The evolution of plant regulatory networks: what Arabidopsis cannot say for itself.
Genetic and molecular analyses in the dicot model plant Arabidopsis thaliana have begun to shed some light on regulatory networks in plants. However, comparisons with other species are necessary to validate networks identified in model species on the evolutionary scale. Many key regulatory proteins are encoded by members of transcription factor gene families. Orthologous genes can be identified by phylogenetic reconstructions based on conserved protein domains and functionally substantiated by gene expression patterns and mutant analyses. Recent comparative analyses of different pathways involved in shoot meristem development reveal not only conservation from basal land plants to angiosperms but also evolutionary freedom for significant adaptations in the course of plant speciation.


Prediction of the response to chemoradiation and prognosis in oesophageal squamous cancer.
The sensitivity of cancer cells to chemotherapy and radiation therapy depends on various biological properties. This study investigated the expression of p53, CDC25B and metallothionein (MT), and evaluated their clinical significance in chemoradiation therapy (CRT) for oesophageal squamous cell carcinoma. The expression of p53, CDC25B and MT was evaluated by immunohistochemistry using biopsy specimens taken before CRT for 77 patients with oesophageal squamous cell carcinoma, and correlated with the pathological effects of CRT and survival. p53-positive tumours and MT-positive tumours had a poor response to CRT, whereas tumours with strong CDC25B expression were associated with a good response. When each patient was scored for the presence of the three biological factors, there was a strong correlation between the sensitivity score and the pathological effect of CRT (P < 0.001), and a (non-significant) difference in the 5-year survival rate between patients with a high score and those with a low score (67 versus 34 per cent respectively; P = 0.12). The combined evaluation of p53, CDC25B and MT may help to identify patients with advanced oesophageal squamous cell carcinoma who will benefit from preoperative CRT.


Ambipolar remote graphene doping by low-energy electron beam irradiation.
We employ low-energy electron beam irradiation to induce both n- and p-doping in a graphene layer. Depending on the applied gate voltage during the irradiation, either n- or p-doping can be achieved, and by setting an appropriate irradiation protocol, any desired doping levels can be achieved.


Left bundle branch area pacing prevents pacing induced cardiomyopathy in long-term observation.
Left bundle branch area pacing (LBBAP) is one of the methods to deliver conduction system pacing which potentially avoids the negative impact of conventional right ventricular pacing. To assess echocardiographic outcomes in a long-term observation in patients with LBBAP implemented for bradyarrhythmia indications. A total of 151 patients with symptomatic bradycardia and LBBAP pacemaker implanted, were prospectively included in the study. Subjects with left bundle branch block and CRT indications (n = 29), ventricular pacing burden <40% (n = 11), and loss of LBBAP (n = 10) were excluded from further analysis. At baseline and the last follow-up visit, echocardiography with global longitudinal strain (GLS) assessment, 12-lead ECG, pacemaker interrogation, and blood level of NT-proBNP were performed. The median follow-up period was 23 months (15.5-28). None of the analyzed patients fulfilled the criteria for pacing induced cardiomyopathy (PICM). Improvement in left ventricular ejection fraction (LVEF) and GLS was observed in patients with LVEF <50% at baseline (n = 39): 41.4 ± 9.2% versus 45.6 ± 9.9%, and 12.9 ± 3.6% versus 15.5 ± 3.7%, respectively. In the subgroup with preserved EF (n = 62), LVEF and GLS remained stable at follow-up: 59.3 ± 5.5% versus 60 ± 5.5%, and 19 ± 3.9% versus 19.4 ± 3.8%, respectively. LBBAP prevents PICM in patients with preserved LVEF and improves left ventricle function in subjects with depressed LVEF. LBBAP might be the preferred pacing modality for bradyarrhythmia indications.


The role of endoscopy in caustic ingestion in the pediatric population: experience in a tertiary center.
caustic ingestion in children is rare but has potentially serious consequences. to analyze the clinical and endoscopic features and the type of caustic ingested in our population. the upper endoscopies performed in this setting, as well as the characteristics of patients and caustics, were analyzed from 2010 to 2018. fifty-one endoscopies were performed (48 cases of witnessed intake or high suspicion and three with a low suspicion) in patients with a mean age of 2.55 years. Alkali ingestion was more frequent (88.2 %) and 56.9 % of the endoscopies were normal, which was more frequent among those who ingested bleach (72 %). Alkali tended to produce more esophageal injuries (31.1 %) and acids tended to produce esophageal (20 %) and esophageal-gastric injuries (20 %). Four patients developed esophageal stenosis during follow-up. even though more than half of the studies were normal, endoscopy is important in the diagnosis and prognosis of these patients.


Synthesis and characterization of a luminescence metallosupramolecular hyperbranched polymer.
A luminescence supramolecular hyperbranched polymer is reversibly fabricated by successively adding acid and base to a solution of an AB2 platinum(II) monomer in dichloromethane on the basis of acid-base controllable host-guest recognition of dibenzo[24]crown-8 moieties with dialkylammonium ion centers.


The effects of distraction on threat-related changes in standing balance control.
Research indicates that threat-induced changes in standing balance are associated with shifts in attention focus. This study investigated whether distracting attention modifies threat-induced changes in standing balance. Twenty-five healthy young adults stood without (No Threat) and with (Threat) the possibility of receiving a temporally unpredictable anteroposterior support surface translation. In both conditions, participants completed a distractor task that consisted of counting how often a pre-selected letter occurred in an auditory sequence, or no distractor task. Emotional responses to threat were quantified using electrodermal activity and self-report measures, while attention focus was quantified using self-report. Centre of pressure (COP) was measured to assess changes in standing balance. Results indicate that postural threat induced an emotional response, as well as broad shifts in attention focus and changes in standing balance. Distracting attention with a cognitive task mitigated threat-induced increases in medium-frequency COP displacements (0.5-1.8 Hz). These results provide support for a relationship between threat-related changes in balance control and attention focus.


Leukotrienes in the pathogenesis of NSAID-induced gastric and intestinal mucosal damage.
Studies in pigs and rats were undertaken to explore further the role of leukotrienes following administration of NSAIDs on the development of gastrointestinal damage. Increased leukotriene C4 production occurred in the gastric circulation in the early stages after administration of a single dose of indomethacin (10 mg/kg i.g.) to pigs. Gastric and intestinal mucosal lesions by NSAIDs were prevented by both prior (2-5 h)+ 0.25 or 0h oral dosing of the 5-lipoxygenase inhibitor, MK-886, but not when only one of these doses was given. These results show the importance of enhanced peptidoleukotriene production in relation to microvascular damage from cyclooxygenase inhibition by NSAIDs.


Deep mutational scans for ACE2 binding, RBD expression, and antibody escape in the SARS-CoV-2 Omicron BA.1 and BA.2 receptor-binding domains.
SARS-CoV-2 continues to acquire mutations in the spike receptor-binding domain (RBD) that impact ACE2 receptor binding, folding stability, and antibody recognition. Deep mutational scanning prospectively characterizes the impacts of mutations on these biochemical properties, enabling rapid assessment of new mutations seen during viral surveillance. However, the effects of mutations can change as the virus evolves, requiring updated deep mutational scans. We determined the impacts of all single amino acid mutations in the Omicron BA.1 and BA.2 RBDs on ACE2-binding affinity, RBD folding, and escape from binding by the LY-CoV1404 (bebtelovimab) monoclonal antibody. The effects of some mutations in Omicron RBDs differ from those measured in the ancestral Wuhan-Hu-1 background. These epistatic shifts largely resemble those previously seen in the Alpha variant due to the convergent epistatically modifying N501Y substitution. However, Omicron variants show additional lineage-specific shifts, including examples of the epistatic phenomenon of entrenchment that causes the Q498R and N501Y substitutions present in Omicron to be more favorable in that background than in earlier viral strains. In contrast, the Omicron substitution Q493R exhibits no sign of entrenchment, with the derived state, R493, being as unfavorable for ACE2 binding in Omicron RBDs as in Wuhan-Hu-1. Likely for this reason, the R493Q reversion has occurred in Omicron sub-variants including BA.4/BA.5 and BA.2.75, where the affinity buffer from R493Q reversion may potentiate concurrent antigenic change. Consistent with prior studies, we find that Omicron RBDs have reduced expression, and identify candidate stabilizing mutations that ameliorate this deficit. Last, our maps highlight a broadening of the sites of escape from LY-CoV1404 antibody binding in BA.1 and BA.2 compared to the ancestral Wuhan-Hu-1 background. These BA.1 and BA.2 deep mutational scanning datasets identify shifts in the RBD mutational landscape and inform ongoing efforts in viral surveillance.


Quantitative analysis of estrogen receptor-alpha and -beta and exon 5 splicing variant mRNA in endometrial hyperplasia in perimenopausal women.
We used real-time reverse transcription-polymerase chain reaction (QRT-PCR) to detect wild-type ERalpha and ERbeta and their isoforms as well as exon 5 splicing variant mRNA ERalpha in various types of endometrial hyperplasia in perimenopausal women. Our data suggest that the exon 2 and 7 deletion ERalpha mRNA isoforms are present in endometrial tissue undergoing various hyperplastic states. Wild type ERbeta mRNA and their isoforms 2, 4, 5, 6 were observed in each type of assessed endometrial specimens, and ERalpha/delta5 was found only in hyperplasia complex group.


Type 1 diabetes and celiac disease in adults: glycemic control and diabetic complications.
The prevalence of celiac disease (CD) in patients with type 1 diabetes mellitus (T1DM) is 4.5 %. Objective of the study is to investigate (1) the course of glycemic control at CD diagnosis and after the initiation of a gluten-free diet (GFD) in T1DM patients; (2) the prevalence of diabetic complications in T1DM patients with adult onset of CD. In 20 hospitals in the Netherlands, we identified T1DM patients diagnosed with CD at adult age. We retrospectively collected glycated hemoglobin (HbA1c) levels before CD diagnosis, at CD diagnosis, and the most recent HbA1c levels as well as the presence of nephropathy and retinopathy. The control group consisted of patients with T1DM and negative CD serology matched for age, gender, T1DM duration, and HbA1c levels. Thirty-one patients were eligible with a median duration of T1DM and CD of 27 years (IQR 14-37) and 3 years (IQR 1-8), respectively. The matched control group consisted of 46 patients. HbA1c levels at the moment of CD diagnosis were 7.5 % (IQR 7.1-8) [58 mmol/mol] and at the most recent visit 7.4 % (IQR 6.9-7.9, P = 0.15) [57 mmol/mol] indicating no difference. Prevalence of retinopathy was lower in T1DM + CD group compared with controls, (38.7 vs 67.4 %, P < 0.05), whereas no difference in the prevalence of nephropathy was found between the groups (P = 0.09). In conclusion, T1DM + CD patients have less retinopathy compared to T1DM patients without CD. A GFD possibly favorable affects the development of vascular complications in T1DM patients.


