Volatile Droplets on Water are Sculpted by Vigorous Marangoni-Driven Subphase Flow.
The shapes of highly volatile oil-on-water droplets become strongly asymmetric when they are out of equilibrium. The unsaturated organic vapor atmosphere causes evaporation and leads to a strong Marangoni flow in the bath, unlike that previously seen in the literature. Inspecting these shapes experimentally on millisecond and submillimeter time and length scales and theoretically by scaling arguments, we confirm that Marangoni-driven convection in the subphase mechanically stresses the droplet edges to an extent that increases for organic droplets of smaller contact angle and accordingly smaller thickness. The viscous stress generated by the subphase overcomes the thermodynamic Laplace pressure. The oil droplets develop copious regularly spaced fingers, and these fingers develop spike-shaped and branched treelike structures. Unlike this behavior for single-component (surfactant-free) oil droplets, droplets composed of two miscible (surfactant-free) organic liquids develop a rim of the less volatile component along the droplet perimeter, from which jets of monodisperse smaller droplets eject periodically due to the Rayleigh-Plateau instability. When evaporation shrinks droplets to μm size, their shapes fluctuate chaotically, and ellipsoidal shapes rupture into smaller daughter droplets when subphase convection flow pulls them in opposite directions. The shape of the evaporating oil droplets is kneaded and sculpted by vigorous flow in the water subphase.


Relationships among sporophytic and gametophytic traits of 27 subtropical montane moss species.
Moss sporophytes differ strongly in size and biomass partitioning, potentially reflecting reproductive and dispersal strategies. Understanding how sporophyte traits are coordinated is essential for understanding moss functioning and evolution. This study aimed to answer: (1) how the size and proportions of the sporophyte differ between moss species with and without a prominent central strand in the seta, (2) how anatomical and morphological traits of the seta are related, and (3) how sporophytic biomass relates to gametophytic biomass and nutrient concentrations. We studied the relationships between seta anatomical and morphological traits, the biomass of seta, capsule, and gametophyte, and carbon, nitrogen, and phosphorus concentrations of 27 subtropical montane moss species. (1) Moss species with a prominent central strand in the seta had larger setae and heavier capsules than those without a prominent strand. (2) With increasing seta length, setae became thicker and more rounded for both groups, while in species with a prominent central strand, the ratio of transport-cell area to epidermal area decreased. (3) In both groups, mosses with greater gametophytic biomass tended to have heavier sporophytes, but nitrogen and phosphorus concentrations in the gametophyte were unrelated to sporophytic traits. Our study highlights that the central strand in the seta may have an important functional role and affect the allometry of moss sporophytes. The coordinated variations in sporophyte morphological and anatomical traits follow basic biomechanical principles of cylinder-like structures, and these traits relate only weakly to the gametophytic nutrient concentrations. Research on moss sporophyte functional traits and their relationships to gametophytes is still in its infancy but could provide important insights into their adaptative strategies.


[The acute appendicitis' diagnostic Alvorado's system].
The recent studies prove that the treatment of the acute appendicitis should aim the preservation of the organ, considering the important functions of the least. The combined antimicrobial therapy allows the successful conservative treatment of all cases of the acute appendicitis but the gangrenous, which should be treated operatively. The use of glucocorticosteroids together with antibiotics is pathogenetically substantiated. To improve the diagnostics of the acute appendicitis, the modernized Alvorado's system was suggested by the authors. The least is adopted for the diagnostics of intraabdominal abscesses and gangrenous appendicitis.


Treatment, no treatment and early death in Danish stage I lung cancer patients.
Stage I lung cancer is curable with surgery as the treatment of choice. Other effective and curative treatments exist. Nevertheless, some patients only receive palliative treatment and some receive no treatment at all. Using the Danish Lung Cancer Registry (DLCR), we assessed treatment distribution for a population-based Danish cohort of stage I lung cancer patients diagnosed from 2011 to 2014. We assessed one-year mortality according to treatment. Furthermore, in a nested case-control study based on data from medical records, we assessed the reason for not undergoing treatment among patients in favourable performance status (PS) with no treatment registration in the DLCR. We identified 2985 patients, 68% (n = 2021) were treated surgically and 17% (n = 508) were managed with curative oncological therapy. The unadjusted odds ratio (OR) for death within one year was 2.5 (95% CI, 1.8-3.3) for the oncologically managed vs. the surgically treated. After adjusting for age, lung function and PS, the OR was 1.2 (95% CI, 0.8-1.9). Among 129 patients with a PS of 0-1 and no treatment registration, we established the reason for not undergoing treatment in 122 (95%). The majority (70%) were misclassified and did either not have lung cancer, had more advanced disease or were curatively treated. The 36 (30%) patients that did not undergo treatment, had a lower prevalence of adenocarcinomas (17 vs. 51%, p = 0.003), more comorbidites (median Charlson comorbidity index score 2 vs. 1, p < 0.001) and high alcohol intake (19 vs. 7%, p = 0.04) as compared to surgically treated controls. The primary reasons for no treatment were; comorbidity, patient decision and disease progression. Difference in outcome between the two major treatment groups was confounded by age, lung function and PS. Comorbidity, high alcohol intake and histology were associated with not undergoing curative treatment in spite of a favourable PS.


Identification of Urine Metabolic Biomarkers for Vogt-Koyanagi-Harada Disease.
The diagnosis of Vogt-Koyanagi-Harada (VKH) disease is mainly based on a complex clinical manifestation while it lacks objective laboratory biomarkers. To explore the potential molecular biomarkers for diagnosis and disease activity in VKH, we performed an untargeted urine metabolomics analysis by ultra-high-performance liquid chromatography equipped with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS). Through univariate and multivariate statistical analysis, we found 9 differential metabolites when comparing VKH patients with healthy controls, and 26 differential metabolites were identified when comparing active VKH patients with inactive VKH patients. Pathway enrichment analysis showed that glycine, serine and threonine metabolism, and arginine and proline metabolism were significantly altered in VKH versus healthy controls. Lysine degradation and biotin metabolism pathways were significantly altered in active VKH versus inactive VKH. Furthermore, the receiver operating characteristic (ROC) curve analysis revealed that the combination of acetylglycine and gamma-glutamylalanine could differentiate VKH from healthy controls with an area under the curve (AUC) of 0.808. A combination of ureidopropionic acid and 5'-phosphoribosyl-5-amino-4-imidazolecarboxamide (AICAR) had an excellent AUC of 0.958 for distinguishing active VKH from inactive VKH. In summary, this study identified abnormal metabolites in urine of patients with VKH disease. Further studies are needed to confirm whether these metabolites are specific for this disease.


Risk of head and neck squamous cell cancer and death in patients with Fanconi anemia who did and did not receive transplants.
Hematopoietic stem cell transplant (SCT) is currently the only therapy that can restore normal hematopoiesis in patients with Fanconi anemia (FA). Patients with FA have a high baseline risk of squamous cell cancers (SCCs) of the head, neck, and esophagus, and SCT conditioning may increase SCC incidence. We evaluated the risks of SCC and death in 145 patients with FA in the North American Survey (NAS) cohort who did not receive transplants, and 117 patients with FA in the Hôpital Saint Louis (SLH) cohort who did receive transplants. The age-specific hazard of SCC was 4.4-fold higher in patients who received transplants than in those who did not (P = .003), and SCCs occurred at significantly younger ages in the former (respective medians, 18 and 33 years, P = .004). Survival after SCC was similarly poor in both cohorts (P = .135, median, 13 months). The hazard of SCC increased at a greater than linear rate, to 4.4% per year by age 40 in NAS and 4.7% per year by 10 years after transplant in SLH. In SLH, the hazard of non-SCC death was biphasic, declining significantly (P = .004) from 7.1% per month during the first 6 months after transplant to 0.13% per month (1.6% per year) after the first year. Acute and chronic graft-versus-host diseases were significant SCC risk factors. Adverse event rates in these cohorts provide historical control rates to assess emerging therapies for FA.


Circulating miRNAs as novel potential biomarkers for esophageal squamous cell carcinoma diagnosis: a meta-analysis update.
Early detection of esophageal squamous cell carcinoma (ESCC) is urgently needed to reduce the high morbidity and mortality of disease. Circulating microRNAs (miRNAs) are promising molecular biomarkers for ESCC prediction. We performed a comprehensive meta-analysis to systematically evaluate the diagnostic accuracy of circulating miRNAs in diagnosis of ESCC patients. Eligible studies were identified and assessed for quality employing multiple search strategies. Summary estimates for sensitivity, specificity, and other measures of accuracy of miRNAs in the diagnosis of ESCC were pooled using the bivariate random effects model. A total of 27 studies from 11 published articles were included in the meta-analysis. The overall sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio of circulating miRNAs for the diagnosis of ESCC were 79.9% (95% confidence intervals [CI]: 76.2%-83.1%), 81.3% (95% CI: 75.7-85.9), 4.27 (95%CI: 3.27-5.58), 0.25 (95% CI: 0.21-0.29), and 17.29 (95% CI: 12.01-24.86), respectively. The area under the summary receiver operating characteristic curve was 0.87 (95% CI: 0.84-0.90). The subgroup analyses based on research country (China vs. Japan), specimen type (plasma vs. serum), miRNAs profiling (single vs. multiple), and test method (screening vs. candidate; Taqman vs. SYBR) indicated no significant difference in the diagnostic accuracy of each subgroup. Collectively, our findings indicate that circulating miRNAs have significant potential to be used as noninvasive biomarkers for early detection of ESCC. Moreover, the subgroup analyses demonstrated the feasibility of using blood miRNAs as an ESCC diagnostic biomarker in Japanese and Chinese populations. Further, both plasma and serum are recommended as clinical specimens for miRNA detection. Further studies will be needed to validate these findings using larger numbers of patients.


