An integrated genetic and functional analysis of the role of type II transmembrane serine proteases (TMPRSSs) in hearing loss.
Building on our discovery that mutations in the transmembrane serine protease, TMPRSS3, cause nonsyndromic deafness, we have investigated the contribution of other TMPRSS family members to the auditory function. To identify which of the 16 known TMPRSS genes had a strong likelihood of involvement in hearing function, three types of biological evidence were examined: 1) expression in inner ear tissues; 2) location in a genomic interval that contains a yet unidentified gene for deafness; and 3) evaluation of hearing status of any available Tmprss knockout mouse strains. This analysis demonstrated that, besides TMPRSS3, another TMPRSS gene was essential for hearing and, indeed, mice deficient for Hepsin (Hpn) also known as Tmprss1 exhibited profound hearing loss. In addition, TMPRSS2, TMPRSS5, and CORIN, also named TMPRSS10, showed strong likelihood of involvement based on their inner ear expression and mapping position within deafness loci PKSR7, DFNB24, and DFNB25, respectively. These four TMPRSS genes were then screened for mutations in affected members of the DFNB24 and DFNB25 deafness families, and in a cohort of 362 sporadic deaf cases. This large mutation screen revealed numerous novel sequence variations including three potential pathogenic mutations in the TMPRSS5 gene. The mutant forms of TMPRSS5 showed reduced or absent proteolytic activity. Subsequently, TMPRSS genes with evidence of involvement in deafness were further characterized, and their sites of expression were determined. Tmprss1, 3, and 5 proteins were detected in spiral ganglion neurons. Tmprss3 was also present in the organ of Corti. TMPRSS1 and 3 proteins appeared stably anchored to the endoplasmic reticulum membranes, whereas TMPRSS5 was also detected at the plasma membrane. Collectively, these results provide evidence that TMPRSS1 and TMPRSS3 play and TMPRSS5 may play important and specific roles in hearing.


Tutor-led teaching of procedural skills in the skills lab: Complexity, relevance and teaching competence from the medical teacher, tutor and student perspective.
In current medical curricula, the transfer of procedural skills has received increasing attention. Skills lab learning and tutor-led teaching have become an inherent part of all medical curricula at German medical faculties. In 2011, the initial basis for the classification of clinical skills in medical school was created by the German Association for Medical Education (GMA) Committee's consensus statement on procedural skills. As a recommendation for medical curricula, the National Competency-based Catalogue of Learning Objectives (NKLM, 2015) lists procedural skills according to their curriculum integration and competency level. However, classification in regard to the perceived complexity, relevance, or teaching competency is still lacking. The present study aimed to investigate procedural skills taught at the Medical Faculty of Heidelberg in regard to their complexity, relevance, and required teaching skills. To achieve this aim (1) the specific procedural skills in terms of complexity, that is, the degree of difficulty, and (2) the perceived relevance of taught procedural skills for studying and subsequent medical profession as well as (3) the personal preparation and required teaching skills were assessed in medical teachers, tutors and students. During the winter semester 2014/2015, the evaluations of all medical teachers, student tutors, and medical students in the skills lab teaching departments of internal medicine, surgery, pediatrics, gynecology, and otorhinolaryngology at the Medical Faculty of Heidelberg were assessed via a quantitative cross-sectional questionnaire survey using 7-point Likert scales. The questionnaire comprised four item sets concerning 1) demographic details, 2) procedural skill complexity, 3) practical relevance, and 4) required preparation and teaching skills. Descriptive, quantitative analysis was used for questionnaire data. The survey included the data from 17 of 20 physicians (return rate: 85 %), 10 of 10 student tutors (return rate: 100 %) and a total of 406 of 691 students (return rate: 58.8 %). In terms of complexity and relevance, no major differences between medical teachers, tutors, and students were found. Procedural skills, assigned to the competence level of final year medical education in the NKLM, were also perceived as more complex than other skills. All skills were considered equally relevant, and student tutors were seen to have equally competent teaching skills as experienced medical teachers. This study largely underpins the NKLM's classification of procedural skills. The complexity assessment allows for conclusions to be drawn as to which skills are perceived to require particularly intensive training. Finally, our study corroborates extant findings that student tutors are apt at teaching procedural skills if they have been properly trained.


S6 phosphorylation results from prothoracicotropic hormone stimulation of insect prothoracic glands: a role for S6 kinase.
The insect prothoracic glands are the source of steroidal molting hormone precursors and the glands are stimulated by a brain neuropeptide, prothoracicotropic hormone (PTTH). Previous work from this laboratory revealed that PTTH acts via a cascade including Ca2+/calmodulin activation of adenylate cyclase, protein kinase A, and the subsequent phosphorylation of a 34 kDa protein (p34) hypothesized, but not proven, to be the S6 protein of the 40S ribosomal subunit. The immunosuppressive macrolide, rapamycin, is a potent inhibitor of cell proliferation, a signal transduction blocker, and also prevents ribosomal S6 phosphorylation in mammalian systems. We demonstrate here that rapamycin inhibited PTTH-stimulated ecdysteroidogenesis in vitro by the prothoracic glands of the tobacco hornworm, Manduca sexta, with half-maximal inhibition at a concentration of about 5 nM. At concentrations above 5 nM, there was a 75% inhibition of ecdysteroid biosynthesis. Similar results were observed with the calcium ionophore (A23187), a known stimulator of ecdysteroidogenesis. Most importantly, the inhibition of ecdysteroid biosynthesis was accompanied by the specific inhibition of the phosphorylation of p34, indicating that p34 indeed is ribosomal protein S6. In vivo assays revealed that injection of rapamycin into day 6 fifth instar larvae resulted in a decreased hemolymph ecdysteroid titer and a dose-dependent delay in molting and metamorphosis. When S6 kinase (S6K) activity was examined using rapamycin-treated prothoracic glands as the enzyme source and a synthetic peptide (S6-21) or a 40S ribosomal subunit fraction from Manduca tissues as substrate, the date revealed that rapamycin inhibited S6K activity.(ABSTRACT TRUNCATED AT 250 WORDS)


The phosphorylation of eukaryotic initiation factor eIF4E in response to phorbol esters, cell stresses, and cytokines is mediated by distinct MAP kinase pathways.
Initiation factor eIF4E binds to the 5'-cap of eukaryotic mRNAs and plays a key role in the mechanism and regulation of translation. It may be regulated through its own phosphorylation and through inhibitory binding proteins (4E-BPs), which modulate its availability for initiation complex assembly. eIF4E phosphorylation is enhanced by phorbol esters. We show, using specific inhibitors, that this involves both the p38 mitogen-activated protein (MAP) kinase and Erk signaling pathways. Cell stresses such as arsenite and anisomycin and the cytokines tumor necrosis factor-alpha and interleukin-1beta also cause increased phosphorylation of eIF4E, which is abolished by the specific p38 MAP kinase inhibitor, SB203580. These changes in eIF4E phosphorylation parallel the activity of the eIF4E kinase, Mnk1. However other stresses such as heat shock, sorbitol, and H2O2, which also stimulate p38 MAP kinase and increase Mnk1 activity, do not increase phosphorylation of eIF4E. The latter stresses increase the binding of eIF4E to 4E-BP1, and we show that this blocks the phosphorylation of eIF4E by Mnk1 in vitro, which may explain the absence of an increase in eIF4E phosphorylation under these conditions.


Circadian expression of clock genes in the rat eye and brain.
The light sensing system in the eye directly affects the circadian oscillator in the mammalian suprachiasmatic nucleus (SCN). To investigate this relationship in the rat, we examined the circadian expression of clock genes in the SCN and eye tissue during a 24 h day/night cycle. In the SCN, rPer1 and rPer2 mRNAs were expressed in a clear circadian rhythm like rCry1 and rCry2 mRNAs, whereas the level of BMAL1 and CLOCK mRNAs decreased during the day and increased during the night with a relatively low amplitude. It seems that the clock genes of the SCN may function in response to a master clock oscillation in the rat. In the eye, the rCry1 and rCry2 were expressed in a circadian rhythm with an increase during subjective day and a decrease during subjective night. However, the expression of Opn4 mRNA did not exhibit a clear circadian pattern, although its expression was higher in daytime than at night. This suggests that cryptochromes located in the eye, rather than melanopsin, are the major photoreceptive system for synchronizing the circadian rhythm of the SCN in the rat.


[Vaccination priorities for traveller's children].
Routine, recommended and required immunization are important for traveller's children. All required immunization. The most frequent vaccine vaccine preventable infection travellers to developing counties in hepatitis A. Influenza is estimated to be 1%. Routine immunization against poliomyelitis is important for travel to north Africa and parts of Asia. It should be considered that many immunizations are recommended for special risk groups only. If health professionals do not comply with rule, serious problems my arise as a traveller my be refused entry to the country.


Chronic illness and loneliness in older adulthood: The role of self-protective control strategies.
This study examined whether levels of chronic illness predict enhanced feelings of loneliness in older adulthood. In addition, it investigated whether engagement in health-related self-protection (e.g., positive reappraisals), but not in health engagement control strategies (e.g., investment of time and effort), would buffer the adverse effect of chronic illness on older adults' feelings of loneliness. Loneliness was examined repeatedly in 2-year intervals over 8 years in a longitudinal study of 121 community-dwelling older adults (Time 1 age = 64 to 83 years). In addition, levels of chronic illness, health-related control strategies, and sociodemographic variables were assessed at baseline. Growth-curve models showed that loneliness linearly increased over time and that this effect was observed only among participants who reported high, but not low, baseline levels of chronic illness. In addition, health-related self-protection, but not health engagement control strategies, buffered the adverse effect of chronic illness on increases in loneliness. Loneliness increases in older adulthood as a function of chronic illness. Older adults who engage in self-protective strategies to cope with their health threats might be protected from experiencing this adverse effect.


