. The following were studied: multivariate calibration using partial least squares and univariate calibration using the area and height of several selected emission lines. The notable normalization mode for most models was the Euclidean norm. No analyte showed promising results for univariate calibrations. Micronutrients, P and S, were also tested, and no multivariate models presented satisfactory results. The models obtained for Ca, K, and Mg showed good results. The standard error of calibration ranged from 2.3 g/kg for Ca in soy leaves without petioles with two latent variables to 5.0 g/kg for K in soy leaves with petioles with two latent variables.


Grid-based diffusion Monte Carlo for fermions without the fixed-node approximation.
A diffusion Monte Carlo algorithm is introduced that can determine the correct nodal structure of the wave function of a few-fermion system and its ground-state energy without an uncontrolled bias. This is achieved by confining signed random walkers to the points of a uniform infinite spatial grid, allowing them to meet and annihilate one another to establish the nodal structure without the fixed-node approximation. An imaginary-time propagator is derived rigorously from a discretized Hamiltonian, governing a non-Gaussian, sign-flipping, branching, and mutually annihilating random walk of particles. The accuracy of the resulting stochastic representations of a fermion wave function is limited only by the grid and imaginary-time resolutions and can be improved in a controlled manner. The method is tested for a series of model problems including fermions in a harmonic trap as well as the He atom in its singlet or triplet ground state. For the latter case, the energies approach from above with increasing grid resolution and converge within 0.015E_{h} of the exact basis-set-limit value for the grid spacing of 0.08 a.u. with a statistical uncertainty of 10^{-5}E_{h} without an importance sampling or Jastrow factor.


Mutation in Chek2 triggers von Hippel-Lindau hemangioblastoma growth.
Von Hippel-Lindau (VHL) is a rare inherited disease mainly characterized by the growth of tumours, predominantly hemangioblastomas (Hbs) in the CNS and retina, and renal carcinomas. The natural history of VHL disease is variable, differing in the age of onset and its penetrance, even among relatives. Unfortunately, sometimes VHL shows more severe than average: the onset starts in adolescence, and surgeries are required almost every year. In these cases, the factor that triggers the appearance and growth of Hbs usually remains unknown, although additional mutations are suspected. We present the case of a VHL patient whose first surgery was at 13 years of age. Then, along his next 8 years, he has undergone 5 surgeries for resection of 10 CNS Hbs. To clarify this severe VHL condition, DNA from a CNS Hb and white blood cells (WBC) was sequenced using next-generation sequencing technology. Massive DNA sequencing of the WBC (germ line) revealed a pathogenic mutation in CHEK2 and the complete loss of a VHL allele (both tumour suppressors). Moreover, in the tumour sample, several mutations, in BRAF1 and PTPN11 were found. Familiar segregation studies showed that CHEK2 mutation was in the maternal lineage, while VHL was inherited by paternal lineage. Finally, clinical history correlated to the different genotypes in the family, concluding that the severity of these VHL manifestations are due to both, VHL-and-CHEK2 mutations. This case report aims to notice the importance of deeper genetic analyses, in inherited rare diseases, to uncover non-expected mutations.


Nurses' Experiences as Care Providers for Syrian Refugees With Noncommunicable Diseases: A Qualitative Study.
Noncommunicable diseases (NCDs) are the leading cause of disability and death in the world. In Syria, the incidence of NCDs in refugees is 45%. Cardiovascular diseases, cancers, chronic respiratory diseases, diabetes, and other NCDs are the most common causes of morbidity in Syria. Nurses have challenges caring for Syrian refugees with NCDs. The purpose of the study was to explore nurses' experiences of caring for Syrian refugees with NCDs in Turkey. A phenomenology design was used. Inclusion criteria were nurses working experience of more than 1 year, caring for Syrian refugees with NCDs, and willingness and ability to participate in an individual interview. The participants were 20 nurses who worked with Syrian refugees at a public hospital in Kilis Province the border with Syria. Data were collected using semistructured interviews and analyzed by the thematic analysis method of Braun and Clarke. Three major themes and six subthemes were identified. Major themes included the communication experience, cultural differences, and Syrian refugees' lack of knowledge about NCDs. The results provide insight related to nursing care in Turkey for Syrian refugees with NCDs. The study revealed that nurses encountered challenges when caring for Syrian refugees with NCDs. Culturally competent assessment and interventions for refugees with NCDs should be encouraged considering these three themes.