Density-dependent foraging behaviors in a parasitoid lead to density-dependent parasitism of its host.
Empirical studies of spatial heterogeneity in parasitism by insect parasitoids have focused largely on patterns, while the many possible underlying mechanisms have been little studied in the field. We conducted experimental and observational studies on Tachinomyia similis (Diptera: Tachinidae) attacking western tussock moths (Orgyia vetusta; Lepidoptera: Lymantriidae) on lupine bushes at Bodega Bay, Calif., USA. We examined several foraging behaviors that have been hypothesized to create density-dependent variation in parasitism rates, including spatial aggregation of parasitoids to high host density, mutual interference among searching parasitoids and decelerating functional responses of the parasitoid. At the spatial scale of individual bushes, we detected both aggregation to a high density and a decelerating functional response. The resulting spatial pattern of parasitism was best fit by two models; one included an effect of parasitoid aggregation and the other included an effect of aggregation and a decelerating functional response. Most of the variation in parasitism was not correlated with density of O. vetusta.


Lysinibacillus mangiferahumi sp. nov., a new bacterium producing nematicidal volatiles.
A Gram-positive bacterium, designated M-GX18(T), was isolated from the rhizosphere soil of mango (Guangxi Province, China). The isolate produced nematicidal volatile compounds with activities against the root-knot nematode Meloidogyne incognita. The organism was motile, catalase- and oxidase-positive, spore-forming and rod shaped. The predominant menaquinone was MK-7 and the major cellular fatty acid profiles were iso-C(15:0), anteiso-C(15:0) and iso-C(16:0). The DNA G+C content was 38.9%. A phylogenetic analysis based on 16S rRNA gene sequences showed that this organism represented a new species of the genus Lysinibacillus. Strain M-GX18(T) exhibited high 16S rRNA gene sequence similarity with its closest neighbors Lysinibacillus sphaericus (98.5%), Lysinibacillus fusiformis (98.1%) and Lysinibacillus xylanilyticus (98.6%). The physiological, biochemical and chemotaxonomic data, including DNA-DNA hybridization relatedness data, indicate that strain M-GX18(T) can be distinguished from all the related species of the genus Lysinibacillus. Therefore, on the basis of the polyphasic taxonomic data presented, a new species of the genus Lysinibacillus, Lysinibacillus mangiferahumi, with the type strain M-GX18(T) (=DSM 24076(T) = CCTCC AB 2010389(T)) is proposed.


Pathology of human immunodeficiency virus infection: noninfectious conditions.
Diagnostic anatomic pathologists play a crucial role in the battle against acquired immunodeficiency syndrome (AIDS). Not only are they intimately involved in the treatment of individual patients with human immunodeficiency virus (HIV) infection, but also they make important observations that result in the expansion of the scientific understanding of its pathogenesis. Pathologists studying tissue from patients with HIV infection should be familiar with the conditions to which these patients are susceptible. Although opportunistic infections are important causes of morbidity and mortality, noninfectious conditions frequently make substantial contributions to the disease course. Patients with HIV infection may be at increased risk for neoplastic disease. They do not, however, have an increased incidence of the most common tumors affecting the general population, such as breast, colon, and prostate carcinoma. Immunodeficiency results in increased susceptibility to malignant neoplasms, both by decreased immunologic response to abnormal cells and increased susceptibility to infection by viruses. All of the malignant neoplastic diseases that are Centers for Disease Control and Prevention (CDC) AIDS indicator conditions have been shown to have an association with a virus: Kaposi sarcoma (KS) with herpes hominis virus 8 (HHV-8), malignant lymphoma with Epstein-Barr virus (EBV), and cervical carcinoma with human papilloma virus (HPV). Patients with HIV infection also can develop reactive processes that are attributable to direct effects of HIV or immune system alterations. Such conditions include salivary gland cystic lymphoepithelial lesion, lymphadenopathy, lymphocytic interstitial pneumonitis, encephalopathy, enteropathy, nephropathy, hepatic conditions, dermatologic conditions and anemia.


Lectin from green speckled lentil seeds (Lens culinaris) triggered apoptosis in nasopharyngeal carcinoma cell lines.
The green speckled lentil seed (Lens culinaris) lectin (GSLL) exhibits hemagglutinating activity, and possesses some properties distinct from those of other lentil lectins (e.g., molecular size, biological activities) that deserve further investigation. This study aims to investigate the basic properties (e.g., molecular size, amino acid sequence, sugar specificity) and biological activities (e.g., antiproliferative activity) of GSLL. GSLL was purified by successive fractionation on SP-Sepharose, Affi-gel blue gel, Mono Q, and Superdex 75. The biochemical properties of GSLL were investigated by SDS-PAGE, mass spectrometry, N-terminal amino acid sequencing, and sugar inhibition tests. For the biological activities, purified lyophilized GSLL was sterilized, adjusted to concentrations from 1 to 0 mg/mL (by twofold serial dilution) in Dulbecco's modified Eagle's medium with fetal bovine serum, and examined by using the MTT assay, flow cytometry, and western blotting after treatment of nasopharyngeal carcinoma CNE1 and CNE2 cell lines with the lectin. GSLL appeared as a 21-kDa band in non-reducing SDS-PAGE. It was composed of two subunits with molecular sizes of 17 and ~4 kDa. It exhibited specificity in binding to glucose and mannose, as well as glucosides and mannosides. Mass spectrometry and N-terminal amino acid sequencing revealed similarity of GSLL to L. culinaris lectin (LcL), especially higher coverage of the β-chain of LcL. A 48-h treatment with GSLL exerted antiproliferative effects on nasopharyngeal carcinoma CNE1 and CNE2 cell lines with significant inhibition at 0.125 mg/mL (P < 0.001) and 1 mg/mL (P = 0.004), respectively, and these effects were attenuated in the presence of glucose and mannose. GSLL induced apoptosis in nasopharyngeal carcinoma CNE1 cells, with detectable phosphatidylserine externalization, mitochondrial depolarization, and cell cycle arrest. Western blot analysis suggested that GSLL triggered the extrinsic apoptotic pathway involving caspase 3, 8, and 9 in CNE1 cells. GSLL possessed some different properties from LcL (e.g., lower pI), and increased caspase 3, 8, and 9 activity in CNE1 cells.


Hepatocyte growth factor predicts failure of Fontan circulation.
This study aimed to assess the value of the hepatocyte growth factor (HGF) as an independent predictor of a Fontan circulation failure. This retrospective case-control study included 34 consecutive patients (19 men and 15 women) who underwent a post-operative cardiac catheterization after a Fontan operation at the Saitama Medical University International Medical Center between April 2017 and December 2019. We divided the patients into two groups according to the HGF level: HGF < 0.4 ng/mL (n = 20, normal HGF group) and HGF ≥ 0.4 ng/mL (n = 14, elevated HGF group). The age at the time of the cardiac catheterization was 59.3 ± 7.9 months. The range of the duration between the Fontan operation and the cardiac catheterization was 37.5 ± 7.9 months. The age (P = 0.417), gender (P = 0.08), morphology of the functional ventricle (P = 0.99), presence or closure of the Fontan fenestration (P = 0.704), and rate of medication use (angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers) (P = 0.99) were equivalent between the two groups. Laboratory parameters including the brain natriuretic peptide level (P = 0.085), serum creatinine level (P = 0.27), and aspartate aminotransferase level (P = 0.235) were similar between the two groups. The elevated HGF group had a higher C-reactive protein level than the normal HGF group (0.42 ± 0.14 and 0.05 ± 0.01 mg/dL, P = 0.005). The elevated HGF group had a higher central venous pressure (CVP) level than the normal HGF group (13.4 ± 0.7 and 9.7 ± 0.4 mmHg, P < 0.0001), and the HGF was positively correlated with the CVP (P = 0.0004, r2 = 0.33). The SvO2 level was significantly lower in the elevated HGF group than in the normal HGF group (61.9 ± 2.3% and 75.0 ± 1.2%, P < 0.0001), and the HGF was negatively correlated with the SvO2 (P < 0.0001, r2 = 0.65). Of the 34 patients, six underwent catheter interventions. Patients who underwent catheter interventions had a higher HGF level than those who did not (0.44 ± 0.03 and 0.37 ± 0.01 ng/mL, P = 0.032). The receiver operating characteristic curve created for the discrimination of a catheter intervention revealed that an HGF value of >0.405 ng/mL could detect the need for a catheter intervention with 75.0% sensitivity and 83.3% specificity. A multivariable regression analysis showed that an elevated HGF was an independent predictor of an elevated CVP (β-coefficient 21.2, SE 5.5, P = 0.0005) and decreased SvO2 (β-coefficient -92.9, SE 12.4, P < 0.0001). The HGF is an independent predictor of a failure of a Fontan circulation. The HGF is an indicator for an additional catheter intervention after a Fontan operation.


Trouble shooting during bioanalytical estimation of drug and metabolites using lc-ms/ms: a review.
Bioanalysis frequently involves the measurement of very low analyte concentrations in complex and potentially variable matrices. An initial attempt has been made to apply a risk management tool to the bioanalytical method development like selection of spiked plasma volume, selection of internal standard to minimize processing error, selection of medium and extraction procedure, setting of mobile phase and pH, determination of chromatographic conditions etc. and to minimize instrumental error like; ion suppression and matrix effect.


Community health worker case-detection of asthma or reactive airways disease in a resource-poor community in Nicaragua.
Asthma is a major cause of morbidity and mortality in children worldwide, but many cases may remain undiagnosed. Community health worker (CHW) programs have improved detection of other diseases such as childhood pneumonia, but none have been validated for detection of asthma in resource-poor settings. We hypothesized that a CHW administered questionnaire would be effective in case-detection of asthma in a poor Nicaraguan community. We enrolled children aged 2-17 from a small semiurban Nicaraguan community. A trained CHW administered a questionnaire based on a previously validated school-based screening questionnaire, which was compared to pediatric pulmonologist evaluation as a reference standard. We determined the questionnaire's sensitivity, specificity, and positive and negative likelihood ratios at different score cut-points. A total of 199 out of 218 eligible children were enrolled. Total asthma prevalence based on physician diagnosis was 33%. Mean scores on the CHW questionnaire were 3.6 points out of 22 (SD = 4.3) for nonasthmatics and 11.0 points (SD = 5.3) for children with asthma (p < .001). Area under the curve was 0.87. Multivariable analysis showed increased association of asthma/reactive airways disease with respiratory infection in the first 3 months of life and with family history of asthma. Prevalence of asthma in this community was high compared to previously reported national prevalence (15.2%), possibly due to increased exposure to risk factors. The questionnaire had a high area under the receiver operating characteristic curve, making it an excellent screening tool. This questionnaire could greatly increase the detection of asthma, allowing for education and referral for ongoing care.