Weight Loss After Laparoscopic Sleeve Gastrectomy Ameliorates the Cardiac Remodeling in Obese Chinese.
This study aimed to investigate the impact of weight loss after laparoscopic sleeve gastrectomy (LSG) on cardiac structural and functional remodeling in obese Chinese. A total of 44 obese participants were enrolled consecutively. The physical, laboratory, electrocardiographic, and echocardiographic parameters of pre-and postoperative were recorded. The average follow-up time was 12.28 ± 5.80 months. The body mass index (BMI) of the patients with obesity was decreased from 41.6 ± 7.44 to 30.3 ± 5.73kg/m2 (P<0.001) after LSG. The systolic and diastolic blood pressure of the subjects was significantly reduced from 137.9 ± 15.7mmHg to 123.0 ± 16.0 and 83.4 ± 10.8 to 71.3 ± 11.7mmHg (P<0.001), respectively. The levels of fasting insulin and fasting blood glucose were significantly decreased (38.8 ± 32.1 to 8.43 ± 4.16 mU/L, P<0.001; 6.95 ± 2.59 to 4.64 ± 0.50mmol/L, P<0.001). Total cholesterol (TC, 4.66 ± 0.84 to 4.23 ± 0.75mmol/L, P<0.001) and triglyceride (TG, 1.92 ± 1.21 to 0.85 ± 0.30mmol/L, P<0.001) decreased significantly. Cardiovascular geometric parameters including aortic sinus diameter (ASD, 32.9 ± 2.83mm to 32.0 ± 3.10mm, P<0.05), left atrial diameter (LAD, 38.8 ± 4.03 to 36.2 ± 4.12mm, P<0.001), and interventricular septum thickness(IVS, 10.2 ± 0.93 to 9.64 ± 0.89mm, P<0.001) were significantly reduced. The ratio of weight loss (RWL) was positively correlated with the changes of LAD. The change of IVS was negatively correlated with the change of fasting blood glucose (GLU). Weight loss after LSG could effectively improve cardiac structural, but not functional, abnormality in obese Chinese.


Development of mental health and psychosocial support (MHPSS) guidelines for deaf and hard of hearing children in the Gaza Strip.
Deaf and hard of hearing children in the Gaza Strip may be at risk of mental health conditions and psychological distress, as a result of social exclusion and limited accessible communication. This article presents the process and research methods used to develop guidelines for schools in the Gaza Strip on mental health and psychosocial support for deaf and hard of hearing children. The process was guided by the GIN-McMaster guideline development checklist across four steps: (1) priority settings; (2) searching for evidence; (3) developing recommendations; (4) evaluation. Priority setting was spearheaded by local and international researchers, and a local steering committee comprised of deaf and hard of hearing representatives, school administration and staff, mental health specialists, family members and government officials. In searching for evidence, and in order to generate evidence-based recommendations for the guidelines, we utilised a scoping review of global mental health support for deaf and hard of hearing children and qualitative research with deaf and hard of hearing children and adults, families and teachers. Two pilot studies were conducted in mainstream and specialist educational settings as way of evaluation. The scoping review and qualitative research identified various content for the guidelines, including the importance of information on disability and deafness, promoting social inclusion and self-esteem, and accessible learning environments. The pilot studies demonstrated feasibility and acceptability among teachers and deaf and hard of hearing children, although teachers need sufficient support and resources to implement. Now finalised, the guidelines are being distributed to schools in the Gaza Strip to support the mental health and wellbeing of deaf and hard of hearing children.


Front and Back Flipping for Neurobiology! Developing a Hybrid Upper-Division Lab Course.
Flipped instruction using online enrichment is a popular way to enhance active learning in the laboratory setting. Graduate student teaching assistants at University of California, Irvine flipped an upper division undergraduate neurobiology and behavior lab using the new online software platform "Rocketmix." The following research study compares the impact of pre-lab online instruction (front flipping) and post-lab online instruction (back flipping) on student exam performance. We describe a novel method for unbiased categorization of exam questions by degree of difficulty. Multi-choice instruction encourages students to consider all distractors and discourages verbal cues and process of elimination techniques. Eighteen identical questions were evenly distributed across exam versions with multiple choice instruction (single answer) or a more challenging multi-choice instruction (more than one answer). Student performance on multiple choice questions were used to categorize the degree of difficulty of questions that were presented in multi-choice format. Our findings reveal that pre-lab instruction resulted in better student performance compared with post-lab instruction on questions of moderate difficulty. This effect was significant for both male and female students. Student survey data on the flipped lab format is provided, indicating that students appreciated the online instructional modules, finding them both informative and useful during lab exercises and exams.


Metabolic routes along digestive system of licorice: multicomponent sequential metabolism method in rat.
This study was conducted to establish the multicomponent sequential metabolism (MSM) method based on comparative analysis along the digestive system following oral administration of licorice (Glycyrrhiza uralensis Fisch., leguminosae), a traditional Chinese medicine widely used for harmonizing other ingredients in a formulae. The licorice water extract (LWE) dissolved in Krebs-Ringer buffer solution (1 g/mL) was used to carry out the experiments and the comparative analysis was performed using HPLC and LC-MS/MS methods. In vitro incubation, in situ closed-loop and in vivo blood sampling were used to measure the LWE metabolic profile along the digestive system. The incubation experiment showed that the LWE was basically stable in digestive juice. A comparative analysis presented the metabolic profile of each prototype and its corresponding metabolites then. Liver was the major metabolic organ for LWE, and the metabolism by the intestinal flora and gut wall was also an important part of the process. The MSM method was practical and could be a potential method to describe the metabolic routes of multiple components before absorption into the systemic blood stream. Copyright © 2015 John Wiley & Sons, Ltd.


Differences Between Patients with and without Atherosclerosis in Expression Levels of Inflammatory Mediators in the Adipose Tissue Around the Coronary Artery.
Perivascular adipose tissue (PVAT) secretes large amounts of inflammatory mediators and plays a certain role in atherosclerosis formation from the exterior of the vessel. In the present study, we examined the expression level of inflammation-related mediators using adipose tissue samples harvested from patients with and without coronary artery disease (CAD). The subjects were 23 patients who underwent elective coronary bypass surgery (CAD group) and 17 patients who underwent elective mitral valve surgery (non-CAD group) between January 2017 and March 2018. The adipose tissue was harvested from three sites: the ascending aorta (AO), subcutaneous fat (SC), and pericoronary artery (CO) for the measurement of the expression levels of interleukin (IL) -1β, IL-6, IL-10, tumor necrosis factor (TNF) -α, interferon (INF) -γ, and arginase (Arg) -1. In both the non-CAD and CAD groups, the expression levels of all mediators, except Agr-1, which showed a tendency to have higher levels in the SC than in the AO and CO, tended to upregulate in the AO than in the SC and CO. The CAD group had higher values of almost all mediators, except Arg-1. Most importantly, the expression levels of IL-1β, IL-6, and IL-10 in the coronary artery were significantly higher in the CAD group. The expression levels of inflammatory mediators in the pericoronary adipose tissue were significantly higher in the CAD than in the non-CAD group. The adipose tissue appears to influence atherosclerosis formation from the exterior of the coronary artery.


Genotoxic and inflammatory effects of depleted uranium particles inhaled by rats.
Depleted uranium (DU) is a radioactive heavy metal coming from the nuclear industry and used in numerous military applications. Uranium inhalation can lead to the development of fibrosis and neoplasia in the lungs. As little is known concerning the molecular processes leading to these pathological effects, some of the events in terms of genotoxicity and inflammation were investigated in rats exposed to DU by inhalation. Our results show that exposure to DU by inhalation resulted in DNA strand breaks in broncho-alveolar lavage (BAL) cells and in increase of inflammatory cytokine expression and production of hydroperoxides in lung tissue suggesting that the DNA damage was in part a consequence of the inflammatory processes and oxidative stress. The effects seemed to be linked to the doses, were independent of the solubility of uranium compounds and correlating with the type of inhalation. Repeated inhalations seemed to induce an effect of potentiation in BAL cells and also in kidney cells. Comet assay in neutral conditions revealed that DNA damage in BAL cells was composed partly by double strands breaks suggesting that radiation could contribute to DU genotoxic effects in vivo. All these in vivo results contribute to a better understanding of the pathological effect of DU inhalation.


PASTASpark: multiple sequence alignment meets Big Data.
One basic step in many bioinformatics analyses is the multiple sequence alignment. One of the state-of-the-art tools to perform multiple sequence alignment is PASTA (Practical Alignments using SATé and TrAnsitivity). PASTA supports multithreading but it is limited to process datasets on shared memory systems. In this work we introduce PASTASpark, a tool that uses the Big Data engine Apache Spark to boost the performance of the alignment phase of PASTA, which is the most expensive task in terms of time consumption. Speedups up to 10× with respect to single-threaded PASTA were observed, which allows to process an ultra-large dataset of 200 000 sequences within the 24-h limit. PASTASpark is an Open Source tool available at https://github.com/citiususc/pastaspark. email@example.com. Supplementary data are available at Bioinformatics online.


Methodology effects on determining the energy concentration and the apparent total tract digestibility of components in diets fed to growing pigs.
An experiment was conducted to investigate the effects of different diet formulations: F1 (Two complicated basal diets containing different crude protein levels plus tested feedstuff) vs F2 (A simple corn soybean meal [SBM] basal diet plus tested feedstuff) combined with total collection (TC) or chromic oxide (Cr2O3) marker or acid-insoluble ash (AIA) marker method, and freeze-dry or oven-dry (OD) technique on estimation of nutrient digestibility in diets fed to growing pigs. In F1, twelve barrows were allocated to two 6×4 Youden Squares. The treatment diets included a high protein basal (HPB) diet, a low protein basal (LPB) diet, a corn diet and a wheat bran (WB) diet formulated based on the HPB diet, and a SBM diet and a rapeseed meal (RSM) diet formulated based on the LPB diet. In F2, eight barrows were allocated to two 4×4 Latin Squares. The treatment diets included a corn basal diet, a SBM basal diet formulated based on the corn diet, and a WB diet and a RSM diet formulated based on the SBM diet. Concentration of digestible (DE) and metabolizable energy (ME), and the apparent total tract digestibility of gross energy, ash, neutral detergent fibre, and acid detergent fibre determined by Cr2O3 marker method were greater than those determined by TC and AIA marker methods in HPB, LPB, and RSM diets formulated by F1 and in corn diet formulated by F2 (p<0.05). The DE values in WB and both DE and ME values in SBM and RSM estimated using F1 were greater than those estimated using F2 (p<0.05). From the accuracy aspect, the AIA marker or TC method combined with OD technique is recommended for determining the energy concentration and nutrient digestibility of components in diets fed to growing pigs.


Hydroxyeyhyl starch: Controversies revisited.
Hydroxyethyl starch (HES) family has been one of the cornerstones in fluid management for over four decades. Recent evidence from clinical studies and meta-analyses has raised few concerns about the safety of these fluids, especially in certain subpopulations of patients. High-quality clinical trials and meta-analyses have emphasized nephrotoxic effects, increased risk of bleeding, and a trend toward higher mortality in these patients after the use of HES solutions. Scientific evidence was derived from international guidelines, aggregated research literature, and opinion-based evidence was obtained from surveys and other activities (e.g., internet postings). On critical analysis of the current data available, it can be summarized that further large scale trials are still indicated before HES can be discarded.