A Quasi-Experimental Study of a Basics of Evidence-Based Practice Educational Intervention for Health and Social Care Professionals.
Education is one of the central interventions to promote evidence-based practice (EBP) in service organizations. An educational intervention to promote EBP among health and social care professionals was implemented in a Finnish hospital. The aim of this study was to explore the outcomes of an educational intervention, focusing on the basics of EBP for health and social care professionals, using a quasi-experimental study design. The data were collected with a questionnaire before, immediately after, and 6 months after the education (n = 48). The data were analyzed with descriptive statistics and nonparametric tests. Immediately after the education, an increase was found in the EBP knowledge of participants, in participants' confidence in their own ability to conduct database searches and read scientific articles, and in the number of participants using databases at work. Six months after the education, improvements were still found between the first and the third measurement in the participants' knowledge and confidence in their own ability to conduct database searches and read scientific articles. The number of those who had made an initiative about a research topic regarding the development of their own work had increased from the first to the third measurement. The educational intervention produced a statistically significant improvement on most of the areas evaluated. Significant improvements were often found even 6 months after the education was finished. However, the low completion rate and a quasi-experimental before and after design limit the conclusions that can be derived from this study.


Development of aqueous size exclusion chromatography conditions to characterize polyzwitterion-block-N-isopropyl acrylamide copolymers.
Block copolymers that exhibit both an upper critical solution temperature and a lower critical solution temperature are difficult to characterize due to inherent solubility difference between the two blocks. For example, accurate determination of both the molar mass and molar mass distribution is challenging for polyzwitterion-block-N-isopropyl acrylamide (NIPAM) copolymers in aqueous solutions due to self-assembly. However, there are a few examples of using size exclusion chromatography (SEC) for characterization, in which hexafluoro isopropanol (HFIP) is used in all cases. Yet, researchers are hesitant to use this solvent due to how expensive and hazardous HFIP is. Therefore, alternatives to HFIP for SEC analysis would be desirable. Here, a systematic methodology featuring aqueous SEC is demonstrated using several solvent conditions to enable the elution of polyzwitterion-block-NIPAM copolymers on Agilent PolarGel† and Tosoh TSKgel† column sets. These SEC conditions include 0.2 M KI in water on the PolarGel columns and 0.2 M KI/ 30% DMF in water on the PolarGel and TSKgel columns. These aqueous systems can be utilized for the characterization of similar water-soluble block copolymers that are relevant for drug delivery and other biomedical applications.


Controlling chemistry with cations: photochemistry within zeolites.
The alkali ions present in the supercages of zeolites X and Y interact with included guest molecules through quadrupolar (cation-pi), and dipolar (cation-carbonyl) interactions. The presence of such interactions can be inferred through solid-state NMR spectra of the guest molecules. Alkali ions, as illustrated in this article, can be exploited to control the photochemical and photophysical behaviors of the guest molecules. For example, molecules that rarely phosphoresce can be induced to do so within heavy cation-exchanged zeolites. The nature (electronic configuration) of the lowest triplet state of carbonyl compounds can be altered with the help of light alkali metal ions. This state switch (n pi*-pi pi*) helps to bring out reactivity that normally remains dormant. Selectivity obtained during the singlet oxygen oxidation of olefins within zeolites illustrates the remarkable control that can be exerted on photoreactions with the help of a confined medium that also has active sites. The reaction cavities of zeolites, like enzymes, are not only well-defined and confined, but also have active sites that closely guide the reactant molecule from start to finish. The examples provided here illustrate that zeolites are far more useful than simple shape-selective catalysts.


Impacts of COVID-19 on urban rail transit ridership using the Synthetic Control Method.
The outbreak of COVID-19 in 2020 has had drastic impacts on urban economies and activities, with transit systems around the world witnessing an unprecedented decline in ridership. This paper attempts to estimate the effect of COVID-19 on the daily ridership of urban rail transit (URT) using the Synthetic Control Method (SCM). Six variables are selected as the predictors, among which four variables unaffected by the pandemic are employed. A total of 22 cities from Asia, Europe, and the US with varying timelines of the pandemic outbreak are selected in this study. The effect of COVID-19 on the URT ridership in 11 cities in Asia is investigated using the difference between their observed ridership reduction and the potential ridership generated by the other 11 cities. Additionally, the effect of the system closure in Wuhan on ridership recovery is analyzed. A series of placebo tests are rolled out to confirm the significance of these analyses. Two traditional methods (causal impact analysis and straightforward analysis) are employed to illustrate the usefulness of the SCM. Most Chinese cities experienced about a 90% reduction in ridership with some variation among different cities. Seoul and Singapore experienced a minor decrease compared to Chinese cities. The results suggest that URT ridership reductions are associated with the severity and duration of restrictions and lockdowns. Full system closure can have severe impacts on the speed of ridership recovery following resumption of service, as demonstrated in the case of Wuhan with about 22% slower recovery. The results of this study can provide support for policymakers to monitor the URT ridership during the recovery period and understand the likely effects of system closure if considered in future emergency events.


