The adherence-outcome relationship is not altered by diary-driven adjustments of microelectronic monitor data.
The purpose of this study was to determine whether diary-driven adjustment of Medication Event Monitoring System (MEMS) data based on Supporting Information strengthens the relationship between measured antiretroviral medication adherence and plasma HIV viral load (VL). HIV+ adolescents on antiretroviral treatment were monitored with MEMS for 30 days preceding a VL measurement. The primary outcome was VL ≥ 400 copies/mL. Handwritten diaries were used to comprehensively record deviations from recommended use (bottle opened but dose not taken or bottle not opened and dose taken). Data were adjusted ("cleaned") based on diary events. Data were "capped" at the prescribed number of doses/day. Receiver operator characteristic analysis compared the relationships between (i) raw MEMS data, (ii) diary-cleaned, (iii) capped, or (iv) cleaned and capped MEMS data and VL. Over 30 days preceding VL measurements, 273 adolescents had 465 diary events. Capping resulted in fewer patients classified as 95% adherent (65.2%) compared with raw data (71.4%), p < 0.001. Adherence was highly associated with VL (OR 1.05, p < 0.001). The area under the receiver operating characteristic curve for continuous adherence compared with VL was 0.89 (95%CI: 0.82-0.95). Neither diary-cleaning, capping, nor cleaning and capping MEMS data significantly altered the association between adherence and VL (p = 0.14, 0.40, and 0.19, respectively). Medication Event Monitoring System data-cleaning based on diary entries did not affect the adherence-VL relationship.


Long-term temporal trends in incidence rate and case fatality of sepsis and COVID-19-related sepsis in Norwegian hospitals, 2008-2021: a nationwide registry study.
To estimate temporal trends in incidence rate (IR) and case fatality during a 14-year period from 2008 to 2021, and to assess possible shifts in these trends during the COVID-19 pandemic. All Norwegian hospitals 2008-2021. 317 705 patients ≥18 year with a sepsis International Classification of Diseases 10th revision code retrieved from The Norwegian Patient Registry. Annual age-standardised IRs with 95% CIs. Poisson regression was used to estimate changes in IRs across time, and logistic regression was used to estimate ORs for in-hospital death. Among 12 619 803 adult hospitalisations, a total of 317 705 (2.5%) hospitalisations in 222 832 (70.0%) unique patients met the sepsis criteria. The overall age-standardised IR of a first sepsis admission was 246/100 000 (95% CI 245 to 247), whereas the age-standardised IR of all sepsis admissions was 352/100 000 (95% CI 351 to 354). In the period 2009-2019, the annual IR for a first sepsis episode was stable (IR ratio (IRR) per year, 0.999; 95% CI 0.994 to 1.004), whereas for recurrent sepsis the IR increased (annual IRR, 1.048; 95% CI 1.037 to 1.059). During the COVID-19 pandemic, the IRR for a first sepsis was 0.877 (95% CI 0.829 to 0.927) in 2020 and 0.929 (95% CI 0.870 to 0.992) in 2021, and for all sepsis it was 0.870 (95% CI 0.810 to 0.935) in 2020 and 0.908 (95% CI 0.840 to 0.980) in 2021, compared with the previous 11-year period. Case fatality among first sepsis admissions declined in the period 2009-2019 (annual OR 0.954 (95% CI 0.950 to 0.958)), whereas case fatality increased during the COVID-19 pandemic in 2020 (OR 1.061 (95% CI 1.001 to 1.124) and in 2021 (OR 1.164 (95% CI 1.098 to 1.233)). The overall IR of sepsis increased from 2009 to 2019, due to an increasing IR of recurrent sepsis, and indicates that sepsis awareness with updated guidelines and education must continue.


A human strain of Oxalobacter (HC-1) promotes enteric oxalate secretion in the small intestine of mice and reduces urinary oxalate excretion.
Enteric oxalate secretion that correlated with reductions in urinary oxalate excretion was previously reported in a mouse model of primary hyperoxaluria, and in wild type (WT) mice colonized with a wild rat strain (OXWR) of Oxalobacter (Am J Physiol 300:G461–G469, 2010). Since a human strain of the bacterium is more likely to be clinically used as a probiotic therapeutic, we tested the effects of HC-1 in WT. Following artificial colonization of WT mice with HC-1, the bacteria were confirmed to be present in the large intestine and, unexpectedly, detected in the small intestine for varying periods of time. The main objective of the present study was to determine whether the presence of HC-1 promoted intestinal secretion in the more proximal segments of the gastrointestinal tract. In addition, we determined whether HC-1 colonization led to reductions in urinary oxalate excretion in these mice. The results show that the human Oxalobacter strain promotes a robust net secretion of oxalate in the distal ileum as well as in the caecum and distal colon and these changes in transport correlate with the beneficial effect of reducing renal excretion of oxalate. We conclude that OXWR effects on intestinal oxalate transport and oxalate homeostasis are not unique to the wild rat strain and that, mechanistically, HC-1 has significant potential for use as a probiotic treatment for hyperoxaluria especially if it is also targeted to the upper and lower gastrointestinal tract.


The role of the endothelium in severe acute respiratory syndrome coronavirus 2 infection and pathogenesis.
Endothelial cell (EC) dysfunction is a characteristic complication of coronavirus-19 (COVID-19). This review discusses the role of the endothelium during the pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with a focus on different vascular beds, possible routes of infectivity and the impact of EC dysfunction across multiple organ systems. It is now known that COVID-19 disease elicits a distinct transcriptomic and molecular profile that is different to other viral infections, such as Influenza A (H1N1). Interestingly, there is also a suggested interplay between the heart and lungs that promotes the amplification of inflammatory cascades, leading to an exacerbation in disease severity. Multiomic studies have informed common pathways that may be responsible for endothelial activation while also highlighting key differences in COVID-19 pathogenesis between organ systems. At a pathological level, endothelialitis is an endpoint result regardless of either a direct viral infection or via indirect effects independent of infection. Understanding if ECs are directly targeted by SARS-CoV-2 or are collaterally damaged amid a cytokine storm originating from other cells and organs can provide novel insights into disease progression and may highlight possible new therapeutic opportunities targeted at the damaged endothelium.


Differential expression of miRNAs and their relation to active tuberculosis.
The aim of this work was to screen miRNA signatures dysregulated in tuberculosis to improve our understanding of the biological role of miRNAs involved in the disease. Datasets deposited in publically available databases from microarray studies on infectious diseases and malignancies were retrieved, screened, and subjected to further analysis. Effect sizes were combined using the inverse-variance model and between-study heterogeneity was evaluated by the random effects model. 35 miRNAs were differentially expressed (12 up-regulated, 23 down-regulated; p < 0.05) by combining 15 datasets of tuberculosis and other infectious diseases. 15 miRNAs were found to be significantly differentially regulated (7 up-regulated, 8 down-regulated; p < 0.05) by combining 53 datasets of tuberculosis and malignancies. Most of the miRNA signatures identified in this study were found to be involved in immune responses and metabolism. Expression of these miRNA signatures in serum samples from TB subjects (n = 11) as well as healthy controls (n = 10) was examined by TaqMan miRNA array. Taken together, the results revealed differential expression of miRNAs in TB, but available datasets are limited and these miRNA signatures should be validated in future studies.


A Simulation Curriculum for Management of Trauma and Surgical Critical Care Patients.
Expectations continue to rise for residency programs to provide integrated simulation training to address clinical competence. How to implement such training sustainably remains a challenge. We developed a compact module for first-year surgery residents integrating theory with practice in high-fidelity simulations, to reinforce the preparedness and confidence of junior residents in their ability to manage common emergent patient care scenarios in trauma and critical care surgery. The 3-day module features a combination of simulated patient encounters using standardized patients and electronic manikins, didactic sessions, and hands-on training. Manikin-based scenarios developed in-house were used to teach trauma and critical care management concepts and skills. Separate scenarios in collaboration with the regional organ donation program addressed communication in difficult situations such as brain death. Didactic material based on contemporary evidence, as well as skills stations, was developed to complement the scenarios. Residents were surveyed before and after training on their confidence in meeting the 14 learning objectives of the curriculum on a 5-point Likert scale. Data from 15 residents who underwent this training show an overall improvement in confidence across all learning objectives defined for the module, with confidence scores before to after training improving significantly from 2.8 (σ = 0.85, median = 3) to 3.9 (σ = 0.87, median = 4) of 5, p < 0.001. Although female residents reported higher posttraining confidence scores compared with male residents (average 4.2 female vs 3.8 male, p = 0.002), there were no other significant differences in confidence scores or changes to scores owing to resident sex or program status (categorical or preliminary). We successfully implemented a multimodal simulation-based curriculum that provides skills training integrated with the clinical context of managing trauma and critical care patients, simultaneously addressing a range of clinical competencies. Results to date show consistent improvement in residents' confidence in meeting learning objectives. Development of the curriculum continues for sustainability, as well as measures to embed objective evaluations of resident competence.


Myofibroblastic tumor of the right ventricle causing bilateral pulmonary embolism in a 31 year-old woman.
The myofibroblastic tumor (MFT) is a very rare tumor, initially described in the lungs, and which involves exceptionally the heart. We report the unusual case of a 31 year-old female patient, in whom the tumor produced a bilateral pulmonary embolism and whose unique clinical demonstration was a longstanding fever. The tumor, located in the right ventricle, has been surgically completely excised with excellent results. We also make a review of literature of the various aspects of this pathology.


[Postnatal development of transbasal skull openings: carotid canal, jugular foramen, hypoglossal canal, condylar canal and foramen magnum].
The above mentioned portals and channels of the skull were measured at 98 skulls of infants with variable stages of life and discussed with the results of former investigators. Length, width, angles and distances to different points of the skull base and the median sagittal plane were measured.


The stress response and exploratory behaviour in Yucatan minipigs (Sus scrofa): Relations to sex and social rank.
According to the coping styles hypothesis, an individual demonstrates an integrated behavioural and physiological response to environmental challenge that is consistent over time and across situations. Individual consistency in behavioural responses to challenge has been documented across the animal kingdom. Comparatively few studies, however, have examined inter-individual variation in the physiological response, namely glucocorticoid and catecholamine levels, the stress hormones secreted by the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system, respectively. Variation in coping styles between individuals may be explained in part by differences in social rank and sex. Using 20 Yucatan minipigs (Sus scrofa) we: (1) investigated the existence of consistent inter-individual variation in exploratory behaviour and the hormonal stress response, and tested for correlations as predicted by the coping styles hypothesis; and (2) evaluated whether inter-individual behavioural and hormonal variation is related to social rank and sex. Salivary stress biomarkers (cortisol, alpha-amylase, chromogranin A) were assessed in the presence and absence of a stressor consisting of social isolation in a crate for 10 min. Principal components analysis on a set of behavioural variables revealed two traits, which we labelled exploratory tendency and neophobia. Neither exploratory tendency nor neophobia predicted the physiological stress response. Subordinate pigs exhibited higher catecholamine levels compared to dominant conspecifics. We observed sex differences in the repeatability of salivary stress markers and reactivity of the stress systems. The results do not provide support for the existence of behavioural-physiological coping styles in pigs. Sex is an important determinant of the physiological stress response and warrants consideration in research addressing behavioural and hormonal variation.