Ischemic strokes in a young patient with dermatomyositis, systemic lupus erythematosus and secondary antiphospholipid syndrome mimicking herpetic encephalitis.
A 44-year-old right-handed Caucasian male was initialy diagnosed in 2007 with dermatomyositis (DM) and in 2009 with systemic lupus erythematosus (SLE) (overlap syndrome). He was treated with Methylprednisolone and Hydroxychloroquine. He interrupted the treatment in the last three years. The patient presented with fever (39.8 degrees C), left zoster ophthalmicus, headache and psychomotor agitation. The cerebral CT scan showed left hemispheric hypodense lesions. Herpetic encephalitis was suspected. The patient was referred to the Institute of Infectious Diseases. The patient's neurological status worsened, he presented spastic tetraparesis and aphasia. DW-MRI, ADC, DS and AngioMRI were done, the patient proved to have an ischemic stroke due to acute thrombosis of the left internal carotid artery and multiple watershed infarctions. An infectious pathology, including HSV-1, was excluded by PLEX ID performed from CSF. Acyclovir, anti vitamin K, steroidal intravenous pulse therapy was started. The patient was referred after two weeks to the Department of Neurology. Mild inflammatory syndrome, tests for anti-double stain DNA (dsDNA), anti-Sm, anti-SSA, IgM and IgG anti-cardiolipin antibodies and lupus anticoagulant were positive. He was currently treated with Methylprednisolone (48 mg/d), anti vitamin K, statin, symptomatics. The outcome was favorable, with good laboratory response. Overlap syndrome may be associated with a significant increase in the risk of stroke. Our case presented without clinically susceptible symptoms of stroke but found to have stroke after neurological assessment associated with overlap syndrome (DM and SLE).


Deuterium NMR of Val1...(2-2H)Ala3...gramicidin A in oriented DMPC bilayers.
Deuterium NMR is used to study the selectively labeled Val1...(2-2H)Ala3...gramicidin A molecule to investigate the structure and dynamics of the C alpha-2H bond in the Ala3 residue of gramicidin. Val1...(2-2H)Ala3...gramicidin A is synthesized, purified, and characterized and then incorporated into oriented bilayers of dimyristoylphosphatidylcholine sandwiched between glass coverslips. Phosphorus NMR line shapes obtained from this sample are consistent with the presence of the bilayer phase and indicate that no nonbilayer phases are present in significant amounts. Deuterium NMR line shapes obtained from this sample indicate that the motional axis of the gramicidin Ala3 residue is parallel to the coverslip normal, that the distribution of motional axis orientations has a width of 2 degrees, and that only one major conformational and dynamical state of the Ala3 C alpha-2H bond is observed on the NMR time scale. Furthermore, the Ala3 C alpha-2H bond angle relative to the motional axis is 19-20 degrees if fast axial rotation is assumed to be the only motion present but is less than or equal to 19-20 degrees in the absence of such an assumption. This result indicates that various double-stranded, helical dimer models are very unlikely to represent the structure of gramicidin in the sample studied but that the single-stranded, beta 6.3 helical dimer models are consistent with the experimental data. However, a definitive distinction between the left-handed, single-stranded, beta 6.3 helical dimer model and the right-handed, single-stranded, beta 6.3 helical dimer model cannot be made on the basis of the experimental data obtained in this study.


Cyr61 and YB-1 are novel interacting partners of uPAR and elevate the malignancy of triple-negative breast cancer.
The triple-negative breast cancer (TNBC) is a very aggressive tumor type often occurring in young women and is associated with a bad prognosis for the patients. TNBC lacks established targets for breast cancer therapy, such as the estrogen receptor (ER), progesterone receptor (PR) and the human epidermal growth factor receptor 2 (HER2). Therefore, novel therapeutic targets and strategies are needed for an improved treatment of this breast cancer subtype. TNBC and respective cell lines often overexpress proteins of the urokinase plasminogen activator system (uPAS) including uPA, its receptor uPAR and inhibitor PAI-1, which together with co-factors contribute to the malignancy of TNBC. Here, two novel interacting partners of uPAR, the cysteine-rich angiogenic inducer 61 (Cyr61) and the Y-box-binding protein 1 (YB-1) were identified and their differential expression demonstrated in TNBC cells as well as in tumors. In the TNBC cohort, both interactors significantly correlated with expression levels of cathepsin B, c-Met and the tumor grade. In addition, expression levels of Cyr61 significantly correlated with cathepsin D (p=0.03), insulin receptor (p≤0.001), insulin-like growth factor receptor 1 (IGF1R, p=0.015) and also with YB-1 (p=0.0004) levels. The interactions of uPAR with Cyr61 significantly correlated with expression levels of tumor-promoting biomarkers including plasminogen (p=0.0014), cathepsin B (p=0.032), c-Met (p=0.0192) as well as with the tumor grade (p=0.02). In multivariate survival analysis, YB-1 showed independent prognostic value (p=0.01). As the novel interacting partners, also together with uPAR, contribute to tumor progression and metastasis, both may be potential therapeutic targets in breast cancer.


Endoscopic transtympanic cartilage push-through myringoplasty without tympanomeatal flap elevation for tympanic membrane perforation.
The elevation of the tympanomeatal flap in endoscopic myringoplasty will cause considerable tissue damage. To analyze anatomic and audiological results of tympanic membrane perforation underwent endoscopic transtympanic cartilage push-through myringoplasty without tympanomeatal flap elevation (EPM) and their relationship with the size of perforation. A clinical retrospective study was performed on 75 cases of tympanic membrane perforation that underwent EPM from January 2019 to March 2021. Graft success and hearing outcomes were evaluated 3 months after surgery. The overall graft success rate for EPM was 94.7% (71/75). The total rate of hearing success, postoperative ABG ≤ 20 dB was achieved in 96.0% (72/75). The overall mean AC threshold of 35.1 ± 5.6 dB was lowered to 25.0 ± 4.8 dB postoperatively (p < .01). The mean pre- and postoperative ABG of all patients were 20.5 ± 4.6 dB and 10.4 ± 3.9 dB (p < .01), respectively. The graft success rates for the small, middle and large perforations groups were 100% (11/11), 100% (34/34) and 86.7% (26/30), respectively. It is revealed that EPM is an effective method to repair perforation of tympanic membrane. The size of the tympanic membrane perforation may be a risk factor for perforation healing and hearing recovery, although EPM is available for large perforations.


The signaling pathway in photoresponses that may be mediated by visual pigments in erythrophores of Nile tilapia.
The ability to increase the synthesis or vary the distribution of pigment in response to light is an important feature of many pigment cells. Unlike other light-sensitive pigment cells, erythrophores of Nile tilapia change the direction of pigment migration depending on the peak wavelength of incident light: light near 365, 400 or 600 nm induces pigment aggregation, while dispersion occurs in response to light at 500 nm. How these phenomena are achieved is currently unknown. In the present study, the phototransduction involved in the pigment dispersion caused by light at 500 nm or the aggregation by light at 600 nm was examined, using pertussis toxin, cholera toxin, blockers of ion channels, various chemicals affecting serial steps of signaling pathways and membrane-permeable cAMP analog. The results show that light-induced bidirectional movements in tilapia erythrophores may be controlled by cytosolic cAMP levels via Gi- or Gs-type G proteins. In addition, RT-PCR demonstrated for the first time the expression of mRNAs encoding red and green opsins in tilapia fins, only where erythrophores exist. Here, we suggest that multiple cone-type visual pigments may be present in the erythrophores, and that unique cascades in which such opsins couple to Gi or Gs-type G proteins are involved in the photoresponses in these pigment cells. Thus, tilapia erythrophore system seems to be a nice model for understanding the photoresponses of cells other than visual cells.


Decomposition analysis of the decline in binary and triad undernutrition among preschool children in India.
To examine the socio-demographic factors associated with the decline in undernutrition among preschool children in India from National Family Health Survey (NFHS)-3, 2005-06 to NFHS- 5, 2019-21. For this study data were obtained from India's nationally representative datasets such as NFHS-3 and NFHS-5. The outcome variables for this study were Binary undernutrition which were defined as the coexistence of anemia and either stunting or wasting and Undernutrition triad which were defined as the presence of Iron deficiency anemia, stunting and wasting, respectively. Decomposition analysis was used to study the factors responsible for a decline in undernutrition. This method was employed to understand how these factors contributed to the decline in undernutrition whether due to change in the composition (change in the composition of the population) or propensity (change in the health-related behaviour of the population) of the population over a period of 16 years. Results showed that rate, which contributes 85.26% and 65.64%, respectively, to total change, was primarily responsible for a decline in both binary undernutrition and undernutrition triad. Reduction in Binary undernutrition was mainly explained by the change in the rate of education level of the mothers and media exposer during the inter-survey period. On the other hand, the decline in the Undernutrition triad can be explained by household wealth index, mother's education, birth order and a change in people's knowledge or practice about the preceding birth interval. Identifying important factors and understanding their relationship with the decline of undernutrition can be beneficial for reorienting nutrition-specific policies to achieve the targets of the Sustainable Development Goals by 2030.


Single Molecule Study on Polymer-Nanoparticle Interactions: The Particle Shape Matters.
The study on the nanoparticle-polymer interactions is very important for the design/preparation of high performance polymer nanocomposite. Here we present a method to quantify the polymer-particle interaction at single molecule level by using AFM-based single molecule force spectroscopy (SMFS). As a proof-of-concept study, we choose poly-l-lysine (PLL) as the polymer and several different types of polyoxometalates (POM) as the model particles to construct several different polymer nanocomposites and to reveal the binding mode and quantify the binding strength in these systems. Our results reveal that the shape of the nanoparticle and the binding geometry in the composite have significantly influenced the binding strength of the PLL/POM complexes. Our dynamic force spectroscopy studies indicate that the disk-like geometry facilitate the unbinding of PLL/AlMo6 complexes in shearing mode, while the unzipping mode becomes dominate in spherical PLL-P8W48 system. We have also systematically investigated the effects of charge numbers, particle size, and ionic strength on the binding strength and binding mode of PLL/POM, respectively. Our results show that electrostatic interactions dominate the stability of PLL/POM complexes. These findings provide a way for tuning the mechanical properties of polyelectrolyte-nanoparticle composites.