The use of guided tissue regeneration principles in endodontic surgery for induced chronic periodontic-endodontic lesions: a clinical, radiographic, and histologic evaluation.
Chronic periodontic-endodontic lesions are not uncommon in clinical practice and their regenerative capacity has long been questioned. However, there are no published studies investigating the application of guided tissue regeneration techniques in combination with endodontic surgery using an induced perio-endo defect model. This study evaluated the clinical, radiographic, and histologic outcomes of three surgical procedures used to treat induced perio-endo lesions. Pulpal necrosis was induced in foxhounds along with surgical removal of radicular buccal bone. After 4 weeks, chronic lesions were clinically and radiographically assessed. Treatment surgery consisted of apicoectomy, root canal instrumentation, and retrofilling with mineral trioxide aggregate. Teeth were then assigned to one of the following treatment groups: open flap debridement only (OFD), OFD with bioabsorbable porcine-derived collagen membrane (BG), or OFD with BG and anorganic bovine bone matrix (BO/BG). Clinical parameters and standardized radiographs were assessed at defect creation; treatment surgery; and at 1, 2, 4, and 6 months. Animals were sacrificed at 6 months and specimens prepared for histometric analysis. Clinical and radiographic conditions improved during the study period. Mean epithelial attachment was similar between all groups. Mean connective tissue attachment for groups OFD, BG, and BO/BG was 3.79 mm, 2.63 mm, and 1.75 mm, respectively, and mean radicular bone height was 2.16 mm, 3.24 mm, and 3.45 mm, respectively. Statistically significant increases in the amount of new cementum were observed in groups BG and BO/BG when compared with OFD (P <0.05). Treatment of combined induced perio-endo lesions using bioabsorbable collagen membranes alone or in combination with anorganic bovine bone matrix resulted in increased amounts of bone, periodontal ligament, and significant increases in the amount of new cementum when compared to open flap debridement in a canine model.


A Research Program on Implementing Integrated Care for Older Adults with Complex Health Needs (iCOACH): An International Collaboration.
Health and social care systems across western developed nations are being challenged to meet the needs of an increasing number of people aging with multiple complex health and social needs. Community based primary health care (CBPHC) has been associated with more equitable access to services, better population level outcomes and lower system level costs. Itmay be well suited to the increasingly complex needs of populations; however the implementation of CBPHC models of care faces many challenges. This paper describes a program of research by an international, multi-university, multidisciplinary research team who are seeking to understand how to scale up and spread models of Integrated CBPHC (ICBPHC). The key question being addressed is "What are the steps to implementing innovative integrated community-based primary health care models that address the health and social needs of older adults with complex care needs?" and will be answered in three phases. In the first phase we identify and describe exemplar models of ICBPHC and their context in relation to relevant policies and performance across the three jurisdictions (New Zealand, Ontario and Québec, Canada). The second phase involves a series of theory-informed, mixed methods case studies from which we shall develop a conceptual framework that captures not only the attributes of successful innovative ICBPHC models, but also how these models are being implemented. In the third phase, we aim to translate our research into practice by identifying emerging models of ICBPHC in advance, and working alongside policymakers to inform the development and implementation of these models in each jurisdiction. The final output of the program will be a comprehensive guide to the design, implementation and scaling-up of innovative models of ICBPHC.


Functional evaluation of cystic duct patency with Gd-EOB-DTPA MR imaging: an alternative to hepatobiliary scintigraphy for diagnosis of acute cholecystitis?
To determine if MR cholangiography with Gd-EOB-DTPA can be used to assess cystic duct patency and to establish normal time range for reflux of contrast material into the cystic duct/gallbladder. This retrospective study is HIPAA-compliant and IRB-approved with waiver for informed consent granted. From September 2008 to June 2009, 300 patients who underwent Gd-EOB-DTPA-enhanced MR imaging for various clinical indications, not specifically limited to evaluation for acute cholecystitis, were identified. 112 patients were excluded: prior cholecystectomy (n = 93), severe technical limitations (n = 9), or absence of appropriate clinical follow-up (n = 10). 188 total patients (82 male, 106 female, mean age 51.0 years) were included in the final dataset. Time between contrast administration and contrast reflux into the cystic duct/gallbladder on delayed phase imaging was measured. Reflux of contrast into the gallbladder was identified in 130/188 patients (69.1%) on delayed phase imaging. Average time to gallbladder reflux was 15:24 ± 5:51 minutes (range: 6:01-41:05 min). 58/188 patients (30.9%) demonstrated no reflux of contrast into the gallbladder at time of final delayed phase images. Of 58 patients who demonstrated no reflux into cystic duct/gallbladder, 15 patients demonstrated no extrahepatic biliary excretion, limiting evaluation of cystic duct patency. A total of 173 patients demonstrated biliary excretion of contrast with 76% overall sensitivity of detection of cystic duct patency. MR cholangiography with hepatobiliary MR contrast agents such as Gd-EOB-DTPA can demonstrate cystic duct patency with high sensitivity. MR protocols can be designed within a clinically feasible timeframe to optimize diagnosis of acute cholecystitis.


Generalized anxiety disorder in older adults: examining the relation between clinician severity ratings and patient self-report measures.
Generalized anxiety disorder (GAD) is the most prevalent of the chronic anxiety disorders for older adults. Although a variety of self-report measures are beginning to be utilized to assess anxiety and related symptoms in older adults, there is a paucity of data regarding the convergence of self-report measures with clinician ratings of symptom severity. This situation is problematic in that interpretability of assessment data is limited, as is our broader understanding of the construct of GAD in an older adult population. To address these issues, we examined convergence across assessment modalities among 64 older adults who met diagnostic criteria for GAD. In addition to two Anxiety Disorders Interview Schedule for DSM-IV (ADIS-IV) interviews conducted by independent raters, participants completed four self-report measures (Penn State Worry Questionnaire [PSWQ], Worry Scale [WS], State-Trait Anxiety Inventory [STAI], Beck Depression Inventory [BDI]) as part of a more extensive pretreatment assessment battery. Results revealed significant correlations between clinician-rated GAD severity and the BDI, STAI, and PSWQ. Regression analyses indicated that the BDI (r2 = .15) and the PSWQ (r2 = .07) were particularly useful predictors of clinician-rated GAD severity. A comorbid mood disorder, however, was identified as an important mediator of these relations. Specifically, presence of coexistent depression accounted for 17% of the variance in clinician severity ratings (CSR; P < .01), with individuals diagnosed with a comorbid mood disorder receiving higher clinician severity ratings. The only self-report measure that accounted for additional significant variance was the PSWQ (7%). The study highlights the need to address coexistent psychological conditions when examining convergence between assessment modalities, and expands upon the relatively neglected area of anxiety assessment in older individuals. Specifically, the BDI and the PSWQ are identified as particularly useful screening instruments that may be helpful in conceptualizing GAD severity within an older adult population.


N-GlycositeAtlas: a database resource for mass spectrometry-based human N-linked glycoprotein and glycosylation site mapping.
N-linked glycoprotein is a highly interesting class of proteins for clinical and biological research. The large-scale characterization of N-linked glycoproteins accomplished by mass spectrometry-based glycoproteomics has provided valuable insights into the interdependence of glycoprotein structure and protein function. However, these studies focused mainly on the analysis of specific sample type, and lack the integration of glycoproteomic data from different tissues, body fluids or cell types. In this study, we collected the human glycosite-containing peptides identified through their de-glycosylated forms by mass spectrometry from over 100 publications and unpublished datasets generated from our laboratory. A database resource termed N-GlycositeAtlas was created and further used for the distribution analyses of glycoproteins among different human cells, tissues and body fluids. Finally, a web interface of N-GlycositeAtlas was created to maximize the utility and value of the database. The N-GlycositeAtlas database contains more than 30,000 glycosite-containing peptides (representing > 14,000 N-glycosylation sites) from more than 7200 N-glycoproteins from different biological sources including human-derived tissues, body fluids and cell lines from over 100 studies. The entire human N-glycoproteome database as well as 22 sub-databases associated with individual tissues or body fluids can be downloaded from the N-GlycositeAtlas website at http://nglycositeatlas.biomarkercenter.org.


Construct validity and reliability of ultrasound disease activity score in assessing joint inflammation in RA: comparison with DAS-28.
To investigate the construct validity and reliability of US DAS compared with 28-joint DAS (DAS-28) in assessing joint inflammation and in prediction of structural damage in patients with RA. Ninety patients with active RA were prospectively recruited and followed up during the 6 months of treatment. The patients underwent clinical, laboratory and X-ray assessment, along with blinded power Doppler US (PDUS) and grey-scale (GS) US (GSUS) examination at baseline and 6 months. A subgroup of 25/90 randomly assigned patients underwent MRI examination of their hands at baseline. A PDUS examination of 22 joints and GSUS examination for effusion/hypertrophy (E/H) of 28 joints were performed by two independent examiners, blinded to clinical findings. E/H was qualitatively assessed as absent or present, and PD signal was semi-quantitatively graded from 0 to 3. PDUS score for synovitis in 22 joints and GS score for E/H in 28 joints were included in US DAS calculation. Clinical scoring, PDUS and GSUS inter-observer reliability were evaluated. Strong correlation was found between US DAS and standard assessment of disease activity such as the DAS-28, ESR and CRP levels. Correlation between US DAS and patients' and physicians' visual analogue scale of activity was moderate, whereas correlations of US DAS with Health Assessment Questionnaire - Disability Index (HAQ-DI) and Short Form 36 Health Survey (SF-36) were weak to moderate. US DAS correlated with X-ray, MRI and US parameters and rates of joint damage. US DAS better anticipated future joint damage than standard DAS-28.


Triamcinolone hexacetonide protects against fibrillation and osteophyte formation following chemically induced articular cartilage damage.
Although corticosteroids have been shown to cause articular cartilage degeneration, recent studies of experimentally induced osteoarthritis indicate that under certain conditions they may protect against cartilage damage and osteophyte formation. The present study examines the in vivo effect of triamcinolone hexacetonide on the degeneration of articular cartilage which occurs following intraarticular injection of sodium iodoacetate. Three weeks after a single injection of iodoacetate into the knees of guinea pigs, ipsilateral femoral condylar cartilage exhibited fibrillation, loss of staining with Safranin O, depletion of chondrocytes, and prominent osteophytes. In striking contrast, when triamcinolone hexacetonide was injected into the ipsilateral knee 24 hours after the intraarticular injection of iodoacetate, fibrillation was noted in only 1 of 6 samples, osteophytes were much less prominent, pericellular staining with Safranin O persisted, and cell loss was less extensive. Knees of animals which received only one-tenth as much intraarticular triamcinolone hexacetonide after the iodoacetate injection also exhibited marked reduction in size and extent of osteophytes. However, the degree of fibrillation, loss of Safranin O staining, and chondrocyte depletion was similar to that observed in animals injected with iodoacetate but not treated with intraarticular steroid. No apparent morphologic or histochemical changes were observed after intraarticular injection of the steroid preparation alone. Thus, triamcinolone hexacetonide produced a marked, dose-dependent protective effect in this model of chemically induced articular cartilage damage.