Cerium/polyacrylic acid modified porphyrin metal-organic framework as fluorescence and photothermal sensor for ascorbic acid measurement.
A fluorescence and photothermal dual-signal assay was developed for the determination of ascorbic acid (AA). Cerium/polyacrylic acid modified porphyrin metal-organic frameworks (PCN-224@PAA-Ce MOFs) exhibit oxidase-like activity and can effectively oxidize 3,3 ', 5,5 '-tetramethylbenzidine (TMB) from colorless substrates to blue substrates (oxTMB). The absorption spectrum of oxTMB overlaps with the emission spectrum of PCN-224@PAA-Ce, resulting in quenching of fluorescence emission of PCN-224@PAA-Ce. oxTMB, as an excellent photothermal agent, converts the optical signal into the thermal signal (temperature increasing) driven by 808 nm laser. In the presence of AA, the blue oxTMB was reduced to colorless TMB, which led to the fluorescence recovery of PCN-224@PAA-Ce and at the same time, the photothermal signal was changed with the temperature decreasing under the driving of 808 nm laser. The detection limits (LOD) of fluorescence/photothermal dual-mode AA sensor strategies were as low as 0.73 μM and 1.4 μM, respectively. Rapid analysis of ascorbic acid was accomplished with the present procedure, AA in vitamin C tablets and human serum samples were validated.


A novel tetracycline from Actinomadura brunnea. Fermentation, isolation and structure elucidation.
A novel tetracycline antibiotic, Sch 33256, was isolated from a culture broth of a new species of Actinomadura. The antibiotic was isolated by solvent extraction, Sephadex G-25 column chromatography and crystallization. The structure was determined by comparison of the spectra with that of chlortetracycline. Spectroscopic analysis of the compound yielded 2'-N-methyl-8-methoxychlortetracycline as the proposed structure.


Is discussion of colorectal cancer screening options associated with heightened patient confusion?
Clinical guidelines recommend offering patients options for colorectal cancer (CRC) screening, but the modalities vary by frequency, accuracy, preparations, discomfort, and cost, which may cause confusion and reduce screening rates. We examined whether patients reported confusion about the options and whether confusion was associated with socio-demographic characteristics, number of options discussed, and adherence. Patients ages 50 to 75 years who had visited a clinician within 2 years were randomly selected for a cross-sectional study (n = 6,100). A questionnaire mailed in 2007 asked the following: whether a clinician had ever discussed CRC screening options; which of four recommended tests (i.e., fecal occult blood testing, flexible sigmoidoscopy, colonoscopy, and barium enema) were presented; and whether the options were confusing. Analyses were restricted to respondents who reported discussing one or more screening options (n = 1,707). Weighted frequencies were calculated and multivariate logistic regression was done. The sample was 55.5% female, 15.6% African American, and 83.2% adherent to screening recommendations, and 56.0% had discussed two or more screening options. In adjusted analyses, nonadherent patients reported greater confusion than adherent patients (P < 0.01). Adults who discussed two or more options were 1.6 times more likely to be confused than those who discussed one option [95% confidence interval (CI), 1.08-2.26]. Patients who reported being confused were 1.8 times more likely to be nonadherent to screening than those who did not (95% CI, 1.14-2.75). Our study provides the first empirical evidence linking multiple options with confusion and confusion with screening adherence. Confusion may act as a barrier to screening and should be considered in public health messages and interventions.


[Emotions in chronic pain : Changes in the course of day clinic interdisciplinary multimodal pain therapy].
The present study examined the extent to which emotional experience and emotional competence (EC) change in people with chronic pain during interdisciplinary multimodal pain treatment (IMPT). The study included N = 184 adult German-speaking individuals with non-cancer-related chronic pain. They completed a day clinic IMPT. The frequency of specific emotions (anger, etc.) and EC was assessed at three measurement time points using the Questionnaire for Emotion-Specific Self-Assessment of Emotional Competencies (ERSQ-ES) and the Emotional Competency Questionnaire (ECQ). The course results were analyzed descriptively, inferentially, and using linear regression. Positive emotions were experienced more frequently (effect size r = 0.40; p < 0.001) and negative emotions less frequently (r = 0.39, p < 0.001) at end of therapy. The experience of anger decreased particularly strongly (r = 0.52; p < 0.001). Self-assessed EC did not change during the IMPT (χ2ECQ_total (2) = 0.09; p = 0.956). EC largely explained the variance in the frequency experience of positive (R2 = 0.468) and negative emotions (R2 = 0.390). Improvements in patient-reported frequencies of positive and negative emotions during IMPT were demonstrated. Further research should validate these results using a control group. Even though no explicit increase in competence was perceivable for the studied subjects, EC had a high predictive value for emotion frequency. Future therapy designs and evaluations should focus more on changes of emotional experience.


Direct application of the INNO-LiPA Rif.TB line-probe assay for rapid identification of Mycobacterium tuberculosis complex strains and detection of rifampin resistance in 360 smear-positive respiratory specimens from an area of high incidence of multidrug-resistant tuberculosis.
The INNO-LiPA Rif.TB assay for the identification of Mycobacterium tuberculosis complex strains and the detection of rifampin (RIF) resistance has been evaluated with 360 smear-positive respiratory specimens from an area of high incidence of multidrug-resistant tuberculosis (MDR-TB). The sensitivity when compared to conventional identification/culture methods was 82.2%, and the specificity was 66.7%; the sensitivity and specificity were 100.0% and 96.9%, respectively, for the detection of RIF resistance. This assay has the potential to provide rapid information that is essential for the effective management of MDR-TB.


Analysis of Metabolic Pathways by 13C-Labeled Molecular Probes and HRMAS Nuclear Magnetic Resonance Spectroscopy: Isotopologue Identification and Quantification Methods for Medical Applications.
The use of 13C-labeled molecular probes is essential to explore altered metabolic pathways in human pathologies. The analysis of the different 13C isotopologues resulting from these changes in metabolic pathways is essential to understand the different biological processes involved. We propose an NMR methodology consisting of eight different NMR experiments performed under HRMAS conditions to explore metabolic pathways in unprocessed pathological cells and tissues. This methodology has the potential to study human pathologies in the medical field and to enable the analysis of the mode of action of therapeutic treatments.


Overview of expression of hepatitis B surface antigen in transgenic plants.
Hepatitis B virus (HBV), a pathogen for chronic liver infection, afflicts more than 350 million people world-wide. The effective way to control the virus is to take HBV vaccine. Hepatitis B surface antigen (HBsAg) is an effective protective antigen suitable for vaccine development. At present, "edible" vaccine based on transgenic plants is one of the most promising directions in novel types of vaccines. HBsAg production from transgenic plants has been carried out, and the transgenic plant expression systems have developed from model plants (such as tobacco, potato and tomato) to other various plant platforms. Crude or purified extracts of transformed plants have been found to conduct immunological responses and clinical trials for hepatitis B, which gave the researches of plant-based HBsAg production a big boost. The aim of this review was to summarize the recent data about plant-based HBsAg development including molecular biology of HBsAg gene, selection of expression vector, the expression of HBsAg gene in plants, as well as corresponding immunological responses in animal models or human.


Intrafamilial variability in SPTAN1-related disorder: From benign convulsions with mild gastroenteritis to developmental encephalopathy.
Mutations in SPTAN1 gene are responsible for a wide spectrum of neurodevelopmental disorders including early-onset epileptic encephalopathy with progressive brain atrophy, severe intellectual disability with cerebellar malformations, and relatively milder phenotypes with or without epilepsy. Herein, we report three affected individuals including two siblings of 13 and 8 years and their 39-year-old mother, carrying a novel pathogenic variant in SPTAN1 gene. The phenotype of the index cases and their mother was remarkable for the variable expressivity, including benign convulsions with mild gastroenteritis, intellectual disability and developmental encephalopathy with epilepsy. Our clinical observation suggests for the first time that variants in SPTAN1 gene might be involved in the aetiology of benign convulsions correlated with mild gastroenteritis.


Morel-Lavallee lesions. Size matters? Treatment and time of disability.
Degloving soft-tissue injuries are serious and potentially devastating medical conditions where an early recognition is a crucial step for a favorable outcome. One of the most important types is Morel-Lavallée lesions (MLL); a significant soft-tissue injury associated with pelvic trauma (30%) and thigh (20%), located over the greater trochanter. In this retrospective study we selected adult patients diagnosed with MLL between 2010 and 2019 at our trauma center. We then identified 9 cases and followed them up for a minimum of two years. CT scans were performed to measure the size of the degloved zone. we did not found direct relationship between greater dimensions of MLL injury and the need for an increase of days to return to work. We rather identified an association between bigger dimensions of MLL injury and higher energy trauma. These patients waited an average of 133 days to return to work after being injured; which is a longer period compared to non-op patients. MLL lesions generally take several days to develop and many may be missed on initial evaluation. Once identified, compression dressings should be applied, especially when diagnosed acutely. Early identification would lead to early operative debridement. Also, drainage should be performed, since the pathophysiology of the injury will result in the failure of observation or simple aspiration. MLL diagnosis and treatment must be identified as early as possible. We didn't find a correlation between MLL size and the treatment performed. In our study all patients returned to their jobs and normal life. Patients following conservative treatment take longer time to recover and could require more patient's implication, but -at least- would avoid possible surgical complications.