Effects of climate warming and prolonged snow cover on phenology of the early life history stages of four alpine herbs on the southeastern Tibetan Plateau.
Much research has focused on plant responses to ongoing climate change, but there is relatively little information about how climate change will affect the early plant life history stages. Understanding how global warming and changes in winter snow pattern will affect seed germination and seedling establishment is crucial for predicting future alpine population and vegetation dynamics. In a 2-year study, we tested how warming and alteration in the snowmelt regime, both in isolation and combination, influence seedling emergence phenology, first-year growth, biomass allocation, and survival of four native alpine perennial herbs on the southeastern Tibetan Plateau. Warming promoted seedling emergence phenology of all four species and biomass per plant of two species but reduced seedling survival of three species. Prolonged snow cover partly mediated the affects of warming on Primula alpicola (survival and biomass), Pedicularis fletcheri (phenology, biomass, and root:shoot ratio) and Meconopsis integrifolia (survival). For the narrowly distributed species M. racemosa, seedling growth was additively decreased by warming and prolonged snow cover. Both warming and alteration of the snow cover regime can influence plant recruitment by affecting seedling phenology, growth, and survival, and the effects are largely species-specific. Thus, climate change is likely to affect population dynamics and community structure of the alpine ecosystem. This is the first experimental demonstration of the phenological advancement of seedling emergence in the field by simulated climate warming.


Antibacterial Character of Cationic Polymers Attached to Carbon-Based Nanomaterials.
The preparation of hybrid polymeric systems based on carbon derivatives with a cationic polymer is described. The polymer used is a copolymer of a quaternizable methacrylic monomer with another dopamine-based monomer capable of anchoring to carbon compounds. Graphene oxide and graphene as well as hybrid polymeric systems were widely characterized by infrared, Raman and photoemission X-ray spectroscopies, electron scanning microscopy, zeta potential and thermal degradation. These allowed confirming the attachment of copolymer onto carbonaceous materials. Besides, the antimicrobial activity of hybrid polymeric systems was tested against Gram positive Staphylococcus aureus and Staphylococcus epidermidis and Gram negative Escherichia coli and Pseudomonas aeruginosa bacteria. The results showed the antibacterial character of these hybrid systems.


Effects of phase-transited lysozyme on adhesion, migration and odontogenic differentiation of human dental pulp cells: An in vitro study.
To explore the effects of phase-transited lysozyme (PTL) coated dentine slices on cell adhesion, migration and odontogenic differentiation of human dental pulp cells (HDPCs). Cell growth and cell cycle analysis were conducted to verify the biocompatibility of PTL for HDPCs. Cell adhesion, cell morphology and proliferation were explored by DiI staining, Scanning electron microscopy and MTT assay. Cell migration was investigated by Transwell assay. The effects of PTL on odontogenesis and mineralization of HDPCs were assessed by real-time quantitative polymerase chain reaction and Western blot. The mineralization of HDPCs was evaluated by Alizarin red staining. HDPCs were isolated from extracted third molars. The level of statistically significant difference was accepted at p < .05. PTL showed no negative effect on cell cycle of HDPCs and compared with the blank group, HDPCs labelled with DiI staining showed significantly more adhered cells at 48 h (p < .05), extending cell processes and more finger-like or reticular pseudopodia on PTL-coated dentine slices. The results of MTT and Transwell assay showed that PTL promoted the proliferation (p < .05) and migration (p < .01) of HDPCs, respectively. Compared with the blank group, the gene expression of dentine sialophosphoprotein (DSPP), osteopontin and bone sialoprotein in HDPCs cultured on PTL was significantly upregulated on day 3 and 7 (p < .05), while the protein expression of DSPP showed no significant change on both day 7 and day 14. Alizarin red staining showed that PTL promoted more mineralization nodules formation of HDPCs (p < .05). PTL promoted the adhesion, proliferation and migration of HDPCs on dentine slices, and positively affected odontogenic differentiation and mineralization of HDPCs.