Military boot attenuates axial loading to the lower leg.
Biomechanical tests to understand injury mechanisms and derive injury tolerance information using Post-Mortem Human Subjects (PMHS) have not used foot protection and they have primarily focused on civilian environments such as automotive and athletic- and sports-related events. As military personnel use boots, tests with the boot are required to understand their effect on attenuating lower leg loads. The purpose of this study was therefore, to determine the modulation of human lower leg kinematics with boot compressions and share of the force absorbed by the boot from underbody blast loading. Axial impacts were delivered to the Hybrid III dummy lower leg in the neutral position. The dummy leg was instrumented with its internal upper and lower tibia load cells, and in addition, a knee load cell was attached to the proximal end. Tests were conducted at 4.4 to 8.9 m/s, with and without boots, and repeat tests were done. Morphologies of the force-time responses were similar at the three load cell locations and for all input combinations and booted and unbooted conditions. However, booted tests resulted in considerably lower maximum forces (approximately two-third reduction) than unbooted tests. These results clearly show that boots can absorb a considerable share of the impact energy and decrease impact loads transmitted to the lower leg under vertical loading, thus necessitating the generation of tolerance data using PMHS for this environment.


How I do it: Simple and effortless approach to identify thoracodorsal nerve on axillary clearance procedure.
Breast cancer surgery frequently involves an axillary clearance procedure for nodal metastases. Injury to the thoracodorsal nerve is one of the complications related to the axillary dissection. The thoracodorsal nerve innervates the latissimus dorsi muscle which facilitates in certain movements of the arm. Moreover, it can be used as a nerve graft in long thoracic nerve injury whether in trauma or surgery. Understanding the anatomy structures and good surgical technique in the axillary clearance procedure can identify and prevent such an injury to the thoracodorsal nerve. Here, we demonstrate a simple and effortless technique for identification of the thoracodorsal nerve during axillary surgery.


Early Screening of Children With Autism Spectrum Disorder Based on Electroencephalogram Signal Feature Selection With L1-Norm Regularization.
Early screening is vital and helpful for implementing intensive intervention and rehabilitation therapy for children with autism spectrum disorder (ASD). Research has shown that electroencephalogram (EEG) signals can reflect abnormal brain function of children with ASD, and screening with EEG signals has the characteristics of good real-time performance and high sensitivity. However, the existing EEG screening algorithms mostly focus on the data analysis in the resting state, and the extracted EEG features have some disadvantages such as weak representation capacity and information redundancy. In this study, we utilized the event-related potential (ERP) technique to acquire the EEG data of the subjects under positive and negative emotional stimulation and proposed an EEG Feature Selection Algorithm based on L1-norm regularization to perform screening of autism. The proposed EEG Feature Selection Algorithm includes the following steps: (1) extracting 20 EEG features from the raw data, (2) classification with support vector machine, (3) selecting appropriate EEG feature with L1-norm regularization according to the classification performance. The experimental results show that the accuracy for screening of children with ASD can reach 93.8% and 87.5% under positive and negative emotional stimulation and the proposed algorithm can effectively eliminate redundant features and improve screening accuracy.


Influence of media and regulatory changes on prescribing of cotrimoxazole and trimethoprim in Ireland.
In 1985 the Committee for Safety of Medicines warned that cotrimoxazole was likely to cause adverse effects, particularly bone marrow suppression and death in patients over 65 years. Fears regarding the safety of cotrimoxazole received media attention in 1994 and by 1995 the indications for use of cotrimoxazole were restricted. We studied the prescribing patterns of cotrimoxazole and trimethoprim within the state-supported General Medical Services (GMS) scheme in Ireland to document the influence of media and regulatory advice on prescribing patterns. The decline in prescribing of cotrimoxazole (by some 70,000 prescriptions within a year) preceded the change in its licensed indications emphasizing the strong influence of media reports on prescribing patterns. At present the prescribing rates of cotrimoxazole appear greater than is warranted and is similar among children (18/1000 patients) and the elderly (15/1000 patients) which is in contrast to the prescribing rates for trimethoprim in children (17/1000 patients) and the elderly (101/1000 patients). The most common length of therapy for both antibiotics was 7 days despite evidence that shorter courses of these antibiotics are suitable for treating uncomplicated urinary tract infections. Cotrimoxazole is still being prescribed to a significant degree across all age groups despite its revised indications. The need for a continuous input by regulatory agencies is clear. Copyright (c) 2000 John Wiley & Sons, Ltd.


Muscle Tension Line Groups Reconstruction in Bilateral Cleft Lip Repair.
Bilateral cleft lip is considered to be the most difficult cleft lip to repair. More and more surgeries are concerned about the reconstruction of orbicularis muscle and the pursuit of philtrum shaping in bilateral cleft lip repair, but most have little success. Years of study on the orbicularis muscle of children with cleft lip resulted in authors' creation of muscle tension line groups theory. Through implementation of this theory, the authors have achieved favorable results in microform cleft lip repair. The authors also applied this concept to bilateral cleft lip repair. Between January 2010 and December 2014, 31 children with bilateral cleft lip received operations in authors' department, and underwent muscle tension line group reconstruction in accordance with the theory of muscle tension line groups. Two third-party doctors judged postoperative results using a 3-point visual analogue scale. Twenty-two of the 31 children completed a follow-up 6 months to 1 year after surgery. Most postoperative and follow-up results were satisfactory. Fully reconstructed muscle tension line groups can not only assist with close fractures, but, for example, also help adduct the nasal alar, and elevate the nasal floor. Furthermore, the surgery can be used to reconstruct the 3-dimensional structure of the philtrum. Ultimately, surgical application of the muscle tension line groups theory proved its feasibility and potential for further development.


An assay for the measurement of the protein content of cells immobilized in carrageenan.
A reliable and reproducible method for the estimation of the protein content of fungal cells immobilized in a carrageenan gel is described. The procedure depends upon the acid lability of the polysaccharide gel at 90 degrees C and on the acetone solubility of accumulated phenolics. Freeze-dried gel beads (2-3 mm) containing entrapped cells of Penicillium urticae were ground to a fine powder and samples of powder (approximately 20 mg) were sequentially extracted with hot 1 N HCl - 0.9% NaCl and acetone. The precipitated residue contained the cell protein, which was then solubilized with 1 N NaOH at 90 degrees C and quantitated by the Folin-Lowry method. Interferences from both carrageenan and phenols were thus eliminated. The presence of carrageenan (20-25 mg) did not affect the recovery of varying amounts (0-2500 micrograms) of bovine serum albumin. The recovery of radiolabeled protein from immobilized cells was parallel to that of Folin-Lowry positive material over a range of 0-60 beads (0-60 mg powder). Cycloheximide (0-100 micrograms/mL) was shown to progressively inhibit the incorporation of L-[U-14C]leucine so that the radioactivity present in the initial HCl-NaCl extract (i.e., [14C]leucine) increased as that in the final NaOH extract (i.e., 14C-labeled protein) decreased. Using this new assay for cell protein, free and immobilized cell cultures were found to exhibit virtually identical kinetics of glucose utilization, growth, and patulin production. In addition to providing a means of comparing the specific productivity of free versus immobilized cell preparations, this assay accurately measures the incorporation of [14C]leucine into cellular protein and could be used as a measure of cell viability.


Dural Bleeding After Endoscopic Sinus Surgery.
We present a case of an 80-year-old female patient who had an extensive dural bleed after endoscopic sinus surgery. A review of the literature regarding the surgical tools and materials used to treat dural hemorrhage was performed. We describe our preferred method of using the combination of endoscopic bipolar, DuraGen Plus, and DuraMatrix to stop significant dural bleeding and show effective hemostatic regulation.


Recent advances in HIV-associated Kaposi sarcoma.
Kaposi sarcoma (KS) is a mesenchymal tumour caused by KS-associated herpesvirus and is an AIDS-defining illness. Despite a decline in incidence since the introduction of combination anti-retroviral therapy, KS remains the most common cancer in people living with HIV in sub-Saharan Africa, where it causes significant morbidity and mortality. This review reflects on recent epidemiological data as well as current management, unmet needs and future perspectives in the treatment of HIV-associated KS with particular emphasis on the potential role of immune checkpoint inhibitors.


BDNF Val66Met and childhood adversity on response to physical exercise and internet-based cognitive behavioural therapy in depressed Swedish adults.
The genetic effect of Brain-derived neurotrophic factor (BDNF) on treatment response in depression is not consistent in the literature. Childhood adversity is a known risk factor for depression which has been reported to increase depression susceptibility by interacting with BDNF genetic variation. We aimed to explore whether the BDNF variation Val66Met and childhood adversity (CA) predicted the treatment response to a 12-week intervention with physical exercise (PE) or internet-based cognitive behavioural therapy (ICBT) when compared with treatment as usual (TAU). A prospective cohort study nested within a randomised control trial was conducted using data from 547 participants with mild to moderate depression. Depression severity at baseline and follow-up was measured using the Montgomery-Åsberg Depression Rating Scale. Met allele carriers without exposure to CA and current antidepressant use showed higher treatment response to PE than Val homozygotes. There was no evidence to support that BDNF Val66Met or CA alone predicted treatment response to PE and ICBT. The Met carriers had higher serum mature BDNF level. These data suggest that Met allele carriers benefit more from PE treatment but only if they are not exposed to early adversity.


Internal equilibrium of the hammerhead ribozyme is altered by the length of certain covalent cross-links.
A method was developed that permits covalent cross-links of different linker lengths to be introduced into RNA at defined positions. The previous observation that a cross-link between stems I and II of the hammerhead ribozyme was confirmed and further explored. By examining the catalytic consequences of varying the position and length of this cross-link, we conclude that the previously proposed conformational dampening model cannot sufficiently explain the increase in ligation rate induced by the cross-link. Rather, the cross-link constrains the cleaved hammerhead into a structure that more closely resembles the transition state, thereby increasing the reverse ligation rate relative to a non-cross-linked control.