Preliminary data from a field trial of the PFA-100 system.
The PFA-100 system (Dade International Inc., Miami, FL) is a platelet function analyzer, the design of which is based on the technology of the Thrombostat 4000 VDG, Seeon, Germany. It was developed to measure primary, platelet dependent hemostasis in citrated whole blood in vitro. A first pilot study was conducted with the instrument to assess performance characteristics. Healthy subjects (normals) who had not ingested any medications, and patients (abnormals) with primary, platelet-related hemostasis defects, which included users of aspirin, were studied with two test cartridges; collagen/ADP and collagen/epinephrine. Before the study certain variables were tested that ascertained that blood drawn into either 3.8% or 3.2% sodium citrate containing vacutainers (rather than syringes) could be used for testing. Tests must be performed within a five-hour time span from drawing to testing, and blood must be kept at room temperature. Normal reference values were 77-133 seconds closure times for collagen/ADP and 98-185 seconds for collagen/epinephrine. Precision testing revealed a CV of < 10% for within-day and between-day (five days) analyses on collagen/ADP cartridges and a CV of 5-14% for both runs on the collagen/epinephrine cartridges. No clinically important differences were found between measurements in the two positions of the instrument, although one follows the other.(ABSTRACT TRUNCATED AT 250 WORDS)


Reconstruction of the action potential of ventricular myocardial fibres.
1. A mathematical model of membrane action potentials of mammalian ventricular myocardial fibres is described. The reconstruction model is based as closely as possible on ionic currents which have been measured by the voltage-clamp method.2. Four individual components of ionic current were formulated mathematically in terms of Hodgkin-Huxley type equations. The model incorporates two voltage- and time-dependent inward currents, the excitatory inward sodium current, i(Na), and a secondary or slow inward current, i(s), primarily carried by calcium ions. A time-independent outward potassium current, i(K1), exhibiting inward-going rectification, and a voltage- and time-dependent outward current, i(x1), primarily carried by potassium ions, are further elements of the model.3. The i(Na) is primarily responsible for the rapid upstroke of the action potential, while the other current components determine the configuration of the plateau of the action potential and the re-polarization phase. The relative importance of inactivation of i(s) and of activation of i(x1) for termination of the plateau is evaluated by the model.4. Experimental phenomena like slow recovery of the sodium system from inactivation, frequency dependence of the action potential duration, all-or-nothing re-polarization, membrane oscillations are adequately described by the model.5. Possible inadequacies and shortcomings of the model are discussed.


Placental microRNAs: Responders to environmental chemicals and mediators of pathophysiology of the human placenta.
MicroRNAs (miRNAs) are epigenetic modifiers that play an important role in the regulation of the expression of genes across the genome. miRNAs are expressed in the placenta as well as other organs, and are involved in several biological processes including the regulation of trophoblast differentiation, migration, invasion, proliferation, apoptosis, angiogenesis and cellular metabolism. Related to their role in disease process, miRNAs have been shown to be differentially expressed between normal placentas and placentas obtained from women with pregnancy/health complications such as preeclampsia, gestational diabetes mellitus, and obesity. This dysregulation indicates that miRNAs in the placenta likely play important roles in the pathogenesis of diseases during pregnancy. Furthermore, miRNAs in the placenta are susceptible to altered expression in relation to exposure to environmental toxicants. With relevance to the placenta, the dysregulation of miRNAs in both placenta and blood has been associated with maternal exposures to several toxicants. In this review, we provide a summary of miRNAs that have been assessed in the context of human pregnancy-related diseases and in relation to exposure to environmental toxicants in the placenta. Where data are available, miRNAs are discussed in their context as biomarkers of exposure and/or disease, with comparisons made across-tissue types, and conservation across studies detailed.


[Evaluation of the cryosurgical treatment of retinal detachment].
The authors present the results of retinal detachment surgery by means of cryopexy and Arruga's cerclage of the eye ball. Among 267 operated patients a favourable result has been obtained in 220, i.e. in 82.4%. A repeated retinal detachment in the late postoperative period occurred in 9.5% of the patients.


Intracellular events associated with autonomic stimulation of salivary secretion.
Stimulation of salivary acinar cells by muscarinic and alpha-adrenergic agonists results in a complex series of intracellular and ion transport events which ultimately result in the secretion of salivary fluid. The full functional significance of many of these events and the way in which they are coordinated to produce the final secretory response is currently under active investigation.


Prognostic Significance of HER3 Expression in Patients with Cervical Cancer.
HER3 has been recognized to have an oncogenic role in various types of cancer. However, its prognostic significance has not been elucidated in cervical cancer. The aim of this study was to investigate the prognostic significance of HER3 expression in cervical cancer using immunohistochemistry (IHC). HER3 immunohistochemical staining was performed on the tumor tissue samples of 336 cervical cancer patients. The association between the clinicopathological characteristics and patient survival analysis was assessed according to HER3 expression. HER3 IHC staining was positive in 31.0% (104/336) of the cervical cancer patients. A higher proportion of adeno-/adenosquamous carcinoma was observed in the HER3-positive group (34.6%) than in the HER3-negative group (18.8%). In survival analysis, HER3 expression was significantly associated with poorer disease-free survival (DFS) and overall survival (OS) (p < 0.001 and p = 0.002, respectively). Multivariate analysis also indicated that HER3 expression was an independent prognostic factor for DFS (hazard ratio (HR) = 2.58, 95% confidence interval (CI) 1.42−4.67, p = 0.002) and OS (HR = 3.21, 95% CI, 1.26−8.14, p = 0.014). HER3 protein expression was a poor prognostic factor of survival in patients with cervical cancer. This finding could help to provide individualized management for these patients.


Environmental life cycle assessment (E-LCA) and social impact assessment (SIA) of small-scale biorefineries implemented in rural zones: the avocado (Persea Americana var. Americana) case in Colombia.
The objective of this study is to compare the environmental and social performance of two small-scale avocado biorefineries implanted in a rural zone in the North of Colombia. Two small-scale biorefineries were proposed. Small-B1 addressed to produce avocado oil and animal feed, and Small-B2 focused on the guacamole production. The environmental analysis was done by applying the life cycle assessment methodology. Then, agronomic information and process simulation were required to complete the analysis. Moreover, the water footprint of the avocado crops was estimated. Both biorefineries were compared with the direct avocados production and commercialization. The social assessment was achieved by the estimation of quantitative indicators related to wages, jobs, and working hours. The agricultural carbon and water footprints of the creole avocado crop were 0.59 kg CO2-eq/kg and 2.13 m3/kg. In the same way, Small-B1 and Small-B2 obtained a carbon and water footprints of 8.99 kg CO2-eq/kg and 6.63 m3/kg and 0.72 kg CO2-eq/kg and 1.38 m3/kg, respectively. The hotspots of the creole avocado crop are related to the use of fertilizers and fungicides. Then, new strategies should be implemented to reduce the farmer's dependency. The social analysis exhibit a high resilience of the Small-B1 biorefinery since a salary increase to worker about 50% can be proposed. In addition, the installation of this biorefinery can create more than ten jobs. A disjunction was found between the economic, environmental, and social analyses. Thus, the need to establish a multidimensional strategy to design sustainable biorefineries is presented.


Pathophysiological associations of transcallosal dysfunction in ALS.
Involvement of the corpus callosum has been identified as a feature of amyotrophic lateral sclerosis (ALS), particularly through neuropathological studies. The aim of the present study was to determine whether alteration in transcallosal function contributed to the development of ALS, disease progression and thereby functional disability. Transcallosal function and motor cortex excitability were assessed in 17 ALS patients with results compared to healthy controls. Transcallosal inhibition (interstimulus intervals (ISI) of 8-40 ms), short interval intracortical facilitation (SICF) and inhibition (SICI) were assessed in both cerebral hemispheres. Patients were staged utilising clinical and neurophysiological staging assessments. In ALS, there was prominent reduction of transcallosal inhibition (TI) when recorded from the primary and secondary motor cortices compared to controls (F = 23.255, p < 0.001). This reduction of TI was accompanied by features indicative of cortical hyperexcitability, including reduction of SICI and increase in SICF. There was a significant correlation between the reduction in TI and the rate of disease progression (R = -0.825, p < 0.001) and reduction in muscle strength (R = 0.54, p = 0.031). The present study has established that dysfunction of transcallosal circuits was an important pathophysiological mechanism in ALS, correlating with greater disability and a faster rate of disease progression. Therapies aimed at restoring the function of transcallosal circuits may be considered for therapeutic approaches in ALS.


Properties of r mutants of bacteriophage T4 photodynamically induced in the presence of thiopyronin and psoralen.
About 4 x 10(-4)r mutants were induced per lethal hit, a frequency characteristic of weak mutagens. Collections of mutants produced in the presence of either dye were indistinguishable in most of their properties. The rII mutants differed sharply from spontaneous mutants in their mutational spectra (fine scale map distribution) and their reversion responses to specific mutagens. Few or none of the induced mutants were induced to revert with proflavine (sign mutants; reading frame shift mutants). A majority were induced to revert with base analogues (base pair substitution mutants), and about half of these also responded to the hydroxymethylcytosine-specific agent hydroxylamine. A large minority of the mutants reverted spontaneously but failed to respond either to proflavine or to base analogues. We believe these mutants, as well as some of the mutants which did respond to base analogues, to be transversions (base pair substitutions which reverse the purine-pyrimidine orientation).


Comparing three quantification methods on N/Si ratio analysis using electron energy loss spectroscopy (EELS).
Precision elemental analysis by EELS at a nano-meter scale is a desirable goal for industrial application, as well as basic scientific research on advanced material analysis. However, sample thickness variation leads to a systematic error in element quantification due to electron plural scattering events and prevents it to be a useful quantitative analytic method. In this paper, we compared three methods to minimize thickness effect: Fourier-log deconvolution, Jump ratio, and Si K-edge by quantifying the N/Si ratio versus different thickness on a standard Si3N4 crystal sample. The results indicated that Jump ratio method exceeded other two methods owing to its higher accuracy, short data acquisition time as well as minimum requirement for spectroscopy instrument. The jump ratio method was applied to calculate N/Si ratio in storage nitride layer of 3D NAND trench wafer and blanket wafer, both illustrated that the jump ratio method successfully corrected the thickness effect on EELS composition quantification and largely reduced the relative error compared with the non-corrected result.


Developmental changes in cerebral NAD and neuroenergetics of an antioxidant compromised mouse model of schizophrenia.
Defects in essential metabolic regulation for energy supply, increased oxidative stress promoting excitatory/inhibitory imbalance and phospholipid membrane dysfunction have been implicated in the pathophysiology of schizophrenia (SZ). The knowledge about the developmental trajectory of these key pathophysiological components and their interplay is important to develop new preventive and treatment strategies. However, this assertion is so far limited. To investigate the developmental regulations of these key components in the brain, we assessed, for the first time, in vivo redox state from the oxidized (NAD+) and reduced (NADH) form of Nicotinamide Adenine Dinucleotide (NAD), energy and membrane metabolites, inhibitory and excitatory neurotransmitters by 31P and 1H MRS during the neurodevelopment of an SZ animal model with genetically compromised glutathione synthesis (gclm-KO mice). When compared to age-matched wild type (WT), an increase in NAD+/NADH redox ratio was found in gclm-KO mice until early adulthood, followed by a decrease in full adults as observed in patients. Especially, in early postnatal life (P20, corresponding to childhood), levels of several metabolites were altered in gclm-KO mice, including NAD+, NAD+/NADH, ATP, and glutamine + glutamate, suggesting an interactive compensation for redox dysregulation between NAD, energy metabolism, and neurotransmission. The identified temporal neurometabolic regulations under deficits in redox regulation provide insights into preventive treatment targets for at-risk individuals, and other neurodevelopmental disorders involving oxidative stress and energetic dysfunction.