Unexpectedly low drug exposures among Ugandan patients with TB and HIV receiving high-dose rifampicin.
We characterized the pharmacokinetics of standard- and high-dose rifampicin in Ugandan adults with tuberculosis and HIV taking dolutegravir- or efavirenz-based antiretroviral therapy. A liver model with saturable hepatic extraction adequately described the data, and the increase in exposure between high and standard doses was 4.7-fold. This was lower than what previous reports of dose-exposure nonlinearity would predict and was ascribed to 38% lower bioavailability of the rifampicin-only top-up formulation compared to the fixed-dose combination.


Biomarker monitoring of controlled dietary acrylamide exposure indicates consistent human endogenous background.
The aim of the present study was to explore the relation of controlled dietary acrylamide (AA) intake with the excretion of AA-related urinary mercapturic acids (MA), N-acetyl-S-(carbamoylethyl)-L-cysteine (AAMA) and N-acetyl-S-(1-carbamoyl-2-hydroxyethyl)-L-cysteine (GAMA). Excretion kinetics of these short-term exposure biomarkers were monitored under strictly controlled conditions within a duplicate diet human intervention study. One study arm (group A, n = 6) ingested AA via coffee (0.15-0.17 µg/kg bw) on day 6 and in a meal containing an upper exposure level of AA (14.1-15.9 μg/kg bw) on day 10. The other arm (group B) was on AA minimized diet (washout, 0.05-0.06 µg/kg bw) throughout the whole 13-day study period. On day 6, these volunteers ingested 13C3D3-AA (1 μg/kg bw). In both arms, urinary MA excretion was continuously monitored and blood samples were taken to determine hemoglobin adducts. Ingestion of four cups of coffee resulted in a slightly enhanced short-term biomarker response within the background range of group B. At the end of the 13-day washout period, group B excreted an AAMA baseline level of 0.14 ± 0.10 µmol/d although AA intake was only about 0.06 µmol/d. This sustained over-proportional AAMA background suggested an endogenous AA baseline exposure level of 0.3-0.4 µg/kg bw/d. The excretion of 13C3D3-AA was practically complete within 72-96 h which rules out delayed release of AA (or any other MA precursor) from deep body compartments. The results provide compelling support for the hypothesis of a sustained endogenous AA formation in the human body.


Appendicitis update.
The diagnostic approach to children with possible appendicitis remains challenging. Although advances in imaging have improved diagnostic accuracy over clinical judgment alone, new management strategies continue to evolve. This review serves as an update on imaging, biomarkers, and management of appendicitis. Abdominal computed tomography (CT) and ultrasound continue to be the ancillary radiologic studies of choice for appendicitis. Recent studies on the use of CT have focused on the need for intravenous or enteral contrast. Despite lower diagnostic performance, ultrasound has the advantage of sparing patients from radiation exposure. MRI is being evaluated as an additional diagnostic modality. New biomarkers, beyond a standard white blood cell count or absolute neutrophil count, continue to be investigated, but these are not being routinely used in practice. Different management approaches are also being investigated, including nonoperative treatment with antibiotic therapy for early, acute appendicitis. The best use of advanced radiologic imaging for children with possible appendicitis is actively debated. CT continues to show superior accuracy as compared with ultrasound; however, screening ultrasounds for nonobese children have advantages. The combination of robust decision rules that incorporate biomarkers and the judicious use of CT will help define diagnostic strategies for appendicitis over the next decade.


Factors regulating macrophage production and growth: identity of colony-stimulating factor and macrophage growth factor.
The activities of a colony-stimulating factor (CSF), which stimulates granulocyte-macrophage colony formation by mouse hemopoietic cells, and macrophage growth factor (MGF), which stimulates proliferation of activated peritoneal macrophages, have been demonstrated by various criteria to reside in the same molecular species. These criteria include occurrence in various sources and copurification of the activities in mouse L-cell-conditioned medium as well as the biological, physicochemical, and antigenic properties of the activities of L-cell-conditioned medium. CSF and MGF activities of L-cell-conditioned medium are ascribable to a glycoprotein of mol wt approximately 60,000 which migrates electrophoretically with alpha-globulin. Human urinary CSF, which also possesses MGF activity, has similar properties and can be neutralized by antiserum to highly purified L-cell medium CSF. A procedure is described for the partial purification of material from L-cell medium that has activity at 1 ng/ml in both MGF and CSF assays.