Patients' attitudes toward resident participation in dermatology outpatient clinics.
The attitudes of patients toward resident participation in a university-based dermatology outpatient clinic were evaluated. Of 206 patients asked to participate, 191 patients completed the self-administered questionnaire (92.7%). The overwhelming majority of patients (99.5%) were satisfied (81.8% "very satisfied" and 17.7% "satisfied") with the resident's participation in their care. Many more patients expressed a willingness to allow residents to take histories (93.6%), perform physical examinations (87.2%), and counsel on preventive measures (74.5%), than to allow surgical excisions of skin cancers (19.7%), perform skin biopsies (43.6%), or prescribe medications (44.7%). Of respondents to the questionnaire, 83.2% self-reported an understanding of the difference between "resident" and "attending" physicians. However, only 31.3% (95% confidence interval 24.5-38.1) were able to broadly categorize the amount of training completed by dermatology residents. Dermatology resident participation in outpatient clinics is essential to quality dermatologic education. Consistent with the results of prior studies in other medical disciplines, our study demonstrated an overwhelming patient satisfaction with the participation of dermatology residents in their care.


The characterization of antibacterial antibodies in bovine immune sera to Staphylococcus aureus.
Humoral antibody responses to the encapsulated Smith diffuse strain of Staphylococcus aureus were examined in cows immunized with the killed vaccine via different systemic routes. The sequential appearance of the antibody within different immunoglobulin classes in the sera during the course of immunization was followed by passive hemagglutination (PHA) and precipitation (PC) reactions and the mouse passive protection test. Repeated intravenous injections with the killed vaccine suspended in buffered saline stimulated production of IgM antibody exclusively during the whole period of immunization. On the contrary, following intramuscular administration with the vaccine incorporated in Freund's incomplete adjuvant, the antibodies appeared predominantly in IgG fractions of the sera. Specific antibody to the homologous strain used for vaccination was prepared from bovine immune sera by an absorption and elution process. The mouse passive protective activity of the antibody preparation was removed by absorption with the capsular polysaccharide antigen as well as by the whole cell adsorbent of the Smith diffuse strain, but not by the Smith compact and Cowan I strains of S. aureus. IgM, IgG1 and IgG2 proteins were isolated from the purified antibody and were compared, on a weight basis, with respect to their biological activities. Slightly higher activity of the IgG over the IgM antibody was demonstrated both in the mouse passive protection test and PC reaction, whereas in the PHA reaction, IgM antibody was shown to possess a significantly higher activity than IgG antibody. These studies suggest that IgG as well as IgM antibody might play an important role in protection against infection with encapsulated strains of S. aureus in cows.


Characterization of a cis-acting regulatory mutation that maps at the distal end of the Escherichia coli glyA gene.
We have isolated a phage Mu cts-generated glyA mutant with only 30% of the normal level of serine hydroxymethyltransferase activity. Genetic and physical mapping studies show that Mu cts has inserted between the end of the glyA structural gene and its proposed transcription termination site. The mutation is cis acting and shows that sequences distal to the glyA structural gene play an important role in the expression of this gene.


Comprehensive red blood cell and platelet antigen prediction from whole genome sequencing: proof of principle.
There are 346 serologically defined red blood cell (RBC) antigens and 33 serologically defined platelet (PLT) antigens, most of which have known genetic changes in 45 RBC or six PLT genes that correlate with antigen expression. Polymorphic sites associated with antigen expression in the primary literature and reference databases are annotated according to nucleotide positions in cDNA. This makes antigen prediction from next-generation sequencing data challenging, since it uses genomic coordinates. The conventional cDNA reference sequences for all known RBC and PLT genes that correlate with antigen expression were aligned to the human reference genome. The alignments allowed conversion of conventional cDNA nucleotide positions to the corresponding genomic coordinates. RBC and PLT antigen prediction was then performed using the human reference genome and whole genome sequencing (WGS) data with serologic confirmation. Some major differences and alignment issues were found when attempting to convert the conventional cDNA to human reference genome sequences for the following genes: ABO, A4GALT, RHD, RHCE, FUT3, ACKR1 (previously DARC), ACHE, FUT2, CR1, GCNT2, and RHAG. However, it was possible to create usable alignments, which facilitated the prediction of all RBC and PLT antigens with a known molecular basis from WGS data. Traditional serologic typing for 18 RBC antigens were in agreement with the WGS-based antigen predictions, providing proof of principle for this approach. Detailed mapping of conventional cDNA annotated RBC and PLT alleles can enable accurate prediction of RBC and PLT antigens from whole genomic sequencing data.


Engineering degrons of yeast ornithine decarboxylase as vehicles for efficient targeted protein degradation.
Ornithine decarboxylase (ODC), which catalyzes the first step of polyamine biosynthesis, undergoes rapid targeted degradation (TPD) with the help of its two degron sequences, namely the N-terminal 50 residues (N50) and α/β domain (α/β) housing antizyme binding element (AzBE), in response to increased polyamine levels. Antizyme binds to AzBE of ODC and delivers it to proteasome for degradation. Entire ODC was used as a tag to demonstrate TPD of chimeric proteins. Here we fashioned three peptide sequences from yeast ODC to test their capability to act as degrons, namely N50, α/β and Nα/β (a combination of N50 and α/β), and monitored their degradation potentials in chimeric proteins. We have examined the correlation between degradation potentials and structural integrity of the peptides, to find mechanistic explanations. Nα/β with two signals in tandem is a better degron, under the regulation of antizyme. N50 like N44 reported earlier could drive chimeric proteins to degradation, while α/β could not act as an independent degron. Strong correlation was observed between functional efficacy of the peptides and their structural integrity. N50, which was believed to be unstructured, displayed propensity for helical conformation. Nα/β exhibited optimal structure, while α/β failed to adopt native like conformation. Functional efficacy of the degron Nα/β is a consequence of its structural integrity. Nα/β and N50 could target chimeric proteins to degradation. However, α/β failed in the quest. Nα/β, regulated by antizyme, is better suited than N50 for TPD to understand the function of novel proteins.


Association of virulent and avirulent strains of bluetongue virus serotype 11 with premature births of late-term bovine fetuses.
Two strains of bluetongue virus serotype 11 (BTV 11), UC-2 avirulent and UC-8 neurovirulent in newborn mice, were inoculated into late-term bovine fetuses to investigate whether infection with these two BTV strains in late gestation would produce congenital infection and pathological changes. Fetuses were inoculated by intramuscular injection through the uterine wall at 243 days gestation and recovered after spontaneous delivery. In calves inoculated with UC-8, births occurred 15 to 27 days before expected parturition, resulting in small, weak calves. These calves had a mild encephalitis and were unthrifty at birth. Calves inoculated with UC-2 appeared healthy when born 7 to 11 days prior to expected parturition. No lesions were found in these calves at necropsy. All calves seroconverted by the time of birth. Viraemia was present in the calves inoculated with UC-8 and in one calf inoculated with UC-2. Plasma cortisol concentrations were prematurely elevated, particularly in the calves inoculated with UC-8, indicating that they were stressed by the infection. The elevated cortisol, associated with an active congenital infection caused by bluetongue virus serotype 11 strain UC-8, is capable of causing premature delivery of low birth-weight, weak calves.


Submillisecond kinetics of glutamate release from a sensory synapse.
Exocytosis-mediated glutamate release from ribbon-type synaptic terminals of retinal bipolar cells was studied using AMPA receptors and simultaneous membrane capacitance measurements. Release onset (delay <0.8 ms) and offset were closely tied to Ca2+ channel opening and closing. Asynchronous release was not copious and we estimate that there are approximately 5 Ca2+ channels per docked synaptic vesicle. Depending on Ca2+ current amplitude, release occurred in a single fast bout or in two successive bouts with fast and slow onset kinetics. The second, slower bout may reflect a mobilization rate of reserve vesicles toward fusion sites that is accelerated by increasing Ca2+ influx. Bipolar cell synaptic ribbons thus are remarkably versatile signal transducers, capable of transmitting rapidly changing sensory input, as well as sustained stimuli, due to their large pool of releasable vesicles.


Association between a casein kinase 1 ε gene polymorphism and schizophrenia in a Chinese Han population.
The casein kinase 1 (Csnk1) family of serine/threonine kinases regulates dopamine receptor (DR) signaling by phosphorylating the 32-kDa dopamine- and cAMP-regulated phosphoprotein DARPP-32, leading to inhibition of protein phosphatase 1 and a shift in the phosphorylation state of many downstream proteins. By modulating DR-activated phosphorylation cascades, Csnk1 plays a central role in neuropsychiatric disorders and modulates the stimulant response to amphetamine. No published study, however, has established a correlation between Csnk1 gene polymorphisms and schizophrenia. We genotyped the rs135745C/G polymorphism of the Csnk1ε gene in 384 schizophrenic patients and 502 healthy controls drawn from the Chinese Han population. There were significantly higher CG and CC genotype frequencies in schizophrenic patients compared to control subjects (CG, p = 0.0086, odds ratio (OR) = 1.477, 95% confidence interval (CI), 1.103-1.978; CC, p = 0.0431, OR = 2.571; 95% CI, 0.998-6.624). The C allele frequency was also higher in the schizophrenics (p = 0.0022; OR = 1.474; 95% CI, 1.149-1.891). In the dominant model, subjects with genotypes CC or CG were at greater risk for schizophrenia (p = 0.0032; OR = 1.532; 95% CI, 1.153-2.037), suggesting that a genetic variant in the Csnk1ε gene significantly enhances the probability of schizophrenia in the Chinese Han population.


Biological and clinical features of trisomy 21 in adult patients with acute myeloid leukemia.
Trisomy 21 is frequently noted in patients with AML. In adults, +21 has traditionally been considered an intermediate-risk cytogenetic aberration. We analyzed 90 patients with newly diagnosed AML harboring +21. Four cytogenetic subgroups were defined based on associated cytogenetic abnormalities: +21 alone, +21 with favorable, +21 with intermediate, and +21 with unfavorable cytogenetics. Fifty-four percent of patients with +21 AML achieved a complete remission (CR) or CR with incomplete platelet recovery (CRp) after induction therapy with a trend toward improved CR/CRp rates in patients with +21 alone/+21 with favorable cytogenetics compared with patients with +21 with intermediate/+21 with unfavorable cytogenetics (76% vs. 50%; P = .057). Time to progression (TTP) was 12 months (range, 5-19) and overall survival (OS) was 9 months (range, 7-11) for the entire group. TTP was longer for patients with +21 alone (not reached) or with +21 with favorable cytogenetics (101 months) compared with those with +21 with intermediate cytogenetics (2 months) or +21 with unfavorable cytogenetics (11 months) (P = .02). Similarly, OS was improved in patients with +21 with favorable cytogenetics (not reached) or +21 alone (107 months), compared with +21 with unfavorable cytogenetics (9 months) or +21 with intermediate cytogenetics (8 months) (P < .001). The differences in TTP and OS were maintained on multivariate analysis (P = .04 and P = .001; respectively). Isolated +21 hitherto classified as intermediate-risk cytogenetics might actually behave as a favorable-risk cytogenetics in adult AML patients.