An in-frame insertion in exon 3 and a nonsense mutation in exon 2 of the insulin receptor gene associated with severe insulin resistance in a patient with Rabson-Mendenhall syndrome.
We have studied the structure and function of the insulin receptor in a patient (PK) with severe insulin resistance and Rabson-Mendenhall syndrome. Insulin binding to cultured fibroblasts from PK was almost not detectable and insulin-induced insulin receptor autophosphorylation and glucose uptake was abolished. The structure of the receptor gene was analysed by sequencing amplified products of the 22 exons with the flanking intron regions directly as well as after subcloning in pUCBM20 plasmids. Two mutant alleles of the insulin receptor gene were detected. One allele contains in-frame 12 additional base pairs in exon 3 coding for the amino acids Leu-His-Leu-Val located between Asp-261 and Leu-262 in the receptor's extracellular domain, being the first report of an insertion mutation of the insulin receptor gene. In the other allele Arg-86 in exon 2 is changed into a stop codon. Therefore, PK is compound heterozygous at the insulin receptor locus. Direct cDNA sequencing indicates that both mutant alleles are expressed in the patient's fibroblasts. Studies of the parents' fibroblasts revealed that PK inherited the insertion mutation from the father and the nonsense mutation from the mother. Insulin binding to fibroblasts of the mother was reduced (63% of control cells) and hormone binding to the father's cells shows a larger reduction (37% of control cells), but less severe than the patient's cells (11% of control). This investigation provides further evidence that the Rabson-Mendenhall syndrome is causally related to mutations in the insulin receptor gene.


The Association of Pregnancy with Disease Progression in Patients Previously Treated for Differentiated Thyroid Cancer: A Propensity Score-Matched Retrospective Cohort Study.
Background: Differentiated thyroid cancer (DTC) is increasingly common in women of reproductive age. However, whether pregnancy increases the risk of DTC progression/recurrence after treatment remains controversial. The study aimed to assess the association of pregnancy with risk of progression in patients previously treated for DTC. Methods: This was a retrospective cohort study following 123 pregnant women and 1376 nonpregnant women at Peking University Third Hospital after initial treatment for DTC between January 2012 and December 2022. To control the effect of confounding, we carefully matched pregnancy (n = 107) and nonpregnancy groups (n = 298) in terms of baseline characteristics by using propensity score matching (PSM). Results: At baseline, the pregnancy and nonpregnancy groups were balanced in all matched variables. At follow-up, the percentage of DTC progression in the two groups was 12 (11.8%) and 47 (15.8%), respectively. Regression models showed no evidence of association of pregnancy with the risk of progression (odds ratio: 0.74 and 95% confidence interval: 0.37-1.50; p = 0.404), and remained consistent across long/short follow-up and other subgroup variables. We found that the shorter the time interval between treatment and pregnancy, the higher the risk of DTC progression (ptrend = 0.019). Conclusions: The risk of DTC progression in pregnant women was not higher than that in the well-matched, nonpregnant women. For young women previously treated for DTC, disease progression might not be a concern for their future pregnancy plan, but it seems safer to wait at least 1 year before pregnancy compared with immediate pregnancy.


Inferior tibiofibular joint mobilization with movement and taping does not improve chronic ankle dorsiflexion stiffness: a randomized placebo-controlled trial.
This study compared the modification of musculoarticular stiffness (MAS) and clinical outcomes after mobilization with movement (MWM) on the inferior tibiofibular joint and a placebo MWM. Moreover, injured and non-injured ankle MAS were compared after MWM therapy. A single-blinded randomized trial was conducted on 75 participants (mean age: 22.3 ± 2.17 years) with chronic self-reported asymmetric perception of ankle dorsiflexion stiffness. Participants were allocated to one of three groups: inferior tibiofibular MWM (ITFMWM), placebo and non-injured. Sinusoidal oscillation methods were used for experimental quantification of the MAS and clinical outcomes were assessed using the weight-bearing lunge test (WBLT), pain and stiffness perception. Three assessments were made: one pre-treatment (T0), one after the manual technique (T1) and one after taping (T2). Two-way ANOVA showed no significant differences between the groups and no interaction effect for the outcome measures. However, a significant difference for the time effect (T0-T1-T2) was found in the three groups for WBLT dorsiflexion range of motion (p < 0.001, Cohen's d = 0.21) and stiffness perception (p < 0.001, Cohen's d = 0.54) but the minimal clinically important differences were not reached for either value. The results could not support that a single session of ITFMWM modifies MAS or the clinical outcomes compared to placebo treatment. Furthermore, injured MAS does not differ from non-injured MAS in chronic ankle dorsiflexion stiffness. Further studies should assess subjects' responsiveness concerning the Mulligan concept and focus on a medium- to long-term follow-up.


Assessment of exposure to volatile organic compounds through urinary concentrations of their metabolites in pet dogs and cats from the United States.
Volatile organic compounds (VOCs) are ubiquitous environmental pollutants, exposure to which is associated with birth defects, neurocognitive and reproductive impairments, and cancer. Little is known, however, about VOC exposure in pet dogs and cats, which represent sentinels for human exposure as well as having value as companion animals. In this study, we determined 38 VOC metabolites (VOCMs) in urine samples collected from 47 dogs and 42 cats from the Albany area of New York State. Seventeen (in cats) to twenty (in dogs) VOCMs were found at detection frequencies (DFs) above 60%. The creatinine-adjusted geometric mean (GM) concentrations of individual VOCMs ranged from 5.43 (EMA) to 761 μg/g (3HPMA) in dog urine and 0.824 (SBMA) to 278 μg/g (ATCA) in cat urine. The ∑20 VOCM concentration in dog urine was 2280 μg/g (geometric mean) and the ∑17 VOCM concentration in cat urine was 847 μg/g. Eight individual VOCMs were significantly more abundant in dog than in cat urine, and the urinary concentrations of several VOCMs in dogs were comparable to those reported for human tobacco smokers. Metabolites of acrolein accounted for 43% of ∑20 VOCM concentration in dogs, whereas those of cyanide and benzene accounted for 60% of ∑17 VOCM concentration in cats. Based on acrylamide exposure doses, calculated hazard quotients were above 1 in 77% of dogs and 50% of cats studied, and cancer risk values (using a benchmark of 10-6) from exposure to acrylamide exceeded 1 for all dogs and cats. This is the first study to report VOCM concentrations in urine collected from pet dogs and cats and highlights the need to identify sources and health implications of VOCs exposure in these animals.


Arrhythmias and Their Electrophysiological Mechanisms in Takotsubo Syndrome: A Narrative Review.
Takotsubo syndrome (TTS), an acute and usually reversible condition, is associated with both tachy- and bradyarrhythmias. Such arrhythmias can be life-threatening, e.g. ventricular tachycardia and fibrillation, and associated with cardiac arrest. Others, such as atrioventricular block, persist and require long-term device therapy. In this narrative review, we aim to provide a summary of the current literature on arrhythmias in TTS and their clinical sequelae. PubMed and Medline databases were searched with various permutations of TTS, arrhythmias and beta-adrenoceptors. After application of exclusion criteria and review, 84 articles were included. Although there are no specific electrocardiograph (ECG) findings in TTS to differentiate it from ST-elevation myocardial infarction, suggestive patterns include small QRS amplitude, ST segment elevation without reciprocal ST depression and prolonged QT interval. Atrial tachyarrhythmias (incidence of 5-15%) are associated with a more unwell patient cohort. Ventricular arrhythmias (incidence 4-14%) are often associated with prolonged QT interval and are a cause of sudden death in TTS. Bradyarrhythmias are less common (incidence 1.3-2.5%), but have been reported with TTS, and usually persist beyond the acute phase. Takotsubo syndrome, though considered primarily a disease of the myocardium, carries multiple arrhythmic manifestations that affect short- and long-term prognosis. The management of such arrhythmias represents a constantly evolving area of research.


Dimensional approach to gender dysphoria in Nigeria: Association with socio-demographic and psycho-sexual variables.
Recent changes across the world with respect to gender transitioning of children and adolescents have generated a bio-psycho-socio-cultural discourse among interest groups. This study sought to examine gender dysphoric symptoms among adolescents and young persons in an African population, using a dimensional approach. A total of 747 primary/secondary school and university students aged 10-24 years were studied using the 27-item Gender Identity/Gender Dysphoria Questionnaire for Adolescents and Adults (GIDYQ-AA). Participants were divided into early, mid- and late adolescents. The composite and domain scores were calculated using the criteria described by Deogracias, and comparison of the median scores was done using Mann-Whitney U-test and Kruskal-Wallis test as appropriate. Dunnett's post-hoc test was used for pairwise comparisons. The prevalence of self-identified transgender and self-reported non-heterosexuals was 0.9% (95%CI: 0.36-1.92) and 18.6% (15.85-21.59), respectively. The participants as a group scored 4.56 out of a possible 5 on the gender dysphoria scale, indicating less gender dysphoric symptoms in this cohort. However, participants in mid- and late adolescents had significantly lower scores when compared with early adolescents (P = 0.009). Self-reported transgender had significantly lower scores in the social (P = 0.001) and socio-legal (P < 0.001) indicators of the scale. The findings of this study, although, preliminary demonstrated less gender dysphoric symptoms in this cohort of Nigerian adolescents and young adults compared to the Western population. Nevertheless, some degree of GD was noticed, revealing that this condition is existent in our society.


Partial atlantooccipital assimilation causing atlantoaxial instability and early myelopathy in an adult treated with occipitocervical fusion: A case report.
Atlanto-occipital assimilation is a rare congenital abnormality which can cause atlantoaxial instability. Basilar invagination and instability can lead to cord compression and myelopathy in young individuals. A 37-year-old male presented with gradually worsening axial neck pain for four years duration His deep tendon reflexes are exaggerated in all four limbs but there is no weakness or imbalance. Following radiological evaluation, he was diagnosed to have partial atlantooccipital assimilation causing atlantoaxial instability, basilar invagination and early myelopathy. He was treated with occipital-cervical fusion after the closed reduction of the atlantoaxial joint. Atlanto-axial assimilation can lead to atlantoaxial instability and subsequently myelopathy. Dynamic radiographs and computed tomography are helpful in the diagnosis. Reducible atlantoaxial instability can be managed with closed reduction and occipitocervical fusion.