Ultrasound tissue scatterer distribution imaging: An adjunctive diagnostic tool for shear wave elastography in characterizing focal liver lesions.
Focal liver lesion (FLL) is a prevalent finding in cross-sectional imaging, and distinguishing between benign and malignant FLLs is crucial for liver health management. While shear wave elastography (SWE) serves as a conventional quantitative ultrasound tool for evaluating FLLs, ultrasound tissue scatterer distribution imaging (TSI) emerges as a novel technique, employing the Nakagami statistical distribution parameter to estimate backscattered statistics for tissue characterization. In this prospective study, we explored the potential of TSI in characterizing FLLs and evaluated its diagnostic efficacy with that of SWE. A total of 235 participants (265 FLLs; the study group) were enrolled to undergo abdominal examinations, which included data acquisition from B-mode, SWE, and raw radiofrequency data for TSI construction. The area under the receiver operating characteristic curve (AUROC) was used to evaluate performance. A dataset of 20 patients (20 FLLs; the validation group) was additionally acquired to further evaluate the efficacy of the TSI cutoff value in FLL characterization. In the study group, our findings revealed that while SWE achieved a success rate of 49.43 % in FLL measurements, TSI boasted a success rate of 100 %. In cases where SWE was effectively implemented, the AUROCs for characterizing FLLs using SWE and TSI stood at 0.84 and 0.83, respectively. For instances where SWE imaging failed, TSI achieved an AUROC of 0.78. Considering all cases, TSI presented an overall AUROC of 0.81. There was no statistically significant difference in AUROC values between TSI and SWE (p > 0.05). In the validation group, using a TSI cutoff value of 0.67, the AUROC for characterizing FLLs was 0.80. In conclusion, ultrasound TSI holds promise as a supplementary diagnostic tool to SWE for characterizing FLLs.


The inside out model of emotion recognition: how the shape of one's internal emotional landscape influences the recognition of others' emotions.
Some people are exceptional at reading emotional expressions, while others struggle. Here we ask whether the way we experience emotion "on the inside" influences the way we expect emotions to be expressed in the "outside world" and subsequently our ability to read others' emotional expressions. Across multiple experiments, incorporating discovery and replication samples, we develop EmoMap (N = 20; N = 271) and ExpressionMap (N = 98; replication N = 193) to map adults' experiences of emotions and visual representations of others' emotions. Some individuals have modular maps, wherein emotional experiences and visual representations are consistent and distinct-anger looks and feels different from happiness, which looks and feels different from sadness. In contrast, others have experiences and representations that are variable and overlapping-anger, happiness, and sadness look and feel similar and are easily confused for one another. Here we illustrate an association between these maps: those with consistent and distinct experiences of emotion also have consistent and distinct visual representations of emotion. Finally (N = 193), we construct the Inside Out Model of Emotion Recognition, which explains 60.8% of the variance in emotion recognition and illuminates multiple pathways to emotion recognition difficulties. These findings have important implications for understanding the emotion recognition difficulties documented in numerous clinical populations.


Anthropomorphism as a contributor to the success of human (Homo sapiens) tool use.
Humans anthropomorphize: as a result of our evolved ultrasociality, we see the world through person-colored glasses. In this review, I suggest that an interesting proportion of the extraordinary tool-using abilities shown by humans results from our mistakenly anthropomorphizing and forming social relationships with objects and devices. I introduce the term machination to describe this error, sketch an outline of the evidence for it, tie it to intrinsic reward for social interaction, and use it to help explain overimitation-itself posited as underpinning human technological complexity-by human children and adults. I also suggest pathways for testing the concept's presence and limits, with an explicit focus on context-specific individual and temporal variation. I posit cognitive pressure from time constraints or opaque mechanisms as a cause for machination, with rapid, subconscious attribution of goals or desires to tools reducing cognitive overload. Machination holds promise for understanding how we create and use combinatorial technology, for clarifying differences with nonhuman animal tool use, and for examining the human fascination with objects. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Molecular mechanisms of regulation of neuronal muscarinic receptor sensitivity.
Like other neurotransmitter receptors, muscarinic acetylcholine receptors are subject to regulation by the state of receptor activation. Prolonged increases in the concentration of muscarinic agonists result in a decrease in receptor density and loss of receptor sensitivity, both in vivo and in vitro. On the other hand, when the receptor is deprived of acetylcholine for a long duration in vivo, the receptor becomes more sensitive in responding to muscarinic agonists. However, it has been more difficult to demonstrate increases in receptor concentration that accompany this supersensitive state. The purpose of this review is to provide current information related to the characteristics of muscarinic receptor regulation and the molecular mechanisms underlying this phenomenon, regarding both the density of receptors and their transduction mechanisms. Furthermore, possible feedback regulatory roles of different second messenger signals are discussed. Particular emphasis is dedicated to molecular mechanisms of regulation of neuronal muscarinic receptors.


Laparoscopic Total Pancreatectomy for Chronic Pancreatitis.
Although minimally invasive pancreatectomy has been performed increasingly for pancreatic malignancies, many authors feel that a history of pancreatitis is a contraindication to either laparoscopic or robotic-assisted pancreatectomy. Shown here is a video (Supplemental Digital Content 1, http://links.lww.com/SLE/A172) of a laparoscopic total pancreatectomy with splenectomy for chronic pancreatitis. This patient was denied auto-islet cell transplantation because of insurance restraints. In total, 4 laparoscopic total pancreatectomies have been attempted and completed. Indications for laparoscopic total pancreatectomy have been 2 for diffuse intraductal papillary mucinous neoplasm, 1 for pancreatic adenocarcinoma, and the above-mentioned patient. No patient suffered a biliary leak, and the average length of stay was 5 days (range, 4 to 8 d). History of pancreatitis is a relative contraindication to minimally invasive pancreatectomy. It should be performed by surgeons with expertise in both open and minimally invasive pancreatic surgery.


Effect of Bioactive Glass air Abrasion on Shear Bond Strength of Two Adhesive Resins to Decalcified Enamel.
Bioactive glass air abrasion is a conservative technique to remove initial decalcified tissue and caries. This study examined the shear bond strength of composite resin to sound and decalcified enamel air-abraded by bioactive glass (BAG) or alumina using etch-and-rinse and self-etch adhesives. Forty-eight permanent molars were root-amputated and sectioned mesiodistally. The obtained 96 specimens were mounted in acrylic resin; the buccal and lingual surfaces remained exposed. A demineralizing solution was used to decalcify half the specimens. Both sound and decalcified specimens were divided into two groups of alumina and bioactive glass air abrasion. In each group, the specimens were subdivided into two subgroups of Clearfil SE Bond or OptiBond FL adhesives (n=12). Composite resin cylinders were bonded on enamel surfaces cured and underwent thermocycling. The specimens were tested for shear bond strength. Data were analyzed using SPSS 16.0 and three-way ANOVA (α=0.05). Similar to the experimental groups, the enamel surface of one specimen underwent SEM evaluation. No significant differences were observed in composite resin bond strength subsequent to alumina or bioactive glass air abrasion preparation techniques (P=0.987). There were no statistically significant differences between the bond strength of etch-and-rinse and self-etch adhesive groups (P=1). Also, decalcified or intact enamel groups had no significant difference (P=0.918). However, SEM analysis showed much less enamel irregularities with BAG air abrasion compared to alumina air abrasion. Under the limitations of this study, preparation of both intact and decalcified enamel surfaces with bioactive glass air abrasion results in similar bond strength of composite resin in comparison with alumina air abrasion using etch-&-rinse or self-etch adhesives.


Multi-component peptide hydrogels - a systematic study incorporating biomolecules for the exploration of diverse, tuneable biomaterials.
Peptide-based supramolecular gels can be designed to be functional "smart" materials that have applications in drug delivery, tissue engineering, and supramolecular chemistry. Although many multi-component gel systems have been designed and reported, many of these applications still rely solely on single-component gel systems which limits the functionalities of the materials. Multi-component self-assembly leads to the formation of highly ordered and complex architectures while offering the possibility to generate hydrogels with interesting properties including functional complexity and diverse morphologies. Being able to incorporate various classes of biomolecules can allow for tailoring the materials' functionalities to specific application needs. Here, a novel peptide amphiphile, myristyl-Phe-Phe (C14-FF), was synthesized and explored for hydrogel formation. The hydrogel possesses a nanofiber matrix morphology, composed of β-sheet aggregates, a record-low gelation concentration for this class of compounds, and a unique solvent-dependent helical switch. The C14-FF hydrogel was then explored with various classes of biomolecules (carbohydrates, vitamins, proteins, building blocks of HA) to generate a multi-component library of gels that have potential to represent the complex natural extracellular matrix. Selected multi-component gels exhibit an excellent compatibility with mesenchymal stem cells showing high cell viability percentages, which holds great promise for applications in regenerative therapy.


Nd:YAG laser endoscopic photocoagulation for upper gastrointestinal bleeding.
To appraise the success of neodymium:yttrium-aluminum-garnet laser photocoagulation for the endoscopic control of major upper gastrointestinal bleeding, 19 patients who fulfilled all the criteria of this study underwent laser therapy. Initial hemostasis was achieved in 17 patients (89%). The two patients continuing to bleed underwent surgery but died. Rebleeding occurred in five patients, with laser photocoagulation successful in two and surgery in another two. Nd:YAG lasers offer a safe, effective method for controlling bleeding and, it is hoped, will decrease the morbidity and need for emergency surgery.


Synthesis of Large-Scale High-Quality Metal-Organic Frameworks on Cu(100) via Hierarchical Dehydrogenation Reactions.
Thermal stimulus has been considered as a promising strategy for controlling on-surface reactions, allowing the formation of diverse products on metal substrates. Here, we successfully achieve hierarchical dehydrogenation reactions of amino groups on a Cu(100) surface. By carefully adjusting the experimental parameters, we synthesize large-scale and low-defect density surface metal-organic frameworks on copper surfaces. Our work sheds light on a controllable route for the synthesis of high-quality metal-organic coordination supramolecular structures via on-surface chemistry.