Pulmonary artery catheter induced pulmonary artery rupture in patients undergoing cardiac surgery.
Pulmonary artery rupture is a rare but rapidly fatal complication of pulmonary artery catheter insertion and use. Rapid diagnosis and appropriate treatment are essential to avoid mortality. Two cardiac surgical patients who suffered pulmonary artery rupture as a result of pulmonary artery catheter insertion and use are presented. These patients demonstrate two different presentations and the treatment of pulmonary artery rupture. A discussion of diagnosis, treatment, pathogenesis and prevention are presented.


Tracking demands for seeking psychological help before and during the COVID-19 pandemic: a quanti-qualitative study.
The COVID-19 pandemic has placed unprecedented burdens on individuals and communities around the world. The isolation, fear, and uncertainty caused by the virus has led to increased rates of anxiety, depression, and other mental health issues. The pandemic has also had a disproportionate impact on individuals and communities with low income and socioeconomic status.ObjectiveTo shed light on the consequences of the pandemic on individuals from minorities and low-income areas, we investigate the main reasons that led patients who were referred to a social clinic of a private university in Rio de Janeiro to seek psychological treatment before (2019) and during the pandemic (2020 and 2021).MethodsWe conducted a quanti-qualitative study with a lexical analysis that evaluated 549 complaint forms of patients seeking treatment in these two distinct periods. Our analyses included descending hierarchical analysis (DHA) and correspondence factor analysis (CFA).ResultsFamily dynamics and communication factors play a dominant role in the reason for seeking therapy and psychological treatment. Additionally, our study suggested an increase in anxiety and panic attacks among other mental health issues associated with grief and losses during the pandemic years.ConclusionBased on these analyses, we can begin to identify a few changes in the main demand and redirection of complaints of patients during the period of COVID-19.


Radiosensitivity testing, virulence indices, and stromal reaction in carcinoma of the cervix uteri.
A relatively simple, clinically applicable, analytic-pathologic approach to the complex problem of carcinoma of the uterine cervix is given. Careful study of control and post-test radiation cervical biopsies and evaluation of the type and grade of the carcinoma, the lymphatic vessel involvement, the stromal host reaction, and the tumor response to test radiation offer additional parameters in the therapeutic approach, aiming at the improvement of prognosis. We also hope that this work offers a contribution to the complex problem of tumor biology and pathology.


Treatment of Cushing's disease with adrenal blocking drugs and megavoltage therapy to the pituitary.
Eighteen patients with Cushing's disease were seen over a 40-month period and considered for treatment by pituitary irradiation and adrenal blocking drugs. Fourteen patients entered the study and each received megavoltage therapy to give a mean dose of 4600 rad to the pituitary over 31 days. Each patient was treated for one (two patients) or two (12 patients) years with one or both of the adrenocortical enzyme inhibitors, metyrapone or aminoglutethmide to suppress cortisol secretion. Doses were adjusted to maintain urinary free cortisol secretion below 300 nmol/24 h. One patient failed to complete the trial. Normal urinary free cortisol excretion and plasma cortisol concentration were maintained after treatment in eight of the remaining 13 patients after therapy. Only one patient required cortisol replacement and normal menstrual function was restored in five of the six women. The remaining five patients relapsed and four were subsequently treated by total adrenalectomy. It was noted that the patients who responded to treatment were substantially younger than the therapeutic failures. It is suggested that this treatment is most useful in the management of younger patients.


IncP plasmids are unusually effective in mediating conjugation of Escherichia coli and Saccharomyces cerevisiae: involvement of the tra2 mating system.
Mobilizable shuttle plasmids containing the origin-of-transfer (oriT) region of plasmids F (IncFI), ColIb-P9 (IncI1), and RP4/RP1 (IncPalpha) were constructed to test the ability of the cognate conjugation system to mediate gene transfer from Escherichia coli to Saccharomyces cerevisiae. Only the Palpha system caused detectable mobilization to yeast, giving peak values of 5 x 10(-5) transconjugants per recipient cell in 30 min. Transfer of the shuttle plasmid required carriage of oriT in cis and the provision in trans of the Palpha Tra1 core and Tra2 core regions. Genes outside the Tra1 core did not increase the mobilization efficiency. All 10 Tra2 core genes (trbB, -C, -D, -E, -F, -G, -H, -I, -J, and -L) required for plasmid transfer to E. coli K-12 were needed for transfer to yeast. To assess whether the mating-pair formation (Mpf) system or DNA-processing apparatus of the Palpha conjugation system is critical in transkingdom transfer, an assay using an IncQ-based shuttle plasmid specifying its own DNA-processing system was devised. RP1 but not ColIb mobilized the construct to yeast, indicating that the Mpf complex determined by the Tra2 core genes plus traF is primarily responsible for the remarkable fertility of the Palpha system in mediating gene transfer from bacteria to eukaryotes.


Enhancing biohydrogen production from lignocellulosic biomass of Paulownia waste by charge facilitation in Zn doped SnO2 nanocatalysts.
The goal of this research was to study the role of excess charges in regulating biohydrogen production from Paulownia. The excess charges were generated through charge compensation in SnO2 nanocatalysts by Zn doping. The maximum hydrogen yield of 335 mL was observed at 8%Zn doping with a concentration of 150 mg/L, 47% higher as compared to standard sample. It was observed that the hydrogen production rate increased with Zn doping and the highest value (77 mL/h) was observed for 8%Zn at 24 h. The decrease in the total amount of byproducts (2.52 g/L from 4.28 g/L) at 8% Zn indicates an increase in bacterial metabolism. The lowest value of oxidation-reduction potential (-525 mV) at 24 h for 8%Zn confirms that Zn doping provides excessive electrons to the fermentative medium which helps the bacteria to transfer electrons faster during the redox reaction, hence, enhancing the enzymatic process and eventually hydrogen production.


Anatomical References to Evaluate Thoracic Aorta Calcium by Computed Tomography.
Thoracic aortic calcium (TAC) has received some interest in recent studies as an important subclinical marker of atherosclerosis. Besides that, using computed tomography (CT) scans performed with cardiac or chest protocols, ECG-gated, or non-gated, TAC can be easily evaluated with no addition in radiation dose. This review discusses the particularities of the aortic wall calcium formation, as well as the differences between the aortic segments and summarizes the current status of TAC evaluation, mainly concerning the anatomical references used in the studies. The studies have evaluated TAC considering different anatomical references. It was identified two different study groups. In the first one, researchers have analyzed the aorta as the sum of calcium in the ascending aorta (ATAC), aortic arch (AAC), and descending thoracic aorta (DTAC). The second group has used cardiac CT scans to assess TAC; therefore, they did not include AAC; however, the aortic root calcium (ARC) was added in the analysis. So, caution is advisable when interpreting and comparing studies that used different TAC anatomical references. The broad methodological variability, in addition to the variations in the population characteristics of the studies on TAC, may be in part contributing to the differences between results of different studies. Currently TAC does not have a role in clinical decisions, so it is necessary to create a standard protocol for the aortic calcium research as well as exists for the coronary artery calcium evaluation.


Melatonin inhibits the expression of the inducible isoform of nitric oxide synthase and nuclear factor kappa B activation in rat skeletal muscle.
This study investigated whether the induction of inducible nitric oxide synthase (iNOS) produced by acute exercise in rat skeletal muscle could be prevented by melatonin and whether iNOS down-regulation was related to inhibition of nuclear factor kappaB (NF-kappaB) activation. Male Wistar rats received melatonin i.p. at a dose of 1.0 mg/kg body weight 30 min before being exercised for 60 min on a treadmill at a speed of 25 m/min and a 10% slope. Exercise caused a significant induction of iNOS protein levels and a marked activation of NF-kappaB that were significantly prevented in rats treated with melatonin. Exercise also resulted in increased IkappaB kinasealpha (IKKalpha) and phosphorylated IkappaBalpha protein levels, whereas IkappaBalpha content decreased. These effects were blocked by melatonin administration. The increase in the muscle concentration of thiobarbituric acid reactive substances and in the oxidized/reduced glutathione ratio induced by exercise was partially prevented by melatonin. Our data indicate that melatonin has potent protective effects against damage caused by acute exercise in rat muscle, preventing oxidative stress, NF-kappaB activation and iNOS over-expression. These findings support the view that melatonin treatment, by abolishing the IKK/NF-kappaB signal transduction pathway, might block the production of noxious mediators involved in the inflammatory process.


Pharmacodynamic modeling of beta-lactam antibiotics for the empiric treatment of secondary peritonitis: a report from the OPTAMA program.
In this report of the OPTAMA (Optimizing Pharmacodynamic Target Attainment using the MYSTIC Antibiogram) program, we utilized Monte Carlo simulation to compare the probabilities of achieving bactericidal time above the minimum inhibitory concentration (MIC) (%T > MIC) exposures for imipenem-cilastatin 500 mg q6h and 1000 mg q8h, meropenem 500 mg q6h and 1000 mg q8h and piperacillin/tazobactam 3.375 g q6h and 4.5 g q8h in the empiric treatment of secondary peritonitis. The prevalence of pathogens causing secondary peritonitis was identified from the primary surgical and infectious diseases literature. Data for these pathogens with respect to MIC were obtained from the 2003 MYSTIC surveillance study and weighted by the prevalence of each pathogen. A sensitivity analysis varying the prevalence of P. aeruginosa was performed with two additional models to determine the robustness of the data. Pharmacokinetic parameters, obtained from previously published studies in healthy volunteers were used to simulate the %T > MIC for 10,000 patients receiving imipenem-cilastatin, meropenem, and piperacillin/tazobactam. The likelihood of obtaining bactericidal exposure is reported. Empiric utilization of imipenem-cilastatin and meropenem 500 mg q6h and 1000 mg q8h regimens achieved 99.6%-99.7% likelihood of bactericidal exposure. Piperacillin/ tazobactam 3.375 g q6h and 4.5 g q8h produced bactericidal target attainments of 92.9% and 85.2%, respectively. Models simulating higher prevalence of P. aeruginosa reduced the likelihood of bactericidal exposure for piperacillin/tazobactam regimens significantly and had little effect on the carbapenems. All of the beta-lactams used in the current analysis were predicted to achieve high target attainment consistently for the empiric treatment of secondary peritonitis. However, imipenem-cilastatin 500 mg q6h and 1000 mg q8h, meropenem 1000 mg q8h and 500 mg q6h, and piperacillin/tazobactam 3.375 g q6h achieved the highest likelihood. These, in particular, would be effective choices for the empiric treatment of secondary peritonitis.