Reconstitution mechanism of nucleosome core particles mediated by poly(L-glutamic acid).
Poly(L-glutamic acid) has been reported to mediate in vitro nucleosome assembly (Stein, A., Whitlock, J.P., Jr. and Bina, M. (1979) Proc. Natl. Acad. Sci. U.S.A. 76,5000-5004). To study the reaction mechanism, we have reconstituted nucleosome core particles from chicken erythrocyte core DNA and core histones in the presence of poly(L-glutamic acid) and analyzed the assembly products by polyacrylamide gel electrophoresis. Poly(L-glutamic acid), which binds and forms a large complex with core histones, is replaced with core DNA in the reconstitution process. When histone-poly(L-glutamic acid) complex and core DNA are mixed with a histone:DNA ratio of 1.0, the yield of core particles increases by prolonged reconstitution time. Two phases with a distinct time range appear in the process. In the fast phase within 30 min, 60% of the DNA is involved in products containing histones: reconstituted core particles, a larger nucleoprotein complex and aggregation. In the second phase, the remaining DNA and the DNA in the aggregation decrease, and the core particles increase slowly. The yield of core particles is approx. 60% after 24 h. The slow phase is not observed by reconstitution with a histone:DNA ratio of 2.0 in the initial mixture. The reaction scheme of the assembly process derived from these data is given. Based on the in vitro reaction scheme, the possible role of in vivo 'nucleosome assembly factors' is also discussed.


A spitting image: molecular diagnostics applied to saliva enhance detection of Streptococcus pneumoniae and pneumococcal serotype carriage.
Despite strong historical records on the accuracy of saliva testing, oral fluids are considered poorly suited for pneumococcal carriage detection. We evaluated an approach for carriage surveillance and vaccine studies that increases the sensitivity and specificity of pneumococcus and pneumococcal serotype detection in saliva samples. Quantitative PCR (qPCR)-based methods were applied to detect pneumococcus and pneumococcal serotypes in 971 saliva samples collected from 653 toddlers and 318 adults. Results were compared with culture-based and qPCR-based detection in nasopharyngeal samples collected from children and in nasopharyngeal and oropharyngeal samples collected from adults. Optimal C q cut-offs for positivity in qPCRs were determined via receiver operating characteristic curve analysis and accuracy of different approaches was assessed using a composite reference for pneumococcal and for serotype carriage based on isolation of live pneumococcus from the person or positivity of saliva samples determined with qPCR. To evaluate the inter-laboratory reproducibility of the method, 229 culture-enriched samples were tested independently in the second center. In total, 51.5% of saliva samples from children and 31.8% of saliva samples from adults were positive for pneumococcus. Detection of pneumococcus by qPCR in culture-enriched saliva exhibited enhanced sensitivity and higher agreement with a composite reference compared to diagnostic culture of nasopharyngeal samples in children (Cohen's κ: 0.69-0.79 vs. 0.61-0.73) and in adults (κ: 0.84-0.95 vs. 0.04-0.33) and culture of oropharyngeal samples in adults (κ: 0.84-0.95 vs. -0.12-0.19). Similarly, detection of serotypes with qPCR in culture-enriched saliva exhibited enhanced sensitivity and higher agreement with a composite reference compared to nasopharyngeal culture in children (κ: 0.73-0.82 vs. 0.61-0.73) and adults (κ: 0.90-0.96 vs. 0.00-0.30) and oropharyngeal culture in adults (κ: 0.90-0.96 vs. -0.13 to 0.30). However, results of qPCRs targeting serotype 4, 5, and 17F and serogroups 9, 12, and 35 were excluded due to assays' lack of specificity. We observed excellent quantitative agreement for qPCR-based detection of pneumococcus between laboratories. After exclusion of serotype/serogroup-specific assays with insufficient specificity, moderate agreement (κ 0.68, 95% CI 0.58-0.77) was observed. Molecular testing of culture-enriched saliva samples improves the sensitivity of overall surveillance of pneumococcal carriage in children and adults, but limitations of qPCR-based approaches for pneumococcal serotypes carriage detection should be considered.


Synthetic scope of Ru(OH)x/Al2O3-catalyzed hydrogen-transfer reactions: an application to reduction of allylic alcohols by a sequential process of isomerization/Meerwein-Ponndorf-Verley-type reduction.
Reduction of allylic alcohols can be promoted efficiently by the supported ruthenium catalyst Ru(OH)x/Al2O3. Various allylic alcohols were converted to saturated alcohols in excellent yields by using 2-propanol without any additives. This Ru(OH)x/Al2O3-catalyzed reduction of a dienol proceeds only at the allylic double bond to afford the corresponding enol, and chemoselective isomerization and reduction can be realized under similar conditions. The catalysis is truly heterogeneous and the high catalytic performance can be maintained during at least three recycles of the Ru(OH)x/Al2O3 catalyst. The transformation of allylic alcohols to saturated alcohols consists of three sequential reactions: oxidation of allylic alcohols to alpha,beta-unsaturated carbonyl compounds; reduction of alpha,beta-unsaturated carbonyl compounds to saturated carbonyl compounds; and reduction of saturated carbonyl compounds to saturated alcohols.


Total and regional microfiber transport characterization in a 15th - Generation human respiratory airway.
Fiber transport and deposition in the complete respiratory airway is of great significance for human health risk assessment. Thus far, the literature has mainly focused on limited branches of the upper airway and assumes spherical particles by neglecting fiber anisotropy. To fill the gap, this paper utilized an extended realistic respiratory airway from the nasal cavity to the distal bronchial tracts, up to the 15th generation. Fibers with aerodynamic diameters from 2 to 12 μm and aspect ratios of 1, 10, and 50 were released at the inlet of the respiratory airway model, and the coupled translational and rotational motion were computed. Overall and regional fiber deposition fractions, including the nasal cavities, laryngeal airway, and lungs were predicted and compared with earlier numerical results. The study also investigated: 1) secondary flow and distributions of the fibers at the lower respiratory airway entrance; 2) upstream conditions toward fiber deposition efficiencies; 3) fiber deposition patterns and detailed deposition fractions in the five lobes. Utilizing the realistic fiber transport model, the current study found that the upstream airway geometry and the flow condition have a significant impact on the fiber transport and deposition in the downstream airway regions. The fiber depositions in the lower and middle lobes are sensitive to the fiber aerodynamic diameter, but insensitive in the upper lobes. This study expects to generate innovative knowledge on the unique fiber motion characteristics toward potential inhalation health risks.


Airway proteoglycans are differentially altered in fatal asthma.
It has been suggested that airway remodelling is responsible for the persistent airway obstruction and decline in lung function observed in some asthmatic patients. The small airways are thought to contribute significantly to this functional impairment. Proteoglycans (PGs) are important components of the extracellular matrix (ECM) in the lungs. Besides controlling biophysical properties of the ECM, they play important roles in the regulation of some cytokines. Increased subepithelial PG deposition in the airways of mild asthmatics has been reported. However, there are no data on the PG content in small airways in asthma. This study has compared the content and distribution of PGs in large and small airways of patients who died of asthma with those in control lungs. Immunohistochemistry and image analysis were used to determine the content of lumican, decorin, biglycan, and versican in large (internal perimeter >6 mm) and small (internal perimeter < or =6 mm) airways of 18 patients who had died of asthma (A) and ten controls (C). The results were expressed as PG area (microm2)/epithelial basement membrane length (microm). The main differences between asthmatics and controls were observed in the small airways. There was a significant decrease in decorin and lumican contents in the external area of small airways in asthmatics (decorin: A = 1.05 +/- 0.27 microm, C = 3.97 +/- 1.17 microm, p = 0.042; lumican: A = 1.97 +/- 0.37 microm, C = 5.66 +/- 0.99 microm, p = 0.002). A significant increase in versican content in the internal area of small and large airways in asthmatics was also observed (small: A = 7.48 +/- 0.84 microm, C = 5.16 +/- 0.61 microm, p = 0.045; large: A = 18.38 +/- 1.94 microm, C = 11.90 +/- 2.86 microm, p = 0.028). The results show that PGs are differentially expressed in the airways of fatal asthma and may contribute to airway remodelling. These data reinforce the importance of the small airways in airway remodelling in asthma.


Dosage-dependent absorption of cadmium in the rat intestine measured in situ.
Previous studies have shown that the disposition of cadmium (Cd) following oral administration is dosage dependent and may possibly be due to dosage-dependent intestinal absorption of Cd. Though extensively studied, the precise nature of Cd absorption by the intestine remains unclear. Similarly, the role of metallothionein (MT) in the intestinal absorption of Cd remains equivocal. The present study was designed (1) to characterize the intestinal absorption of Cd in the rat, and (2) to determine the role of MT in intestinal Cd absorption. The study has been conducted with an isolated intestinal loop preparation in situ, which allows direct measurement of intestinal absorption under nearly physiological conditions. Under urethane-induced anesthesia. Cd (0.1, 10, 100, 1000, or 10,000 micrograms/kg) was injected intraluminally into the isolated intestinal loop in situ and all mesenteric venous (portal) blood exiting from the loop was collected for 90 min. Absorption of Cd into the portal circulation was low at all dosages studied. The percentage of the dosage absorbed ranged from 0.09% at the 0.1 microgram/kg dosage to 3.4% at the 10,000 micrograms/kg dosage. At low dosages (0.1 and 10 micrograms/kg), little difference was noted in the fractional absorption of Cd (0.09 and 0.14% of the dosage, respectively). However, the fractional absorption of Cd was 10-fold greater in rats administered 100 micrograms Cd/kg (1.1% of the dosage). Administration of higher dosages of Cd (1000 and 10,000 micrograms/kg) further increased the percentage of the dosage absorbed (1.8 and 3.4%, respectively). To evaluate the role of MT in the intestinal absorption of Cd. rats were subcutaneously injected with zinc (Zn) for 4 days (30 mg/kg/day) and the absorption of an intermediate dosage of Cd (100 micrograms/kg) was subsequently assessed in situ. Zn pretreatment increased the endogenous concentration of MT in the intestine 25-fold. Following intraluminal administration. 93% of Cd in intestinal cytosol of Zn-treated rats was bound to MT whereas 40% of the cytosolic Cd was bound to MT in saline-treated (control) rats. Moreover, the amount of Cd in intestinal cytosol was 2-fold greater in Zn-treated rats than in control rats. However, the intestinal absorption of Cd in rats pretreated with Zn demonstrated no difference from that in saline-treated rats. These results indicate that the intestinal absorption of Cd is dosage independent at low dosages of Cd (less than 10 micrograms/kg) and dosage dependent at high dosages (greater than 10 micrograms/kg). Furthermore, saturation of intestinal MT is not a major determinant of the observed dosage-dependent absorption of Cd.