An Overview of Heart Rate Variability Metrics and Norms.
Healthy biological systems exhibit complex patterns of variability that can be described by mathematical chaos. Heart rate variability (HRV) consists of changes in the time intervals between consecutive heartbeats called interbeat intervals (IBIs). A healthy heart is not a metronome. The oscillations of a healthy heart are complex and constantly changing, which allow the cardiovascular system to rapidly adjust to sudden physical and psychological challenges to homeostasis. This article briefly reviews current perspectives on the mechanisms that generate 24 h, short-term (~5 min), and ultra-short-term (<5 min) HRV, the importance of HRV, and its implications for health and performance. The authors provide an overview of widely-used HRV time-domain, frequency-domain, and non-linear metrics. Time-domain indices quantify the amount of HRV observed during monitoring periods that may range from ~2 min to 24 h. Frequency-domain values calculate the absolute or relative amount of signal energy within component bands. Non-linear measurements quantify the unpredictability and complexity of a series of IBIs. The authors survey published normative values for clinical, healthy, and optimal performance populations. They stress the importance of measurement context, including recording period length, subject age, and sex, on baseline HRV values. They caution that 24 h, short-term, and ultra-short-term normative values are not interchangeable. They encourage professionals to supplement published norms with findings from their own specialized populations. Finally, the authors provide an overview of HRV assessment strategies for clinical and optimal performance interventions.


Flurbiprofen-sepharose chromatography of the prostaglandin synthetase from bovine seminal vesicles.
Flurbiprofen-Sepharose and Acetyl-Sepharose have been prepared by coupling dl-2-(2-fluoro-4-biphenylyl)propionic acid [Flurbiprofen] and acetic acid, respectively, to 3-(N-[3-aminopropyl)aminopropyl Sepharose 4B using a water soluble carbodiimide. The arachidonic acid oxygenase activity of solubilized bovine seminal vesicle microsomes is retarded during chromatography on Flurbiprofen-Sepharose but not Acetyl-Sepharose. Thus binding of the oxygenase to Flurbiprofen-Sepharose results from interaction with the immobilized inhibitor. However, the impure oxygenase is either not bound and/or not eluted in a biospecific manner since the abilities of flufenamic acid, R(+) and S(-)-5-cyclohexylindan-1-carboxylic acid, and R and S-Naproxen to remove the enzyme from Flurbiprofen-Sepharose do not parallel the relative efficacies of these compounds as prostaglandin synthesis inhibitors. Nevertheless, gradient elution of arachidonic acid oxygenase activity from Flurbiprofen-Sepharose with flufenamic acid provides a 15 fold enrichment of the enzyme from solubilized bovine seminal vesicle microsomes in 80% yield indicating that this chromatographic reagent can be a powerful tool for use in purification of the prostaglandin synthetase.


A pilot study of motivational interviewing in adolescents with diabetes.
To obtain preliminary data on the impact of motivational interviewing, a counselling approach to behaviour change, on glycaemic control, wellbeing, and self-care of adolescents with diabetes. Twenty two patients aged 14-18 years participated in motivational interviewing sessions during a six month intervention. The effects of the intervention on HbA1c and a range of psychological factors were assessed. Mean HbA1c decreased from 10.8% to 9.7% during the study and remained significantly lower after the end of the study. Fear of hypoglycaemia was reduced and diabetes was perceived as easier to live with. There were no other significant changes in the psychological measures. By contrast no reduction in HbA1c values was observed in a comparison group who did not receive the motivational interviewing intervention. The findings of this pilot study indicate that motivational interviewing may be a useful intervention in helping adolescents improve their glycaemic control. A larger, longer term randomised controlled study is indicated to clarify the mechanisms and extent of these benefits.


Nickel-catalyzed asymmetric alpha-arylation of ketone enolates.
An atropisomeric dipyridyldiphosphine, P-Phos, can effect highly enantioselective Ni-catalyzed alpha-arylation of ketone enolates with aryl halides to install an all-carbon quaternary stereogenic center in up to 98% ee and excellent yields.


Measurement of placental oxygenation by transabdominal near-infrared spectroscopy.
The uteroplacental circulation in the placenta can have a major impact on the fetus. Near infrared spectroscopy (NIRS) is the noninvasive method of measuring changes in blood volumes and oxygen concentrations in living tissue. The purpose of this study is to monitor changes in placental tissue oxygen index (TOI) levels, in patients with intrauterine fetal growth restriction during pregnancy, using NIRS. We measured placental TOI values of 15 normal pregnant woman and 15 patients with intrauterine growth restriction admitted to our hospital. The placenta was assessed by ultrasound examination and NIRS was performed on all patients. The TOI values of the IUGR group when hospitalized was 78.6 +/- 1.6 (SD). This value was significantly higher than that of the controls (78.6 +/- 1.6 [SD] versus 70.2 +/- 0.4 [SD]). And the TOI values of the IUGR group, when measured before delivery, were 77.8 +/- 1.6 (SD). The TOI values of the IUGR group before delivery were significantly higher than those of the control group (77.8 +/- 1.6 [SD] versus 70.3 +/- 0.4 [SD]). We propose that NIRS is a candidate, noninvasive method for assessing placental oxygen dynamics on a real-time basis. In the near future it may contribute to perinatal medical practice.


Limited dCTP availability accounts for mitochondrial DNA depletion in mitochondrial neurogastrointestinal encephalomyopathy (MNGIE).
Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a severe human disease caused by mutations in TYMP, the gene encoding thymidine phosphorylase (TP). It belongs to a broader group of disorders characterized by a pronounced reduction in mitochondrial DNA (mtDNA) copy number in one or more tissues. In most cases, these disorders are caused by mutations in genes involved in deoxyribonucleoside triphosphate (dNTP) metabolism. It is generally accepted that imbalances in mitochondrial dNTP pools resulting from these mutations interfere with mtDNA replication. Nonetheless, the precise mechanistic details of this effect, in particular, how an excess of a given dNTP (e.g., imbalanced dTTP excess observed in TP deficiency) might lead to mtDNA depletion, remain largely unclear. Using an in organello replication experimental model with isolated murine liver mitochondria, we observed that overloads of dATP, dGTP, or dCTP did not reduce the mtDNA replication rate. In contrast, an excess of dTTP decreased mtDNA synthesis, but this effect was due to secondary dCTP depletion rather than to the dTTP excess in itself. This was confirmed in human cultured cells, demonstrating that our conclusions do not depend on the experimental model. Our results demonstrate that the mtDNA replication rate is unaffected by an excess of any of the 4 separate dNTPs and is limited by the availability of the dNTP present at the lowest concentration. Therefore, the availability of dNTP is the key factor that leads to mtDNA depletion rather than dNTP imbalances. These results provide the first test of the mechanism that accounts for mtDNA depletion in MNGIE and provide evidence that limited dNTP availability is the common cause of mtDNA depletion due to impaired anabolic or catabolic dNTP pathways. Thus, therapy approaches focusing on restoring the deficient substrates should be explored.


Peptidoglycan plasticity in bacteria: stress-induced peptidoglycan editing by noncanonical D-amino acids.
It has been generally assumed that the role of D-amino acids in bacterial physiology is rather limited. However, recent new evidence demonstrated that millimolar concentrations of noncanonical D-amino acids are synthesized and released to the environment by bacteria from diverse phyla. These D-amino acids help bacteria adapt to environmental challenges by modulating the structure and composition of the peptidoglycan (PG). This regulation, which appears to be well conserved among bacterial species, occurs principally through the incorporation of the D-amino acids into the terminus of the peptide moiety of muropeptides. These findings revived interest in studies investigating D-amino acids as an exciting and trendy topic in current microbiology, which considers them as fundamental players in different aspects of bacterial physiology. In this article, we provide an overview of the origins of research on the effects of D-amino acids in the biology of bacterial cell walls, including their recent implication as key factors for stress-associated PG remodeling.


Outdoor air pollution and asthma in children.
Asthma, a chronic inflammatory disease of the airways, is associated with reversible airway obstruction and hyperresponsiveness to triggers; clinical symptoms include wheezing, episodic cough, shortness of breath, and increased mucous production. Ambient or outdoor environmental exposure to ozone, particulate matter, sulfur dioxide, and nitrogen oxides has been well documented to exacerbate asthma. Children appear to be most vulnerable to the harmful effects of ambient air pollutants. As their lungs are not completely developed, children may experience greater exposure to environmental pollutants than adults and the higher doses of varied composition may remain in their lungs for a greater duration. Altogether, the negative effects of air pollutants on pulmonary function place children at a greater risk of air pollutant-induced exacerbation of asthma for the duration of their lives. The aim of this review was to assess recently published literature regarding the influence of air pollution on asthma in children. For this work, we reviewed articles found in PubMed using the key words "outdoor air pollution, asthma, and children" which were published between 2006 and 2009. Only those articles that had a full version available in PubMed were analyzed. We reviewed studies published between 2006 and 2009 examining the effect of outdoor air pollution on asthma in children. In total, we evaluated 25 articles; of these, 9 were published in 2006, 3 in 2007, 8 in 2008, and 5 in 2009. Of these 25 studies, 1 was a clinical trial, 6 were cross-sectional, 4 were case-control (2 with a case-crossover design), 12 were cohort prospective, and 2 were cohort retrospective studies with varied follow-up times ranging from 10 days to 7 years. The ages of children also differed, ranging from birth to 18 years of age. All studies reviewed in this work indicate that outdoor air pollution affects the appearance and exacerbation of asthma in children. Although these findings are of great interest, the limitations of noted works make future investigations of the effect of air pollution on asthma in children essential.


A New Approach of Extraction of α-Amylase/trypsin Inhibitors from Wheat (Triticum aestivum L.), Based on Optimization Using Plackett-Burman and Box-Behnken Designs.
Wheat is one of the most consumed foods in the world and unfortunately causes allergic reactions which have important health effects. The α-amylase/trypsin inhibitors (ATIs) have been identified as potentially allergen components of wheat. Due to a lack of data on optimization of ATI extraction, a new wheat ATIs extraction approach combining solvent extraction and selective precipitation is proposed in this work. Two types of wheat cultivars (Triticum aestivum L.), Julius and Ponticus were used and parameters such as solvent type, extraction time, temperature, stirring speed, salt type, salt concentration, buffer pH and centrifugation speed were analyzed using the Plackett-Burman design. Salt concentration, extraction time and pH appeared to have significant effects on the recovery of ATIs (p < 0.01). In both wheat cultivars, Julius and Ponticus, ammonium sulfate substantially reduced protein concentration and inhibition of amylase activity (IAA) compared to sodium chloride. The optimal conditions with desirability levels of 0.94 and 0.91 according to the Doehlert design were: salt concentrations of 1.67 and 1.22 M, extraction times of 53 and 118 min, and pHs of 7.1 and 7.9 for Julius and Ponticus, respectively. The corresponding responses were: protein concentrations of 0.31 and 0.35 mg and IAAs of 91.6 and 83.3%. Electrophoresis and MALDI-TOF/MS analysis showed that the extracted ATIs masses were between 10 and 20 kDa. Based on the initial LC-MS/MS analysis, up to 10 individual ATIs were identified in the extracted proteins under the optimal conditions. The positive implication of the present study lies in the quick assessment of their content in different varieties especially while considering their allergenic potential.