Host cell subversion by Toxoplasma GRA16, an exported dense granule protein that targets the host cell nucleus and alters gene expression.
After invading host cells, Toxoplasma gondii multiplies within a parasitophorous vacuole (PV) that is maintained by parasite proteins secreted from organelles called dense granules. Most dense granule proteins remain within the PV, and few are known to access the host cell cytosol. We identify GRA16 as a dense granule protein that is exported through the PV membrane and reaches the host cell nucleus, where it positively modulates genes involved in cell-cycle progression and the p53 tumor suppressor pathway. GRA16 binds two host enzymes, the deubiquitinase HAUSP and PP2A phosphatase, which exert several functions, including regulation of p53 and the cell cycle. GRA16 alters p53 levels in a HAUSP-dependent manner and induces nuclear translocation of the PP2A holoenzyme. Additionally, certain GRA16-deficient strains exhibit attenuated virulence, indicating the importance of these host alterations in pathogenesis. Therefore, GRA16 represents a potentially emerging subfamily of exported dense granule proteins that modulate host function.


Tinnitus and bilateral sensorineural hearing loss: ankylosing spondylitis or a side-effect of sulphasalazine treatment?
We report the case of a young male patient with ankylosing spondylitis treated with sulphasalazine who developed bilateral sensorineural hearing loss with tinnitus. Discontinuation of sulphasalazine led to complete resolution of tinnitus and an improvement in hearing loss. We discuss the features of this case and also review the relevant literature.


Antioxidative effect of luteolin pretreatment on simulated ischemia/reperfusion injury in cardiomyocyte and perfused rat heart.
To investigate the antioxidative effect and mechanism of luteolin on rat cardiomyocytes and isolated hearts followed by simulated ischemia/reperfusion (SI/R) injury. The left ventricular cardiomyocytes and the isolated hearts from adult rats were subjected to SI/R injury. The experiment groups included control, SI/R, luteolin + SI/R (Lut + SI/R), vitamin E (Vit E) + SI/R, and LY294002 + luteolin + SI/R (LY + Lut + SI/R) groups. Cell viability, shortening amplitude, lactate dehydrogenase (LDH) release, superoxide dismutase (SOD) activity, the production of reactive oxygen species (ROS) and malondialdehyde (MDA), expression levels of Akt, phosphorylated Akt, NOX2 (gp91phox), NOX2 mRNA, mitogen-activated protein kinase (p38 MAPK) and phosphorylated p38MAPK were all measured after 3-h simulated ischemia and 2-h simulated reperfusion procedure in cardiomyocytes. Vit E was used as a standard control. The contractile function of isolated hearts was further observed after they were subjected to 30-min global ischemia and 120-min reperfusion. Pretreatment with 8-μmol/L luteolin substantially increased cell viability and shortening amplitude, while reducing evidence of oxidative stress-induced damage in the cells. In addition, the expression of NOX2, NOX2 mRNA and phosphorylation of p38MAPK were all downregulated. Furthermore, pretreatment with 40-μmol/L luteolin improved the recovery of myocardial contractile function following SI/R-induced injury, and luteolin markedly increased phosphorylation of Akt. However, all of the above effects were partially inhibited by the phosphatidylinositol 3-kinase (PI3K) inhibitor, LY294002. Luteolin prevents SI/R-induced myocardial damage by reducing oxidative stress-induced injury in isolated rat hearts and cardiomyocytes, and the cardioprotection induced by luteolin was partially mediated by the PI3K/Akt pathway.


Statistical modeling and investigation of thermal characteristics of a new nanofluid containing cerium oxide powder.
In this paper, the thermal conductivity (knf) of cerium oxide/ethylene glycol nanofluid is extracted for different temperatures (T = 25, 30, 35, 40, 45, and 50 °C) and the volume fraction of nanoparticles ( φ = 0, 0.25, 0.5, 0.75, 1, 1.5, 2 and 2.5%) and then knf is predicted by two methods including Artificial Neural Network (ANN) and fitting method. For both methods, the results have been presented and compared. The experiments showed that with increasing φ and temperature, the thermal conductivity ratio (TCR) of nanofluid increases. It was also observed that when the experiments are performed at high temperatures, the rate of increase in knf is much higher than the change in the same amount of φ change at low temperatures. An ANN with 7 neurons has a correlation coefficient very close to 1 and this proves that the outputs are compatible with experimental results. Also, it can be seen that the ANN could predict the thermal behavior of cerium oxide/ethylene glycol nanofluid more accurately.


Herbivory below ground and biological weed control: life history of a root-boring weevil on purple loosestrife.
The life history of the root-boring weevil Hylobius transversovittatus was studied in north and central Europe. The weevil develops on Lythrum salicaria, a perennial marshland plant that has become a problem weed in North America. It was found in all habitats of its host plant with the exception of permanently flooded sites. It also attacked L. salicaria in an early successional stage, devastating large parts of the storage tissue. The beetle was found in two-thirds of the field populations examined with a mean attack rate of 76.3%. Larvae developed according to a 1- or 2-year generation cycle depending on the time of oviposition. Adult beetles developing within 1 year emerged between July and October, whereas beetles with a 2-year larval period emerged within 3 weeks in July and August. Adults were long-lived and could hibernate several times. Beetles of the new generation mated right on the spot and some oviposited prior to overwintering. Hibernated females had an oviposition period from May to early September and produced 3-4 eggs/day during the peak oviposition period. Specific mortality factors were scarce. Dispersal flights ensure the regular occurrence of H. transversovittatus in scattered L. salicaria populations. The severe impact of the weevil is expected to reduce the competitive ability of its host plant after introduction into North America.


Terminal right heart failure due to complex congenital cardiac disease successfully managed by home peritoneal drainage.
A man, aged 32, who had undergone surgical correction of complex congenital cardiac disease, had chronic severe right heart failure. Increasing reliance on diuretics led to deteriorating renal function, and he was rejected as a candidate for cardiac transplantation. By inserting a Tenckhoff catheter, and training him to drain his ascites at home, we achieved a dramatic improvement in both his cardiac and renal function. As far as we can ascertain, this is the first time this technique has been used for such a patient. We discuss the mechanisms of improvement, and suggest that other such patients with congenital cardiac disease might benefit from similar management.


Practical diagnosis of cirrhosis in non-alcoholic fatty liver disease using currently available non-invasive fibrosis tests.
Unlike for advanced liver fibrosis, the practical rules for the early non-invasive diagnosis of cirrhosis in NAFLD remain not well defined. Here, we report the derivation and validation of a stepwise diagnostic algorithm in 1568 patients with NAFLD and liver biopsy coming from four independent cohorts. The study algorithm, using first the elastography-based tests Agile3+ and Agile4 and then the specialized blood tests FibroMeterV3G and CirrhoMeterV3G, provides stratification in four groups, the last of which is enriched in cirrhosis (71% prevalence in the validation set). A risk prediction chart is also derived to allow estimation of the individual probability of cirrhosis. The predicted risk shows excellent calibration in the validation set, and mean difference with perfect prediction is only -2.9%. These tools improve the personalized non-invasive diagnosis of cirrhosis in NAFLD.


Asynchronous exponential growth in an age structured population of proliferating and quiescent cells.
A model of a proliferating cell population is analyzed. The model distinguishes individual cells by cell age, which corresponds to phase of the cell cycle. The model also distinguishes individual cells by proliferating or quiescent status. The model allows cells to transit between these two states at any age, that is, any phase of the cell cycle. The model also allows newly divided cells to enter quiescence at cell birth, that is, cell age 0. Sufficient conditions are established to assure that the cell population has asynchronous exponential growth. As a consequence of this asynchronous exponential growth the population stabilizes in the sense that the proportion of the population in any age range, or the fraction in proliferating or quiescent state, converges to a limiting value as time evolves, independently of the age distribution and proliferating or quiescent fractions of the initial cell population. The asynchronous exponential growth is proved by demonstrating that the strongly continuous linear semi-group associated with the partial differential equations of the model is positive, irreducible, and eventually compact.


The efficacy of intravenous fluid supplementation for neonatal hyperbilirubinemia: a meta-analysis of randomized controlled studies.
The efficacy of intravenous fluid supplementation for neonatal hyperbilirubinemia remains controversial. We conduct a systematic review and meta-analysis to explore the influence of intravenous fluid supplementation on treatment efficacy of neonatal hyperbilirubinemia. We search PubMed, Embase, Web of Science, EBSCO, and Cochrane Library databases through June 2019 for randomized controlled trials (RCTs) assessing the efficacy of intravenous fluid supplementation for neonatal hyperbilirubinemia. This meta-analysis is performed using the random-effect model. Six RCTs are included in the meta-analysis. Overall, compared with control group for neonatal hyperbilirubinemia, intravenous fluid supplementation is associated with decreased TSB at 8 h (std. MD = -0.82; 95% CI = -1.46 to -0.17; p = .01), 12 h (std. MD = -0.46; 95% CI = -0.81 to -0.10; p = .01), 24 h (std. MD = -0.47; 95% CI = -0.78 to -0.16; p = .003) and 36 h (std. MD = -0.37; 95% CI = -0.73 to -0.02; p = .04), as well as reduced incidence of exchange transfusion (RR = 0.29; 95% CI = 0.14-0.59; p = .0006), but has no significant impact on duration of phototherapy (std. MD = -0.34; 95% CI = -0.88-0.21; p = .22). Intravenous fluid supplementation can provide additional benefits for the treatment of neonatal hyperbilirubinemia.


The emerging epidemiology of hypomania and bipolar II disorder.
The literature on the lifetime prevalence of the bipolar spectrum suggests rates of 3-6.5%. The Zurich cohort study identified a prevalence rate up to age 35 of 5.5% of DSM-IV hypomania/mania and a further 2.8% for brief hypomania (recurrent and lasting 1-3 days). The validity of DSM-IV hypomania and brief hypomania was demonstrated by a family history of mood disorders, a history of suicide attempts and treatment for depression. Comorbidity with anxiety disorders and substance abuse was found equally in both subtypes of hypomania. The study suggests that recurrent brief hypomania belongs to the bipolar spectrum. The findings should be verified on larger national cohorts in other epidemiological and clinical studies.


Characterization of the novel HLA-DQA1*01:81 allele by sequencing-based typing.
HLA-DQA1*01:81 differs from HLA-DQA1*01:02:01:01 by one nucleotide substitution in codon 153 in exon 3.