Nuclear magnetic resonance imaging in multiple sclerosis.
Ten patients with definite multiple sclerosis underwent hydrogen nuclear magnetic resonance imaging with a 3.5 kilogauss superconducting magnet, using the inversion recovery and spin-echo techniques of signal acquisition. Results were compared with high-resolution x-ray computed tomography. Spin-echo images demonstrated abnormal regions as areas of variably increased signal intensity. The contrast between abnormal and normal white matter improved as the intervals between sequential radiofrequency pulses and between pulse administration and signal sampling were increased. Inversion recovery images demonstrated abnormal areas as regions of decreased signal intensity but did not visualize lesions as well as spin-echo imaging. Spin-echo and inversion recovery imaging each demonstrated more extensive abnormalities than did computed tomography.


Mapping molecular adhesion sites inside SMIL coated capillaries using atomic force microscopy recognition imaging.
Capillary zone electrophoresis (CZE) is a powerful analytical technique for fast and efficient separation of different analytes ranging from small inorganic ions to large proteins. However electrophoretic resolution significantly depends on the coating of the inner capillary surface. High technical efforts like Successive Multiple Ionic Polymer Layer (SMIL) generation have been taken to develop stable coatings with switchable surface charges fulfilling the requirements needed for optimal separation. Although the performance can be easily proven in normalized test runs, characterization of the coating itself remains challenging. Atomic force microscopy (AFM) allows for topographical investigation of biological and analytical relevant surfaces with nanometer resolution and yields information about the surface roughness and homogeneity. Upgrading the scanning tip to a molecular biosensor by adhesive molecules (like partly inverted charged molecules) allows for performing topography and recognition imaging (TREC). As a result, simultaneously acquired sample topography and adhesion maps can be recorded. We optimized this technique for electrophoresis capillaries and investigated the charge distribution of differently composed and treated SMIL coatings. By using the positively charged protein avidin as a single molecule sensor, we compared these SMIL coatings with respect to negative charges, resulting in adhesion maps with nanometer resolution. The capability of TREC as a functional investigation technique at the nanoscale was successfully demonstrated.


Rapid rise of serum acid phosphatase after irradiation of metastatic carcinoma of prostate.
An eighty-two-year-old man with metastatic prostatic adenocarcinoma was treated with radiation therapy to the lumbar region of the spinal column. A rapid rise in his acid phosphatase activities developed, increasing thirty-eight-fold in two days. He died on the second day post-therapy of hemorrhagic complications. The rapid increase in acid phosphatase activity was due to release from injured or dying prostatic adenocarcinoma cells.


Biochemical and genetic analysis of an acatalasic rho+ mutant of Saccharomyces cerevisiae.
The previously described acatalasic rho+ strain R-6 has been studied in order to determine the type of mutation responsible for its inability to produce catalase. Induction conditions for catalase activity and temperature influence on the behaviour of this strain were assayed. Furthermore, haploid progeny arising from crosses between R-6 and other strains (rho+, rho- and rho0) was examined for catalase levels. From the data obtained a hypothetical interaction between nuclear and mitochondrial genomes in relation to catalase biosynthesis is discussed.


Theory-Driven Longitudinal Study Exploring Indoor Tanning Initiation in Teens Using a Person-Centered Approach.
Younger indoor tanning initiation leads to greater melanoma risk due to more frequent and persistent behavior. Despite this, there are no published studies exploring the predictors of indoor tanning initiation in teen populations. This longitudinal study uses latent profile analysis to examine indoor tanning initiation in indoor tanning risk subgroups from a national sample of female adolescents. Latent profile analysis used indoor tanning beliefs and perceptions to identify indoor tanning initiation risk subgroups. The teens in each subgroup were reassessed on indoor tanning initiation after a year. Three subgroups were identified: a low risk, anti-tanning subgroup (18.6 %) characterized by low scores on positive indoor tanning belief scales and high scores on beliefs about indoor tanning dangers; a moderate risk aware social tanner subgroup (47.2 %) characterized by high scores on positive indoor tanning belief scales but also high scores on beliefs about indoor tanning dangers; and a high risk risky relaxation tanner subgroup (34.2 %) characterized by high scores on positive indoor tanning belief scales and low scores on beliefs about indoor tanning dangers. Teens in the aware social tanner and risky relaxation tanner subgroups were significantly more likely to initiate indoor tanning in the following year. These findings highlight the need to identify teens at risk for indoor tanning initiation and develop tailored interventions that will move them to the lowest risk subgroup. Subgroup correlates suggest parent and peer-based interventions may be successful.


Common genetic variation near MC4R is associated with waist circumference and insulin resistance.
We carried out a genome-wide association study (318,237 SNPs) for insulin resistance and related phenotypes in 2,684 Indian Asians, with further testing in 11,955 individuals of Indian Asian or European ancestry. We found associations of rs12970134 near MC4R with waist circumference (P = 1.7 x 10(-9)) and, independently, with insulin resistance. Homozygotes for the risk allele of rs12970134 have approximately 2 cm increased waist circumference. Common genetic variation near MC4R is associated with risk of adiposity and insulin resistance.


Exosomal miR-338-3p suppresses non-small-cell lung cancer cells metastasis by inhibiting CHL1 through the MAPK signaling pathway.
Globally, lung cancer remains one of the most prevalent malignant cancers. However, molecular mechanisms and functions involved in its pathogenesis have not been clearly elucidated. This study aimed to evaluate the specific regulatory mechanisms of exosomal miR-338-3p/CHL1/MAPK signaling pathway axis in non-small-cell lung cancer. Western blotting and qRT-PCR (reverse transcription-polymerase chain reaction) were used to determine the expression levels of CHL1 and exosomal miR-338-3p in NSCLC (non-small-cell lung cancer). The CHL1 gene was upregulated and downregulated to evaluate its functions in NSCLC progression. In vitro MTS and apoptotic assays were used to investigate the functions of CHL1 and exosomal miR-338-3p in NSCLC progression. The high-throughput sequencing was used to explore differently expressed exosomal miRNAs. The biological relationships between MAPK signaling pathway and CHL1 and exosomal miR-338-3p in NSCLC were predicted through bioinformatics analyses and verified by western blotting. Elevated CHL1 levels were observed in NSCLC tissues and cells. Upregulated CHL1 expression enhanced NSCLC cells' progression by promoting tumor cells proliferation while suppressing their apoptosis. Conversely, the downregulation of the CHL1 gene inhibited NSCLC cells' growth and promoted tumor cells' apoptotic rate. Additionally, CHL1 activated the MAPK signaling pathway. Besides, we confirmed that miR-338-3p directly sponged with CHL1 to mediate tumor cells progression. Moreover, exosomal miR-338-3p serum levels in NSCLC patients were found to be low. BEAS-2B cells can transfer exosomal miR-338-3p to A549 cells and SK-MES-1 cells. In addition, elevated exosomal miR-338-3p levels significantly inhibited tumor cells proliferation and promoted their apoptosis by suppressing activation of the MAPK signaling pathway. Exosomal miR-338-3p suppresses tumor cells' metastasis by downregulating the expression of CHL1 through MAPK signaling pathway inactivation.


Post-authorization safety surveillance of Ad.26.COV2.S vaccine: Reports to the Vaccine Adverse Event Reporting System and v-safe, February 2021-February 2022.
On 2/27/2021, FDA authorized Janssen COVID-19 Vaccine (Ad.26.COV2.S) for use in individuals 18 years of age and older. Vaccine safety was monitored using the Vaccine Adverse Event Reporting System (VAERS), a national passive surveillance system, and v-safe, a smartphone-based surveillance system. VAERS and v-safe data from 2/27/2021 to 2/28/2022 were analyzed. Descriptive analyses included sex, age, race/ethnicity, seriousness, AEs of special interest (AESIs), and cause of death. For prespecified AESIs, reporting rates were calculated using the total number of doses of Ad26.COV2.S administered. For myopericarditis, observed-to-expected (O/E) analysis was performed based on the number verified cases, vaccine administration data, and published background rates. Proportions of v-safe participants reporting local and systemic reactions, as well as health impacts, were calculated. During the analytic period, 17,018,042 doses of Ad26.COV2.S were administered in the United States, and VAERS received 67,995 reports of AEs after Ad26.COV2.S vaccination. Most AEs (59,750; 87.9 %) were non-serious and were similar to those observed during clinical trials. Serious AEs included COVID-19 disease, coagulopathy (including thrombosis with thrombocytopenia syndrome; TTS), myocardial infarction, Bell's Palsy, and Guillain-Barré syndrome (GBS). Among AESIs, reporting rates per million doses of Ad26.COV2.S administered ranged from 0.06 for multisystem inflammatory syndrome in children to 263.43 for COVID-19 disease. O/E analysis revealed elevated reporting rate ratios (RRs) for myopericarditis; among adults ages 18-64 years, the RR was 3.19 (95 % CI 2.00, 4.83) within 7 days and 1.79 (95 % CI 1.26, 2.46) within 21 days of vaccination. Of 416,384 Ad26.COV2.S recipients enrolled into v-safe, 60.9 % reported local symptoms (e.g. injection site pain) and 75.9 % reported systemic symptoms (e.g., fatigue, headache). One-third of participants (141,334; 33.9 %) reported a health impact, but only 1.4 % sought medical care. Our review confirmed previously established safety risks for TTS and GBS and identified a potential safety concern for myocarditis.


Nonalcoholic Fatty Liver Disease and the Heart: JACC State-of-the-Art Review.
Nonalcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD) are both manifestations of end-organ damage of the metabolic syndrome. Through multiple pathophysiological mechanisms, CVD and NAFLD are associated with each other. Systemic inflammation, endothelial dysfunction, hepatic insulin resistance, oxidative stress, and altered lipid metabolism are some of the mechanisms by which NAFLD increases the risk of CVD. Patients with NAFLD develop increased atherosclerosis, cardiomyopathy, and arrhythmia, which clinically result in cardiovascular morbidity and mortality. Defining the mechanisms linking these 2 diseases offers the opportunity to further develop targeted therapies. The aim of this comprehensive review is to examine the association between CVD and NAFLD and discuss the overlapping management approaches.


[State of the mitochondria and nuclear chromatin in cerebral cortex nerve cells during laser irradiation].
Effect of laser irradiation (PPM-mv/cm2, gamma = 632.8 nm) on respiratory and phosphorylating activities of mitochondria as well as on structure-functional state of nuclear chromatin from rat brain cortex neurones were studied. The irradiation stimulated the activities studied suggesting possible increase in functional potentialities of brain tissue under these experimental conditions.