Ketamine in depression and electroconvulsive therapy.
The antidepressant effect of subanesthetic doses of ketamine was recognized 20 years ago. This review briefly summarizes the current understanding of the antidepressant mechanisms and the available clinical research on the use of racemic ketamine and enantiomer esketamine for depression. The antidepressant effect of subanesthetic doses of ketamine is currently considered to be predominantly mediated by improved neuroplasticity in cortico-limbic areas in the brain. Single dose of 0.5 mg/kg of ketamine infused intravenously over 40 min, or single intranasal dose of esketamine cause rapid antidepressant and antisuicidal effects within hours of administration, and the antidepressant effect may last up to a week. Repeated administration of nasal spray esketamine is considered to prevent relapse of depression. Longitudinal studies are currently insufficient. When used in various doses for anesthetic induction for electroconvulsive therapy, ketamine improves seizure quality and may possibly diminish posttherapy cognitive impairment. A rapid onset antidepressive effect of ketamine and esketamine has been proven conclusively. The results of extensive basic science research of the mechanism of action of low-dose ketamine doses has led to an alternative hypothesis of the pathophysiology of depression and the development of a novel neurotrophic concept of depression. Further longitudinal studies are warranted to determine the safety and efficacy of repeated administration of ketamine and its analogs to prevent relapse and recurrence of depression.


Cell hybridization and cell agglutination. I. Enhancement of cell hybridization by lectins.
A great increase in hybridization frequency of cultured rodent cells was obtained when conventional cell fusion using 50% polyethylene glycol (PEG) was combined with a cell agglutination produced by plant lectins. The rate of appearance of hybrid colonies was found to be correlated with the extent of cell agglutination by lectin, as well as with cell fusion induced by subsequent PEG treatment. Phytohemagglutinin (PHA), wheat germ agglutinin, Wistaria floribunda agglutinin and concanavalin A were all active; the most effective was PHA. When parental cells in a monolayer were treated with PHA followed by PEG, the resulting hybridization frequency was very low because of markedly decreased viability, whereas the same cells in suspension yielded hybrid colonies at a higher rate. These results suggest that the enhancement of hybridization by PHA/PEG treatment was brought about by the ability of lectin to agglutinate cells.


AOA Critical Issues: Perceptions on the State of Diversity, Equity, and Inclusion in Orthopaedic Surgery: A Survey of the AOA Membership.
Orthopaedic surgery continues to trail other specialties in increasing diversity among its physician workforce. Various efforts have been and are currently being made to not only increase diversity, but also promote equity and inclusion in the field. The purpose of this study was to survey members of the American Orthopaedic Association (AOA) to determine how leaders in orthopaedics view diversity, equity, and inclusion (DEI) at the present time and to understand their perspective while moving into the future. An anonymous 11-question survey was disseminated online to AOA members in May 2022. These individuals were identified by the AOA membership directory and the email ListServe. The survey included free-response and multiple-choice questions. Demographic information was self-identified, and both qualitative and quantitative data were collected. Of the 1,657 AOA members who were provided the survey, 262 (15.8%) responded. Approximately 29.5% (77) and 45.6% (119) of the surveyed population ranked "retention of underrepresented populations in orthopaedic residency (women, URiM)" as "very important" or "absolutely essential," respectively. The answers to the free-response questions identified multiple core themes that responders were passionate about, namely resident and attending physician recruitment and retention, as well as resident selection. Leaders in the field of orthopaedic surgery desire for action to be taken in the field of DEI. The findings of this survey denote positive attitudes even though many inequalities still pervade the field of orthopaedics. Through mentorship, objective evaluation, transparency, and continued intentional action, orthopaedic surgery is well-positioned to continue to move forward with DEI.


Daily uplifts during the COVID-19 pandemic: what is considered helpful in everyday life?
Knowledge of what is uplifting and helpful during pandemics could inform the design of sustainable pandemic recommendations in the future. We have explored individuals' views on helpful and uplifting aspects of everyday life during the coronavirus disease 2019 (COVID-19) pandemic. Participants answered a brief, daily survey via text messages during 14 consecutive days in July-August, 2020. The survey included the question: "During the past 24 hours, is there anything that has made you feel good or helped you in your life?" We used content analysis to compile responses from 693 participants, who provided 4,490 free-text answers, which resulted in 24 categories subsumed under 7 themes. Positive aspects during the COVID-19 pandemic primarily related to social interactions, in real life or digitally, with family, friends and others. Other important aspects concerning work, colleagues and maintaining everyday life routines. One theme concerning vacations, going on excursions and being in nature. Leisure and recreation activities, such as hobbies and physical exercise, also emerged as important, as did health-related factors. Bodily sensations, thoughts, feelings and activities that benefited well-being were mentioned frequently. Lastly, people commented on the government strategies for containing COVID-19, and whether to comply with restrictions. To summarize, daily uplifts and helpful aspects of everyday life centered around social relationships. To comply with recommendations on physical distancing, people found creative ways to maintain social connections both digitally and face-to-face. Social interaction, maintenance of everyday life routines, hobbies and physical activity appeared to be important for well-being.


Crossed cerebellar diaschisis in Alzheimer's disease.
Crossed cerebellar diaschisis (CCD) is characterized by hypometabolism and hypoperfusion on molecular imaging in the cerebellum due to a supratentorial lesion on the contralateral side. CCD is a well-established phenomenon in acute or subacute conditions such as infarction but it has been less well described in chronic conditions such as neurodegenerative dementias. Here, we investigate CCD in a large sample of 830 people meeting research criteria for Alzheimer's disease (AD) using [18F]fluorodeoxyglucose-positron emission tomography (FDG-PET). This study is based on FDG-PET data collected at baseline as part of two large-scale Phase III clinical trials of a novel tau aggregation inhibitor medication, methylthioninium in mild to moderate AD participants. Quantification of FDG-PET hypometabolism was carried out using standardized uptake value ratio (SUVR), with the pons as the comparison region. SUVR was compared in different regions of interest between the right and left hemispheres of the brain and cerebellum in people with mild AD (Mini-Mental State Examination score ≥ 20). Comparison of SUVR in different brain regions demonstrated significant differences in the temporal, occipital and cerebellar cortices. Right and left asymmetry was noted with lower SUVR in the left temporal and occipital regions, whereas SUVR was lower in the right side of the cerebellum. Here, we found robust evidence of CCD in a large sample of people with AD, a chronic neurodegenerative condition. The presence of this phenomenon in AD opens up a new avenue of research in AD pathogenesis and has the potential to change future diagnostic and therapeutic strategies.


Relationship between morphological change and crystalline phase transitions of polyethylene-poly(ethylene oxide) diblock copolymers, revealed by the temperature-dependent synchrotron WAXD/SAXS and infrared/Raman spectral measurements.
The phase transition behaviors of low-molecular-weight polyethylene-poly(ethylene oxide) (PE-b-PEO) diblock copolymers with the monomeric units of PE/PEO = 17/40 and 39/86 have been successfully investigated through the temperature-dependent measurements of wide-angle X-ray diffraction (WAXD), small-angle X-ray scattering (SAXS), infrared and Raman spectra, as well as thermal analysis. These diblock copolymers had been believed to show only order-to-disorder transition of lamellar morphology in a wide temperature region, but it has been found here for the first time that this copolymer clearly exhibits the three stages of transitions among lamella, gyroid, cylinder, and spherical phases in the heating and cooling processes. The WAXD and IR/Raman spectral measurements allowed us to relate these morphological changes to the microscopic changes in the aggregation states of PEO and PE segments. In the low-temperature region the PEO segments form the monoclinic crystal of (7/2) helical chain conformation and the PE segments of planar-zigzag form take the orthorhombic crystalline phase. These crystalline lamellae of PEO and PE segments are alternately stacked with the long period of 165 Angstroms. In a higher temperature region, where the PEO crystalline parts are on the way of melting but the PE parts are still in the orthorhombic phase, the gyroid morphology is detected in the SAXS data. By heating further, the gyroid morphology changes to the hexagonally packed cylindrical morphology, where the orthorhombic phase of PE segments is gradually disordered because of thermally activated molecular motion and finally transforms to the pseudohexagonal or rotator phase. Once the PE segments are perfectly melted, the higher-order structure changes from the cylinder to the spherical morphology. These morphological transitions might relate to the thermally activated motions of two short chain segments of the diblock copolymer, although the details of the transition mechanism are unclear at the present stage.


Neuropathologic differentiation of progressive supranuclear palsy and corticobasal degeneration.
Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are usually sporadic multi-system degenerations associated with filamentous tau inclusions in neurons and glia. As such they can be considered sporadic tauopathies in contrast to familial tauopathies linked to mutations in the tau gene. Mutations have not been found in the tau gene in either PSP or CBD. The clinical syndromes and neuroimaging of typical cases of PSP and CBD are distinct; however, atypical cases are described that have overlapping clinical and pathologic features. Both PSP and CBD have similar biochemical alterations in the tau protein, with the abnormal tau protein containing predominantly four-repeat tau. While there is overlap in the pathology in PSP and CBD, there are sufficient differences to continue the present day trend to consider these separate disorders. Several important pathologic features differentiate PSP from CBD. Ballooned neurons are frequent and nearly a sine qua non for CBD, but they are found in PSP at a frequency similar to that of other neurodegenerative diseases, such as Alzheimer's disease. Astrocytic lesions are different, with tufted astrocytes found in motor cortex and striatum in PSP and astrocytic plaques in focal atrophic cortices in CBD. The most characteristic neuronal tau pathology in CBD is wispy, fine filamentous inclusions within neuronal cell bodies, while affected neurons in PSP have compact, dense filamentous aggregates characteristic of globose neurofibrillary tangles. Thread-like processes in gray and white matter are much more numerous and widespread in CBD than in PSP. The brunt of the pathology in CBD is in the cerebrum, while the basal ganglia, diencephalon and brainstem are the targets of PSP. Further clinicopathologic studies will refine our understanding of these disorders and open the possibility that common etiologic factors may be identified for these unusual sporadic tauopathies.