Avatar-Based Strategies for Breast Cancer Patients: A Systematic Review.
There is a lack of studies to determine if avatar-based protocols could be considered an efficient and accurate strategy to improve psychological well-being in oncology patients, even though it represents a growing field of research. To the best of our knowledge, this is the first systematic review addressing the effectiveness of avatar-based treatments to enhance quality of life (QoL) and psychological well-being in breast cancer patients. The purpose of this study was to review the scientific literature of those studies involving avatar-based technology and breast cancer patients in order to answer the following questions. (1) Are avatar-based strategies useful to im-prove QoL and psychological well-being (anxiety and depression symptoms) in breast cancer patients? (2) Which is the best way to develop avatar-based protocols for breast cancer patients? We conducted a systematic review of the peer-reviewed literature from EBSCO, Ovid, PubMed, Scopus, and Web of Science (WOS), following the PRISMA statements and using "avatar + breast cancer" or "avatar + cancer" as keywords. Studies which were published in either English or Spanish and which addressed QoL and psychological well-being in breast cancer patients were reviewed. The results will contribute to developing innovative avatar-based strategies focused on breast cancer patients.


Microfabrication of a micron-scale microbial-domestication pod for in situ cultivation of marine bacteria.
Through the hyphenation of microfabrication, microfluidics and microbiology, we report the development of a μMicrobial-Domestication Pod (μMD Pod). This in situ cultivation device facilitates cell signaling from neighbouring species and interactions with environmental stimuli for marine bacterial growth to overcome current barriers faced by standard laboratory cultivation methods.


Biochemical markers of mood: a proton magnetic resonance spectroscopy study of normal human brain.
Elevated brain Cho has been shown within the basal ganglia and frontal (i.e., orbitofrontal and cingulate) cortices in patients with mood disorders utilizing Proton Magnetic Resonance Spectroscopy (1H-MRS). We sought to determine the relationship between Cho and mood in a cohort of healthy young subjects. Twenty-seven subjects without neurologic or psychiatric disorders were evaluated with the Positive and Negative Affect Scale and underwent 1H-MRS of bilateral frontal and occipito-parietal white matter. We found that Cho in the left frontal lobe was inversely correlated with Positive Affect [F(1,24) = 19.2, p <.001, r(2) =.45]. Our results highlight the important involvement of Cho underlying the integration of affective processing within prefrontal circuitry, and may indicate increased myelin turnover in subjects with lower Positive Affect. Further efforts will be necessary to determine if high Cho is associated with increased incidence of mood disorders throughout life.


Charge transfer complexes: Emerging and promising colorimetric real-time chemosensors for hazardous materials.
After introducing the concept of charge transfer (CT) complex formation by Mulliken and the discovery of crystalline picrate (association of picric acid and aromatic hydrocarbons) by Fritzsches, a large interest has been drawn in this field. CT complexes have been explored and exploited for different applications for several decades. The research has been aimed mostly for discovering and characterizing new CT materials and exploring applications mainly in the field of optoelectronic properties, antimicrobial activities and DNA/protein binding properties for the last six years. However, nowadays, CT complexes are exploited for their photocatalytic activities and designing chemosensors for the colorimetric real-time detection of hazardous materials like nitro explosives, anions and toxic heavy metal ions in an aqueous medium. This review sheds light on updates on CT complexes, their types, synthesis and applications. The brief discussion on the emergence of CT complexes as highly potential chemosensors along with the explanation of sensing mechanism through article summarization is the centerpiece of this review. The final outcomes are discussed and concluded.


Multi-platform analytical evaluation of the Beckman Coulter Access high-sensitivity troponin I assay across different laboratory sites using Barricor plasma.
Previous analytical evaluations of the Beckman Coulter Access high sensitivity troponin (hsTn) I assay have focused on single platforms and laboratory sites. The purpose of this study was to determine assay robustness across different platforms at multiple sites, platform-specific characteristics, and equivalence to other hsTn methods in a large laboratory network. Barricor plasma was used to assess imprecision, linearity, sensitivity (limit of blank and detection, LOB/LOD), and comparability to the conventional AccuTnI+3 and other hsTn assays. Various studies were conducted across a total of 9 laboratories using Beckman DxI800 and Access2 platforms. Within-laboratory precision was <10% across all target patient pool concentrations, however, DxI800 mean values were 20% higher than Access2 in the range of 3.6-44.9 ng/L. LOBs and LODs were lower on DxI800, 0.27 and 0.90 ng/L, respectively, compared to 2.9 and 3.2 ng/L, on Access2. Both showed excellent linearity across the full range. In method comparison to AccuTnI+3, DxI800 had a higher slope (0.9417 versus 0.8495) and positive bias (+18.1% versus -9.9%) compared to Access2, a trend further pronounced at concentrations <150 ng/L. At values <150 ng/L, there was good agreement with Abbott hsTnI (slope = 1.017, r = 0.932), but poor agreement with the Roche hsTnT assay (slope = 1.687, r = 0.589). Inter-laboratory split sample comparisons across 2 DxI800 and 7 Access2 sites showed close agreement, except at low concentrations <10 ng/L where DxI800 was 2.8 ng/L higher (p<0.001). The Beckman hsTnI assay showed robust analytical performance across different laboratories and platforms. However, discrepancies between platforms were found at low concentrations where rapid acute myocardial infarction (AMI) rule-out decisions occur. These differences have important implications for AMI risk assessment, suggesting that laboratories should develop platform-specific parameters rather than using them interchangibly.


Potentially inappropriate medication use as predictors of hospitalization for residents in nursing home.
Hospitalization of nursing home (NH) residents impose a significant healthcare burden. However, there is still a lack of information regarding the risk of hospitalization from inappropriate prescribing in NH residents. We aimed to estimate the nationwide prevalence of potentially inappropriate medication (PIM) use among NH residents using the Korean tool and 2019 Beers criteria and to assess their associations with hospitalization or emergency department (ED) visits. We included older adults aged 65 years or above who were admitted to NHs between July 2008 and December 2018 using national senior cohort database. The prevalence of PIM use based on the Korean medication review tool and Beers criteria on the date of admission to NH was estimated. And the adjusted hazard ratios (aHRs) of polypharmacy, numbers of PIM, each PIM category for hospitalization/ED visits within 30 days of admission to NH was calculated using Cox proportional hazard model to show the association. Among 20,306 NH residents, the average number of medications per person was 7.5 ± 4.7. A total of 89.3% and 67.9% of the NH residents had at least one PIM based on the Korean tool and 2019 Beers criteria, respectively. The risk of ED visits or hospitalization significantly increased with the number of PIMs based on the Korean tool (1-3: aHR = 1.24, CI 1.03-1.49; ≥4: aHR = 1.46, CI 1.20-1.79). Having four or more PIMs based on the Beers criteria increased the risk significantly (aHR = 1.30, CI 1.06-1.53) while using 1-3 PIMs was not significantly associated (aHR = 1.07, CI 0.97-1.19). Residents with any potential medication omission according to the Korean criteria, were at 23% higher risk of hospitalization or ED visits (aHR = 1.23, CI 1.07-1.40). This study demonstrated that PIMs, based on the Korean tool and Beers criteria, were prevalent among older adults living in NHs and the use of PIMs were associated with hospitalization or ED visits. The number of PIMs based on the Korean tool showed dose-response increase in the risk of hospitalization or ED visits.


Leading components and pressure-induced color changes in N-doped lutetium hydride.
Recent experimental study by Dasenbrock-Gammon et al. (Nature 2023;615:244) claims to have discovered room-temperature superconductivity in lutetium-nitrogen-hydrogen system at 1 GPa, which sheds light on the long-held dream of ambient superconductivity. However, all follow-up experiments found no evidence of superconductivity. The compositions and the crystal structures of the lutetium-nitrogen-hydrogen system remain unknown. By employing the density functional theory based structure prediction algorithm, we suggest that in lutetium-nitrogen-hydrogen the major component is LuH2 (Fm3¯m), together with minor LuN (Fm3¯m). The blue LuH2 at ambient pressure will turn into purple and red color at higher pressures, possibly accompanied by the formation of vacancies at hydrogen-sites. In LuH2 and LuN, the density of states at the Fermi level is dominated by the Lu-5d orbitals, while those from hydrogen and nitrogen are very small, leading to the absence of superconductivity in these two compounds. Nitrogen-doping to LuH2 fails to enhance the superconductivity as well. In this work, we identify the leading components in N-doped lutetium hydride, explain its intriguing color changes under pressure, and elucidate why superconductivity is absent in the follow-up experiments.


Rethinking urban-rural designations in public health surveillance of the overdose crisis and crafting an agenda for future monitoring.
Rurality has served as a key concept in popular and scientific understandings of the US overdose crisis, with White, rural, and low-income areas thought to be most heavily affected. However, we observe that overdose trends have risen nearly uniformly across the urban-rural designations employed in most research, implying that their importance has likely been overstated or incorrectly conceptualized. Nevertheless, urbanicity/rurality does serve as a key axis to understand inequalities in overdose mortality when assessed with more nuanced modalities-employing a more granular analysis of geography at the sub-county level, and intersecting rurality sociodemographic indices such as race/ethnicity. Using national overdose data from 1999-2021, we illustrate the intersectional importance of rurality for overdose surveillance. Finally, we offer recommendations for integrating these insights into drug overdose surveillance moving forward.


Control of cell protein degradation. Changes in activities of lysosomal proteases.
In cycloheximide-treated fibroblasts, the rate of cell proteolysis and the specific activity of cathepsin D show a rapid, concurrent, and proportional decrease over a 48 h period. Cathepsin B1 also decreases, but other lysosomal enzymes show litte or no change in specific activity. These findings are consistent with the hypothesis that the rate of proteolysis in the cell is in part controlled by the specific activities of lysosomal proteases.