[Electrocardiographical changes and rhythm disorders in Barlow's syndrome].
Mitral valve prolapse ( MVP ) , responsible for most of the symptoms which had previously been interpreted as being due to neurocirculatory disorders or cardiac neurosis , is being recognised more often and has an incidence of about 6-8 % in an unselected population . Although this condition was considered for a long time to be a benign auscultatory abnormality , it may be the cause of serious cardiac complication . Arrhythmias predominate with an incidence of 60 to 80 % on continuous electrocardiography . In a series of 245 patients with mitral valve prolapse confirmed on echocardiography , 52 patients chosen at random were studied to determine the incidence pf ST changes , disturbances of heart rate , QT interval , changes of QRS , arrhythmias with resting , exercise and continuous ECG over 24 hours ( HMS = Holter Monitoring System ) . Abnormalities of ventricular repolarisation , especially flattening of the T wave and , less commonly , St depression were observed in about one third of the patients . These changes were more common in the inferior but were also found in the left precordial leads . 73 % of the 52 patients had a heart rate of 75/mn and their QT intervals showed the following changes : 30.7 % Had a duration greater than the 120 th percentile ; 19.2 % had a duration greater than the upper limit of normal . The other 50 % had a QT interval of around the 100 th percentile . None had a duration of less than the 90 th percentile . In 22.5 % patients , QRS changes due to conduction defects were recorded ( 15 % right bundle branch block - RBBB - , 7.5 % incomplete RBBB ) . HMS is the method of choice for detection of arrhythmias . Resting ECG only showed premature ventricular contractions ( PVCs ) in 12.5 % , compared to 32.5 % on exercise ECG and 62.5 % on HMS . 50 % PVCs were monomorphic , 5 % polymorphic , 7.5 % in salvos and 7.4 % supraventricular in origin . The circadian variation of PVC was striking with a high incidence during periods of activity . There was no statistical correlation between the incidence of PVCs , age , sex , type of MVP and the symptoms and auscultatory findings . The theories on the pathogenesis of the arrhythmias are divided between that based on an underlying cardiomyopathy ( confirmed by the presence of degenerated myocytes on electron microscopy ) and the mechanical hypothesis ( chordae tendinae irritating the endocardium or traction on the papillary muscle with resulting ischaemia ) which provide a better explanation of the clear predominance of monomorphic PVCs . The treatment of Barlow's syndrome is discussed . In our opininon , therapy is only required for ventricular arrhythmias detected by a sufficiently sensitive method such as HMS . Most authors use beta blockers , eventually in association with quinidine Therapeutic successes have also been observed with mexiletine , amiodarone , aprindine and less commonly with disopyramide .


Mathematical Simulation of Transport Kinetics of Tumor-Imaging Radiopharmaceutical 99mTc-MIBI.
The proposed model describes in a quality way the process of tumor-imaging radiopharmaceutical 99mTc-MIBI distribution with taking into account radiopharmaceutical accumulation, elimination, and radioactive decay. The dependencies of concentration versus the time are analyzed. The model can be easily tested by the concentration data of the radioactive pharmaceuticals in the blood measured at early time point and late time point of the scanning, and the obtained data can be used for determination of the washout rate coefficient which is one of the existing oncology diagnostics methods.


Emerging quinoline- and quinolone-based antibiotics in the light of epidemics.
Pandemics are large-scale outbreaks of infectious disease that can greatly increase morbidity and mortality all the globe. Since past 1990 till twentieth century, these infectious diseases have been major threat all over the globe associated with poor hygiene and sanitation. In light of these epidemics, researches have gained enormous rise in the developing the potential therapeutic treatment. Thus, revolutionized antibiotics have led to the near eradication of such ailments. Around 50 million prescription of antibiotics written in US per year according to center for disease control and prevention (CDC) report. There is a wide range of antibiotics available which differ in their usage and their mechanism of action. Among these quinoline and quinolone class of antibiotics get attention as they show tremendous potential in fighting the epidemics. Quinoline and quinolone comprise of two rings along with substitutions at different positions which is synthetically obtained by structural modifications of quinine. Quinoline and quinolone antibiotics exhibit extensive activities approved by FDA in the treatment of the several ailments such as gastrointestinal infections, urinary tract infections, prostate inflammation, malaria, gonorrhea, skin infection, colorectal cancer, respiratory tract infections. These are active against both gram-negative and gram-positive bacteria. This basic core of quinoline and quinolone is vital due to its capability of targeting the pathogen causing disease and beneficial in treating the infectious disease. They inhibit the synthesis of nucleic acid of bacteria which results in the rupture of bacterial chromosome due to the interruption of enzymes such as DNA gyrase and topoisomerase IV. There are various quinoline and quinolone compounds that are synthetically derived by applying different synthesis approaches which show a wide range of pharmacological activities in several diseases. The most commonly used are fluoro, chloro, and hydroxychloro derivatives of quinoline and quinolone. These compounds are helpful in the treatment of numerous epidemics as a chief and combination therapy. These quinoline and quinolone pharmacophore fascinate the interest of researchers as they inhibit the entry of virus in host cell and cease its replication by blocking the host receptor glycosylation and proteolytic processing. They act as immune modulator by inhibiting autophagy and reduction of both lysosomal activity and production of cytokine. Therefore, quinoline and quinolone derivatives attain significance in area of research and treatment of various life-threatening epidemics such as SARS, Zika virus, Ebola virus, dengue, and COVID-19 (currently). In this chapter, the research and advancements of quinoline- and quinolone-based antibiotics in epidemic management are briefly discussed.


Dose response of succinylcholine at the adductor pollicis of children with cerebral palsy during propofol and nitrous oxide anesthesia.
Children with cerebral palsy may be resistant to paralysis induced by nondepolarizing neuromuscular blocking drugs. Potency of a bolus of succinylcholine in children with cerebral palsy has not been studied previously. Therefore, we measured the response of the adductor pollicis to succinylcholine in children with cerebral palsy anesthetized with propofol and nitrous oxide. Forty children between the ages of 2 and 10.2 yr with spastic quadriplegic cerebral palsy were randomly assigned to receive 100, 175, 250, or 375 micrograms/kg of succinylcholine during anesthesia with propofol and nitrous oxide. The ulnar nerve was stimulated with a train-of-four supramaximal stimulus every 10 s and the compound electromyogram of the adductor pollicis recorded by a Datex NMT monitor. Plasma cholinesterase activity was measured in all patients with three different substrates (propionylthiocholine, benzoylcholine, and succinylcholine). Dibucaine number was also determined using inhibition of benzoylcholine degradation. ED50 of succinylcholine was 146.8 micrograms/kg with 95% confidence intervals of 111.4-193.7 micrograms/kg. ED95 of succinylcholine was 360.5 micrograms with 95% confidence intervals of 273.3-475.5 micrograms/kg. We conclude that children with cerebral palsy are slightly sensitive to succinylcholine, but probably not sufficiently to be clinically important.


A general exact reconstruction for cone-beam CT via backprojection-filtration.
In this paper, we prove a generalized backprojection-filtration formula for exact cone-beam image reconstruction with an arbitrary scanning locus. Our proof is independent of the shape of the scanning locus, as long as the object is contained in a region where there is a chord through any interior point. As special cases, this generalized formula can be applied with cone-beam scanning along nonstandard spiral and saddle curves, as well as in an n-PI window setting. The algorithmic implementation and numerical results are described to support the correctness of our general claim.


Biomechanical investigation of prolonged driving in an ergonomically designed truck seat prototype.
A postural evaluation during a prolonged driving task was conducted to determine the ergonomic validity of a new freely adjustable truck seat prototype. Twenty participants were recruited to perform two 2-h simulated driving sessions. Postures were assessed using motion capture, accelerometers and pressure pads. Subjective discomfort was also monitored in 15-min increments using ratings of perceived discomfort (RPD) and the Automotive Seating Discomfort Questionnaire. Participants had a more neutral spine posture during the first hour of the drive and reported lower RPDs while sitting in the prototype. Pairing the gluteal backrest panel with the adjustable seat pan helped reduce the average sitting pressure. The industry-standard truck seat may lead to the development of poor whole body posture, and the proposed ergonomic redesign of a new truck seat helped improve sitting posture and reduce perceived discomfort. Practitioner Summary: A new freely adjustable truck seat prototype was compared to an Industry standard seat to assess hypothesised improvements to sitting posture and discomfort for long haul driving. It was found that the adjustable panels in the prototype helped promote spine posture, reduce sitting pressure and improved discomfort ratings.


[Chronic Obstructive Pulmonary Disease as a Factor of Unfavorable Cardiovascular Prognosis After Percutaneous Coronary Interventions in Ischemic Heart Disease].
to elucidate effect of concomitant chronic obstructive pulmonary disease (COPD) on remote results of percutaneous coronary intervention (PCI) with stent implantation in patients with ischemic heart disease (IHD). We analyzed data of long term follow-up of 346 IHD patients after PCI with stenting. Groups of patients with and without COPD had comparable baseline clinical and functional characteristics. During follow-up we registered cardiovascular events (cardiovascular death, myocardial infarction, stroke, revascularization), as well as time to first event with the construction of Kaplan-Meier curves. Difference in relative frequency of occurrence of studied events between groups was not significant (24 and 17% among patients with and without COPD respectively, p=0.13), but in patients with COPD events occurred significantly earlier (p=0.02). Patients with adverse cardiovascular events during follow-up at baseline had lower exercise tolerance and glomerular filtration rate, more often had diabetes.


Predictive factors for disease progression in hospitalized patients with coronavirus disease 2019 in Wuhan, China.
A few studies have revealed the clinical characteristics of hospitalized patients with COVID-19. However, predictive factors for the outcomes remain unclear. Attempted to determine the predictive factors for the poor outcomes of patients with COVID-19. This is a single-center, retrospective study. Clinical, laboratory, and treatment data were collected and analyzed from 111 hospitalized patients with laboratory-confirmed COVID-19 in Union Hospital. The gathered data of discharged and deteriorated patients were compared. Among these 111 patients, 93 patients were discharged and 18 patients were deteriorated. The lymphocyte count (0.56 G/L [0.47-0.63] vs 1.30 G/L [0.95-1.65]) was lower in the deteriorated group than those in the discharged group. The numbers of pulmonary lobe involved (5.00 [5.00-5.00] vs 4.00 [2.00-5.00]), serum C-reactive protein (CRP, 79.52 mg/L [61.25-102.98] vs 7.93 mg/L [3.14-22.50]), IL-6 (35.72 pg/mL [9.24-85.19] vs 5.09 pg/mL [3.16-9.72]), and IL-10 (5.35 pg/mL [4.48-7.84] vs 3.97 pg/mL [3.34-4.79]) concentrations in deteriorated patients were elevated compared with discharged patients. Multivariate logistic regression analysis showed that male gender (OR, 24.8 [1.8-342.1]), comorbidity (OR, 52.6 [3.6-776.4]), lymphopenia (OR, 17.3 [1.1-261.8]), and elevated CRP (OR, 96.5 [4.6-2017.6]) were the independent risk factors for the poor prognosis in COVID-19 patients. This finding would facilitate the early identification of high-risk COVID-19 patients.