Highlighting earthworm contribution in uplifting biochemical response for organic matter decomposition during vermifiltration processing sewage sludge: Insights from proteomics.
A vermifilter (VF) was steadily operated to explore the mechanism of lower microbial biomass and higher enzymatic activities due to the presence of earthworms, with a conventional biofilter (BF) as a control. The analysis of 2-DE indicated that 432 spots and 488 spots were clearly detected in the VF and BF biofilm. Furthermore, MALDI-TOF/TOF MS revealed that six differential up-regulated proteins, namely Aldehyde Dehydrogenase, Molecular chaperone GroEL, ATP synthase subunit alpha, Flagellin, Chaperone protein HtpG and ATP synthase subunit beta, changed progressively. Based on Gene Ontology annotation, these differential proteins mainly performed 71.38% ATP binding and 16.23% response to stress functions. Taken the VF process performance merits into considerations, it was addressed that earthworm activities biochemically strengthened energy releasing of the microbial metabolism in an uncoupled manner.


Antipsychotics can modulate the cytokine profile in schizophrenia: attenuation of the type-2 inflammatory response.
We recently reported that the type-2 cytokine response is increased in schizophrenia. The aim of this study was to analyse the effects of antipsychotic drugs on the serum levels of type-1 (TNF-α, IFN-γ), type-2 (IL-4, IL-10), type-17 (IL-17) and regulatory cytokines (TGF-β, IL-27 and IL-6). Cytokine measurements in the patients were performed on day 0 and day 30 of the treatment using standard ELISA assays. Three groups of subjects were studied: patients that were unmedicated with First Episode Psychosis (FEP; n=88), patients that were treated with antipsychotics with Schizophrenia in relapse (SC in relapse; n=45) and healthy controls (n=36). TGF-β levels were increased in both patient groups and were further enhanced after treatment in the FEP group (p=0.014) but not in the SC relapse group. Antipsychotic treatment was correlated with lower levels of IL-4, IL-6 and IL-27 (p<0.005) in the FEP group. Finally, the serum levels of IL-17 were not significantly altered between the two measurements but were significantly lower in the FEP group (p<0.001) when compared with healthy controls. After therapy, patients with SC who were in relapse had decreased serum levels of IL-4 (p=0.006) and IL-6 (p=0.007). We also observed a weak negative correlation between the IFN-γ/TGF-β ratio and the total PANSS score and between the IL-17/TGF-β ratio and the negative and general psychopathology subscales. The increased type-2 cytokine serum levels in schizophrenia appear to be downregulated by antipsychotic treatment.


Kinematic and fatigue biomechanics of an interpositional facet arthroplasty device.
Although approximately 30% of chronic lumbar pain can be attributed to the facets, limited surgical options exist for patients. Interpositional facet arthroplasty (IFA) is a novel treatment for lumbar facetogenic pain designed to provide patients who gain insufficient relief from medical interventional treatment options with long-term relief, filling a void in the facet pain treatment continuum. This study aimed to quantify the effect of IFA on segmental range of motion (ROM) compared with the intact state, and to observe device position and condition after 10,000 cycles of worst-case loading. In situ biomechanical analysis of the lumbar spine following implantation of a novel IFA device was carried out. Twelve cadaveric functional spinal units (L2-L3 and L5-S1) were tested in 7.5 Nm flexion-extension, lateral bending, and torsion while intact and following device implantation. Additionally, specimens underwent 10,000 cycles of worst-case complex loading and were testing in ROM again. Load-displacement and fluoroscopic data were analyzed to determine ROM and to evaluate device position during cyclic testing. Devices and facets were evaluated post testing. Institutional support for implant evaluation was received by Zyga Technology. Range of motion post implantation decreased versus intact, and then was restored post cyclic-testing. Of the tested devices, 6.5% displayed slight movement (0.5-2 mm), all from tight L2-L3 facet joints with misplaced devices or insufficient cartilage. No damage was observed on the devices, and wear patterns were primarily linear. The results from this in situ cadaveric biomechanics and cyclic fatigue study demonstrate that a low-profile, conformable IFA device can maintain position and facet functionality post implantation and through 10,000 complex loading cycles. In vivo conditions were not accounted for in this model, which may affect implant behavior not predictable via a biomechanical study. However, these data along with published 1-year clinical results suggest that IFA may be a valid treatment option in patients with chronic lumbar zygapophysial pain who have exhausted medical interventional options.


Differential lipid control of (Na+ + K+)-ATPase in homeotherms and poikilotherms.
1. (Na+ + K+)-ATPase from homeotherms and poikilotherms demonstrate non-linear thermal dependence for ATP hydrolysis. Apparent energies of activation from crab nerve preparations are less than those of brain or kidney preparations from beef, rabbit, sheep or ground squirrel. 2. Crab nerve (Na+ + K+)-ATPase is less sensitive to inhibition by ouabain than that from beef or ground squirrel; lower rates of [3H]-ouabain binding and reduced amount of drug bound at equilibrium are found. 3. K+-activated acyl-phosphatase is similar in all preparations. 4. Fluorescence polarization of 12-AS labelled membranes demonstrate greater mobility of crab nerve lipids compared to beef brain which has a thermal transition at 20-25 degrees C. Crab nerve is linear in this range.


Clinical features and prognosis of herpetic anterior uveitis: a retrospective study of 111 cases.
To describe the clinical features and outcomes in patients with herpetic anterior uveitis. We reviewed the records of 111 patients with a clinical diagnosis of herpetic anterior uveitis seen at the Department of Ophthalmology, Istanbul Faculty of Medicine, from January 1996 to December 2006. Demographic and clinical features, recurrence rate, and visual outcome were analyzed. Fifty patients were male, 61 were female. Mean age at presentation was 39.2 ± 16.5 (6-74) years. Three atopic patients had bilateral involvement. Twelve patients had active or a past episode of herpes zoster ophthalmicus. Ocular findings were granulamatous anterior uveitis (93%), active keratitis or corneal scars (57%), elevated intraocular pressure (51%), iris atrophy (48%), distorted pupil (25%), and posterior synechiae (26%). Secondary glaucoma developed in two patients. None of the patients had posterior segment complications. The recurrence rate was 0.45/person-year. Topical corticosteroids and oral antiviral therapy were administered to all patients during active episodes. Long-term prophylactic oral acyclovir was used in 13%. Final visual acuity was worse than 0.5 in 17% of the involved eyes and was due to corneal scarring or cataract formation. Patients with iridocyclitis only had no permanent visual loss. Herpetic anterior uveitis is a recurrent granulomatous disease commonly associated with corneal involvement, iris atrophy, and transient intraocular pressure rise. Visual prognosis is good, especially in patients who have only anterior uveitis without corneal disease.


Normal values for haemoglobin concentration and red cell indices in preschool children on the Highveld.
Data on haemoglobin concentration, red cell count, packed cell volume, mean cell volume, mean cell haemoglobin and mean cell haemoglobin concentration for 'normal' children aged 1-4 years living on the Highveld (altitude 1400-1800 m) are presented in yearly age groups. The children were defined as normal on the basis of having growth attainment and iron, folate and vitamin B12 nutrition within accepted normal limits. The results obtained differ from the standard reference values published for children resident at sea level. It is suggested that the mean (+/- 2 SD) ranges presented be used as normal ranges in the population studied.


Coblation tonsillectomy: a systematic review and descriptive analysis.
Coblation is one of the more recent techniques for tonsillectomy; however, it remains unclear whether it exhibits any benefit or increased risk when compared to other techniques. This review provides an updated assessment of coblation tonsillectomy and how it compares to other tonsillectomy techniques. Systematic review and descriptive analysis of published literature. Electronic searches of MEDLINE, EMBASE, Web of Science and the Cochrane Database were performed. We included all randomized control trials comparing coblation tonsillectomy (not 'tonsillotomy') with any other tonsillectomy technique. Studies were excluded if tonsils, rather than individuals, were randomized. 16 eligible studies were identified, including a total of 567 patients, both adults and children. Coblation was compared with a variety of other tonsillectomy techniques. Outcomes included pain, primary and secondary haemorrhage, intraoperative bleeding and operation time. Postoperative pain was the primary outcome in most studies. There was a trend towards less pain in the coblation group in seven of the included studies. More recent studies appeared to fare more favourably in terms of pain outcomes and operating time. The coblation technique appears to be comparable with other commonly employed techniques for tonsillectomy; however, there is still no strong evidence to suggest that it possesses any definitive benefits. Findings would advocate further work being done through carefully designed randomised control trials, which compare coblation with cold dissection as the 'gold standard' and place an emphasis on reducing the amount of adjuvant electrocautery used so as to maximise the benefits of coblation and the lower temperature it generates.


Primary Mycobacterium tuberculosis complex cutaneous infection: report of two cases and literature review.
Compared to other organs, skin is an uncommon site of tuberculosis involvement. In the era of HIV infection, increased intravenous drug abuse, and the use of immunosuppressive therapy for various systemic diseases, tuberculosis in all its forms, including skin tuberculosis, has re-emerged. We report two cases of primary cutaneous tuberculosis in immunocompetent patients and review the literature of all cases described since 1935.


Pulmonary arterial hypertension in systemic sclerosis: Diagnosis and treatment according to the European Society of Cardiology and European Respiratory Society 2015 guidelines.
Scleroderma (systemic sclerosis) is an autoimmune connective tissue disease which presents endothelial dysfunction and fibroblast dysregulation, resulting in vascular and fibrotic disorders. Pulmonary hypertension is frequent in patients with systemic sclerosis: the natural evolution of the disease can induce the development of different forms of pulmonary hypertension, representing one of the main causes of death. Among the different forms of pulmonary hypertension in systemic sclerosis, pulmonary arterial hypertension is the most frequent one (rate of occurrence is estimated between 7% and 12%). This pulmonary vascular complication should be treated with a combination of drugs that is able to counteract endothelial dysfunction, antagonizing the endothelin-1 system and replacing prostaglandin I2 and nitric oxide activity. A correct diagnosis is mandatory, because it is possible only for pulmonary arterial hypertension to use specific drugs that are able to control the symptomatic condition and the evolution of the disease. According to the most recent guidelines, for the patients with systemic sclerosis, also without pulmonary hypertension symptoms, echocardiography screening for the detection of pulmonary hypertension is recommended. Pulmonary arterial hypertension screening programs in systemic sclerosis patients is able to identify milder forms of the disease, allowing earlier management and better long-term outcome.