A novel technique for rat liver transplantation using Quick Linker system: a preliminary result.
The clinical success of liver transplantation is founded upon years of experimental research. Since Kamada and colleagues developed the "two-cuff" technique, the rat has become the best model for extensive investigations. Although the Kamada technique is technically complex and not easy to master, it is still the mainstay of orthotopic liver transplantation in rodents. We have developed a modified three-cuff version of this technique that facilitates anastomosis and markedly reduces warm ischemia time. The new technique involves a set of five microinstruments (the Quick-Linker system) designed and manufactured by our group. It was tested in male Lewis rats (group 1, donors n = 10, recipients n = 10). The graft was explanted as usual and standard cuffs were attached to the portal vein and the supra- and infrahepatic vena cavae. Corresponding vessels in the recipient were isolated, and Quicker-Linker holding rings were attached to each. The vessels were then clamped and the native organ removed. Once the graft was positioned in the recipient's abdomen, the holding rings attached to the recipient vessels and the cuffs applied to graft vessels were automatically aligned and joined with the aid of a special alignment tool. Warm ischemia times were always inferior to 6 minutes. Survival at postoperative day 10 was 80%. Liver function was well preserved in all of the surviving rats. The Quick-Linker technique significantly shortens warm ischemia time and allows rapid anastomosis that is relatively independent of operator skill. It can be considered a reliable option for microsurgeons looking for quick results and high success rates.


Recycling of poly (lactic acid)/silk based bionanocomposites films and its influence on thermal stability, crystallization kinetics, solution and melt rheology.
In this study, the effect of silk nanocrystals (SNCs) on the thermal and rheological properties of poly (lactic acid) (PLA) under repetitive extrusion process is investigated. The presence of SNCs facilitates the crystallization process and delaying the thermal degradation of PLA matrix. This leads to the reduction in cold crystallization peak temperature with lower crystallization half-time and higher growth rate. The substantial improvement in nucleation density observed through Polarized Optical Microscope (POM) proves the nucleating effect of SNC in all processing cycles. Moreover, the rheological investigation (complex viscosity, storage and loss modules values) revealed the stabilizing effect of SNC and the drastic degradation of neat PLA (NPLA) in third and fourth cycle is observed to be fortified by the presence of SNC. Cole-Cole plot and cross over frequencies have been correlated with the molar mass distribution of PLA and PLA-Silk composite during processing, which is further supported by the intrinsic viscosity measurement and acid value analysis. This investigation suggests that the melt viscosity and thermal properties of PLA can be stabilized by addition of silk nanocrystals.


The seasonal variation, characteristics and secondary generation of PM2.5 in Xi'an, China, especially during pollution events.
As an important central city in western China, Xi'an has the worst atmospheric pollution record in China and many measures have been taken to improve the air quality in the past few years. In this study, PM2.5 samples were collected across four seasons from 2017 to 2018 in Xi'an. Organic carbon and elemental carbon, water soluble ions, and elements were monitored to assess the air quality. The average annual PM2.5 concentration was (134.9 ± 48.1 μg/m3), with the highest concentration in winter (188.8 ± 93.2 μg/m3), and lowest concentration in summer (71.2 ± 12.1 μg/m3). The secondary generation of sulfate (SO42-) and nitrate (NO3-) was strong in spring, and secondary organic carbon (SOC) was formed in all seasons. The compositions of PM2.5 changed greatly during a sandstorm occurred and the Spring Festival. The sandstorm played a positive role in removing local pollutant NO3-, but also increased the concentration of SO42-, however both the concentration of SO42- and NO3- greatly increased by secondary generation during Spring Festival. Potential source analysis showed that during the sandstorm, pollutants were transported over a long distance from the northwest of China, whereas it was mainly from the local and surrounded emissions during the Spring Festival. Except Ca2+ and geological dust (GM), the other components in PM2.5 increased significantly on the day of the Spring Festival. During sampling time in Xi'an, the positive matrix factorization (PMF) model analysis showed that PM2.5 mainly came from vehicle emission, coal combustion, and biomass burning.


Oncocytic renal cell carcinoma with immunohistochemical properties of renal oncocytoma.
Renal oncocytoma (RO) is a characteristic benign renal tumor. The existence of malignant RO is controversial and anecdotal, partly due to a lack of specific markers for RO. With recent advances in immunohistochemistry, RO can be distinguished from other renal neoplasms with routine stains and with the aid of immunostaining. We report two cases of renal neoplasms with similar histopathological appearances. They were characterized by oncocytic cytoplasm, numerous intra-cytoplasmic vacuoles, uniform round to oval hyperchromatic nuclei with remarkably thick nuclear membranes and prominent nucleoli. The tumor cells were closely packed and disposed in an alveolar pattern. The neoplastic cells were diffusely reactive for CD117 and progesterone receptor, and diffusely or focally reactive for cytokeratin AE1/AE3, and focally reactive for cytokeratin 7, CD10, and racemase. The cells were non-reactive for renal cell carcinoma (RCC) antigen, vimentin, S100, and neuroendocrine markers. One tumor showed lymph node metastasis. Due to the remarkable cytological atypia, lymph node metastasis, and similar immunological features of RO, these two tumors likely represent a distinct subtype of RCC related to RO.


Construction and Validation of a Novel Web-Based Nomogram for Solitary Plasmacytoma of Bone of the Spine: A Real-World Analysis Based on the Surveillance, Epidemiology, and End Results Database.
Solitary plasmacytoma of bone of the spine (SPBS) was rarely detected in the past. However, its incidence has gradually increased with improvements in the diagnosis and understanding of the disease. We aimed to conduct a population-based cohort study to characterize the prevalence and factors associated with SPBS and develop a prognostic nomogram for predicting the overall survival of SPBS patients with a real-world analysis based on the surveillance, epidemiology, and end results database. Patients with SPBS at diagnosis were identified using the SEER database from 2000-2018. Multivariable and univariate logistic regression analyses were used to identify factors for developing a novel nomogram. Nomogram performance was evaluated using the calibration curve, area under the curve (AUC), and decision curve analyses. Kaplan-Meier analysis was used to estimate survival durations. A total of 1,147 patients were selected for survival analysis. Multivariate analysis demonstrated that independent predictors for SPBS were as follows: ages: 61-74 and 75-94, marital status: unmarried, treatment: radiation alone and radiation with surgery. The 1-, 3-, and 5-year AUCs for OS were 0.733, 0.735, and 0.735 in the training cohort and 0.754, 0.777, and 0.791 in the validation cohort, respectively. The C-index values in the 2 cohorts were 0.704 and 0.729. The results indicated that nomograms could satisfactorily identify patients with SPBS. Our model effectively demonstrated the clinicopathological features of SPBS patients. The results indicated that the nomogram had a favorable discriminatory ability, good consistency, and yielded clinical benefits for SPBS patients.


Compliance with 10 years oral hormonal replacement therapy.
To study 10 years compliance with oral hormonal replacement therapy (HRT). One hundred and fifty-one early postmenopausal women were initially randomly allocated to three groups in a double blind, 2-year placebo controlled trial. Fifty women received continuous combined therapy, 50 were placed on sequential therapy, while the last 51 women were given placebo for 2 years and after that no therapy. After the trial, the women were followed in an open investigation for a total of 10 years. One hundred and twenty-six women (83%) out of 151 came to a 10-year interview, 4% had died and the remaining did not want to participate. None of the women in the combined group had changed to other regimens (42% were still in treatment after 10 years). Twenty-four percent from the original sequential group were still in sequential therapy; another 24% of the group had changed to other HRTs (mainly because the women disliked the monthly bleedings). Fifty-three percent of the women from the placebo group had not received any HRT. Eighteen percent were on HRT. Eighty-seven percent of the women who had taken combined therapy for 8 years were still being treated at the tenth years' visit. Long-term compliance was excellent for continuous combined therapy and better than for sequential after 10 years.


Identification of an anti-MRSA dihydrofolate reductase inhibitor from a diversity-oriented synthesis.
The screening of a diversity-oriented synthesis library followed by structure-activity relationship investigations have led to the discovery of an anti-MRSA agent which operates as an inhibitor of Staphylococcus aureus dihydrofolate reductase.


Genome-scale modeling enables metabolic engineering of Saccharomyces cerevisiae for succinic acid production.
In this work, we describe the application of a genome-scale metabolic model and flux balance analysis for the prediction of succinic acid overproduction strategies in Saccharomyces cerevisiae. The top three single gene deletion strategies, Δmdh1, Δoac1, and Δdic1, were tested using knock-out strains cultivated anaerobically on glucose, coupled with physiological and DNA microarray characterization. While Δmdh1 and Δoac1 strains failed to produce succinate, Δdic1 produced 0.02 C-mol/C-mol glucose, in close agreement with model predictions (0.03 C-mol/C-mol glucose). Transcriptional profiling suggests that succinate formation is coupled to mitochondrial redox balancing, and more specifically, reductive TCA cycle activity. While far from industrial titers, this proof-of-concept suggests that in silico predictions coupled with experimental validation can be used to identify novel and non-intuitive metabolic engineering strategies.


EMHP: an accurate automated hole masking algorithm for single-particle cryo-EM image processing.
The Electron Microscopy Hole Punch (EMHP) is a streamlined suite of tools for quick assessment, sorting and hole masking of electron micrographs. With recent advances in single-particle electron cryo-microscopy (cryo-EM) data processing allowing for the rapid determination of protein structures using a smaller computational footprint, we saw the need for a fast and simple tool for data pre-processing that could run independent of existing high-performance computing (HPC) infrastructures. EMHP provides a data preprocessing platform in a small package that requires minimal python dependencies to function. https://www.bitbucket.org/chazbot/emhp Apache 2.0 License. email@example.com. Supplementary data are available at Bioinformatics online.


Computational and spectral analysis of derivatives of 9,9-dimethyl-9,10-dihydroacridine and 10-Phenyl-10H-phenothiazine-5,5-dioxide with hybridized local and charge-transfer excited states for optoelectronic applications.
Aiming to combine the advantages of both prompt fluorescence and thermally activated delayed fluorescence in single emitter, molecular design of emitters with hybridized locally excited and charge transfer states were investigated by computational approaches and optical spectroscopy. Taking into account the results of the theoretical screening, the most promising derivatives of 9,9-dimethyl-9,10-dihydroacridine and 10-phenyl-10H-phenothiazine-5,5-dioxide based with the different linking topology (meta- and para-isomers) were selected for the synthesis and experimental investigations. Both the compounds exhibit ultraviolet LE emission peaking at ca. 360 nm, green ICT peaking at ca. 510 nm, and deep-blue HLCT emission peaking at ca. 430 nm when they are molecularly dispersed in the solid media of the different polarity. The developed emitters allow to obtain deep-blue electroluminescence for the host-containing OLEDs and green electroluminescence of host-free devices with the efficiency of exciton production of 42 and 73%, respectively. Efficient exciton production is due to the spin-flip switching via thermally activated processes which is much more efficient than prompt fluorescence. Showing the impact of the linking topology, the para-isomer demonstrated more efficient triplet harvesting in OLEDs than meta-isomer. A detailed discussion on the structure-property relationships and on some discrepancies between the results of the results of theoretical calculations and spectral analysis allows to obtain important insights on the photophysical properties of these compounds.