Uremic optic neuropathy. A uremic manifestation mandating dialysis.
A 41-year-old male patient in end-stage renal failure presented on two occasions, over an 18-month period, with painless unilateral visual deterioration and optic disc edema. Clinical findings were compatible with a diagnosis of uremic optic neuropathy. On his initial presentation, the patient refused the onset of dialysis, resulting in a permanent visual deficit of the left eye. On his subsequent admission with a similar clinical picture, this time of the right eye, dialysis combined with corticosteroid therapy was promptly instituted. This led to a rapid improvement of the visual acuity and visual field defects of the right eye concomitant with subsidence of the edema of the optic nerve head.


Worldwide mortality from cirrhosis: an update to 2002.
Cirrhosis mortality has registered large changes over the last few decades. Age-standardized (world standard) cirrhosis mortality rates per 100,000 were computed for 41 countries worldwide over the period 1980-2002 using data from the WHO mortality database. In the early 1980s, the highest rates were in Mexico, Chile (around 55/100,000 men and over 14/100,000 women), France, Italy, Portugal, Austria, Hungary and Romania (around 30-35/100,000 men and 10-15/100,000 women). Mortality from cirrhosis has been steadily declining in most countries worldwide since the mid or late 1970s (annual percent change, APC, between -5% and -1.5% in the last decade only for both sexes). In southern Europe, rates in the early 2000s were less than halved compared to earlier decades. In contrast, rates have been rising in Eastern European countries to reach extremely high values in the mid 1990s, and declined only thereafter. In the UK rates were still steadily rising (APC around +7% in men and +3% in women from England and Wales, and +9% in men and +7% in women from Scotland). Mortality from cirrhosis shows favourable trends in most countries of the world, following the reduction in alcohol consumption and hepatitis B and C virus infection. The steady upward trends observed over more recent calendar periods in the UK and central and eastern European countries are attributed to the persistent increase in the prevalence of alcohol consumption.


The LDL receptor locus in familial hypercholesterolemia: multiple mutations disrupt transport and processing of a membrane receptor.
The receptor for low-density lipoprotein (LDL) is synthesized as a 120 kd precursor that undergoes a 40 kd posttranslational increase in apparent molecular weight en route to the cell surface. We describe seven mutations that disrupt synthesis, processing and transport of the receptor in fibroblasts from 77 subjects with the clinical diagnosis of homozygous familial hypercholesterolemia. One mutation obliterates synthesis of immunoprecipitable precursor. Three mutations specify precursors (100, 120 and 135 kd) that fail to undergo normal processing and fail to reach the cell surface. The other three mutations specify precursors (100, 120, and 170 kd) that undergo a normal 40 kd increase in molecular weight and reach the surface, but do not bind LDL normally. Pedigree studies show that each mutation segregates as an allele at the LDL receptor locus. These data imply that signals for transport of receptors from endoplasmic reticulum to the cell surface are contained within the amino acid sequences of the receptors, and that mutations affecting these sequences can disrupt receptor transport.


Etiological Role and Repeated Infections of Sapovirus among Children Aged Less than 2 Years in a Cohort Study in a Peri-urban Community of Peru.
Human sapovirus has been shown to be one of the most important etiologies in pediatric patients with acute diarrhea. However, very limited data are available about the causative roles and epidemiology of sapovirus in community settings. A nested matched case-control study within a birth cohort study of acute diarrhea in a peri-urban community in Peru from 2007 to 2010 was conducted to investigate the attributable fraction (AF) and genetic diversity of sapovirus. By quantitative reverse transcription-real-time PCR (qPCR) sapovirus was detected in 12.4% (37/299) of diarrheal and 5.7% (17/300) of nondiarrheal stools (P = 0.004). The sapovirus AF (7.1%) was higher in the second year (13.2%) than in the first year (1.4%) of life of children. Ten known genotypes and one novel cluster (n = 5) within four genogroups (GI, GII, GIV, and GV) were identified by phylogenetic analysis of a partial VP1 gene. Further sequence analysis of the full VP1 gene revealed a possible novel genotype, tentatively named GII.8. Notably, symptomatic reinfections with different genotypes within the same (n = 3) or different (n = 5) genogroups were observed in eight children. Sapovirus exhibited a high attributable burden for acute gastroenteritis, especially in the second year of life, of children in a Peruvian community. Further large-scale studies are needed to understand better the global burden, genetic diversity, and repeated infections of sapovirus.


Borderline shades: Morphometric features predict borderline personality traits but not histrionic traits.
Borderline personality disorder (BPD) is one of the most diagnosed disorders in clinical settings. Besides the fully diagnosed disorder, borderline personality traits (BPT) are quite common in the general population. Prior studies have investigated the neural correlates of BPD but not of BPT. This paper investigates the neural correlates of BPT in a subclinical population using a supervised machine learning method known as Kernel Ridge Regression (KRR) to build predictive models. Additionally, we want to determine whether the same brain areas involved in BPD are also involved in subclinical BPT. Recent attempts to characterize the specific role of resting state-derived macro networks in BPD have highlighted the role of the default mode network. However, it is not known if this extends to the subclinical population. Finally, we wanted to test the hypothesis that the same circuitry that predicts BPT can also predict histrionic personality traits. Histrionic personality is sometimes considered a milder form of BPD, and making a differential diagnosis between the two may be difficult. For the first time KRR was applied to structural images of 135 individuals to predict BPT, based on the whole brain, on a circuit previously found to correctly classify BPD, and on the five macro-networks. At a whole brain level, results show that frontal and parietal regions, as well as the Heschl's area, the thalamus, the cingulum, and the insula, are able to predict borderline traits. BPT predictions increase when considering only the regions limited to the brain circuit derived from a study on BPD, confirming a certain overlap in brain structure between subclinical and clinical samples. Of all the five macro networks, only the DMN successfully predicts BPD, confirming previous observations on its role in the BPD. Histrionic traits could not be predicted by the BPT circuit. The results have implications for the diagnosis of BPD and a dimensional model of personality.


Shear stress responses of adult blood outgrowth endothelial cells seeded on bioartificial tissue.
Human blood outgrowth endothelial cells (HBOECs) are expanded from circulating endothelial progenitor cells in peripheral blood and thus could provide a source of autologous endothelial cells for tissue-engineered vascular grafts. To examine the suitability of adult HBOECs for use in vascular tissue engineering, the shear stress responsiveness of these cells was examined on bioartificial tissue formed from dermal fibroblasts entrapped in tubular fibrin gels. HBOECs adhered to this surface, deposited collagen IV and laminin, and remained adherent when exposed to 15 dyn/cm(2) shear stress for 24 h. The shear stress responses of HBOECs were compared to human umbilical vein endothelial cells (HUVECs). As with HUVECs, HBOECs upregulated vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 when exposed to tumor necrosis factor (TNF)-α and shear stress decreased the expression of these adhesion molecules on TNF-α-activated monolayers. Nitric oxide production was elevated by shear stress, but did not vary between cell types. Both cell types decreased platelet adhesion to the bioartificial tissue, whereas pre-exposing the cells to flow decreased platelet adhesion further. These results illustrate the potential utility for HBOECs in vascular tissue engineering, as not only do the cells adhere to bioartificial tissue and remain adherent under physiological shear stress, they are also responsive to shear stress signaling.


Repeatability of pupil size measurements with NIDEK OPD-Scan III in myopic children.
To investigate the repeatability of pupil size measurements, determined from the NIDEK OPD-Scan III, of myopic eyes in children wearing single-vision spectacles (SVS), undergoing orthokeratology (OK) and receiving combined treatment of 0.01% atropine and orthokeratology (AOK). A single examiner took two sets of mesopic pupil size measurements from the right eyes of 80 children (SVS:16, OK: 34, AOK: 30) (mesopic 1 and mesopic 2) and two sets of photopic (photopic 1 and photopic 2) pupil size measurements (internal light source) using the NIDEK OPD-Scan III. Each set was taken at a single visit, 15 min apart. Subjects in the OK and AOK groups had undergone treatment for at least 6 months, and the SVS subjects had no previous myopia treatment other than wearing spectacles. Repeatability of measurements was analysed using intraclass correlation coefficient (ICC), Bland-Altman (BA) plot, and coefficient of repeatability (CoR). Mesopic 1 and 2 values were not significantly different among the three groups (p = 0.56, 0.77), hence the data were pooled for each set of measurements (mean [±S.D.] values were 7.09 ± 0.61 and 7.12 ± 0.61 mm, respectively) for further analyses. ICC for repeated mesopic pupil size measurements was 0.98 (95% CI, 0.98-0.99). No significant correlation was found between the means of the mesopic 1 and 2 measurements and their differences (Pearson's r = -0.02, p = 0.83). A BA plot also demonstrated narrow 95% limits of agreement, with a CoR of 0.28 mm. Mean photopic 1 and 2 measurements for the AOK group (3.74 ± 0.46; 3.73 ± 0.43 mm, respectively) were significantly larger (p = 0.01; 0.009) than those of the SVS and OK groups, but no significant difference was found between the latter two groups (p > 0.05). Hence, photopic 1 and 2 measurements for the SVS and OK groups were pooled (SVS-OK) for further analyses. ICC for repeatability of the photopic measurements was 0.98 (95% CI, 0.96 to 0.99) for the SVS-OK and AOK groups. The differences between photopic 1 and 2 measurements were not significantly correlated with their means, either in the AOK group (Pearson's r = -0.25, p = 0.19), or in the pooled SVS-OK group (Pearson's r = -0.04, p = 0.78). BA plots also showed narrow 95% limits of agreement, and CoR was 0.25 mm and 0.23 mm in the AOK and pooled SVS-OK groups, respectively. Mesopic and photopic pupil size measurement using the NIDEK OPD-Scan III was highly repeatable and suitable for use on children.