Cost-Utility Analysis of IEV Drug Regimen Versus ESHAP Drug Regimen for the Patients With Relapsed and Refractory Hodgkin and Non-Hodgkin's Lymphoma in Iran.
Chemotherapy for lymph nodes cancer is often composed of several drugs that are used in a treatment program. The aim of this study was to perform a cost-utility analysis of IEV regimen (ifosfamide, epirubicin and etoposide) versus ESHAP regimen (etoposide, methylprednisolone, high-dose cytarabine, and cisplatin) in patients with lymphoma in the south of Iran. This was a cost-utility analysis done as a cross-sectional study in the south of Iran. Using decision tree, expected costs, quality -adjusted life years (QALYs) and the incremental cost-effectiveness ratio (ICER) were estimated. In addition, the robustness of results was examined by sensitivity analysis. The results of this study indicated that the total lymphoma patients were about 65 people that 27 patients received IEV regimen and 38 patients ESHAP (43 patients with Hodgkin's and 22 with non-Hodgkin lymphoma). The results of decision tree showed that in the IEV arm, the expected cost was $20952.93 and the expected QALYs was 3.89 and in the ESHAP arm, the expected cost was $31691.74 and the expected QALYs was 3.86. Based on the results of the study, IEV regimen was cost-effective alternative to the ESHAP regimen. According to the results of this study, it is recommended that oncologists use IEV instead of ESHAP in the treatment of patients with lymphoma and because of high costs of IEV drug costs, it is suggested that IEV drugs should be covered by insurance.


Crystal structures of an HIV-1 integrase aptamer: Formation of a water-mediated A•G•G•G•G pentad in an interlocked G-quadruplex.
93del is a 16-nucleotide G-quadruplex-forming aptamer which can inhibit the activity of the HIV-1 integrase enzyme at nanomolar concentration. Previous structural analyses of 93del using NMR spectroscopy have shown that the aptamer forms an interlocked G-quadruplex structure in K+ solution. Due to its exceptional stability and unique topology, 93del has been used in many different studies involving DNA G-quadruplexes, such as DNA aptamer and multimer design, as well as DNA fluorescence research. To gain further insights on the structure of this unique aptamer, we have determined several high-resolution crystal structures of 93del and its variants. While confirming the overall dimeric interlocked G-quadruplex folding topology previously determined by NMR, our results reveal important detailed structural information, particularly the formation of a water-mediated A•G•G•G•G pentad. These insights allow us to better understand the formation of various structural elements in G-quadruplexes and should be useful for designing and manipulating G-quadruplex scaffolds with desired properties.


A visual affective analysis of mass media interventions to increase antimicrobial stewardship amongst the public.
In an innovative approach to improve the contribution of health psychology to public health we have analysed the presence and nature of affect within the visual materials deployed in antimicrobial stewardship interventions targeting the public identified through systematic review. A qualitative analysis focused on the affective content of visual materials garnered from a systematic review of antibiotic stewardship (k = 20). A novel method was devised drawing on concepts from semiotics to analyse the affective elements within intervention materials. Whilst all studies examined tacitly rely on affect, only one sought to explicitly deploy affect. Three thematic categories of affect are identified within the materials in which specific ideological machinery is deployed: (1) monsters, bugs, and superheroes; (2) responsibility, threat, and the misuse/abuse of antibiotics; (3) the figure of the child. The study demonstrates how affect is a present but tacit communication strategy of antimicrobial stewardship interventions but has not - to date - been adequately theorized or explicitly considered in the intervention design process. Certain affective features were explored in relation to the effectiveness of antimicrobial resistance interventions and warrant further investigation. We argue that further research is needed to systematically illuminate and capitalize upon the use of affect to effect behaviour change concerning antimicrobial stewardship. Statement of contribution What is already known on this subject? The (mis)use of antibiotics and consequent risk of antimicrobial resistance is a critical public health problem. If sufficient action is not taken, global society will face the 'post-antibiotic' era, in which common infections will lead to death for many millions. Key desirable behavioural changes are decreased patient demands for antibiotics, use of them for targeted purposes alone, and compliance with prescribed dosing. There is a growth of interest in the role of affect in mass media interventions designed to engage publics and produce health-related behavioural change. What does this study add? This article presents a novel analytic approach to understanding and intervening within behaviour change in public health that may complement other types of analysis. We present findings specifically from an 'affective' analysis based on semiotics in which we critically interrogated the visual imagery being deployed in mass media public health interventions concerning antimicrobial stewardship. Three thematic categories of affect are identified within the materials in which specific ideological machinery is deployed and that demonstrate some association with intervention effectiveness worthy of further investigation and testing.


Incidence of uterine leiomyosarcoma and endometrial stromal sarcoma in Nordic countries: results from NORDCAN and NOCCA databases.
Uterine sarcomas are an uncommon and heterogeneous group of malignancies. Their etiology is mainly unknown. Here, we analyzed trends in incidence and occupational variation in risk of uterine leiomyosarcomas (LMS) and endometrial stromal sarcomas (ESS) in the Nordic countries aided by NORDCAN and NOCCA (Nordic Occupational Cancer) databases. Incidence rates per 100,000 and Standardized incidences rates (SIR) obtained from NORDCAN and NOCCA databases. The incidence rates were about 0.3 per 100,000 for ESS and about 0.4 per 100,000 for LMS in Denmark, Finland, Iceland, and Norway. During the study-period (1978-2007), the incidence rates in each country were quite similar and constant. The age-specific incidence of LMS showed a peak around menopause. Significantly increased risk for LMS occurred in shoe and leather workers, farmers and teachers, whereas significantly low risk was detected with packers in the NOCCA data from Finland, Norway, and Sweden. For ESS no occupations showed either increased or decreased incidences. The incidence trends of LMS and ESS in our study were constant in four Nordic countries over time. The elevated risk for LMS with women exposed to leather work and animal dust indicates further exploration.


Arthroscopic osteosynthesis of capitellum fractures: Feasibility study and clinical study on 2 cases.
The current management of displaced capitellum fractures is traditionally surgical. Most authors perform open reduction and internal fixation. The working hypothesis was that closed reduction and internal fixation of capitellum fractures is achievable by arthroscopy. We carried out a cadaveric study on six fresh frozen elbows. We performed two Bryan and Morrey type I fractures of the capitellum, three type II and one type IV using a 15 mm osteotome. Fracture reduction was performed under arthroscopy using a probe hook and an aiming femoral instrument set. Fixation with a lag screw was performed under arthroscopy and radioscopic control. We reviewed, two patients who had been operated on for a type I and type II capitellum fracture and osteosynthesized under arthroscopy with a 7.5 years follow-up. In our cadaveric study, we obtained anatomical reduction and stable osteosynthesis in four cases. We had two failures (2 type II fractures) due to a fracture of the fragment during screwing. In our clinical study, range of motion was very satisfactory with only a 5° extension deficit. The x-rays did not reveal any signs of osteoarthritis or periarticular ossification. One patient had minimal signs of osteonecrosis. Arthroscopic osteosynthesis of capitellum fractures is feasible and reproducible. We recommend cannulated lag screws for Bryan and Morrey type I and IV fractures and adjustable lock pins for type II fractures. We have shown that this technique gives good results on two patients with a 7.5-year follow-up. IV.


Trend of Nutritional Support in Preterm Infants.
Without appropriate nutritional support, preterm infants fail to grow after birth and have malnutrition. The main reason for delayed feeding is fear of immaturity of gastrointestinal function. The principles of nutritional practice should be as follows: (1) minimal early initiation of enteral feeding with breast milk (0.5-1 mL/h) to start on Day 1 if possible and gradual increase as tolerated; (2) early aggressive parenteral nutrition as soon as possible; (3) provision of lipids at rates that will meet the additional energy needs of about 2-3 g/kg/d; and (4) attempt to increase enteral feeding rather than parenteral nutrition.


Effects of muscle activity on lumbar spinal stiffness in asymptomatic adults: An investigation using a novel rolling device.
Device-based measurement of lumbar spinal stiffness has the potential to identify patients with low back pain who are more likely to improve with spinal manipulative therapy. This study evaluates how voluntary contraction of spine muscles may impact stiffness measures. To determine how the contraction of different spinal muscles may influence spinal stiffness at all lumbar levels. Experimental study. A mechanical device was used to measure spinal stiffness (N/mm) from L1 to L5 in 12 asymptomatic participants, while muscle activity from four pairs of thoracolumbar muscles was recorded. A baseline measurement was collected with the participants holding their breath at normal exhalation. Participants stiffness was then measured while performing (1) an isometric hip extension, (2) an isometric shoulder flexion, and (3) a deep held inhalation. Mixed-model ANOVAs were used to evaluate the effects of the perturbations on spinal stiffness at each lumbar level. Friedman's test was then computed to evaluate the differences in muscle activity between the perturbations. Globally, the designed perturbations generated activity in different muscles with different magnitudes (P-values≤0.05). Increased spinal stiffness was observed at each spinal level during the hip extension, and at L5 during the held inhalation (P-values<0.05). A differential effect of the spinal levels on the spinal stiffness was observed during the hip extension and held inhalation (P-values<0.05). This study provides evidence that the magnitude of muscle activity influences spinal stiffness, but not equally between lumbar levels.


Comparison of mesenchymal stem cell attachment efficiency in acellular neural graft for peripheral nerve regeneration.
Decellularized nerve allograft is an alternative to autologous nerve graft for nerve defects but has shown inferior clinical outcomes. Mesenchymal stem cells can play a key role in improving nerve regeneration of decellularized nerve allografts. The purpose of this study was to compare different mesenchymal stem cell seeding methods and to find the most efficient way to attach cells to nerve grafts for peripheral nerve regeneration. Wharton's jelly mesenchymal stem cells were collected from human umbilical cords and were seeded in the acellular nerve graft in five different ways as follows: PBS injection, fibrin glue drop, Matrigel drop, bioreactor, and Matrigel injection. A 6-mm sciatic nerve defect of Sprague-Dawley rats was bridged using mesenchymal stem cells-laden acellular nerve grafts according to the five seeding methods. Two days after implantation, the nerve tissue was biopsied and analyzed by the immunofluorescence staining of nuclei. The number of Wharton's jelly mesenchymal stem cells (+ h Nuclei) was counted in the inside, outside, and the total area of the graft sections under 200X magnification. The highest efficiency of mesenchymal stem cell attachment inside the graft and the highest total number of attached mesenchymal stem cells was observed in the group using Matrigel injection (p < 0.0001). This study showed mesenchymal stem cells can be more effectively attached to decellularized nerve graft using the injection method with Matrigel than other static or dynamic seeding methods in vivo.


Surgical resection of a cerebral arteriovenous malformation for treatment of superficial siderosis: case report.
To our knowledge, there are only two reported cases of cerebral arteriovenous malformation associated with superficial siderosis. In both cases, the patients were asymptomatic and were discovered on retrospective review of magnetic resonance imaging. We describe a case of superficial siderosis in a 47-year-old male with a remote history of closed head injury that presented with progressive hearing loss, cerebellar ataxia, and urinary incontinence. Lumbar puncture was indicative of active subarachnoid bleeding. Cerebral angiography revealed a small vascular malformation that was resected. Pathological examination confirmed the diagnosis of the arteriovenous malformation. Six months after surgery the patient is neurologically stable with no further progression of clinical signs or symptoms. We report the first case of surgical resection of an intracranial arteriovenous malformation for the treatment of superficial siderosis. We emphasize the necessity of a detailed evaluation when superficial siderosis is suspected to localize and resect potential bleeding sources, because the disease is progressive and often irreversible.