Head-dipping in rats with superior collicular, medial frontal cortical and hippocampal lesions.
When tested in a modified "holeboard" apparatus, hooded rats with deep superior collicular lesions were hyperactive, reared less than controls and spent a great deal of time at the apparatus perimeter. They failed to explore holes in the floor and frequently fell into them. Those with lesions restricted to superficial laminae showed reduced rearing, and preference for the perimeter but were normally active and explored floor holes as frequently as controls. The frontal cortical group failed to differ from controls on any measure. Hippocampals exhibited reduced intersession habituation of locomotor activity. It was concluded that superior colliculus, hippocampus and medial frontal cortex have separate functional roles. Differences between deep and superficial collicular lesion effects might arise because deep lesions disrupt both motor integration and attention while superficial lesions disrupt only the latter. Alternatively, since superficial lesions spare lateral tissue subserving attention to stimuli in lower portions of the visual field, they may produce a less global attentional deficiency which has less impact upon motor function.


A novel technique-Prophylactic septal radiofrequency ablation to prevent left ventricular outflow tract obstruction with transcatheter mitral valve replacement (RADIO-TMVR).
Transcatheter mitral valve replacement (TMVR) with off-label use of aortic balloon-expandable transcatheter heart valves has emerged as a therapeutic option in high-surgical risk patients with severe mitral annular calcification. Left ventricular outflow tract (LVOT) obstruction post valve deployment is a major limitation. We describe a case of septal reduction therapy using radiofrequency ablation (RFA) when established methods of septal reduction were either ineffective or not feasible. RFA permitted successful enlargement of the LVOT area and subsequent TMVR.


Aggregation of poorly crystalline and amorphous components of infectious urinary stones is mediated by bacterial lipopolysaccharide.
Poorly crystalline and amorphous precipitate (PCaAP) is one of the components of the so-called infectious urinary stones, which are the result of the activity of urease-producing microorganisms, mainly from the Proteus species, in particular Proteus mirabilis. The main component of this kind of stones is crystalline struvite (MgNH4PO4∙6H2O). Bacteria can build into the structure of the urinary stone and, in this way, they are one of the components of the urinary stone. From these three components - PCaAP, struvite and Proteus mirabilis - PCaAP exhibits the greatest ability to aggregate. The present study focuses on the aggregation of PCaAP. In particular, an influence of lipopolysaccharide (LPS) isolated from Proteus mirabilis on aggregation of PCaAP is presented. An aggregation of PCaAP is characterized by cross-sectional area of aggregates and zeta potential. The results demonstrate that, in artificial urine, the influence of freely suspended LPS on aggregation of PCaAP depends on the concentrations of LPS. Small concentrations of freely suspended LPS enhance the aggregation of PCaAP compared to the control test. For high concentrations of freely suspended LPS the formation of aggregates of PCaAP is inhibited. LPS, which is not freely suspended, but covers polystyrene latex beads, has no such properties. The investigations provide evidence for the importance of biological regulation in the PCaAP aggregation process.


Effect of reserpine on cell proliferation in the developing rat bran: a biochemical study.
Reserpine, a well-known CNS depressant which depletes central monoamine stores, was found to produce in the brains of 11-day-old rats a severe depression in cell proliferation in terms of the rate of [3H]thymidine incorporation into DNA. The effect was studied in detail 12 h after ther administration of the drug (2.5 mg/kg, s.c.) when the rate of in vivo DNA synthesis in the forebrain was about one-third of control: the decrease was less marked in the cerebellum (rate about two-thirds of control). It was possible to exclude side effects of the drug, such as restricted food intake, hypothermia and an elevation of the level of blood corticosteroids being responsible for the reduction of [3H]thymidine incorporation into DNA. Kinetic studies showed that reserpine had no marked effect on the entry of [3H]thymidine from blood to brain, but it caused some retardation in the rate of [3H]thymidine conversion into [3H]thymidine nucleotides. Nevertheless, the severe depression of DNA labelling was evident even after correcting the values on the basis of [3H]thymidine nucleotide concentrations. In contrast to these effects, thymidine kinase activity was normal in the brain of reserpine-treated animals.


The birth of piRNAs: how mammalian piRNAs are produced, originated, and evolved.
PIWI-interacting RNAs (piRNAs), small noncoding RNAs 24-35 nucleotides long, are essential for animal fertility. They play critical roles in a range of functions, including transposable element suppression, gene expression regulation, imprinting, and viral defense. In mammals, piRNAs are the most abundant small RNAs in adult testes and the only small RNAs that direct epigenetic modification of chromatin in the nucleus. The production of piRNAs is a complex process from transcription to post-transcription, requiring unique machinery often distinct from the biogenesis of other RNAs. In mice, piRNA biogenesis occurs in specialized subcellular locations, involves dynamic developmental regulation, and displays sexual dimorphism. Furthermore, the genomic loci and sequences of piRNAs evolve much more rapidly than most of the genomic regions. Understanding piRNA biogenesis should reveal novel RNA regulations recognizing and processing piRNA precursors and the forces driving the gain and loss of piRNAs during animal evolution. Such findings may provide the basis for the development of engineered piRNAs capable of modulating epigenetic regulation, thereby offering possible single-dose RNA therapy without changing the genomic DNA. In this review, we focus on the biogenesis of piRNAs in mammalian adult testes that are derived from long non-coding RNAs. Although piRNA biogenesis is believed to be evolutionarily conserved from fruit flies to humans, recent studies argue for the existence of diverse, mammalian-specific RNA-processing pathways that convert precursor RNAs into piRNAs, perhaps associated with the unique features of mammalian piRNAs or germ cell development. We end with the discussion of major questions in the field, including substrate recognition and the birth of new piRNAs.


[Is it possible to avoid pathological grief if relatives of patients with palliative diseases are supported?].
The transition from normal to pathological grief is smooth. If it is almost impossible to define normal grief with all the existing descriptions of grief phases and systematic models, then it is all the more difficult to define pathological or complicated grief, especially as the existence of remaining grief, or remaining grief that rises to the surface again through memories, are considered normal processes of grief. Remaining grief does not compare with unfinished deep mourning, and so it is not pathological. The response to grief in this case report seems to be pathological or complicated because the process involved in grieving has been replaced by a kind of emotional stagnation, marked by aggression and a feeling of guilt. The family-centred therapeutic approach, taking in the whole family and aimed at discovering potential risk factors for the relatives and the strain they are under, as well as a recognition of the next-of-kin as "secondary patients" have an important role to play in the avoidance of pathological grief.


Cocaine exposure during pregnancy affects rat neonate and maternal brain glycosphingolipids.
Behavioral dysfunctions in offspring exposed in utero to cocaine have been observed, along with alterations in dopamine systems, but few studies of the underlying biochemistry have been conducted. Because of their documented roles in neuronal maturation, glycosphingolipids were analyzed in whole brains of offspring exposed gestationally to cocaine. Rat offspring exposed to cocaine in utero exhibited markedly elevated levels of both total gangliosides (p < 0.001) and neutral glycosphingolipids (p < 0.01) at postnatal day 1. However, by postnatal day 11 levels of gangliosides and neutral glycosphingolipids returned to control values. These effects were not restricted to chronic cocaine exposure early in life, in that ganglioside content of whole maternal brains was also elevated (p < 0.001), though less than that observed with the neonate brains. Qualitatively, no differences in ganglioside nor neutral glycolipid structure distribution were observed between cocaine-exposed and normal animals following separation by HPTLC and HPLC. These elevations are in contrast to those following alcohol exposure, where decreases in brain gangliosides have been observed. Neurochemical consequences of prenatal exposure to cocaine may be far-reaching and may not be restricted to the dopamine system.


Pharmacodynamic comparison of regional drug delivery for non-steroidal anti-inflammatory drugs, using the rat air-pouch model of inflammation.
The inhibition of prostaglandin E2 (PGE2) synthesis by S-(+)-ibuprofen and piroxicam have been assessed following intravenous and regional (intrapouch) drug delivery using the rat air-pouch model of inflammation. Anti-inflammatory response was defined as the decrease in the area under the exudate PGE2 concentration-time curve between 3 and 10 h, following regional administration of the irritant carrageenan. Dose-response studies indicated that bolus regional administration of S-(+)-ibuprofen increased potency 30-fold compared with systemic administration and could be further improved 10-fold by regional infusion, whereas regional administration of piroxicam showed no therapeutic advantage. Examination of the concentration-response using AUC revealed that for a given response, average pouch concentrations for S-(+)-ibuprofen during the PGE2 inflammatory response (3 to 10 h) was similar, irrespective of route or mode of administration. In contrast, an advantage following systemic rather than regional administration was revealed for piroxicam, based on plasma concentration-response data, indicating a major systemic anti-inflammatory component for piroxicam but not for S-(+)-ibuprofen. These observations stress the need to take account of both pharmacodynamics and pharmacokinetics when considering the potential advantage of regional administration.


Complete Genome Sequence of a Japanese Clinical Isolate of Haemophilus influenzae Type a Strain TAMBA230.
Haemophilus influenzae causes severe infections such as pneumonia and meningitis. Here, we report the complete genome of H. influenzae type a strain TAMBA230, which was isolated in 2019 from a patient exhibiting bacteremia. This represents the first case in Japan of an H. influenzae type a strain associated with invasive infection.


Design and application of nickel-titanium olecranon memory connector in treatment of olecranon fractures: a prospective randomized controlled trial.
We carried out this study to test the efficacy of the olecranon memory connector (OMC) in olecranon fractures. We designed a prospective randomised controlled trial involving 40 cases of olecranon fractures. From May 2004 to December 2009, 40 patients with olecranon fractures were randomly assigned into two groups. Twenty patients were treated with OMC, while another 20 patients were fixed with locking plates in our hospital. The DASH score, MEP score, range of motion and radiographs were used to evaluate the postoperative elbow function and complications. For MEP score, OMC was better than the locking plate; for DASH score, complication rate, and range of elbow motion, the two methods presented no significant difference. The study showed that OMC could be an effective alternative to treat olecranon fractures.