Colonization from divergent ancestors: glaciation signatures on contemporary patterns of genomic variation in Collared Pikas (Ochotona collaris).
Identifying the genetic structure of a species and the factors that drive it is an important first step in modern population management, in part because populations evolving from separate ancestral sources may possess potentially different characteristics. This is especially true for climate-sensitive species such as pikas, where the delimitation of distinct genetic units and the characterization of population responses to contemporary and historical environmental pressures are of particular interest. We combined a restriction site-associated DNA sequencing (RADSeq) data set containing 4156 single nucleotide polymorphisms with ecological niche models (ENMs) of present and past habitat suitability to characterize population composition and evaluate the effects of historical range shifts, contemporary climates and landscape factors on gene flow in Collared Pikas, which are found in Alaska and adjacent regions of northwestern Canada and are the lesser-studied of North America's two pika species. The results suggest that contemporary environmental factors contribute little to current population connectivity. Instead, genetic diversity is strongly shaped by the presence of three ancestral lineages isolated during the Pleistocene (~148 and 52 kya). Based on ENMs and genetic data, populations originating from a northern refugium experienced longer-term stability, whereas both southern lineages underwent population expansion - contradicting the southern stability and northern expansion patterns seen in many other taxa. Current populations are comparable with respect to generally low diversity within populations and little-to-no recent admixture. The predominance of divergent histories structuring populations implies that if we are to understand and manage pika populations, we must specifically assess and accurately account for the forces underlying genetic similarity.


The C-terminal domain (CTD) in linker histones antagonizes anti-apoptotic proteins to modulate apoptotic outcomes at the mitochondrion.
The loss of mitochondrial integrity as a consequence of apoptogenic complexes formed on the outer membrane constitutes a key step in controlling progression of apoptotic cascades. Here, we show that multiple members of the linker histone (LH) family of proteins modify apoptotic cascades initiated by the Bcl-2 protein Bak, and impart resistance to its endogenous antagonist Bcl-xL. Our experiments reveal apoptogenic capabilities equivalent to those documented for H1.2 in H1.1 and H1.3 isoforms. Deletion mutants of H1.2 and site-directed mutagenesis of H1.1 and H1.2 implicated the C-terminal domain in apoptogenic activity. In this context, disruption of protein kinase-C activity using chemical inhibitors, dominant-negative approaches and RNA interference coupled with site-directed modifications in H1.1, identified the protein kinase-Cβ1 isoform as a repressor of H1.1/H1.3 apoptogenic activity. Finally, a H1.2 C-terminal tail recombinant attenuated Bcl-xl inhibition of Bak-induced apoptosis, suggesting that the C-terminal domain was necessary and sufficient for apoptogenic functions. Thus, integration with apoptotic intermediates (via C-terminal tail interactions) may constitute a more generalized function of LH isoforms in apoptotic cascades.


A sink-specific H+/monosaccharide co-transporter from Nicotiana tabacum: cloning and heterologous expression in baker's yeast.
A cDNA clone for a monosaccharide transporter (MST1) was isolated from tobacco, which is most strongly expressed in the various sink tissues of mature tobacco plants: roots, flowers, and young leaves. An open reading frame of 1569 bp codes for a protein with 523 amino acids and a calculated molecular weight of 57,717 Da. The protein is homologous to a group of other plant monosaccharide transport proteins from Arabidopsis thaliana and Chlorella kessleri, to human glucose transporters and to Saccharomyces cerevisiae and several bacterial sugar transport proteins. As with these other transporters, the MST1 protein is extremely lipophilic and has 12-putative membrane-spanning domains. Heterologous expression of the MST1 cDNA clone in Saccharomyces cerevisiae allowed its characterization as a putative H+/monosaccharide co-transporter, catalyzing the uptake of hexoses (e.g. D-glucose and D-galactose) or pentoses (e.g. D-xylose) and the energy dependent and uncoupler sensitive accumulation of non-metabolizable substrates (e.g. D-xylose or 3-O-methyl-glucose). Polyclonal antibodies were raised against a fusion protein of beta-galactosidase and the last 27 amino acids of the C-terminus of the MST1 protein. In SDS extracts of transformed yeast cells these antibodies recognize a polypeptide with an apparent molecular weight of 42 kDa, which is absent in extracts from untransformed control cells.


Incidence and epidemiology of irritable bowel syndrome after a large waterborne outbreak of bacterial dysentery.
Postinfectious irritable bowel syndrome (PI-IBS) is a common clinical phenomenon. To better define its incidence and epidemiology, a large cohort study was initiated after the contamination of a municipal water supply led to a large outbreak of acute Escherichia coli 0157:H7 and Campylobacter jejuni gastroenteritis. Local residents were invited to undergo structured assessments at research clinics established 2 years after the outbreak. Permanent adult residents with no prior history of inflammatory bowel disease or IBS were eligible. Standardized questionnaires defined past and current health. The cohort was divided into controls without gastroenteritis, subjects with clinically suspected gastroenteritis, and subjects with only self-reported gastroenteritis that could not be substantiated by another source. A modified Bowel Disease Questionnaire identified IBS according to Rome criteria. The incidence and epidemiology of PI-IBS was characterized. Risk factors were assessed using multiple logistic regression. There were 2069 eligible study participants. Rome I criteria were met by 71 of 701 controls (10.1%) vs 249 of 904 subjects with self-reported gastroenteritis (27.5%) and 168 of 464 subjects with clinically suspected gastroenteritis (36.2%) (all comparisons, P < 001). Independent risk factors for PI-IBS included younger age, female sex, bloody stools, abdominal cramps, weight loss, and prolonged diarrhea. PI-IBS was more likely than sporadic IBS to show diarrhea-predominant features. PI-IBS is common after gastroenteritis from water contamination and often is diarrhea-predominant. Characteristics of the acute illness identify patients at increased risk for PI-IBS.


The use of adhesives in chondrocyte transplantation surgery. Preliminary studies.
This report describes the in-vitro use of mussel adhesive protein (MAP) as a possible adjunct to chondrocyte allograft surgery. Experiments were performed to define the attachment kinetics of chondrocyte onto bone using MAP, and to assess the biocompatibility of this material in vitro. The results indicate that MAP is biocompatible and may have future clinical applications in orthopaedic procedures.


Interplay between low-temperature pathways and light reduction.
Low temperature is one of the major factors that adversely affect crop yields by causing restraints on plant growth and productivity. However, most temperate plants have the ability to acclimate to cooler temperatures. Cold acclimation is a process which increases the freezing tolerance of an organism after exposure to low, non-freezing temperatures. The main trigger is a decrease in temperature levels, but light reduction has also been shown to have an important impact on acquired tolerance. Since the lowest temperatures are commonly reached during the night hours in winter time and is an annually recurring event, a favorable trait for plants is the possibility of sensing an imminent cold period. Consequently, extensive crosstalk between light- and temperature signaling pathways has been demonstrated and in this review interesting interaction points that have been previously reported in the literature are highlighted.


Cellulose-alginate hydrogels and their nanocomposites for water remediation and biomedical applications.
In the last decade, both cellulose and alginate polysaccharides have been extensively utilized for the synthesis of biocompatible hydrogels because of their alluring characteristics like low cost, biodegradability, hydrophilicity, biodegradability, ease of availability and non-toxicity. The presence of abundant hydrophilic functional groups (like carboxyl and hydroxyl) on the surface of cellulose and alginate or their derivatives makes these materials promising candidates for the preparation of hydrogels with appealing structures and characteristics, leading to growing research in water treatment and biomedical fields. These two polysaccharides are typically blended together to improve hydrogels' desired qualities (mechanical strength, adsorption properties, cellulose/alginate yield). So, keeping in view their extensive applicability, in the present review article, recent advances in the development of cellulose/nanocellulose-alginate-based hydrogels and their relevance in water treatment (adsorption of dyes, heavy metals, etc.) and biomedical field (wound healing, tissue engineering, drug delivery) has been reviewed. Further, impact of other inorganic/organic additives in cellulose/nanocellulose-alginate-based hydrogels properties like contaminants adsorption, drug delivery, tissue engineering, etc., has also been studied. Moreover, the current difficulties and future prospects of nanocellulose-alginate-based hydrogels regarding their water purification and biomedical applications are also discussed at the end.


Normalization of deranged signal transduction in lymphocytes of COPD patients by the novel calcium channel blocker H-DHPM.
Investigations on the role of intracellular Ca(2+) ion concentration in the mechanism of development of COPD in smokers and non-smokers were carried out. The intracellular Ca(2+) levels were found to be increased in human lymphocytes in patients with COPD as compared to non-smokers and smokers without COPD. The investigations reveal an association in altered intracellular Ca(2+) regulation in lymphocytes and severity of COPD, by means of significant activation of Protein kinase C and inducible nitric oxide synthase (iNOS). The effect of a novel calcium channel blocker ethyl 4-(4'-heptanoyloxyphenyl)-6-methyl-3,4-dihydropyrimidin-2-one-5-carboxylate (H-DHPM) as a potential candidate for the treatment of COPD was also investigated. H-DHPM treated cells showed a decrease in intracellular Ca(2+) level as compared to the control cells. Molecular studies were carried out to evaluate the expression profile of NOS isoforms in human lymphocytes and it was shown that H-DHPM decreases the increased iNOS in COPD along with reestablishing the normal levels of endothelial nitric oxide synthase (eNOS). The results of H-DHPM were comparable with those of Amlodipine, a known calcium channel blocker. Calcium channel blocker H-DHPM proves to be a potential candidate for the treatment of COPD and further clinical studies are required to prove its role in the treatment of pulmonary hypertension (PH).


Simultaneous computer mapping to facilitate intraoperative localization of accessory pathways in patients with Wolff-Parkinson-White syndrome.
Sixteen patients with the Wolff-Parkinson-White syndrome underwent simultaneous intraoperative computer mapping from multiple sites before surgical division of the accessory pathways. A 16-bipolar electrode band was positioned around the atrioventricular groove. Ventricular epicardial electrograms from single beats were recorded simultaneously during atrial pacing, resulting in maximal preexcitation, and atrial electrograms were recorded during orthodromic supraventricular tachycardia. Four-level transmural plunge needle electrodes were used concomitantly in 3 patients. Electrograms were processed separately using a guarded signal conditioner that isolates, amplifies, filters and analog-to-digitally converts synchronously at 2 kHz with 12-bit accuracy. Digital data were transmitted by fiber optics to a high-density digital recorder and processed with a computer having rapid interactive graphics. Results in the 16 patients revealed 20 distinct Kent bundles. Two patients had only nonsustained supraventricular tachycardia induced intraoperatively and 1 patient manifested intermittent anterograde ventricular preexcitation. Multiple pathways were identified in 4 patients. This simultaneous multiple electrode mapping procedure facilitates intraoperative mapping by requiring only a single beat for analysis of anterograde and retrograde activation times, decreases cardiac manipulation during mapping and obviates the need for cardiopulmonary bypass, and permits analysis of transmural activation patterns. This approach decreases markedly the time required for mapping and permits accurate study of nonsustained arrhythmias as well as rapid identification of multiple accessory pathways.