Polymer Thin Films and Surface Modification by Chemical Vapor Deposition: Recent Progress.
Chemical vapor deposition (CVD) polymerization uses vapor phase monomeric reactants to synthesize organic thin films directly on substrates. These thin films are desirable as conformal surface engineering materials and functional layers. The facile tunability of the films and their surface properties allow successful integration of CVD thin films into prototypes for applications in surface modification, device fabrication, and protective films. CVD polymers also bridge microfabrication technology with chemical and biological systems. Robust coatings can be achieved via CVD methods as antifouling, anti-icing, and antihydrate surfaces, as well as stimuli-responsive or biocompatible polymers and novel nanostructures. Use of low-energy input, modest vacuum, and room-temperature substrates renders CVD polymerization compatible with thermally sensitive substrates and devices. Compared with solution-based methods, CVD is particularly useful for insoluble materials, such as electrically conductive polymers and controllably crosslinked networks, and has the potential to reduce environmental, health, and safety impacts associated with solvents. This review discusses the relevant background and selected applications of recent advances by two methods that display and use the high retention of the organic functional groups from their respective monomers, initiated CVD (iCVD) and oxidative CVD (oCVD) polymerization.


Rare earths stick to rare cyanobacteria: Future potential for bioremediation and recovery of rare earth elements.
Biosorption of metal ions by phototrophic microorganisms is regarded as a sustainable and alternative method for bioremediation and metal recovery. In this study, 12 cyanobacterial strains, including 7 terrestrial and 5 aquatic cyanobacteria, covering a broad phylogenetic diversity were investigated for their potential application in the enrichment of rare earth elements through biosorption. A screening for the maximum adsorption capacity of cerium, neodymium, terbium, and lanthanum was conducted in which Nostoc sp. 20.02 showed the highest adsorption capacity with 84.2-91.5 mg g-1. Additionally, Synechococcus elongatus UTEX 2973, Calothrix brevissima SAG 34.79, Desmonostoc muscorum 90.03, and Komarekiella sp. 89.12 were promising candidate strains, with maximum adsorption capacities of 69.5-83.4 mg g-1, 68.6-83.5 mg g-1, 44.7-70.6 mg g-1, and 47.2-67.1 mg g-1 respectively. Experiments with cerium on adsorption properties of the five highest metal adsorbing strains displayed fast adsorption kinetics and a strong influence of the pH value on metal uptake, with an optimum at pH 5 to 6. Studies on binding specificity with mixed-metal solutions strongly indicated an ion-exchange mechanism in which Na+, K+, Mg2+, and Ca2+ ions are replaced by other metal cations during the biosorption process. Depending on the cyanobacterial strain, FT-IR analysis indicated the involvement different functional groups like hydroxyl and carboxyl groups during the adsorption process. Overall, the application of cyanobacteria as biosorbent in bioremediation and recovery of rare earth elements is a promising method for the development of an industrial process and has to be further optimized and adjusted regarding metal-containing wastewater and adsorption efficiency by cyanobacterial biomass.


Problems and Countermeasures of Financial Risk in Project Management Based on Convolutional Neural Network.
Under the background of market economy, engineering projects are faced with a lot of financial risks. If we cannot prevent them effectively, it will undoubtedly bring serious negative impact to the entire engineering management work. Therefore, it is particularly important to actively manage risks, identify and evaluate risks in a timely and correct manner, manage risks efficiently, and minimize risk losses. At the same time, the development of wireless communication technology has brought many new branches of engineering project management. Some problems in the process of risk management are often not handled by traditional empirical calculation or mathematical methods, so it is necessary to find an appropriate way to define and describe the nonlinear relationship between a large number of uncertain causes and risk losses. In order to match the changes in the background of the development of wireless communication technology, this paper studies the financial risk problems and countermeasures in the engineering management of convolutional neural networks. The financial risk prediction model in network engineering management is constructed, and the volume neural network algorithm referenced by it is tested. The test results are highly consistent with the expert assessment. In the research process, the combination of questionnaire survey and mathematical analysis method was adopted, the extreme value of risk factors was determined by questionnaire survey, and then the accuracy of prediction was verified by a mathematical model. After many calculations, it has been proved that the convolutional neural network simulation system based on the scientific node selection method has greatly improved the accuracy of risk assessment.


Mark-recapture studies of host selection by Anopheles (Anopheles) vestitipennis.
We present herein the results of a series of mark-recapture experiments with female Anopheles vestitipennis. Theses experiments used human and animal hosts to assess the degree of anthropophily of field-caught specimens, originally collected on either host, and of their offspring. Fidelity of mosquitoes to particular hosts was estimated by recapturing marked host-seeking mosquitoes returning for a 2nd blood meal. Results indicated that mosquitoes seeking animal hosts were more faithful (80.48%; 33 of 41) in returning to their original host than were those seeking human hosts (63%; 49 of 78).


Abiraterone in heavily pretreated patients with metastatic castrate-resistant prostate cancer.
The aim of this study was to evaluate the activity and tolerability of abiraterone acetate in patients with metastatic castrate-resistant prostate cancer treated previously with more than three lines of chemotherapy. Patients received 1 g of abiraterone acetate (administered as four 250 mg tablets) orally once daily with prednisone at a dose of 5 mg orally twice daily. The primary endpoint was prostate-specific antigen (PSA) response. From August 2011 to January 2013, 36 patients were enrolled. PSA response was observed in 22 patients (61.1%, 95% confidence interval: 0.41-0.81). The median time to PSA progression was 7.3 months and after a median follow-up of 10.1 months, all patients were alive. The treatment was generally well tolerated; side effects secondary to mineralocorticoid excess resulting from blockade of CYP17 were largely controlled with prednisone. Abiraterone acetate seems to be an effective and well-tolerated treatment option for patients with metastatic castrate-resistant prostate cancer irrespective of the number of chemotherapy lines administered previously.


An exome sequencing study of Moebius syndrome including atypical cases reveals an individual with CFEOM3A and a TUBB3 mutation.
Moebius syndrome is characterized by congenital unilateral or bilateral facial and abducens nerve palsies (sixth and seventh cranial nerves) causing facial weakness, feeding difficulties, and restricted ocular movements. Abnormalities of the chest wall such as Poland anomaly and variable limb defects are frequently associated with this syndrome. Most cases are isolated; however, rare families with autosomal dominant transmission with incomplete penetrance and variable expressivity have been described. The genetic basis of this condition remains unknown. In a cohort study of nine individuals suspected to have Moebius syndrome (six typical, three atypical), we performed whole-exome sequencing to try to identify a commonly mutated gene. Although no such gene was identified and we did not find mutations in PLXND1 and REV3L, we found a de novo heterozygous mutation, p.E410K, in the gene encoding tubulin beta 3 class III (TUBB3), in an individual with atypical Moebius syndrome. This individual was diagnosed with near-complete ophthalmoplegia, agenesis of the corpus callosum, and absence of the septum pellucidum. No substantial limb abnormalities were noted. Mutations in TUBB3 have been associated with complex cortical dysplasia and other brain malformations and congenital fibrosis of extraocular muscles type 3A (CFEOM3A). Our report highlights the overlap of genetic etiology and clinical differences between CFEOM and Moebius syndrome and describes our approach to identifying candidate genes for typical and atypical Moebius syndrome.


Triazine resistance in Amaranthus tuberculatus (Moq) Sauer that is not site-of-action mediated.
While surveying Illinois Amaranthus tuberculatus (Moq) Sauer (tall waterhemp) half-sib populations for herbicide response variability, several were observed to segregate for resistance to atrazine. Studies were conducted on greenhouse-grown A tuberculatus plants to compare atrazine responses among populations that were segregating for resistance (SegR), uniformly sensitive (UniS) or uniformly resistant (UniR). In chlorophyll fluorescence assays, leaves of plants from the SegR and UniS populations displayed changes in fluorescence after treatment with atrazine, indicating that atrazine was inhibiting electron transport of photosystem II in chloroplasts. Sequencing of a fragment of psbA, which encodes the D1 protein, revealed that the SegR population did not contain the amino acid substitution that is typically found in triazine-resistant plants. Whole-plant herbicide dose-response experiments revealed that, relative to the UniS population, atrazine resistances in the UniR and SegR populations were > 770-fold and 16-fold, respectively. The SegR population was also resistant to cyanazine (59-fold), but not to metribuzin, linuron or pyridate. Triazine resistance in the SegR population was shown to be a nuclear inherited trait, unlike maternal inheritance of site-of-action mediated triazine resistance found in the UniR population. Taken collectively, these findings confirm the existence of two distinct triazine resistance mechanisms in A tuberculatus.


[Generation and characterization of monoclonal antibody against GRHPR].
To generate monoclonal antibodies (mAb) against glyoxylate reductase/hydroxypyruvate reductase (GRHPR). Normal human liver tissues were homogenized, and human liver cytosolic proteins were isolated by centrifugation. The total human liver cytosolic proteins were used to immunize BALB/c mice to prepare mAb by hybridoma technique. The mAbs were detected by ELISA, Western blot, and immunohistochemistry. The antibody specificities were identified by mass spectrometry (MS) following immunoprecipitation (IP) and confirmed by Uni-ZAP expression library screening. One hybridoma cell line, ADB291, secreting specific mAb against GRHPR was established. The Ig subclass of the mAb was IgG1(kappa). Data from immunohistochemistry showed that ADB291 can recognize hepatocyte cytoplasm. ADB291 mAb was used to isolate its protein antigen by IP. Proteins captured by the mAb were loaded to SDS-PAGE and subjected to Western blot and MALDI-TOF MS analysis. lambda expression Uni-ZAP XR pre-made liver cDNA library was screened with ADB291 hybridoma supernatants. All of our data demonstrated that ADB291 mAb specially reacted with GRHPR. A hybridoma cell line stably secreting specific mAb against GRHPR is established. The specific mAb against GRHPR would be very useful for the studies of GRHPR functions and distribution.