A review of the role of CpG oligodeoxynucleotides as toll-like receptor 9 agonists in prophylactic and therapeutic vaccine development in infectious diseases.
This article reviews the biology of Toll-like receptors, the current understanding of the mechanism by which CpG oligodeoxynucleotides (ODNs) perturb immune function and the published literature describing their evaluation in the development of vaccines in humans. The role of these molecules as immune modulators in HCV treatment is also considered. There has been considerable research evaluating the role of CpG ODNs as an adjuvant and immune modulator in hepatitis B, hepatitis C and influenza. The safety and immunogenicity of the 1018 ISS compound in combination with Engerix-B was assessed in 99 healthy, adult seronegative volunteers. One month following the first immunization dose, 78.7% in the rHBsAg plus 1018 ISS group versus 11.8% in the Engerix-B group achieved protective titres. One hundred percent of rHBsAg plus 1018 ISS and 18.0% of hepatitis B vaccine-alone recipients were seroprotected 1 week following the second dose of study vaccine. After all doses of vaccine had been administered, seroprotection rates were 100% and 64%, respectively (p < 0.001). CPG 7909 was co-administered with Engerix-B in 56 healthy adults. After the second injection (week 6 time point), seroprotection was achieved in 100% of CPG 7909 recipients (0.5 mg 13/13; 1.0 mg 12/12; 0.125 mg 12/12) compared with 55% (6/11) of control participants (p = 0.0003). Twelve months post prime, all subjects who had received the full course of vaccination maintained seroprotective anti-HBs titres. The safety and immunogenicity of Engerix B plus CPG 7909 was assessed in HIV seropositive patients. All CPG 7909 recipients (n = 19) and 17/19 (89%) control subjects achieved seroprotection by 2 weeks after the third and final injection (10 weeks). Seroprotective titres remained in all CPG 7909 recipients at 48 weeks (100%) versus 12/19 (63%) for controls (p = 0.008). This cohort of HIV-infected patients was followed at 6-month intervals for up to 60 months after enrolment. The difference in seroprotection (> or =10 mIU/L) and GMT between study arms remained significant (p < 0.05) at all time points from month 24 to month 60. There is great potential for CpG ODN as vaccine adjuvants and as therapeutic immune modulators. The use of these molecules as a hepatitis B vaccine adjuvant is most promising.


The pharmacology of local anesthetics.
The pharmacology of local anesthetics is an integration of the basic physiology of excitable cells and the mechanism by which local anesthetics are capable of interrupting conduction of neural messages. The common characteristics of the molecules with local anesthetic action have been identified and can explain the properties of the agents. These same chemical characteristics also explain toxicity of these agents and differences that exist between local anesthetics with similar structure.


Low-residue breakfast during the preparation for colonoscopy using a polyethylene glycol electrolyte solution: a randomised non-inferiority trial.
To test the hypothesis that the use of a low-residue breakfast (LRB) the day prior to colonoscopy was not inferior to consuming clear fluids alone (CFD) in patients undergoing outpatient colonoscopy with a polyethylene glycol (PEG) bowel preparation. Optimal colon cleansing is essential for complete visualisation of the mucosa during colonoscopy. Few studies have examined the effect of diet on the quality of bowel cleansing or tolerance in patients using a PEG bowel preparation for colonoscopy. Randomised, single-blinded non-inferiority trial. Adult patients scheduled for outpatient colonoscopy with PEG solution were randomised to an LRB followed by clear fluids or CFD using either a traditional or split-dose PEG solution for bowel preparation. The primary outcome was colon cleansing based on the Ottawa Bowel Preparation Score (OBPS). On an intention-to-treat (ITT) basis, a total of 109 and 105 patients were included in the CFD and LRB arms, respectively, with 116 and 98 patients, respectively, for the per-protocol (PP) analysis. Although there was no difference in the mean total OBPS between the CFD or LRB arms in either the ITT or PP analysis, the threshold for non-inferiority was not met. Patient acceptance of the regimens was higher in the LRB arm than in the CFD arm in the ITT and PP analyses. This study failed to show the non-inferiority of an LRB in patients receiving bowel preparation with a PEG-based solution. A CFD should be prescribed when using a PEG bowel preparation. This trial is registered at ClinicalTrials.gov (NCT01454388).


Human dihydrolipoamide succinyltransferase: cDNA cloning and localization on chromosome 14q24.2-q24.3.
We isolated cDNA for dihydrolipoamide succinyltransferase from a human fibroblast cDNA library in lambda gt11. The cDNA revealed that the human dihydrolipoamide succinyltransferase lacked a sequence motif of an E3 and/or E1 binding site. This suggests that the human dihydrolipoamide succinyltransferase possesses a unique structure consisting of two domains in contrast with the dihydrolipoamide acyltransferases of other alpha-keto acid dehydrogenase complexes. In addition, we found that the human dihydrolipoamide succinyltransferase gene is located on chromosome 14 at q24.2-q24.3 and that a sequence related to the dihydrolipoamide succinyltransferase gene is located on chromosome 1 at p31. Interestingly, the gene for the dihydrolipoamide acyltransferase of the branched chain alpha-keto acid dehydrogenase complex is also located on chromosome 1p31 (Zneimer et al. (1991) Genomics 10, 740-747).


[Retinopathia centralis serosa--initial symptom of acute lymphoblastic leukemia].
Central serous retinopathy caused a gradual decrease in visual acuity in the left eye of a 14-year-old boy. During a general medical examination systematic investigation revealed an acute lymphoblastic leukemia. As a result of adequate therapy visual acuity improved from 0.1 to 1.0.


Effects of the very late adhesion molecule 4 antagonist WAY103 on human peripheral blood eosinophil vascular cell adhesion molecule 1-dependent functions.
Eosinophil infiltration to the lung in allergic inflammation can be initiated by the tethering of circulating cells through very late adhesion molecule 4 (VLA-4; alpha4beta1, CD49d/CD29) to vascular cell adhesion molecule 1 (VCAM-1) expressed on pulmonary vascular endothelium. Small-molecule VLA-4 antagonists have been proposed as a therapeutic mechanism to prevent eosinophil infiltration in asthma; however, they might affect other eosinophil functions. The small-molecule VLA-4 antagonist (2S)-3-(4-Dimethylcarbamoyloxyphenyl)-2-{[(4R)-5,5-dimethyl-3-(1-methyl-1H-pyrazole-4 sulfonyl)thiazolidine-4-carbonyl]amino}propionic acid (WAY103) was assessed for its effects on eosinophil VLA-4-dependent functions, including adhesion, migration, respiratory burst, and degranulation. Human peripheral blood eosinophils were preincubated with WAY103, anti-alpha4, and/or anti-beta2 integrin mAbs and then assessed for adhesion to recombinant VCAM-1, intercellular adhesion molecule 1, and endothelial cell monolayers. Transmigration was measured by using human pulmonary microvascular endothelial cell monolayers and Transwell filters. Superoxide anion generation was determined by means of cytochrome C reduction and degranulation by means of eosinophil-derived neurotoxin release. WAY103 inhibition of eosinophil adhesion to recombinant VCAM-1 was dose dependent (63% inhibition with 100 nM WAY103, P < .04) and comparable with inhibition caused by anti-alpha4 mAb (60.1% inhibition). Although pretreatment with WAY103 also decreased eosinophil adhesion to TNF-alpha plus IL-4-activated human pulmonary microvascular endothelial cell monolayers, it did not prevent eosinophil transendothelial migration in response to RANTES. Finally, WAY103 inhibited VCAM-1-stimulated superoxide generation but enhanced cytokine-activated eosinophil-derived neurotoxin degranulation. Although small-molecule VLA-4 antagonists, such as WAY103, might reduce eosinophil adhesion, this approach might not be sufficient to eliminate this cell from in vivo allergic airway inflammatory participation and could even promote specific cell activation.


Inhibition of Quorum Sensing Regulated Virulence Factors and Biofilm Formation by Eucalyptus globulus against Multidrug-Resistant Pseudomonas aeruginosa.
The quorum-sensing-inhibitory and anti-biofilm activities of the methanol extract of E. globulus leaves were determined against clinically isolated multidrug-resistant Pseudomonas aeruginosa. The preliminary anti-quorum-sensing (AQS) activity of eucalyptus was investigated against a biosensor strain Chromobacterium violaceum ATCC 12472 (CV12472) by using the agar well diffusion method. The effect of sub-minimum inhibitory concentrations (sub-MICs) of the methanol extract of eucalyptus on different quorum-sensing-regulated virulence factors, such as swarming motility, pyocyanin pigment, exopolysaccharide (EPS), and biofilm formation, against clinical isolates (CIs 2, 3, and 4) and reference PA01 of Pseudomonas aeruginosa were determined using the swarm diameter (mm)-measurement method, chloroform extraction method, phenol (5%)-sulphuric acid (concentrated) method, and the microtiter plate assay respectively, and the inhibition (%) in formation were calculated. The preliminary AQS activity (violacein pigment inhibition) of eucalyptus was confirmed against Chromobacterium violaceum ATCC 12472 (CV12472). The eucalyptus extract also showed concentration-dependent inhibition (%) of swarming motility, pyocyanin pigment, EPS, and biofilm formation in different CIs and PA01 of P. aeruginosa. Our results revealed the effectiveness of the E. globulus extract for the regulation of quorum-sensing-dependent virulence factors and biofilm formation at a reduced dose (sub-MICs) and suggest that E. globulus may be a therapeutic agent for curing and controlling bacterial infection and thereby reducing the possibility of resistance development in pathogenic strains.


New formaldehyde-free adhesives for wood manufacturing: In vitro evaluation of potential toxicity of fine dust collected during wood sawing using a new experimental model to simulate occupational inhalation exposure.
Formaldehyde mainly emitted from wood adhesives, finishing materials, paint for furniture represents, together with wood dust, a potential carcinogenic risk for wood workers. Aims of this multidisciplinary study are to investigate the possibility of replacing urea-formaldehyde (UF) adhesives in the wood industry with organic and/or inorganic-based glues to obtain a final less toxic product and to evaluate the potential toxicity of wood glued with such new adhesives. For this purpose we selected poplar wood to test an organic new adhesive HBP (Hemp Based Protein), a mixture of hemp flour and cross-linker PAE (polyaminoamide epichlorohydrin), and spruce wood to test an inorganic adhesive geopolymer K-PSS (potassium-polysiloxosialate) plus polyvinyl acetate. For the poplar wood, we also used a commercial panel glued with UF for comparison. We reproduced occupational inhalation exposure during sawing activities of mentioned woods, collected and characterized the wood dusts emitted during sawing and evaluated in vitro their potential cyto-genotoxic and inflammatory effects. We used human lung cells (A549) exposed for 24 h to 20 and 100 μg/mL of collected PM2.5 wood dust. We found that both the new adhesives wood dusts induced a slightly higher apoptotic effect than untreated natural wood dusts particularly in spruce wood. Only geopolymer K-PSS wood dust induced membrane damage at the highest concentration and direct and oxidative DNA damage that could be explained by the different chemical composition and the lower particle sizes in respect to organic HBP adhesive wood dust. We found slight induction of IL-6 release, not influenced by K-PSS treatment, at the highest concentration in spruce wood. For poplar wood, IL-6 and IL-8 induction was found particularly for untreated and UF-treated wood at the highest concentration, where hemp adhesive treatment induced lower inflammation while at lower concentration similar slight cytokine induction was found for all tested wood dusts. This preliminary study shows that natural adhesives used to replace UF adhesives represent an interesting alternative, particularly the organic hemp-based adhesive showing very low toxicity.