Neonatal hypoglycaemia in infants of diabetic mothers.
To determine whether umbilical cord blood glucose correlates with subsequent hypoglycaemia after birth in infants of well-controlled diabetic mothers. Thirty-eight term infants of well-controlled diabetic mothers were enrolled. Five mothers had pre-existing diabetes. Of the 33 gestational diabetic mothers, 16 were managed on insulin and 17 on diet. Maternal blood glucose was maintained between 4 and 8 mmol/L during labour and delivery. Infants' plasma glucose levels were measured from venous cord blood and serially, at less than 30 min, 1 h and 2 h of life by glucose hexokinase method. Blood glucose levels were further monitored by bedside Dextrostix for 24 h. Eighteen (47%) infants developed hypoglycaemia (blood glucose level less than 2 mmol/L) during the first 2 h of life. There was no difference in the cord blood glucose levels between infants with or without hypoglycaemia (3.7 +/- 1.1 vs 4.5 +/- 1.1 mmol/L, respectively). Infants of mothers with diabetes diagnosed prior to 28 weeks gestation were at a higher risk of developing hypoglycaemia (8 of 10 vs 10 of 28, OR 7.2, 95%CI 1.3-40.7). Hypoglycaemic infants were of significantly higher birthweight, and were more likely to be born to Caucasian mothers and by Caesarean section. Raised maternal fructosamine blood level, the need for insulin treatment or the infant's haematocrit were not different between infants with or without hypoglycaemia. In well-controlled diabetic mothers, the incidence of early hypoglycaemia in infants is still high, particularly in those mothers who had a longer duration of diabetes. Cord blood glucose level did not identify the infants with hypoglycaemia.


Assessment of cardiac output in children: a comparison between the pressure recording analytical method and Doppler echocardiography.
To assess cardiac output in pediatric patients with the pressure recording analytical method (PRAM) and the Doppler echocardiography method. PRAM derives cardiac output from beat-by-beat analysis of the arterial pressure profile (systolic and diastolic phase) in the time domain. A prospective observational study. Pediatric intensive care unit at a tertiary care children's hospital. Forty-eight patients between the ages of 1 month and 18 yrs. Femoral or radial artery catheterization and mechanical ventilation. Cardiac output was simultaneously estimated by Doppler echocardiography and PRAM. Cardiac output values obtained by Doppler echocardiography (2.7 +/- 1.6 L/min, range 0.92-8.20) were significantly correlated with those estimated by PRAM (2.6 +/- 1.7 L/min, range 0.89-7.48; r2 = .99, p < .01). The mean difference between the two estimates was 0.12 +/- 0.27 L x min(-1) (95% confidence interval, -0.54 to 0.77 L x min(-1)). In the range of ages evaluated, PRAM provides reliable estimates of cardiac output when compared with noninvasive techniques.


Platinum(II) Schiff base as versatile phosphorescent core component in conjugated oligo(phenylene-ethynylene)s.
Novel phosphorescent conjugated oligo(phenylene-ethynylene)s featuring a central tunable platinum(II) Schiff base signalling unit with promising photophysical properties have been investigated to pave their development towards polymeric congeners for sensing applications.


A randomised trial comparing the CEL-100 videolaryngoscope(TM) with the Macintosh laryngoscope blade for insertion of double-lumen tubes.
We performed a randomised trial comparing the CEL-100 videolaryngoscope(TM) with the Macintosh laryngoscope blade in 170 patients undergoing double-lumen tube placement for thoracic surgery. Compared with the Macintosh laryngoscope blade, use of the CEL-100 resulted in significantly more patients with a Cormack and Lehane Grade-1 laryngeal view (90.4% vs 61.0%, p < 0.001), a higher rate of successful intubation on the first attempt (92.8% vs 79.3%, p = 0.012), a lower median (IQR [range]) intubation difficulty score (0 (0-0 [0-60]) vs 15 (0-30 [0-80]), p < 0.001), a higher incidence of correct positioning of the tube (90.3% vs 79.2%, p = 0.041) and significantly fewer patients requiring external laryngeal pressure (19.3% vs 32.9%, p = 0.046). Median (IQR [range]) time to successful intubation was 45 (38-55 [22-132]) s with the CEL-100 compared with 51 (40-61 [30-160] s using the Macintosh laryngoscope blade. We conclude that the CEL-100 videolaryngoscope is superior to the Macintosh laryngoscope blade for double-lumen tube insertion.


Comparative study of thermally activated delayed fluorescent properties of donor-acceptor and donor-acceptor-donor architectures based on phenoxazine and dibenzo[a,j]phenazine.
A new thermally activated delayed fluorescence (TADF) compound based on a donor-acceptor (D-A) architecture (D = phenoxazine; A = dibenzo[a,j]phenazine) has been developed, and its photophysical properties were characterized. The D-A compound is applicable as an emitting material for efficient organic light-emitting diodes (OLEDs), and its external quantum efficiency (EQE) exceeds the theoretical maximum of those with prompt fluorescent emitters. Most importantly, comparative study of the D-A molecule and its D-A-D counterpart from the viewpoints of the experiments and theoretical calculations revealed the effect of the number of the electron donor on the thermally activated delayed fluorescent behavior.


Two-photon absorption enhancement induced by aggregation due to intermolecular hydrogen bonding in V-shaped 2-hydroxypyrimidine derivatives.
The aggregation of V-shaped hydroxypyrimidine derivatives is formed through an intermolecular hydrogen bond in chloroform that cannot form a hydrogen bond with the solute, giving rise to a large enhancement of the two-photon absorption and two-photon induced fluorescence.


The C-terminal region of the hepatitis B virus X protein is required for its stimulation of HBV replication in primary mouse hepatocytes.
Hepatitis B virus (HBV) infection is an important risk factor for hepatocellular carcinoma (HCC). The hepatitis B virus X protein (HBx), a multifunctional regulatory protein encoded by HBV, is known to be involved in stimulation of viral replication by modulating cell cycle status. HBx is required for maximal virus replication in plasmid-based replication assays in immortalized human liver HepG2 cells and in primary rat hepatocytes. Moreover, the C-terminal region of HBx is important for HBV replication in HepG2 cells. However, in normal hepatocytes, the region of HBx that is responsible for its effect on cell cycle regulation and HBV replication is unclear. We have demonstrated that HBx is similarly required for maximal HBV replication in primary mouse hepatocytes and that the C-terminus of HBx is essential for its ability to stimulate HBV replication by inducing quiescent hepatocytes to exit G0 phase of the cell cycle but stall in G1 phase. Our studies establish that primary mouse hepatocytes support HBx-dependent HBV replication, and provide further evidence for the effect of the C-terminal region of HBx on HBV infection and replication.


Merocel compression dressing: a novel modified surgical technique for treating auricular pseudocyst.
Auricular pseudocyst (AP) is a benign, noninflammatory swelling to the ear, located on either the front or side surface. Deroofing surgery with variable compression methods is considered the most effective method. However, post-operative wound pain is the main drawback following compression. We are introducing a novel painless surgical procedure which involves deroofing technique followed by Merocel® compression dressing. From 2015 to 2020, thirty-one patients with AP received this new surgical compression method in our university-affiliated tertiary hospital. Retrospective chart review and the analysis of the results were conducted. All patients had unilateral lesions, with left side lesions (58.1%) predominant. The concha cymba (38.7%) and concha cavum (35.8%) were the most common sites. Previous aspiration or drainage had been performed for the cysts in eight patients (25.8%). Only one patient had the recurrence after post-operative 3 months and received the revised surgery without following recurrence and discomfort. Among all patients, 29 (93.5%) patients claimed minimal pain around 0 or 1 in numeric rating scale of pain score. Three patients had mild ecchymosis but recovered after conservative treatment. One patient had mild auricular deformity after surgery due to pre-treatment partial cartilage necrosis. All patients had follow-up for at least 6 months. This novel Merocel® compression dressing technique to treat AP after deroofing is an effective procedure. Minimal pain, simple to do and easily acquired materials were the advantages of this novel procedure.


Synthesis and in vitro study of novel 7-O-acyl derivatives of Oroxylin A as antibacterial agents.
A series of Oroxylin A derivatives, prepared by alkylation and condensation, were fully characterized by spectroscopic methods. All the derivatives were screened for antibacterial activity against a panel of susceptible and resistant Gram-positive and Gram-negative organisms. It was observed that acylation of 7-OH group in Oroxylin A significantly enhanced the activity as compared to their parent compound (Oroxylin A).


[Aneurysm of the iliac artery in an elderly subject. Role of treatment with covered endoprosthesis].
Coated stents can be an alternative to open surgery for arterial aneurysms, particularly in patients with high operative risk. A 90-year-old man with advanced stage cardiopathy developed a 52 mm aneurysm of the iliac artery. Perioperative imaging (arteriography with marked catheter, CT-scan and endovascular ultrasonography) provided a precise description. The material used (PTFE coated thermal memory endoprosthesis, balloon in the hypogastric) provided effective exclusion. Endovascular treatment can be a useful alternative to open surgery for arterial aneurysm in the very elderly.


Electrochemical behavior of tectoridin and its sensitive determination based on L-arginine modified electrode.
A simple, inexpensive and highly sensitive voltammetric method for the determination of tectoridin was developed using a poly(L-Arginine) modified electrode. The redox character of tectoridin at proposed electrode was studied systematically and some dynamic parameters were calculated for the first time. A reasonable reaction mechanism of tectoridin on the poly(L-Arginine)/GCE was also dicussed and proposed, which could be a reference for the pharmacological action of tectoridin in clinical study. And the electroanalytical method for determination of tectoridin was established by differential pulse voltammograms (DPV). Under optimum conditions, the response peak currents were linear relationship with tectoridin concentrations in the range of 5.0×10(-8)-2.0×10(-6) mol L(-1) with a detection limit of 4.0×10(-8) mol L(-1). Therefore, the high sensitivity for tectoridin sensing at the proposed electrode was achieved, and the proposed method could also be used to detect tectoridin in the Chinese medicinal herb Blackberrylily with satisfactory results.