Safety and Tolerability of Natural and Synthetic Cannabinoids in Older Adults: A Systematic Review and Meta-Analysis of Open-Label Trials and Observational Studies.
Although cannabinoid-based medications are increasingly used by older adults, their safety and tolerability in this age group remain unclear. The purpose of this systematic review was to examine the safety and tolerability of cannabinoid-based medications by conducting a meta-analysis of open-label observational studies of cannabinoid-based medications for all indications in individuals with a mean age of ≥50 years. A systematic search was conducted on PubMed, PsycINFO, MEDLINE, EMBASE and CINHAL. Study quality was assessed using an adapted version of the Grading of Recommendations Assessment, Development and Evaluation criteria and Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were followed. We included studies that (a) were published from 1990 onwards; (b) included older adults (mean age ≥50 years); and (c) provided data on the safety and tolerability of medical cannabinoids. Data were pooled using a random-effects approach. Risk of adverse events, serious adverse events and withdrawals was computed as the incidence rate (IR). Separate analyses were conducted by the cannabinoid-based medication used, for delta-9-tetrahydrocannabinol (THC), cannabidiol (CBD) and a combination of THC and CBD (THC:CBD). Thirty-eight studies were identified (THC = 23; CBD = 6; THC:CBD = 9; N = 2341, mean age: 63.19 ± 8.08 years, men: 53.86%). THC had a very low incidence of all-cause and treatment-related adverse events (IR: 122.18, 95% confidence interval [CI] 38.23-253.56; IR: 84.76, 95% CI 0.13-326.01, respectively) and negligible serious adverse events (IR = 0). Similar IRs for CBD (all cause, IR: 111.91, 95% CI 1.24-495.93; treatment related, IR: 1.76, 95% CI 4.63-23.05) and no serious adverse events (IR = 0). CBD was not associated with a risk of treatment-related withdrawals. THC had a low risk of all-cause and treatment-related withdrawals (IR: 25.18, 95% CI 12.35-42.52; IR: 7.83, 95% CI 3.26-14.38, respectively). The THC:CBD treatment had a low risk of all-cause and treatment-related adverse events (IR: 100.72, 95% CI 0.25-383.00; IR: 55.38, 95% CI 8.61-142.80, respectively), but reported a risk of all-cause and treatment-related serious adverse events (IR: 21.32, 95% CI 0.18-93.26; IR: 3.71, 95% CI 0.21-11.56, respectively), and all-cause and treatment-related withdrawals (IR: 78.63, 95% CI 17.43-183.90; IR: 34.31, 95% CI 6.09-85.52, respectively). Significant heterogeneity (I2 >55%) was present in most analyses. Although cannabinoid-based medications were generally safe and acceptable to adults aged over 50 years, these estimates are limited by the lack of a control condition and considerable heterogeneity. Nevertheless, they complement and are consistent with comparable evidence from randomised controlled trials.


Analysis of procainamide hydrochloride and acecainide hydrochloride in rat feed.
An extraction and GLC assay procedure was developed for quantitation of procainamide hydrochloride and acecainide hydrochloride in rat feed. 4-Amino-N-[2-(dipropylamino)ethyl]benzamide hydrochloride was synthesized and utilized as an internal standard. The assay has good precision and accuracy and was used to establish the stability of acecainide hydrochloride and procainamide hydrochloride in rat feed.


The Effect of Number of Arms on the Aggregation Behavior of Thermoresponsive Poly(N-isopropylacrylamide) Star Polymers.
The thermoresponsive nature of aqueous solutions of poly(N-isopropylacrylamide) (PNIPAAM) star polymers containing 2, 3, 4, and 6 arms has been investigated by turbidity, dynamic light scattering, rheology, and rheo-SALS. Simulations of the thermosensitive nature of the single star polymers have also been conducted. Some of the samples form aggregates even at temperatures significantly below the lower critical solution temperature (LCST) of PNIPAAM. Increasing concentration and number of arms promotes associations at low temperatures. When the temperature is raised, there is a competition between size increase due to enhanced aggregation and a size reduction caused by contraction. Monte Carlo simulations show that the single stars contract with increasing temperature, and that this contraction is more pronounced when the number of arms is increased. Some samples exhibit a minimum in the turbidity data after the initial increase at the cloud point. The combined rheology and rheo-SALS data suggest that this is due to a fragmentation of the aggregates followed by re-aggregation at even higher temperatures. Although the 6-arm star polymer aggregates more than the other stars at low temperatures, the more compact structure renders it less prone to aggregation at temperatures above the cloud point.


Can 5-azacytidine convert the adult stem cells into cardiomyocytes? A brief overview.
From the first report that bone marrow cells (BMC) have stem cells characteristics, several studies have debated the possibility of intervening in myocardial remodeling after injury, for example myocardial infarction, by using BMC. The goal of this paper is to review the concept of whether the demethylating agent 5-azacytidine influences the myogenic differentiation of bone marrow-derived cells. The existing data seem to indicate that in vitro treatment with 5-azacytidine, even if not enough to generate mature CMC, promotes the in vivo and in vitro commitment of BMC into cells that express muscle-specific proteins and genes and, at a very low rate, show spontaneous contractions. It is probable this treatment makes the cells less responsive to other inductive factors secreted by the microenvironment that might modulate the differentiation. These data suggest that this approach may be used to prime cells prior to their transplantation in an injury area in the heart.


Studies on the influence of combustion exhaust gases and the products of their reaction with ammonia on the living organism. II. The influence on aspartate aminotransferase (AspAT) and alanine aminotransferase (AiAt) activities in the liver of guinea pig.
The behaviour of aspartate aminotransferase (AspAT) an alanine aminotransferase (AIAT) in the whole homogenate and subcellular liver fractions of guinea pigs exposed to combustion exhaust gases and the neutralization products of these gases is presented in this paper. In the liver of animals exposed to the chronic action of combustion exhaust gases a decrease of both enzyme activities in the whole homogenate as well as in the subcellular fractions could be noted. Statistically significant changes are shown by AspAT. In the group of animals subjected to the action of neutralization products an increase of AIAT activity was observed. The activity of AspAT still shows a decrease, but less distinct in comparison with group I. An exception here is the mitochondrial fraction in which the AspAT activity is distinctly increased.


Structure and dynamics of oligonucleotides in the gas phase.
By combining ion-mobility mass spectrometry experiments with sub-millisecond classical and ab initio molecular dynamics we fully characterized, for the first time, the dynamic ensemble of a model nucleic acid in the gas phase under electrospray ionization conditions. The studied oligonucleotide unfolds upon vaporization, loses memory of the solution structure, and explores true gas-phase conformational space. Contrary to our original expectations, the oligonucleotide shows very rich dynamics in three different timescales (multi-picosecond, nanosecond, and sub-millisecond). The shorter timescale dynamics has a quantum mechanical nature and leads to changes in the covalent structure, whereas the other two are of classical origin. Overall, this study suggests that a re-evaluation on our view of the physics of nucleic acids upon vaporization is needed.


Vasculopathy-related clinical and pathological features are associated with severe juvenile dermatomyositis.
Outcome of JDM is highly heterogeneous. Our objective was to determine clinical and muscle biopsy features associated with poor outcome and response to treatment. Clinical data and muscle biopsy were obtained from a monocentric cohort of 29 patients. Clinical subgroups were defined by latent class model analysis of initial and follow-up parameters. Myopathological features were analysed using validated scores. Capillary loss was determined on reconstructions of transversal sections and assessed in the different age groups to take into account variations of muscle capillarization during post-natal development. Regression models were used to identify initial predictors of therapeutic response. Two distinct homogeneous subgroups of patients were identified according to clinical severity and pathological findings. The smallest group of patients (7/29) presented with severe JDM. Compared with the other group (22/29), patients had more severe muscle weakness at disease onset, low remission rate at 12 months, frequent subcutaneous limb oedema or gastrointestinal (GI) involvement and higher myopathological scores (capillary dropout, perifascicular necrosis/regeneration, fibres with internal myonuclei and fibrosis subscores). Relevance of capillary dropout to JDM severity was substantiated by age-based analysis, confirming its major role in JDM pathophysiology. Most of these manifestations could be related to vasculopathy (limb oedema, GI involvement, capillary dropout). Furthermore, Childhood Myositis Assessment Scale <34 with either GI involvement or muscle endomysial fibrosis at disease onset were the best predictors of poor response to treatment. Vasculopathy is prominent in severe JDM. Simple criteria can be used at initial evaluation to identify patients requiring a more intensive therapy.


Positron scattering and annihilation from the hydrogen molecule at zero energy.
The confined variational method is used to generate a basis of correlated Gaussians to describe the interaction region wave function for positron scattering from the H2 molecule. The scattering length was approximately = -2.7a(0) while the zero energy Z(eff) of 15.7 is compatible with experimental values. The variation of the scattering length and Z(eff) with internuclear distance was surprisingly rapid due to virtual state formation at R approximately = 3.4a(0).


Potential of Stainless Steel Slag Waste in Manufacturing Self-Compacting Concrete.
The volume of slags generated from the steel industry is a source of possible resources which is constantly increasing. Specifically, in the production of stainless steel, specific and singular slags with unique characteristics are obtained, which allows considering an approach aimed at their use in new recycling ways. This work shows the feasibility of using stainless steel slag as a substitute for limestone filler in the manufacture of self-compacting concrete. The influence of different treatments applied to slags on physical and chemical properties was studied. On the other hand, the mechanical behaviour, as well as the durability acquired in self-compacting concrete, has been analysed. Very encouraging results were obtained, since this research demonstrates the possible application of this stainless steel slag as a construction material, improving sustainability and promoting circular economy processes, which are achieved through the minimisation of the waste disposal and accumulation.


The Generation of Zebrafish Mariner Model Using the CRISPR/Cas9 System.
Targeted genome editing mediated by clustered, regularly interspaced, short palindromic repeat (CRISPR)/CRISPR-associated nuclease 9 (Cas9) technology has emerged as a powerful tool for gene function studies and has great potential for gene therapy. Although CRISPR/Cas9 has been widely used in many research fields, only a few successful zebrafish models have been established using this technology in hearing research. In this study, we successfully created zebrafish mariner mutants by targeting the motor head domain of Myo7aa using CRISPR/Cas9. The CRISPR/Cas9-generated mutants showed unbalanced swimming behavior and disorganized sterocilia of inner ear hair cells, which resemble the phenotype of the zebrafish mariner mutants. In addition, we found that CRISPR/Cas9-generated mutants have reduced number of stereociliary bundles of inner ear hair cells and have significant hearing loss. Furthermore, phenotypic analysis was performed on F0 larvae within the first week post fertilization, which dramatically shortens data collection period. Therefore, results of this study showed that CRISPR/Cas9 is a quick and effective method to generate zebrafish mutants as a model for studying human genetic deafness. Anat Rec, 303:556-562, 2020. © 2019 American Association for Anatomy.