Identification of two bitter components in Zanthoxylum bungeanum Maxim. and exploration of their bitter taste mechanism through receptor hTAS2R14.
Bitterness is an inherent organoleptic characteristic affecting the flavor of Zanthoxylum bungeanum Maxim. In this study, the vital bitter components of Z. bungeanum were concentrated through solvent extraction, sensory analysis, silica gel chromatography, and thin-layer chromatographic techniques and subsequently identified by UPLC-Q-TOF-MS. Two components with the highest bitterness intensities (BIs), such as 7-methoxycoumarin and 8-prenylkaempferol were selected. The bitter taste perceived thresholds of 7-methoxycoumarin and 8-prenylkaempferol were 0.062 mmol/L and 0.022 mmol/L, respectively. Moreover, the correlation between the contents of the two bitter components and the BIs of Z. bungeanum were proved. The results of siRNA and flow cytometry showed that 7-methoxycoumarin and 8-prenylkaempferol could activate the bitter receptor hTAS2R14. The results concluded that 7-methoxycoumarin and 8-prenylkaempferol contribute to the bitter taste of Z. bungeanum.


Visualizing retinoic acid morphogen gradients.
Morphogens were originally defined as secreted signaling molecules that diffuse from local sources to form concentration gradients, which specify multiple cell fates. More recently morphogen gradients have been shown to incorporate a range of mechanisms including short-range signal activation, transcriptional/translational feedback, and temporal windows of target gene induction. Many critical cell-cell signals implicated in both embryonic development and disease, such as Wnt, fibroblast growth factor (Fgf), hedgehog (Hh), transforming growth factor beta (TGFb), and retinoic acid (RA), are thought to act as morphogens, but key information on signal propagation and ligand distribution has been lacking for most. The zebrafish provides unique advantages for genetics and imaging to address gradients during early embryonic stages when morphogens help establish major body axes. This has been particularly informative for RA, where RA response elements (RAREs) driving fluorescent reporters as well as Fluorescence Resonance Energy Transfer (FRET) reporters of receptor binding have provided evidence for gradients, as well as regulatory mechanisms that attenuate noise and enhance gradient robustness in vivo. Here we summarize available tools in zebrafish and discuss their utility for studying dynamic regulation of RA morphogen gradients, through combined experimental and computational approaches.


Predictive values of PD‑L1 expression for survival outcomes in patients with cervical cancer: a systematic review and meta-analysis.
Cervical cancer is one of the most common cancers in women worldwide. Although mortality has declined over the past 30 years in high-income areas, it remains a problem in several countries. Given that the prognosis of patients with recurrent or metastatic disease is poor, it is necessary to identify valuable predictive indicators to estimate survival outcomes in patients with cervical cancer. We searched electronic databases such as PubMed, Web of Science, Embase, Ovid MEDLINE, and the Cochrane Central Register of Controlled Trials, and investigated the relationship between Programmed death-ligand 1(PD-L1) expression and prognosis. Chi squared tests and I2 were utilized to assess study heterogeneity, and publication bias was estimated using Begg's funnel plot and Egger linear regression test. Thirteen eligible studies with 1422 patients were included. Generally, high PD-L1 expression was conclusively associated with poor overall survival (OS) (HR: 1.31; 95% CI 1.03-1.66, p = 0.025). However, PD-L1 expression demonstrated no association with progression-free survival (HR: 0.93; 0.73-1.19, p = 0.57). High PD-L1 expression with a sample size over 100 indicated a shorter OS (HR: 1.51; 95% CI 1.13-2.01). High expression of PD-L1 in Asians represented a lower OS (HR: 1.52; 1.14-2.03). Overexpression of PD-L1 in tumor cells (HR: 1.57; 1.29-2.10) and tumor-infiltrating immune cells (HR: 1.75; 1.02-2.99) predicted poor OS. High PD-L1 expression (HR: 4.04; 2.58-6.31) showed a lower effect on OS with a cut-off value of 5%. Our results indicate that high PD-L1 expression could be a valuable biomarker for predicting clinical outcomes in patients with cervical cancer.


Endothelial markers and HIV infection in the era of highly active antiretroviral treatment.
Many circumstances can induce activation and/or injury of the endothelium that plays a role in the development of vascular complications. Raised plasma levels of endothelial markers such as von Willebrand factor (vWF), soluble thrombomodulin (sTM) and soluble vascular cell adhesion molecule-1 (sVCAM-1) have a prognostic and/or diagnostic value. Human immunodeficiency virus-infected patients (HIV+) have a clustering of conditions that activate or injure the endothelium. Highly active antiretroviral treatment produces adverse effects such as dyslipemia, insulin resistance (IR) and body fat changes (named lipodystrophy syndrome) which may contribute to aggravate their endothelial perturbation. The aim of this study was to measure lipid profile, insulin resistance status, and endothelial markers in 38 HIV+ naive of antiretroviral treatment and 63 HIV+ under highly active antiretroviral treatment (33 with lipodystrophy syndrome and 30 without it). Body fat distribution was also evaluated by dual-energy X-ray absorptiometry (DEXA) analysis. Thirty-one HIV negative subjects were used as controls. We looked for association between variables. Insulin resistance status was a common finding in the four groups. Lipodystrophic patients presented an atherothrombotic lipid profile [elevated levels of triglycerides (TG), low-density lipoprotein cholesterol (LDL-chol) and apolipoprotein-B (APO-B)] and a strong loss of fat in legs and arms (lipoatrophy). All endothelial markers evaluated in our naive patients were higher as compared to control group. sVCAM-1 in HIV+ under therapy without lipodystrophy syndrome showed significantly decreased levels as compared to naive group (487 vs. 666 ng/ml) and vWF and sTM tended to diminish although they did not show a significant difference (130% vs. 170%, 41 vs. 45 ng/ml, respectively). Lipodystrophic patients showed a tendency to increased levels of endothelial activation markers (sVCAM-1: 500 ng/ml and vWF: 154%) together with significantly increased levels of an endothelial injury marker (sTM: 50 ng/ml) with respect to HIV+ under therapy without lipodystrophy syndrome. Plasma levels of sTM, as an endothelial injury marker, correlated with peripheral lipoatrophy (rho = -0.357) in lipodystrophic patients. In conclusion, despite the beneficial immunology effect of highly active antiretroviral treatment and the apparent decrease in the endothelial perturbation, the patients who develop lipodystrophy present altered endothelial markers and other risk factors, such as IR and dyslipemia, which turn them into a high atherothrombotic risk group.


Metabolic syndrome and estimates of cardiovascular disease in cirrhotic patients.
The expected survival rate in patients with liver cirrhosis has increased in recent years, putting them into a clinical scenario in which cardiovascular disease and metabolic syndrome could be common causes of morbidity and mortality. This study aimed to analyze the prevalence of metabolic syndrome and other risk factors and estimate the risk of cardiovascular disease in patients with liver cirrhosis. We conducted a cross-sectional study assessing the patients' lifestyle, and their anthropometric and biochemical data. Their metabolic syndrome and estimates of their risk of cardiovascular disease were calculated, comparing patients with and without liver cirrhosis. The study included 355 patients (99 cirrhotic and 256 non-cirrhotic patients). There were no differences between them in the prevalence of metabolic syndrome (39.4% vs. 45.7%, P = 0.340). In patients with liver cirrhosis, the mean values of criteria for metabolic syndrome increased as the model end-stage liver disease (MELD) score increased (P = 0.01). The mean value of a 10-year risk for cardiovascular disease was lower in the cirrhotic patients (3.4 +/- 3.5% vs. 5.8 +/- 6.8%, P = 0.001). Metabolic syndrome is prevalent in patients with liver cirrhosis, but their estimated risk for cardiovascular disease is lower than in non-cirrhotics. The MELD score is a good marker for assessing the severity of the metabolic syndrome in this group.


Correction to: An Exploratory Study of Hyoid Visibility, Position, and Swallowing-Related Displacement in a Pediatric Population.
This letter notifies the readers of the Dysphagia journal of an error in the original published version of this manuscript, describing hyoid position during swallowing in children using an available pediatric dataset. A previously available open source spreadsheet tool had been used to calculate the position of the hyoid bone on lateral view videofluoroscopic images. An error in the mathematical formula built into the spreadsheet resulted in a reversal of reported results for measures of peak hyoid position in the X and Y planes of measurement. This erratum provides corrections to the results and interpretations of the original manuscript.


Spectrophotometric cell sorter.
A new device can physically separate cells of predetermined optical properties, from large populations of cells in suspension.


Ulnar nonunion after osteoclasis for rotational deformities of the forearm.
Osteoclasis, a minimally invasive technique to rotate the radius and ulna, is used commonly to correct forearm rotational deformities in children. The purpose of this investigation was to evaluate objectively osteotomy healing in patients treated with osteoclasis, with specific attention given to the risk for nonunion. We identified 69 extremities in 65 children treated with osteoclasis and performed retrospective chart and radiographic reviews to evaluate the time to union of the radius and ulna and factors influencing healing. The average rotational correction was 90 degrees. Twenty-one ulnas had either delayed union or nonunion. Forty-eight of the forearms healed in less than 3 months. Factors correlated with a significantly decreased union rate included increased patient age, percutaneous technique, osteoclasis site in the proximal ulna, and primary diagnoses other than congenital radioulnar synostosis. Preoperative forearm position, magnitude of position correction, and treatment of the periosteum were not associated with changes in union rates. Forearm osteoclasis has a delayed union rate of 16%. Timely union of the ulna appears to be influenced by both patient-centered factors and surgical technique. Therapeutic, Level IV.