Stranded pellets in Fildes Peninsula (King George Island, Antarctica): New evidence of Southern Ocean connectivity.
Plastic and microplastic debris is transported by ocean currents over long distances, reaching remote areas, far from its original source. In Polar Regions, microplastics (MPs) can come from local activities or be transported from lower latitudes, with the former being the likely and major source. Although historically Antarctica was considered isolated from the global ocean, there is recent evidence of materials and organisms being transported in and out of the Southern Ocean, despite its multi-front structure. During the austral summer of 2019, beach surveys were conducted on the NW coast of the Fildes Peninsula (King George Island). The beach was characterised, and the first 2 cm of sediment from 5 quadrants (50 × 50 cm) along 100 m of the highest strandline were collected. Large microplastics (LMPs) and mesoplastics (MesoPs) were isolated, counted, measured, weighed and classified by shape. Polymer composition was analysed by FTIR and ageing estimated by Carbonyl Index. We found 293 items of LMPs (188 items) and MesoPs (105 items), with a total average density (±SD) of 234.4 ± 166 items m-2. Foams (130.4 ± 76.3), fragments (58.4 ± 56.0) and pellets (44.0 ± 50.5) were the most abundant shapes. The main polymers found were polystyrene, polypropylene, and polyethylene. We found pellets among the MesoPs, being the first record for beaches in Antarctica. The presence of these primary MPs south of 62°S not only alerts about their possible direct consequences on Antarctic ecosystems, but also gives empirical evidence for the passive entry of plastic debris from lower latitudes through cross-frontal exchanges, providing new evidence of a global connectivity of the Southern Ocean. Despite increasing research, knowledge of plastics dynamics and their impact in the Southern Ocean and Antarctica is still limited but certainly necessary.


Rate of gestational weight gain trajectory is associated with adverse pregnancy outcomes.
To examine the gestational weight gain (GWG) trajectory and its possible association with pregnancy outcomes. GWG trajectories were identified using the latent class growth model. Binary logistic regression was performed to examine the associations between adverse pregnancy outcomes and these trajectories. Negeri Sembilan, Malaysia. Two thousand one hundred ninety-three pregnant women. Three GWG trajectories were identified: 'Group 1 - slow initial GWG but followed by drastic GWG', 'Group 2 - maintaining rate of GWG at 0·58 kg/week' and 'Group 3 - maintaining rate of GWG at 0·38 kg/week'. Group 1 had higher risk of postpartum weight retention (PWR) (adjusted OR (AOR) 1·02, 95 % CI 1·01, 1·04), caesarean delivery (AOR 1·03, 95 % CI 1·01, 1·04) and having low birth weight (AOR 1·04, 95 % CI 1·02, 1·05) compared with group 3. Group 2 was at higher risk of PWR (AOR 1·18, 95 % CI 1·16, 1·21), preterm delivery (AOR 1·03, 95 % CI 1·01, 1·05) and caesarean delivery (AOR 1·02, 95 % CI 1·01, 1·03), but at lower risk of having small-for-gestational-age infants (AOR 0·97, 95 % CI 0·96, 0·99) compared with group 3. The significant associations between group 1 and PWR were observed among non-overweight/obese women; between group 1 and caesarean delivery among overweight/obese women; group 2 with preterm delivery and caesarean delivery were only found among overweight/obese women. Higher GWG as well as increasing GWG trajectories was associated with higher risk of adverse pregnancy outcomes. Promoting GWG within the recommended range should be emphasised in antenatal care to prevent the risk of adverse pregnancy outcomes.


Analysis of rs1864182 and rs1864183 variants in ATG10 gene and antineutrophil cytoplasmic autoantibody-associated vasculitis in Chinese Guangxi population.
To investigate the association of autophagy-associated gene 10 (ATG10) gene polymorphisms (rs1864182 and rs1864183) with antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) in Chinese Guangxi population. The single nucleotide polymorphisms (SNPs) of ATG10 rs1864182 and rs1864183 in 395 participants (195 AAVs and 200 healthy controls) were genotyped. Generalized multiple dimensionality reduction (GMDR) was used to analyze the SNP-SNP interactions among two SNPs of ATG10 gene and other SNPs of autophagy gene previously studied by our research team. In this study, we found that the two ATG10 SNPs were not associated with AAV risk in Chinese Guangxi population. However, there were statistically significant differences in the incidence of hemoptysis, hematuria, and proteinuria among the three genotypes of ATG10 rs1864182 and rs1864183 (p < 0.05). Moreover, permutation test of GMDR suggested that immunity-related GTPase M(IRGM) rs4958847, autophagy-associated gene 7 (ATG7) rs6442260, ATG7 rs2594966, ATG10 rs1864183, protein kinase B(AKT2) rs3730051, and AKT2 rs11552192 might interact with each other in the process of developing AAV (p < 0.05). Our results indicated that there existed no association between ATG10 SNPs and AAV, and SNP-SNP interactions among IRGM rs4958847, ATG7 rs6442260, ATG7 rs2594966, ATG10 rs1864183, AKT2 rs3730051, and AKT2 rs11552192 may confer AAV risk in the Chinese Guangxi population.


Demystifying 'Deaths of Despair': An Interview with Medical Anthropologist Dr. Jennifer J. Carroll.
Healthy North Carolina 2030 aims to increase life expectancy in the state from 77.6 to 82.0 by the end of the current decade. Among the most influential barriers are overdose deaths and suicide rates, which are often referred to as "deaths of despair." In this interview, Managing Editor Kaitlin Ugolik Phillips talks with Jennifer J. Carroll, PhD, MPH, about the evolution of the concept and potential levers for change.


Adolescents' Daily Worry, Morning Cortisol, and Health Symptoms.
To assess short-term effects of daily worries on hypothalamic-pituitary-adrenal axis activity and later implications for adolescents' health symptoms. We hypothesized that heightened worry would be associated with stronger next-morning cortisol awakening response (CAR) to prepare the body for the demands of the upcoming day. Guided by biological adaptation to stress theories, we also hypothesized that dysregulated CAR would heighten associations between worries and later health symptoms, while also testing direct associations between worries and dysregulated CAR and health. Ninety-nine late adolescents during waves 5 and 6 of a longitudinal study reported on 26 worries for 10 days. On 3 of the 10 days, participants also provided morning saliva samples that were assayed for cortisol to capture the CAR. At both waves, participants reported on 22 common health symptoms. Multilevel models showed significant within-person associations between high daily worries and next-morning heightened CAR for females. Contrary to expectation, worries were inversely related to concurrent health symptoms. For the whole sample, CAR moderated the effect of worries on later health symptoms: Worries were positively associated with health symptoms in adolescents with high CAR and inversely associated with health symptoms for those with low CAR. In this sample of typically developing adolescents, worries alone do not increase the risk for common health complaints and may be somewhat protective in the short run. However, high worries in the context of high CAR appear to increase the risk for health symptoms.


Checkpoint control and cancer.
DNA-damaging therapies represent the most frequently used non-surgical anticancer strategies in the treatment of human tumors. These therapies can kill tumor cells, but at the same time they can be particularly damaging and mutagenic to healthy tissues. The efficacy of DNA-damaging treatments can be improved if tumor cell death is selectively enhanced, and the recent application of poly-(ADP-ribose) polymerase inhibitors in BRCA1/2-deficient tumors is a successful example of this. DNA damage is known to trigger cell-cycle arrest through activation of DNA-damage checkpoints. This arrest can be reversed once the damage has been repaired, but irreparable damage can promote apoptosis or senescence. Alternatively, cells can reenter the cell cycle before repair has been completed, giving rise to mutations. In this review we discuss the mechanisms involved in the activation and inactivation of DNA-damage checkpoints, and how the transition from arrest and cell-cycle re-entry is controlled. In addition, we discuss recent attempts to target the checkpoint in anticancer strategies.


Amnesic effects and subjective ratings during repeated dosing of flunitrazepam to healthy volunteers.
Flunitrazepam (1 mg) or placebo was administered once daily over a treatment period of 8 days to healthy, male volunteers to study the time course of the effects on memory functions and on subjective ratings of alertness and tension. The plasma level of flunitrazepam increased by approximately 40% (P < 0.05) during the treatment period. The mean pre-dose level of flunitrazepam on day 4 and day 8 was approximately 0.005 microM, and no residual effects on memory functions were observed. Intake of flunitrazepam decreased the number of freely recalled words by about 85% (P < 0.05) and significantly affected the subjects' rating of attention when tested during the first few hours after drug intake on day 1 of treatment. However, no significant effect on the subjects' rating of relaxation was observed. When tested similarly after 8 days treatment, flunitrazepam significantly affected the subjects' rating of relaxation (P < 0.01). Furthermore, no tolerance developed for the effect of flunitrazepam on free recall (P > 0.3) and the subjects' rating of attention (P > 0.7), and these effects had nearly equal time courses during the treatment period. This may indicate that the amnesic effect of benzodiazepines is at least partially mediated through the effects on attention or general arousal. Two of the subjects in the active drug group reported adverse reactions or incidents of discomfort during the 1st week following the treatment period, whereas none in the placebo group reported such reactions.


Intestinal cholesterol absorption in the chyluria model.
Isotopic methods for the measurement of dietary cholesterol absorption were compared with the lymph cholesterol balance procedure in filarial chyluria patients. After a single intravenous injection of radioactive cholesterol, absorption was found to be 746 +/- 136 mg/day by method I, which is based upon the fecal endogenous neutral steroid mass measurement, and 471 +/- 135 mg/day by the simultaneously measured lymph/plasma ratio of cholesterol specific activity (dpm/mg). The corresponding value, determined as the difference between lymph cholesterol transport on a cholesterol-containing diet (1500 mg) and on a cholesterol-free diet, was 622 mg/day. When radioactive cholesterol (1487 mg/day) was fed daily to a second patient, absorption determined by isotopic fecal recovery (353 mg/day) matched that obtained by the lymph balance procedure (326 mg/day). Transudation of plasma cholesterol into the intestinal lymph, estimated by the single intravenous injection of radioactive beta-sitosterol, was independent of both the luminal content of plant sterols and the absorption of dietary cholesterol. The absorption of endogenous cholesterol was calculated by: 1) subtracting the cholesterol originating from plasma (transudation) together with the absorbed dietary cholesterol found in lymph from the total mass of cholesterol transported in lymph, and 2) the lymph balance method, i.e., after interrupting the endogenous cholesterol mucosal uptake by beta-sitosterol feeding (9 g/day) while on a cholesterol-free diet. Endogenous cholesterol was preferentially absorbed compared to dietary cholesterol, but there was no competition for absorption. The major portion of dietary cholesterol found in lymph was esterified, but esterification was not a prerequisite for absorption.


Crucial roles of MicA and RybB as vital factors for σ-dependent cell lysis in Escherichia coli long-term stationary phase.
σ(E)-dependent cell lysis has been proposed to eliminate damaged cells in the stationary phase in Escherichia coli. In order to explore the relationship of this process to long-term stationary phase existence, we considered that micA and rybB could be important small regulatory RNA (sRNA) genes for σ(E)-dependent cell lysis. A long-term stationary phase was observed at temperatures of <37°C, but not >38°C, and was found even in an rpoS knock-out background. Strains with disrupted micA or rybB were incapable of long-term stationary phase existence. Both strains drastically lost survivability accompanied by a dramatic accumulation of mutations. These findings allow us to speculate that σ(E)-dependent cell lysis plays a key role in the establishment of the long-term stationary phase, presumably by eliminating damaged cells and thus preventing the over-accumulation of mutations.