Components of the Complete Blood Count as a Risk Predictor for Incident Hypertension in a Large Taiwanese Population Follow-up Study.
Previous studies investigating the relationship between hypertension (HT) and hematological parameters report inconsistent results, and most them included a small number of participants or only conducted a cross-sectional analysis of 1 or 2 hematological factors. Moreover, no large cohort follow-up studies have investigated this topic. The aim of this longitudinal study was to explore associations between components of the complete blood count (CBC) and incident HT using data from a large Taiwanese biobankMethods and Results: Hematological parameters including white blood cell (WBC) count, red blood cell (RBC) count, hemoglobin, hematocrit (HCT), and platelet count were evaluated. We included 21,293 participants who did not have HT at baseline and followed them for a mean period of 3.9 years. During follow-up, 3,002 participants with new-onset HT (defined as incident HT) were identified. Univariable analysis revealed that high WBC count, high RBC count, high hemoglobin, high HCT, and low platelet count were associated with incident HT. Multivariable analysis after adjusting potential confounding factors found high WBC count (odds ratio [OR], 1.057; 95% confidence interval [CI], 1.028 to 1.087; P<0.001) and high HCT (OR, 1.023; 95% CI, 1.010 to 1.036; P<0.001) were still significantly associated with incident HT. High WBC count and high HCT were associated with incident HT.


Identification of Caries Risk Determinants in Toddlers: Results of the GUSTO Birth Cohort Study.
The aim of this study was to identify risk determinants leading to early childhood caries (ECC) and visible plaque (VP) in toddlers. Data for mother-child pairs participating in the Growing Up in Singapore towards Healthy Outcomes (GUSTO) birth cohort were collected from pregnancy to toddlerhood. Oral examinations were performed in 543 children during their clinic visit at 24 months to detect ECC and VP. Following logistic regression, ECC and VP were jointly regressed as primary and secondary outcomes, respectively, using the bivariate probit model. The ECC prevalence was 17.8% at 2 years of age, with 7.3% of children having a VP score >1. ECC was associated with nighttime breastfeeding (3 weeks) and biological factors, including Indian ethnicity (lower ECC rate), higher maternal childbearing age and existing health conditions, maternal plasma folate <6 ng/mL, child BMI, and the plaque index, while VP was associated with psychobehavioral factors, including the frequency of dental visits, brushing frequency, lower parental perceived importance of baby teeth, and weaning onto solids. Interestingly, although a higher frequency of dental visits and toothbrushing were associated with lower plaque accumulation, they were associated with increased ECC risk, suggesting that these established caries-risk factors may be a consequence rather than the cause of ECC. In conclusion, Indian toddlers may be less susceptible to ECC, compared to Chinese and Malay toddlers. The study also highlights a problem-driven utilization pattern of dental services (care sought for treatment) in Singapore, in contrast to the prevention-driven approach (care sought to prevent disease) in Western countries.


Genetics in the ADHD Clinic: How Can Genetic Testing Support the Current Clinical Practice?
Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder with a childhood prevalence of 5%. In about two-thirds of the cases, ADHD symptoms persist into adulthood and often cause significant functional impairment. Based on the results of family and twin studies, the estimated heritability of ADHD approximates 80%, suggests a significant genetic component in the etiological background of the disorder; however, the potential genetic effects on disease risk, symptom severity, and persistence are unclear. This article provides a brief review of the genome-wide and candidate gene association studies with a focus on the clinical aspects, summarizing findings of ADHD disease risk, ADHD core symptoms as dimensional traits, and other traits frequently associated with ADHD, which may contribute to the susceptibility to other comorbid psychiatric disorders. Furthermore, neuropsychological impairment and measures from neuroimaging and electrophysiological paradigms, emerging as potential biomarkers, also provide a prominent target for molecular genetic studies, since they lie in the pathway from genes to behavior; therefore, they can contribute to the understanding of the underlying neurobiological mechanisms and the interindividual heterogeneity of clinical symptoms. Beyond the aforementioned aspects, throughout the review, we also give a brief summary of the genetic results, including polygenic risk scores that can potentially predict individual response to different treatment options and may offer a possibility for personalized treatment for the therapy of ADHD in the future.


IL-5; a diffuse biomarker associated with brain inflammation after blast exposure.
Detailed biomolecular mechanisms underlying cognitive issues following blast exposure are unknown. Recently, studies confined to the hippocampus have shown elevated pro-inflammatory factors after blast exposure. In an attempt to understand the diffuse effects from blast, an established rodent model of blast neurotrauma was used. Animals were exposed to a peak overpressure of 117kPa, while controls animals underwent similar conditions however were not exposed to overpressure. Six brain regions were collected at 24 hours following blast and analyzed for various cytokine and chemokine levels using a multiplex bead array. Results indicated that a significant increase in IL-5 was observed in nucleus accumbens (NAC), anterior motor cortex (AMC), prefrontal cortex (PFC), and anterior striatum (AST). While other cytokines had significant variations when compared to controls (GM-CSF, TNF-a, IFN-? and IL-1a), IL-5 had a diffuse presence after blast. In addition, it was noteworthy that NAC had 17/23 cytokines elevated significantly in the blast group which may indicate that NAC is more susceptible to blast injury. Although the role of IL-5 in brain injury is unknown, it has been previously demonstrated that IL-5 is co-expressed with MCP-1 under cell death conditions to initiate the inflammatory process. We speculate that IL-5 could be a key regulator in inflammation after blast injury.


Combining talents for the management of cancer patients.
The combination of talents required to bring to all patients the maximum benefits of combined modality treatment is examined in the following steps: devising treatment strategy, carrying out treatment, extension widely to the community, and treatment research. The devising of strategy should rest upon the theoretical principles of cell kinetics and pharmacokinetics, which in most instances combine local removal in the primary tumor and anticipatory chemotherapy of occult metastases. The delivery of treatment involves implementation of these principles for each individual patient, and its success depends upon continual consultation among the various members of the treatment team. Wide extension of best treatment to all patients with cancer in the community will involve the good will and effective liaison of many individuals in federal, state, and local government, and many professional and lay people. Many problems of treatment are still unsolved, so research must provide new knowledge. While future advances will come in unexpected ways, the three most needed are a quantitative marder for cancer cells, better drug combinations for carcinomas, and an effective was to diagnose and repair immune deficits.


Tyrosine promotes oxidative stress in cerebral cortex of young rats.
Tyrosine accumulates in inborn errors of tyrosine catabolism, especially in tyrosinemia type II, where tyrosine levels are highly elevated in tissues and physiological fluids of affected patients. In tyrosinemia type II, high levels of tyrosine are correlated with eyes, skin and central nervous system disturbances. Considering that the mechanisms of brain damage in these disorders are poorly known, in the present study, we investigated whether oxidative stress is elicited by l-tyrosine in cerebral cortex homogenates of 14-day-old Wistar rats. The in vitro effect of 0.1-4.0mM l-tyrosine was studied on the following oxidative stress parameters: total radical-trapping antioxidant potential (TRAP), total antioxidant reactivity (TAR), ascorbic acid content, reduced glutathione (GSH) content, spontaneous chemiluminescence, thiobarbituric acid-reactive substances (TBA-RS), thiol-disulfide redox state (SH/SS ratio), protein carbonyl content, formation of DNA-protein cross-links, and the activities of the enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glucose-6-phosphate dehydrogenase (G6PDH). TRAP, TAR, ascorbic acid content, SH/SS ratio and CAT activity were significantly diminished, while formation of DNA-protein cross-link was significantly enhanced by l-tyrosine in vitro. In contrast, l-tyrosine did not affect the other parameters of oxidative stress evaluated. These results indicate that l-tyrosine decreases enzymatic and non-enzymatic antioxidant defenses, changes the redox state and stimulates DNA damage in cerebral cortex of young rats in vitro. This suggests that oxidative stress may represent a pathophysiological mechanism in tyrosinemic patients, in which this amino acid accumulates.


Scaffold-in-Scaffold Potential to Induce Growth and Differentiation of Cardiac Progenitor Cells.
The design of reliable biocompatible and biodegradable scaffolds remains one of the most important challenges for tissue engineering. In fact, properly designed scaffolds must display an adequate and interconnected porosity to facilitate cell spreading and colonization of the inner layers, and must release physical signals concurring to modulate cell function to ultimately drive cell fate. In this study, a combination of optimal mechanical and biochemical properties has been considered to design a one-component three-dimensional (3D) multitextured hydrogel scaffold to favor cell-scaffold interactions. A polyethylene glycol diacrylate woodpile (PEGDa-Wp) structure of the order of 100 μm has been manufactured using a microstereolithography process. Subsequently, the PEGDa-Wp has been embedded in a PEGDa hydrogel to obtain a 3D scaffold-in-scaffold (3D-SS) system. Finally, the 3D-SS capability to address cell fate has been assessed using human Lin- Sca-1+ cardiac progenitor cells (hCPCs). Results have shown that a multitextured 3D scaffold represents a favorable microenvironment to promote hCPC differentiation and orientation. In fact, while cultured on 3D-SS, hCPCs adopt an ordered 3D spatial orientation and activate the expression of structural proteins, such as the α-sarcomeric actinin, a specific marker of the cardiomyocyte phenotype, and connexin 43, the principal gap junction protein of the heart. Although preliminary, this study demonstrates that complex multitextured scaffolds closely mimicking the extracellular matrix structure and function are efficient in driving progenitor cell fate. A leap forward will be determined by the use of advanced 3D printing technologies that will improve multitextured scaffold manufacturing and their biological efficiency.


Manipulating letter fluency for words alters electrophysiological correlates of recognition memory.
The mechanisms that give rise to familiarity memory have received intense research interest. One current topic of debate concerns the extent to which familiarity is driven by the same fluency sources that give rise to certain implicit memory phenomena. Familiarity may be tied to conceptual fluency, given that familiarity and conceptual implicit memory can exhibit similar neurocognitive properties. However, familiarity can also be driven by perceptual factors, and its neural basis under these circumstances has received less attention. Here we recorded brain potentials during recognition testing using a procedure that has previously been shown to encourage a reliance on letter information when assessing familiarity for words. Studied and unstudied words were derived either from two separate letter pools or a single letter pool ("letter-segregated" and "normal" conditions, respectively) in a within-subjects contrast. As predicted, recognition accuracy was higher in the letter-segregated relative to the normal condition. Electrophysiological analyses revealed parietal old-new effects from 500-700 ms in both conditions. In addition, a topographically dissociable occipital old-new effect from 300-700 ms was present in the letter-segregated condition only. In a second experiment, we found that similar occipital brain potentials were associated with confident false recognition of words that shared letters with studied words but were not themselves studied. These findings indicate that familiarity is a multiply determined phenomenon, and that the stimulus dimensions on which familiarity is based can moderate its neural correlates. Conceptual and perceptual contributions to familiarity vary across testing circumstances, and both must be accounted for in theories of recognition memory and its neural basis.