Impact of anaemia on lung function and exercise capacity in patients with stable severe chronic obstructive pulmonary disease.
This study intended to search for potential correlations between anaemia in patients with severe chronic obstructive pulmonary disease (COPD; GOLD stage III) and pulmonary function at rest, exercise capacity as well as ventilatory efficiency, using pulmonary function test (PFT) and cardiopulmonary exercise testing (CPET). The study was undertaken at Shanghai Pulmonary Hospital, a tertiary-level centre affiliated to Tongji University. It caters to a large population base within Shanghai and referrals from centres in other cities as well. 157 Chinese patients with stable severe COPD were divided into 2 groups: the anaemia group (haemoglobin (Hb) <12.0 g/dL for males, and <11 g/dL for females (n=48)) and the non-anaemia group (n=109). Arterial blood gas, PFT and CPET were tested in all patients. (1) Diffusing capacity for carbon monoxide (DLCO) corrected by Hb was significantly lower in the anaemia group ((15.3±1.9) mL/min/mm Hg) than in the non-anaemia group ((17.1±2.1) mL/min/mm Hg) (p<0.05). A significant difference did not exist in the level of forced expiratory volume in 1 s (FEV1), FEV1%pred, FEV1/forced vital capacity (FVC), inspiratory capacity (IC), residual volume (RV), total lung capacity (TLC) and RV/TLC (p>0.05). (2) Peak Load, Peak oxygen uptake (VO2), Peak VO2%pred, Peak VO2/kg, Peak O2 pulse and the ratio of VO2 increase to WR increase (ΔVO2/ΔWR) were significantly lower in the anaemia group (p<0.05); however, Peak minute ventilation (VE), Lowest VE/carbon dioxide output (VCO2) and Peak dead space/tidal volume ratio (VD/VT) were similar between the 2 groups (p>0.05). (3) A strong positive correlation was found between Hb concentration and Peak VO2 in patients with anaemia (r=0.702, p<0.01). Anaemia has a negative impact on gas exchange and exercise tolerance during exercise in patients with severe COPD. The decrease in amplitude of Hb levels is related to the quantity of oxygen uptake.


Estrogen regulated gene expression in response to neoadjuvant endocrine therapy of breast cancers: tamoxifen agonist effects dominate in the presence of an aromatase inhibitor.
Estrogens (E) and estrogen receptors (ER) are implicated in breast cancer growth and are targets of hormonal therapies. Such therapies commonly use aromatase inhibitors (AI) to block E production, or antiestrogens like tamoxifen (TAM), which targets ER. Here we compare genes in pre-and post-treatment tumor pairs of patients with ER+ tumors, that were treated preoperatively with the AI exemestane alone, or with exemestane plus TAM. The accompanying manuscript shows that tumors from patients treated with AI + TAM responded less well than tumors treated with AI alone. The present manuscript defines the E-signaling mechanisms underlying these differences, and describes genetic differences between hormone responsive versus intrinsically resistant ER+ tumors. Gene expression profiling was performed on paired tumor biopsies of individual patients before treatment, and after 4 months of treatment with AI or AI + TAM. Separately, E and TAM regulated genes were defined using a human breast cancer xenograft model. We demonstrate: (1) that AI alone alters global gene expression approximately 5 times more than AI + TAM, and is 11 times more effective in modifying expression of E regulated genes; (2) among E regulated genes, there is little overlap between AI and AI + TAM treatment groups. AI + TAM preferentially induce genes, like androgen receptors, expressing TAM "E-like" agonist activity, or genes uniquely regulated by TAM. (3) A pre-treatment 25 gene signature of ER+ tumors may predict response or intrinsic resistance to endocrine therapies. We conclude that in the presence of exemestane, the agonist properties of TAM are paradoxically exposed, diminishing the effectiveness of combination therapy.


BK virus capsid antibodies are associated with protection against subsequent development of PML in HIV-infected patients.
Progressive multifocal leukoencephalopathy (PML) is caused by JC polyomavirus (JCPyV). Because a reciprocal relationship has been described between antibody levels to JCPyV and BK polyomavirus (BKPyV), we performed a nested case control study with pre-diagnostic serum samples from HIV infected subjects to examine the relationship between BKPyV capsid antibodies and the risk of PML. Serum samples collected 0.5-2 years before PML diagnosis from 25 cases (66 samples) and 80 matched controls (204 samples) were tested in ELISA for JCPyV, BKPyV type 1 and type 4 capsid antibodies. High levels of BKPyV 1 and 4 antibodies were associated with a lower risk of PML (BKPyV 1 OR, 0.56, 95% CI, 0.35-0.89; BKPyV 4 OR, 0.40, 95% CI, 0.24-0.0.67). Our study demonstrates that antibodies to BKPyV capsids are an immunological marker of protection against development of PML. Further studies are needed to define the mechanism.


Influence of compost addition on lead and arsenic bioavailability in reclaimed orchard soil assessed using Porcellio scaber bioaccumulation test.
Long-term application of lead arsenate in orchards has led to a significant accumulation of Pb and As in the topsoil. Reclamation of old orchards for agricultural purposes entails the exposure of humans to Pb and As, which can be reduced by adequate remediation actions. In this study, we assessed the remediation efficiency of compost addition, commonly used as a sustainable agricultural practice, in decreasing the human exposure Pb and As by direct ingestion. The remediation was evaluated based on Pb and As bioavailability, assessed by means of a selective non-exhaustive chemical extraction (modified Morgan extraction, MME), with a physiologically based extraction test (PBET) for the assessment of Pb and As bioavailability in ingested soils and with a novel in vivo bioaccumulation test with isopods (Porcellio scaber). All the tests showed that compost addition consistently reduced Pb, but increased As potential bioavailability. The bioaccumulation test with P. scaber was sensitive to changes in Pb and As bioavailability in test soils. However, the results indicate that the bioavailability of As could be under- or overestimated using solely chemical extraction tests. Indirect assessment of trace metal bioavailability with bioaccumulation in isopods can be used as complementary source of data to the existing in vitro chemical extraction test approach for the estimation of human exposure to trace elements in polluted and remediated soil. This is the first report on the use of As accumulation in P. scaber as a tool for the assessment of As bioavailability in contaminated orchard soil.


Direct observation of electron dynamics in the attosecond domain.
Dynamical processes are commonly investigated using laser pump-probe experiments, with a pump pulse exciting the system of interest and a second probe pulse tracking its temporal evolution as a function of the delay between the pulses. Because the time resolution attainable in such experiments depends on the temporal definition of the laser pulses, pulse compression to 200 attoseconds (1 as = 10(-18) s) is a promising recent development. These ultrafast pulses have been fully characterized, and used to directly measure light waves and electronic relaxation in free atoms. But attosecond pulses can only be realized in the extreme ultraviolet and X-ray regime; in contrast, the optical laser pulses typically used for experiments on complex systems last several femtoseconds (1 fs = 10(-15) s). Here we monitor the dynamics of ultrafast electron transfer--a process important in photo- and electrochemistry and used in solid-state solar cells, molecular electronics and single-electron devices--on attosecond timescales using core-hole spectroscopy. We push the method, which uses the lifetime of a core electron hole as an internal reference clock for following dynamic processes, into the attosecond regime by focusing on short-lived holes with initial and final states in the same electronic shell. This allows us to show that electron transfer from an adsorbed sulphur atom to a ruthenium surface proceeds in about 320 as.


Automation of pharmaceutical dissolution testing by flow injection analysis.
The different types of instruments used for monitoring pharmaceutical dissolution testing are presented. Their features and the need for automation are critically discussed. The advantages of flow injection analysis in this respect are illustrated by a variety of examples clearly showing its adaptability to the different problems posed by other automatic and non-automatic alternatives.


Autotrophic cells of the Synechocystis psbH deletion mutant are deficient in synthesis of CP47 and accumulate inactive PS II core complexes.
Cells of the psbH deletion mutant IC7 of the cyanobacterium Synechocystis PCC 6803 grown in the absence of glucose contain strongly reduced levels of chlorophyll when compared with cells grown in the presence of glucose, or compared with wild-type (WT) cells. Low-temperature fluorescence emission spectra revealed decreased content of both active PS II (Photosystem II) and PS I (Photosystem I) complexes. Analysis of thylakoid membrane complexes of IC7 by native electrophoresis showed a similar set of chlorophyll-proteins, namely a PS II core complex and trimeric and monomeric PS II complexes, as in WT. However, in contrast to WT, the (35)S-methionine protein labeling pattern of the mutant exhibited no preferential labeling of the D1 protein in the PS II core complexes, and the labeled D1 and D2 proteins accumulated predominantly in the PS II reaction center lacking CP47. The results show that in autotrophically grown cells of the psbH deletion mutant, selective D1 turnover is inhibited and synthesis of CP47 becomes a limiting step in the PS II assembly.


Selective enrichment of phytosphingosine in glycosphingolipids of isolated human thyrocytes as compared to the whole thyroid.
The glycosphingolipids of isolated human thyrocytes have been analyzed. As compared to the total thyroid gland, the pattern of gangliosides was found to be similar, whereas the neutral glycolipid profile was quite different, with glucosylceramide as the major glycosphingolipid of thyrocytes. Moreover, this glucosylceramide contains almost exclusively phytosphingosine (4-D-hydroxy-sphinganine) which is only a minor component in the long-chain bases of the glycosphingolipids extracted from the whole thyroid gland.


Inducing emotion by unilateral contraction of facial muscles: a new look at hemispheric specialization and the experience of emotion.
Subjects who maintained voluntary contractions of the left facial muscles experienced sadness. Right facial contractions resulted in a more positive but difficult to characterize experience. These contractions had similar effects on the affective tone of stories told about an ambiguous picture. These findings indicate that emotions can be aroused by unilateral muscle contractions without intervening cognitions. They provide a new methodology for studying the roles of the cerebral hemispheres in emotional experience. Finally, they support the conclusion that the right hemisphere is involved with negative emotional experiences and indicate that the left hemisphere is involved with experiences that are more positive but not readily characterized.


Microbial community in Chinese traditional fermented acid rice soup (rice-acid) and its correlations with key organic acids and volatile compounds.
Rice-acid is a unique Chinese traditional fermented acid rice soup and its microbial community plays an important role in the formation of flavour compounds. In the study, rice-acid products from high-temperature and low-temperature fermentation methods were selected to analyze the microbial community, organic acids, and volatile flavour compounds (VFCs). The main bacterial and fungal phyla in Chinese traditional fermented rice-acid were determined to be Firmicutes and Ascomycota, including 62 bacterial genera and 57 fungal genera. The dominant bacterial genera were Lactobacillus, Acetobacter, and Prevotella and the dominant fungal genera were Naumovia, Pichia, Candida, and Saccharomyces. Among organic acids in rice-acid, L-lactic acid had the highest concentration, followed by malic acid, acetic acid, citric acid, oxalic acid, and tartaric acid. Volatile flavour compounds had a high contribution to the flavour, including ethyl acetate, ethanol, acetic acid, propanoic acid, 1-octen-3-ol, 2-nonanol, 2-undecanol, propyl propionate, ethyl propanoate, propyl propionate, and 2,3-butanedione. The microorganisms which were closely correlated with key organic acids in rice-acid included Lactobacillus, Acetobacter, Pichia, Candida, Kluyveromyces and Meyerozyma. The microorganisms which were correlated with VFCs included Acetobacter, Prevotella, Kluyveromyces and Saccharomyces. In particular, Lactobacillus, Pichia, Malassezia, Clavispora, Rhizopus and Cystofilobasidium were significantly positively correlated with lactic acid in rice-acid. Kluyveromyces, Saccharomyces and Emericella were significantly positively correlated with ethanol and ethyl acetate. The study provides the basis for improving the quality of rice-acid.