Polymerase chain reaction testing of vitreous in atypical ocular syphilis.
To illustrate the diagnostic importance of syphilis PCR testing on intraocular fluid for atypical presentations. Retrospective case series. Two cases of atypical intraocular inflammation were confirmed by PCR testing of vitreous for Treponema pallidum DNA. Ocular syphilis may be present in atypical fashion, and delayed treatment may lead to irreversible visual loss. Sampling of intraocular fluid for PCR testing may confirm diagnosis and lead to appropriate treatment.


Management of cerebrospinal fluid rhinorrhea: an evidence-based review with recommendations.
Management strategies employed for cases of cerebrospinal fluid (CSF) rhinorrhea vary widely because of limited evidence-based guidance. A systematic review of the literature was performed using PubMed, EMBASE, and Cochrane databases from January 1990 through September 2014 to examine 5 endoscopic repair techniques and 8 perioperative management strategies for CSF rhinorrhea. Benefit-harm assessments, value judgments, and recommendations were made based on the available evidence. Study exclusion criteria were language other than English, pre-1990 studies, case reports, and nonrhinologic leak. All authors agreed on recommendations through an iterative process. We reviewed 67 studies examining 13 practices pertinent to the management of CSF rhinorrhea, reaching a highest aggregate grade of evidence of B. The literature does not support the routine use of prophylactic antibiotics or lumbar drainage. Various endoscopic repair materials show similar success rates; however, larger defects may benefit from vascularized grafts. There were no relevant studies to address postoperative activity restrictions. Despite relatively low levels of evidence, recommendations for the management of CSF rhinorrhea can be made based on the current literature. Higher-level studies are needed to better determine optimal clinical management approaches.


A speech pronunciation practice system for speech-impaired children: A study to measure its success.
The speech pronunciation practice (SPP) system enables children with speech impairments to practise and improve their speech pronunciation. However, little is known about the surrogate measures of the SPP system. This research aims to measure the success and effectiveness of the SPP system using three surrogate measures: usage (frequency of use), performance (recognition accuracy) and satisfaction (children's subjective reactions), and how these measures are aligned with the success of the SPP system, as well as to each other. We have measured the absolute change in the word error rate (WER) between the pre- and post-training, using the ANOVA test. Correlation co-efficiency (CC) analysis was conducted to test the relation between the surrogate measures, while a Structural Equation Model (SEM) was used to investigate the causal relations between the measures. The CC test results indicate a positive correlation between the surrogate measures. The SEM supports all the proposed gtheses. The ANOVA results indicate that SPP is effective in reducing the WER of impaired speech. The SPP system is an effective assistive tool, especially for high levels of severity. We found that performance is a mediator of the relation between "usage" and "satisfaction".


Soluble amyloid beta oligomers block the learning-induced increase in hippocampal sharp wave-ripple rate and impair spatial memory formation.
Post-learning hippocampal sharp wave-ripples (SWRs) generated during slow wave sleep are thought to play a crucial role in memory formation. While in Alzheimer's disease, abnormal hippocampal oscillations have been reported, the functional contribution of SWRs to the typically observed spatial memory impairments remains unclear. These impairments have been related to degenerative synaptic changes produced by soluble amyloid beta oligomers (Aβos) which, surprisingly, seem to spare the SWR dynamics during routine behavior. To unravel a potential effect of Aβos on SWRs in cognitively-challenged animals, we submitted vehicle- and Aβo-injected mice to spatial recognition memory testing. While capable of forming short-term recognition memory, Aβ mice exhibited faster forgetting, suggesting successful encoding but an inability to adequately stabilize and/or retrieve previously acquired information. Without prior cognitive requirements, similar properties of SWRs were observed in both groups. In contrast, when cognitively challenged, the post-encoding and -recognition peaks in SWR occurrence observed in controls were abolished in Aβ mice, indicating impaired hippocampal processing of spatial information. These results point to a crucial involvement of SWRs in spatial memory formation and identify the Aβ-induced impairment in SWRs dynamics as a disruptive mechanism responsible for the spatial memory deficits associated with Alzheimer's disease.


Normal development imaging pitfalls and injuries in the pediatric shoulder.
The skeletal maturation of the shoulder has been well documented on radiographic and cadaveric studies. Recent increased use of MRI has provided increased understanding of the soft-tissue and osseous changes that occur during development. Thus recognizing normal maturation, imaging manifestations and pitfalls is crucial when evaluating the pediatric shoulder joint. At birth, the humeral diaphysis, midportion of the clavicle, and the body of the scapula are ossified, while the remainder of the bones of the shoulder are composed of non-ossified cartilaginous precursors. During growth, cartilaginous apophyses and epiphyses of the shoulder develop numerous secondary ossification centers, which fuse with the primary ossification centers to form the complete bony components of the shoulder. Additionally changes in the morphology of the growth plates as well as marrow signal occur in an organized manner. This paper affords the reader with an understanding of the normal development of three major components of skeletal maturation in the shoulder: ossification centers, growth plates and marrow signal. These topics are further subdivided into the glenoid, proximal humerus and acromioclavicular joint. We also provide a focus on distinguishing normal anatomy from imaging pitfalls related to skeletal maturation.


Elimination of viruses from domestic wastewater: requirements and technologies.
Domestic wastewater contains various pathogens, which, if not sufficiently eliminated, may enter the receiving water bodies and cause water-transmitted diseases. Among the waterborne pathogens, viruses may occur, survive and/or decay much differently from bacteria in water. In many cases, the diseases caused by viruses are more severe. Therefore, research efforts are mainly directed at the behavior of viruses in water environments, as well as the elimination of viruses from wastewater. In this paper, an overview of the occurrence of viruses in wastewater is presented, together with their categories, methods of detection and potential to cause waterborne diseases. As wastewater treatment plants are critical nodes for the influx and termination of virus transmission, the behavior of viruses at each stage of treatment is reviewed. Particular attention is paid to the unit operations, which play crucial roles in virus removals, such as coagulation and membrane filtration, and that for virus inactivation, such as chemical disinfection and UV irradiation. Future needs for the development of new technologies for virus elimination, source control, and finding more suitable indicators of viral pathogens are also highlighted.


Parallel gradients in comprehensive multidimensional liquid chromatography enhance utilization of the separation space and the degree of orthogonality when the separation mechanisms are correlated.
Comprehensive two-dimensional liquid chromatography (LC×LC) offers increased peak capacity, resolution and selectivity compared to one-dimensional liquid chromatography. It is commonly accepted that the technique produces the best results when the separation mechanisms in the two dimensions are completely orthogonal, which necessitates the use of gradient elution for each second-dimension fraction. Recently, the use of similar separation mechanisms in both dimensions has been gaining popularity, but full or shifted gradients are still used for each second dimension fraction. Herein, we argue that when the separation mechanisms are correlated in the two dimensions, the best results can be obtained with the use of parallel gradients in the second dimension, which makes the technique nearly as user-friendly as comprehensive two-dimensional gas chromatography. This has been illustrated through the separation of a mixture of 39 pharmaceutical compounds using reversed phase in both dimensions. Different selectivity in the second dimension was obtained through the use of different stationary phase chemistries and/or mobile phase organic modifiers. The best coverage of the separation space was obtained when parallel gradients were applied in both dimensions, and the same was true for practical peak capacity.


Small Bowel Obstruction Caused by the Ingestion of a Wooden Toothpick: The CT findings and a Literature Review.
We present a case in which the accidental ingestion of a toothpick caused duodenal perforation and small intestinal obstruction. A 58-year-old man visited our emergency room with acute abdominal pain. Computed tomography (CT) showed obstructive ileus as well as a foreign body penetrating the duodenum, which was identified as a toothpick and removed endoscopically. Unenhanced CT was superior in detecting the object. The patient has been doing well since the operation.


Atypical neuroleptics and diabetes.
Since a few years, an increasing number of cases of atypical neuroleptic-associated diabetes are reported in the literature. But few are dedicated to diabetologists. We report here two cases of patients with a severe deterioration of preexisting diabetes, with clozapine for the first case report and olanzapine for the second one. We also make a literature review and discuss the possible mechanisms involved in this atypical neuroleptic-associated diabetes. We recommend a thigh follow-up of weight, glycemic and lipidic parameters during psychotic patients treatment with atypical neuroleptics, in order to prevent or rapidly treat the metabolic complications described in the literature.


Association of polycyclic aromatic hydrocarbons exposure, systemic inflammation with hearing loss among adults and adolescents.
The association between polycyclic aromatic hydrocarbons (PAHs) exposure and hearing loss is rarely assessed. We aimed to evaluate the relationship of polycyclic aromatic hydrocarbons (PAHs) exposure and hearing loss among US adults and adolescents, and to explore the mediating role of systemic inflammation in the associations. Participants from the National health and Nutrition Examination Surveys (NHANES, 2001-2016) were included. Multiple logistic regression models were used to explore the associations between PAH metabolites and hearing loss. A total of 4200 adults and 1337 adolescents were included in the present analysis. For adults, we found positive association between urinary PAH metabolites and hearing loss, including total, speech-frequency and high-frequency hearing loss. The odds ratios (ORs) and 95% confidence intervals (CIs) for each one-unit increase in the log-transformed level of 3-Hydroxyfluorene (3-OHFlu), 2-Hydroxyfluorene (2-OHFlu) and 2 & 3-Hydroxyphenanthrene (2&3-OHPh) with total hearing loss were 1.17 (1.04-1.31), 1.24 (1.07-1.43), and 1.18 (1.03-1.37), respectively. For adolescents, urinary PAH metabolites were positively associated with total and speech-frequency hearing loss, not with high-frequency. The ORs and 95% CIs for each one-unit increase in the log-transformed level of 3-OHFlu, 2-OHFlu and total urinary PAH metabolites with total hearing loss were 1.34 (1.06-1.68), 1.48 (1.13-1.93), and 1.33 (1.04-1.72), respectively. Each one-unit increase in the log-transformed level 2-OHFlu (β = 0.112, 95%CI = 0.018-0.206) and 2&3-OHPh (β = 0.145, 95%CI = 0.037-0.253) were positively associated with C-reactive protein (CRP) among adolescents, but not among adults. No mediating effect for CRP on the association of urinary PAH metabolites with hearing loss was found (all P > 0.05). 3-OHFlu and 2-OHFlu are associated with increased prevalence of hearing loss among adults and adolescents. Systemic inflammation does not mediate the associations. Further studies should be conducted to verify the results.