Comparison of the signal-to-noise ratio at 1.5 and 2.0 T using a whole-body system.
Signal-to-noise ratios for 1H, 31P, and 13C signals at 1.5 and 2.0 T were compared using a whole-body system with a fast rampable magnet. Results indicate that SNR lies within the predicted values of linear and 7/4th power dependency with the applied magnetic field, for lossy and lossless samples, respectively.


Child Advocacy in Action: If Not You, Who? If Not now, When?
The notion that the physician has a responsibility to both the patient in their care and the community in which they reside has been a source of inspiration and tension within the profession for centuries. The profession of Pediatrics has uniquely incorporated advocacy into its training programs and will likely continue to incorporate advocacy into its professional standards for the foreseeable future. In this article, we review the history of advocacy within the profession, outline the skills needs for successful child health advocacy and offer examples of how advocacy combined with pediatric practice has improved the lives of children.


Renewable methanol and formate as microbial feedstocks.
Methanol and formate are attractive microbial feedstocks as they can be sustainably produced from CO2 and renewable energy, are completely miscible, and are easy to store and transport. Here, we provide a biochemical perspective on microbial growth and bioproduction using these compounds. We show that anaerobic growth of acetogens on methanol and formate is more efficient than on H2/CO2 or CO. We analyze the aerobic C1 assimilation pathways and suggest that new-to-nature routes could outperform their natural counterparts. We further discuss practical bioprocessing aspects related to growth on methanol and formate, including feedstock toxicity. While challenges in realizing sustainable production from methanol and formate still exist, the utilization of these feedstocks paves the way towards a truly circular carbon economy.


Multiple sclerosis in older adults: the clinical profile and impact of interferon Beta treatment.
We examined (1) patient characteristics and disease-modifying drug (DMD) exposure in late-onset (LOMS, ≥50 years at symptom onset) versus adult-onset (AOMS, 18-<50 years) MS and (2) the association between interferon-beta (IFNβ) and disability progression in older relapsing-onset MS adults (≥50 years). This retrospective study (1980-2004, British Columbia, Canada) included 358 LOMS and 5627 AOMS patients. IFNβ-treated relapsing-onset MS patients aged ≥50 (regardless of onset age, 90) were compared with 171 contemporary and 106 historical controls. Times to EDSS 6 from onset and from IFNβ eligibility were examined using survival analyses. LOMS patients (6%) were more likely to be male, with motor onset and a primary-progressive course, and exhibit faster progression and were less likely to take DMDs. Nonetheless, 57% were relapsing-onset, of which 31% were prescribed DMDs, most commonly IFNβ. Among older relapsing-onset MS adults, no significant association between IFNβ exposure and disability progression was found when either the contemporary (hazard ratio [HR]: 0.46; 95% CI: 0.18-1.22) or historical controls (HR: 0.54; 95% CI: 0.20-1.42) were considered. LOMS differed clinically from AOMS. One-third of older relapsing-onset MS patients were prescribed a DMD. IFNβ exposure was not significantly associated with reduced disability in older MS patients.


Group health plans and health insurance issuers relating to coverage of preventive services under the Patient Protection and Affordable Care Act. Final rules.
These regulations finalize, without change, interim final regulations authorizing the exemption of group health plans and group health insurance coverage sponsored by certain religious employers from having to cover certain preventive health services under provisions of the Patient Protection and Affordable Care Act.


A Novel Drug Repositioning Approach Based on Integrative Multiple Similarity Measures.
Drug repositioning refers to discovering new indications for the existing drugs, which can improve the efficiency of drug research and development. In this work, a novel drug repositioning approach based on integrative multiple similarity measure, called DR_IMSM, is proposed. The process of integrative similarity measure contains three steps. First, a heterogeneous network can be constructed based on known drug-disease association, shared entities information for drug pairwise and diseases pairwise. Second, a deep learning method, DeepWalk, is used to capture the topology similarity for drug and disease. Third, a similarity integration and adjusting process is further conducted to obtain more comprehensive drug and disease similarity measure, respectively. On this basis, a Bi-random walk algorithm is implemented in the constructed heterogeneous network to rank diseases for each drug. Compared with other approaches, the proposed DR_IMSM can achieve superior performance in terms of AUC on the gold standard datasets. Case studies further confirm the practical significance of DR_IMSM.


Clinical effects of cognitive behavioral therapy in heart failure patients: a meta-analysis of randomized controlled trials.
About 20-40% of people with Heart failure (HF) suffer from some depression, which is 4-5% greater than the overall population. This depression can lead to undesirable outcomes, including elevated mortality rate and frequent hospitalization. The current study aims to evaluate the impact of cognitive behavioural therapy (CBT) on self-care and the symptoms of depression and anxiety in HF patients. We searched PubMed, Web of Science (WOS), Scopus, and Cochrane Library till 15 October 2022. All relevant randomized controlled trials (RCTs) were included. The data were extracted and pooled using Review Manager software (RevMan 5.4). Continuous data were pooled as mean difference and 95% confidence interval (CI). Our search retrieved 1146 records, and 7 studies (611 patients) were finally included. We assessed the Beck Depression Inventory-II (BDI-II) as the primary outcome of the study. Hamilton Rating Scale for Depression (HRSD-17), Change in Beck Anxiety Inventory, Kansas City Cardiomyopathy Questionnaire (KCCQ), and Self-Care of Heart Failure Index (SCHFI) were also assessed as secondary outcomes. With CBT, BDI-II showed a significant reduction after 4 to 6 months follow-up (MD = -4.87, 95% CI: [-8.06; -1.69], P = 0.003) as well as 8 to 9 months follow-up (MD = -5.71, 95% CI: [-8.95; -2.46], P = 0.0006). But no significant difference was shown with 3 months follow-up (M.D=-4.34; 95%CI: [-10.70; 2.03], P = 0.18). CBT has long-term (4-9 months) significant favorable outcomes decreasing anxiety and depression compared to non-CBT groups. No significant short-term (less than 3 months) impact on HF patients' self-care, depression, or anxiety were shown.


The neuronal nitric oxide synthase inhibitor NANT blocks acetaminophen toxicity and protein nitration in freshly isolated hepatocytes.
3-Nitrotyrosine (3NT) in liver proteins of mice treated with hepatotoxic doses of acetaminophen (APAP) has been postulated to be causative in toxicity. Nitration is by a reactive nitrogen species formed from nitric oxide (NO). The source of the NO is unclear. iNOS knockout mice were previously found to be equally susceptible to APAP toxicity as wildtype mice and iNOS inhibitors did not decrease toxicity in mice or in hepatocytes. In this work we examined the potential role of nNOS in APAP toxicity in hepatocytes using the specific nNOS inhibitor NANT (10 µM)(N-[(4S)-4-amino-5-[(2-aminoethyl)amino]pentyl]-N'-nitroguanidinetris (trifluoroacetate)). Primary hepatocytes (1 million/ml) from male B6C3F1 mice were incubated with APAP (1mM). Cells were removed and assayed spectrofluorometrically for reactive nitrogen and oxygen species using diaminofluorescein (DAF) and Mitosox red, respectively. Cytotoxicity was determined by LDH release into media. Glutathione (GSH, GSSG), 3NT, GSNO, acetaminophen-cysteine adducts, NAD, and NADH were measured by HPLC. APAP significantly increased cytotoxicity at 1.5-3.0 h. The increase was blocked by NANT. NANT did not alter APAP mediated GSH depletion or acetaminophen-cysteine adducts in proteins which indicated that NANT did not inhibit metabolism. APAP significantly increased spectroflurometric evidence of reactive nitrogen and oxygen formation at 0.5 and 1.0 h, respectively, and increased 3NT and GSNO at 1.5-3.0 h. These increases were blocked by NANT. APAP dramatically increased NADH from 0.5-3.0 h and this increase was blocked by NANT. Also, APAP decreased the Oxygen Consumption Rate (OCR), decreased ATP production, and caused a loss of mitochondrial membrane potential, which were all blocked by NANT.


Vessel Noise Promotes Hull Fouling.
Fouling of submerged vessel hulls due to the rapid settlement of algae and invertebrates is a longstanding and costly problem. It is widely thought that the presence of extensive vacant surfaces on vessel hulls is responsible for the rapid attachment and growth of biofouling. We investigated whether noise from vessels in port could also be involved in promoting the settlement and growth of common biofouling organisms on vessel hulls. Three important biofouling species exhibited significantly faster development and settlement and better survival when exposed to vessel noise compared with control species. The extent of these responses appeared to vary in relation to the intensity of the vessel noise and may help to explain differences in biofouling observed on vessel hulls.


Association of organophosphate pesticide exposure and paraoxonase with birth outcome in Mexican-American women.
Epidemiologic studies suggest that maternal organophosphorus (OP) pesticide exposure is associated with poorer fetal growth, but findings are inconsistent. We explored whether paraoxonase (PON1), a key enzyme involved in detoxification of OPs, could be an effect modifier in this association. The study population included 470 pregnant women enrolled in the CHAMACOS Study, a longitudinal cohort study of mothers and children living in an agricultural region of California. We analyzed urine samples collected from mothers twice during pregnancy for dialkyl phosphate (DAP) metabolites of OP pesticides. We analyzed maternal and fetal (cord) blood samples for PON1 genotype (PON1(192) and PON1(-108)) and enzyme activity (paraoxonase and arylesterase). Infant birth weight, head circumference, and gestational age were obtained from medical records. Infants' PON1 genotype and activity were associated with birth outcome, but mothers' were not. Infants with the susceptible PON1(-108TT) genotype had shorter gestational age (β = -0.5 weeks, 95% Confidence Interval (CI): -0.9, 0.0) and smaller head circumference (β = -0.4 cm, 95% CI: -0.7, 0.0) than those with the PON1(-108CC) genotype. Infants' arylesterase and paraoxonase activity were positively associated with gestational age. There was some evidence of effect modification with DAPs: maternal DAP concentrations were associated with shorter gestational age only among infants of the susceptible PON1(-108TT) genotype (p-value(interaction) = 0.09). However, maternal DAP concentrations were associated with larger birth weight (p-value(interaction) = 0.06) and head circumference (p-value(interaction)<0.01) in infants with non-susceptible genotypes. Infants whose PON1 genotype and enzyme activity levels suggested that they might be more susceptible to the effects of OP pesticide exposure had decreased fetal growth and length of gestation. PON1 may be another factor contributing to preterm or low birth weight birth.