Guidelines for antiretroviral therapy for HIV infection. Canadian HIV Trials Network Antiretroviral Working Group.
To develop guidelines for health care providers and their HIV-positive patients on the clinical use of antiretroviral agents for HIV infection. Recommendations published in 1996 by an international panel. Improvement in clinical outcomes or in surrogate markers of disease activity. EVIDENCE AND VALUES: The Canadian HIV Trials Network held a workshop on Oct. 19-20, 1996, to develop Canadian guidelines that incorporate information from recent basic and clinical research. Recommendations for the use of antiretroviral drugs in HIV infection are provided for initial therapy, continuing therapy, primary infection, vertical transmission, pediatric therapy and postexposure prophylaxis. The guidelines are based on consensus of the participants attending the workshop: Canadian investigators, clinicians and invited representatives from the community, government and the pharmaceutical industry. They are subject to review and updating as new information on clinical benefits is published. The workshop was organized by the National Centre of the Canadian HIV Trials Network. Unrestricted educational grants were provided by 8 pharmaceutical companies. Additional support was provided from the National AIDS Strategy of Health Canada.


[Clinical features of children with SARS-CoV-2 infection: an analysis of 13 cases from Changsha, China].
To study the clinical features of children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. A retrospective analysis was performed for the clinical data of 13 children with SARS-CoV-2 infection who hospitalized in a Changsha hospital. All 13 children had the disease onset due to family aggregation. Of the 13 children, 2 had no symptoms, and the other 11 children had the clinical manifestations of fever, cough, pharyngeal discomfort, abdominal pain, diarrhea, convulsions, or vomiting. As for clinical typing, 7 had mild type, 5 had common type, and 1 had severe type. The median duration of fever was 2 days in 6 children. All 13 children had normal levels of peripheral blood lymphocyte counts, immunoglobulins, CD4, CD8, and interleukin-6. The median time to clearance of SARS-CoV-2 was 13 days in the nasopharyngeal swabs of the 13 children. Three children presented false negatives for RT-PCR of SARS-CoV-2. SARS-CoV-2 RNA remained detectable in stools for 12 days after the nasopharyngeal swab test yielded a negative result. Abnormal CT findings were observed in 6 children. All 13 children were cured and discharged and they were normal at 2 weeks after discharge. Intra-family contact is the main transmission route of SARS-CoV-2 infection in children, and there is also a possibility of fecal-oral transmission. Mild and common types are the major clinical types in children with SARS-CoV-2 infection, and cytokine storm is not observed. Children with SARS-CoV-2 infection tend to have a good short-term prognosis, and follow-up is needed to observe their long-term prognosis. Multiple nucleic acid tests should be performed for patients with SARS-CoV-2 infection and their close contacts by multiple site sampling.


Five independent combinations of mutations can result in low-affinity penicillin-binding protein 2x of Streptococcus pneumoniae.
Penicillin-binding protein 2x (PBP 2x) of Streptococcus pneumoniae is one of the high-molecular-weight PBPs involved in the development of intrinsic beta-lactam resistance. Point mutations in the PBP 2x genes (pbpX) have now been characterized in five independent spontaneous laboratory mutants in order to identify protein regions which are important for interaction with beta-lactam antibiotics. All mutant genes contained two to four mutations resulting in amino acid substitutions within the penicillin-binding domain of PBP 2x, and none of the mutants carried an identical set of mutations. For one particular mutant, C606, carrying four mutations in pbpX, the mutations at positions 601 and 597 conferred first- and second-level resistance when introduced into the susceptible parent strain S. pneumoniae R6. However, the other two mutations, at amino acid positions 289 and 422, which were originally selected at the fifth and sixth isolation steps, did not contribute at all to resistance in similar experiments. This suggests that they are phenotypically expressed only in combination with mutations in other genes. Three PBP 2x regions were mutated in from two to all four mutants carrying a low-affinity PBP 2x. However, in a fifth mutant containing a PBP 2x with apparent zero affinity for beta-lactams, the three mutations in pbpX mapped at entirely different positions. This demonstrates that different mutational pathways exist for remodeling this PBP during resistance development.


Ototoxin-induced cellular damage in neuromasts disrupts lateral line function in larval zebrafish.
The ototoxicity of a number of marketed drugs is well documented, and there is an absence of convenient techniques to identify and eliminate this unwanted effect at a pre-clinical stage. We have assessed the validity of the larval zebrafish, or more specifically its lateral line neuromast hair cells, as a microplate-scale in vivo surrogate model of mammalian inner ear hair cell responses to ototoxin exposure. Here we describe an investigation of the pathological and functional consequences of hair cell loss in lateral line neuromasts of larval zebrafish after exposure to a range of well known human and non-human mammalian ototoxins. Using a previously described histological assay, we show that hair cell damage occurs in a concentration-dependent fashion following exposure to representatives from a range of drug classes, including the aminoglycoside antibiotics, salicylates and platinum-based chemotherapeutics, as well as a heavy metal. Furthermore, we detail the optimisation of a semi-automated method to analyse the stereotypical startle response in larval zebrafish, and use this to assess the impact of hair cell damage on hearing function in these animals. Functional assessment revealed robust and significant attenuation of the innate startle, rheotactic and avoidance responses of 5 day old zebrafish larvae after treatment with a number of compounds previously shown to induce hair cell damage and loss. Interestingly, a startle reflex (albeit reduced) was still present even after the apparent complete loss of lateral line hair cell fluorescence, suggesting some involvement of the inner ear as well as the lateral line neuromast hair cells in this reflex response. Collectively, these data provide evidence to support the use of the zebrafish as a pre-clinical indicator of drug-induced histological and functional ototoxicity.


Electromagnetic optimization of the integrated magnetorheological jet polishing tool and its application in millimeter-scale discontinuous structure processing.
To meet the special demands in small-scale discontinuous optical surface fabrication, the integrated magnetorheological jet polishing (IMJP) tool with multiple motion degrees is introduced in this paper. Four jetting models are implemented and investigated by means of the IMJP tool for practical manufacture. To ensure steady jetting in a long distance, ideal distribution characteristics of the magnetic field in the structure is proposed, based on electromagnetic theory. The magnetic field distribution is simulated subsequently using the finite element analysis method, and three key parameters in the IMJP tool structure are optimized through the simulations. The actual magnetic flux density is measured and spot polishing experiments are conducted in different standoff distances, verifying the effectiveness of the optimization. A processing experiment of a millimeter scale structure with milling tool marks located on a surface with nonuniform curvatures was conducted using the IMJP tool. The roughness of the polishing region converged to 4.86 nm Ra from a low initial quality after processing, and the tool marks have been efficiently removed. The experimental results reveal the reliability of the setup design and the remarkable roughness convergence ability of the IMJP tool for small complex structures.


[Monitoring for contamination of food commodities and food products with toxic elements].
The results of hygienic assessment of toxic elements in food produced locally. The estimation of the levels of foodborne contaminants (lead, cadmium, arsenic, copper, zinc, mercury) on the basis of data on average food consumption has been presented. That the traditional products of mass consumption (dairy products, vegetables) were shown to make most significant contribution to the overall burden of priority contaminants. Child population of Saratov region has a greater risk to health from the peroral route of toxic elements in food.


Addition of whole, semiskimmed, and skimmed bovine milk reduces the total antioxidant capacity of black tea.
Epidemiological studies have shown that populations consuming fruits, vegetables, tea, cocoa, and red wine have lower incidences of cardiovascular disease, certain cancers, and eye disease. These health effects have largely been attributed to the polyphenol content of the foods and drinks studied. Black tea is rich in a range of polyphenolic compounds that could potentially have health-promoting properties. The scale of consumption of tea in the United Kingdom means that it could be an appropriate vehicle for increasing the antioxidant activity and polyphenol content of human plasma. However, it is common practice in the United Kingdom to add milk to tea, and some studies have suggested that this may decrease the overall antioxidant capacity. The objective of the present study was to analyze and compare the antioxidant capacity of 5 brands of tea and to test the hypothesis that the addition of different volumes of whole milk, semiskimmed, and skimmed milk may affect the antioxidant capacity. Each of the teas analyzed was a significant source of antioxidants. The addition of 10, 15, and 20 mL of whole, semiskimmed, and skimmed bovine milk to a 200-mL tea infusion decreased the total antioxidant capacity of all the brands of tea. Skimmed milk decreased the total antioxidant capacity of the tea infusion significantly (P < .05) more than either whole milk or semiskimmed milk. We conclude that black tea is a valuable source of antioxidants and that the effect of milk on the total antioxidant capacity may be related to the fat content of the milk.


In vivo microdialysis sampling of cytokines from rat hippocampus: comparison of cannula implantation procedures.
Cytokines are signaling proteins that have been of significant importance in the field of immunology, since these proteins affect different cells in the immune system. In addition to their immune system significance, these proteins have recently been referred to as a third chemical communication network within the CNS. The role that cytokines play in orchestrating the immune response within tissues after a mechanical injury leads to potential complications if the source of cytokines (i.e., trauma vs disease) is of interest. Microdialysis sampling has seen wide use in collection of many different solutes within the CNS. Yet, implantation of microdialysis guide cannulas and the probes creates tissue injury. In this study, we compared the differences in cytokine levels in dialysates from 4 mm, 100 kDa molecular weight cutoff (MWCO) polyethersulfone membrane microdialysis probes implanted in the hippocampus of male Sprague-Dawley rats. Comparisons were made between animals that were dialyzed immediately after cannula implantation (day 0), 7 days post cannula implantation (day 7), and repeatedly sampled on day 0 and day 7. Multiplexed bead-based immunoassays were used to quantify CCL2 (MCP-1), CCL3 (MIP-1α), CCL5 (RANTES), CXCL1 (KC/GRO), CXCL2 (MIP-2), IL-1β, IL-6, and IL-10 in dialysates. Differences in cytokine concentrations between the different treatment groups were observed with higher levels of inflammatory cytokines measured in day 7 cannulated animals. Only CCL3 (MIP-1α), CXCL1 (KC/GRO), CXCL2 (MIP-2), and IL-10 were measured above the assay limits of detection for a majority of the dialysates, and their concentrations were typically in the low to high (10-1000) picogram per milliliter range. The work described here lays the groundwork for additional basic research studies with microdialysis sampling of cytokines in rodent CNS.