Computational resources for ribosome profiling: from database to Web server and software.
Ribosome profiling is emerging as a powerful technique that enables genome-wide investigation of in vivo translation at sub-codon resolution. The increasing application of ribosome profiling in recent years has achieved remarkable progress toward understanding the composition, regulation and mechanism of translation. This benefits from not only the awesome power of ribosome profiling but also an extensive range of computational resources available for ribosome profiling. At present, however, a comprehensive review on these resources is still lacking. Here, we survey the recent computational advances guided by ribosome profiling, with a focus on databases, Web servers and software tools for storing, visualizing and analyzing ribosome profiling data. This review is intended to provide experimental and computational biologists with a reference to make appropriate choices among existing resources for the question at hand.


Clinical Course of Early Postoperative Hypothyroidism Following Thyroid Lobectomy in Pediatrics.
Introduction: Thyroid lobectomy reduces risks of surgical complications and need for levothyroxine (LT4). We aimed at identifying the clinical course and risk factors for postlobectomy hypothyroidism to optimize surgical counseling and management in pediatric patients undergoing lobectomy. Methods: Clinical and biochemical presentations pre- and postlobectomy were retrospectively reviewed for 110 patients who underwent thyroid lobectomy between 2008 and 2020 at the Children's Hospital of Philadelphia. Results: Approximately 28.2% of patients (31/110) developed postlobectomy hypothyroidism defined by an elevated thyrotropin (TSH) level, including 24.5% (27/110) with subclinical hypothyroidism (TSH >4.5 and <10.0 mIU/L) and 3.6% (4/110) with overt hypothyroidism (TSH >10.0 mIU/L). LT4 was initiated in 12.7% (14/110) of cases. Most patients (81.6%; 84/103) recovered euthyroidism within 12 months postlobectomy. When excluding patients with autonomous nodule(s), median preoperative TSH was 1.09 (interquartile range [IQR] = 0.70-1.77) mIU/L and 1.80 (IQR = 1.02-2.68) mIU/L in euthyroid and hypothyroid patients, respectively, with multivariate logistic regression confirming the association between an increased preoperative TSH and postlobectomy hypothyroidism (odds ratio = 1.8 [confidence interval 1.08-3.13], p = 0.024). Of the patients who underwent thyroid lobectomy and developed postoperative hypothyroidism (n = 31), 38.7% (12/31) had a preoperative diagnosis of an autonomously functioning thyroid nodule. Conclusions: Thyroid function should be evaluated postlobectomy to assess the need for LT4. LT4 should be considered if the TSH remains elevated, especially if an upward trend is observed or TSH is >10.0 mIU/L. Suppressed preoperative TSH associated with autonomous nodules is an independent risk factor for postlobectomy hypothyroidism.


Deprotonation of C-alkyl groups of cationic N-heterocyclic ligands.
The C-alkyl groups of C-alkylpyrazinium-derived ligands have been selectively deprotonated by K[N(SiMe(3))(2)], through charge-controlled processes, to give neutral products that contain C-alkylidenepyrazine-derived ligands.


Convenient synthesis of branched-chain glycosamines by radical addition of nitromethane to glycals.
Radical addition-reduction-acetylation is the simple three-step sequence for the synthesis of branched-chain glycosamines 3 from glycals 1 and nitromethane (2). The intermediary formed 2-C-nitromethyl-pyranosides are valuable precursors for the synthesis of C-2 branched disaccharides.


Recurrence risks in families of children with symmetrical spasticity.
This study was undertaken to evaluate the recurrence risks for sibs of patients with symmetrical spasticity (either quadriplegia or diplegia) in the absence of factors known to cause spastic cerebral palsy (e.g. pre-term birth, perinatal hypoxia). Among 669 children in the West Midlands with spastic cerebral palsy, 24 had symmetrical spasticity and normal birth histories. This group was clinically and genetically heterogenous. Among their 55 sibs, six had a spastic disorder similar to that in the index patient, and one further sib, who had died young, had been mentally retarded. Of particular interest were two families with an autosomal recessive condition of post-natal microcephaly, myoclonic epilepsy and spastic quadriplegia; and one family, and possibly a sporadic case of X-linked athetoid cerebral palsy. The recurrence risk in this series of approximately 1 in 9 suggests that about half the children with symmetrical spastic cerebral palsy and a normal birth history may have a recessive condition.


Veterinarians' attitudes and practices regarding opioid-related vet shopping practices in tri-state Appalachian counties: an exploratory study.
The opioid crisis continues to grow in the United States with 46,700 drug overdose deaths due to opioids in 2017 alone. Vet shopping, the practice of soliciting veterinarians for prescription medications, has been receiving national media attention in recent years. A 2014 review of Prescription Monitoring Drug Programs found less than 10 veterinary shoppers nationwide. Still much is unknown about the role of vet shopping and the opioid crisis. This study sought to understand the practice of vet shopping through the eyes of veterinarians practicing in Appalachian counties within the states of Kentucky, Tennessee, and Virginia, United States. Fourteen veterinarians were asked a set of 13 questions related to vet shopping. Results indicated that 13 veterinarians in the study had heard of the phenomenon of vet shopping and eight veterinarians had personally encountered vet shopping in their practices. Qualitative analysis of the interviews identified six key themes including a need for interprofessional communication and how important a valid veterinary-client-patient-relationship is within the profession. The study hopefully sheds some light on the how often vet shopping is encountered in practice, concerns of veterinarians regarding vet shopping, and potential areas for improvement.


A proteomic analysis of liver after ethanol binge in chronically ethanol treated rats.
Binge ethanol in rats after chronic ethanol exposure augments necrosis and steatosis in the liver. In this study, two-dimensional gel electrophoresis proteomic profiles of liver of control, chronic ethanol, control-binge, and chronic ethanol- binge were compared. The proteomic analysis identified changes in protein abundance among the groups. The levels of carbonic anhydrase 3 (CA3) were decreased after chronic ethanol and decreased further after chronic ethanol-binge. Ethanol binge alone in control rats had no effect on this protein suggesting its possible role in increased susceptibility to injury by binge after chonic ethanol treatment. A protein spot, in which both cytosolic isocitrate dehydrogenase (IDH1) and glutamine synthetase (GS) were identified, showed a small decrease after chronic ethanol binge but western blot demonstrated significant decrease only for glutamine synthetase in chronic ethanol treated rats. The level of gluathione S-transferase mu isoform (GSTM1) increased after chronic ethanol but was lower after chronic ethanol-binge compared to chronic ethanol treatment. The protein levels of the basic form of protein disulfide isomerase associated protein 3 (PDIA3) were significantly decreased and the acidic forms were increased after chronic ethanol- binge but not in chronic ethanol treated rats or ethanol binge in control rats. The significant changes in proteome profile in chronic ethanol binge were accompanied by a marked increase in liver injury as evidenced by enhanced steatosis, necrosis, increased 4-hydroxynonenal labeled proteins, CYP2E1 expression, and decreased histone H2AX phosphorylation. Given the role of CA3, IDH1 and GST in oxidative stress; PDIA3 in protein quality control, apoptosis and DNA repair and decreased glutamine synthetase as a sensitive marker of pericentral liver injury this proteome study of chronic ethanol-binge rat model identifies these proteins for the first time as molecular targets with potential role in progression of liver injury by binge ethanol drinking.


An intramembrane chaperone complex facilitates membrane protein biogenesis.
Integral membrane proteins are encoded by approximately 25% of all protein-coding genes1. In eukaryotes, the majority of membrane proteins are inserted, modified and folded at the endoplasmic reticulum (ER)2. Research over the past several decades has determined how membrane proteins are targeted to the ER and how individual transmembrane domains (TMDs) are inserted into the lipid bilayer3. By contrast, very little is known about how multi-spanning membrane proteins with several TMDs are assembled within the membrane. During the assembly of TMDs, interactions between polar or charged amino acids typically stabilize the final folded configuration4-8. TMDs with hydrophilic amino acids are likely to be chaperoned during the co-translational biogenesis of membrane proteins; however, ER-resident intramembrane chaperones are poorly defined. Here we identify the PAT complex, an abundant obligate heterodimer of the widely conserved ER-resident membrane proteins CCDC47 and Asterix. The PAT complex engages nascent TMDs that contain unshielded hydrophilic side chains within the lipid bilayer, and it disengages concomitant with substrate folding. Cells that lack either subunit of the PAT complex show reduced biogenesis of numerous multi-spanning membrane proteins. Thus, the PAT complex is an intramembrane chaperone that protects TMDs during assembly to minimize misfolding of multi-spanning membrane proteins and maintain cellular protein homeostasis.


Pomegranate (Punica granatum L.) and its phytochemicals as anxiolytic; an underreported effect with therapeutic potential: A systematic review.
Anxiety is a mental disorder characterized by excessive concern about possible future threats that, if prolonged, becomes a pathology that must be controlled through psychotherapy and medication. Currently, the pharmacological treatment for anxiety involves the use of antidepressants and benzodiazepines; however, these treatments often come with adverse effects. Thus, there is a need to seek natural compounds that can help alleviate anxiety and reduce these side effects. On the other hand, pomegranate (PG) fruit is known to have important health benefits, which have been compiled in several reviews. However, its anxiolytic effect has not been thoroughly studied, and clinical research on this topic is lacking. The aim of this work was to conduct a systematic review of studies exploring the anxiolytic-like effect of PG and its phytochemicals. Databases such as Pubmed, ScienceDirect, Springer link, Google scholar, Worldwide science, and Web of science were searched for articles using predetermined terms. Inclusion criteria were established, and original articles that met these criteria were selected. The data collected included information on PG part and variety, species, sample size, anxiety model, dose, route and time of administration, reference drug, main results, and the mechanisms of action. Fifty-nine studies were found that reported the anxiolytic-like effect of PG and its phytochemicals such as anthocyanins, flavonoids, tannins, organic acids, and xanthonoids. The literature suggests that the mechanisms of action behind this effect involved the inhibition of the GABAergic receptor, NMDA, CaMKII/CREB pathway; the reduction of oxidative stress, inhibiting TLR4 and nNOS; modulation of cytokines and the expression of NFkB, GAD67, and iNOS, as well as the activation of Nrf2 and AMPK. PG and some of its phytochemicals could be considered as a novel alternative for the treatment of pathological anxiety. This review is the first to document the anxiolytic-like effect of PG.