Occupational asthma due to a repair process for polyethylene-coated electrical cables.
We report the case of an electrical cable repairer who presented with symptoms suggestive of occupational asthma. A supervised workplace challenge test confirmed this diagnosis and laboratory challenge studies implicated heated polyethylene repair tape containing the chemical cross-linking agent dicumyl peroxide as the cause. Similar cross-linking processes are widely used in the cable manufacturing industry and the possibility of occupational asthma occurring in other settings may need to be considered.


Effect of renal impairment on multiple-dose pharmacokinetics of extended-release ranolazine.
Ranolazine is a novel compound under development as an antianginal agent. The multiple-dose pharmacokinetics of extended-release ranolazine and 3 major metabolites was investigated in healthy subjects (N = 8) and subjects with mild to severe renal impairment (N = 21). The ranolazine AUC(0-12) (area under the concentration-time curve between 0 and 12 hours after dosing) geometric mean ratio versus healthy subjects at steady state was 1.72 (90% confidence interval [CI], 1.07-2.76) in subjects with mild impairment, 1.80 (90% CI, 1.13-2.89) in those with moderate impairment, and 1.97 (90% CI, 1.23-3.16) in those with severe renal impairment. Creatinine clearance was negatively correlated with AUC(0-12) and the maximum observed concentration for ranolazine and the O-dearylated metabolite (P < .05 for all variables), as well as the N-dealkylated metabolite (P < .001), but not for the O-demethylated metabolite. Less than 7% of the administered dose was excreted unchanged in all groups, indicating that factors other than reduced glomerular filtration rate contributed to the increase in ranolazine concentrations in renal impairment. No serious adverse events were observed in the study.


Sodium dodecyl sulphate (SDS) induced changes in propensity and kinetics of α-lactalbumin fibrillation.
Understanding surfactants induced changes on protein folding, aggregation, and fibrillation has a lot of implications in their laboratory and industrial applications. The effect of an anionic surfactant, sodium dodecyl sulphate (SDS), on fibrillation of an acidic protein α-lactalbumin (α-LA) at neutral pH condition was investigated. SDS at lower concentrations increased the lag time by nearly two-fold whereas the fibril elongation rate was not significantly altered. At the concentrations above 0.2mM, SDS lengthened the lag time by many-fold (∼60), but fibril elongation was accelerated by 3-6 fold. At the concentrations above 2mM, SDS inhibited α-LA fibrillation and led it to the formation of amorphous aggregates. These results were compared with the effect of SDS on the fibrillation of lysozyme, a basic protein. Though fibril inhibition was observed on both the proteins at the micellar concentrations of SDS, there were differences in the effect on lag time and elongation rate at the lower concentrations of SDS. This suggests that the inhibition of protein fibrillation by SDS-micelles might be a common mechanism irrespective of the surface charges on protein.


Generation of human induced pluripotent stem cell lines from a patient with ITM2B-related retinal dystrophy and a non mutated brother.
Human induced pluripotent stem cell (iPSC) lines were generated from fibroblasts of a patient affected with an autosomal dominant retinal dystrophy carrying the mutation c.782A>C, p.Glu261Ala in ITM2B and from an unaffected brother. Three different iPSC lines were generated and characterized from primary dermal fibroblasts of the affected subject and two from the unaffected brother. All iPSC lines expressed the pluripotency markers, were able to differentiate into the three germ layers and presented normal karyotypes. This cellular model will provide a powerful tool to study this retinal dystrophy and better understand the role of ITM2B.


Structure relationship of non-covalent interactions between phenolic acids and arabinan-rich pectic polysaccharides from rapeseed meal.
Covalent and non-covalent interactions between polyphenols and polysaccharides produced vital consequences on the sensory and nutritive qualities of the many foods. In the present study, the structure dependence of the non-covalent interactions between phenolic acids (PAs) and an arabinan-rich pectic polysaccharide from rapeseed meal (ARPP) was explored. Native RAPP and its hydrolysates as well as twenty-seven structurally diversified PAs were applied. The interaction was determined as the micrograms of PAs adsorbed by per milligram of polysaccharides (Qe, μg/mg). On one hand, the molecular weight (Mw) of ARPP displayed a significant effect on the Qe of ferulic acid and a highest value (412.28 μg/mg) was obtained for the ARPP hydrolysate having a Mw of 76 kDa. On the other hand, the substituent profile of PAs greatly affected their Qe values onto ARPP, although the results are monomer and substituent specific. Specifically, in terms of Qe, hydroxylation favored the interaction by 35.78% to 271.22%, while methylation and esterification weakened the absorption by 44.78% to 230.71% and 16.48% to 78.68%, respectively. The case of esterification is more complicated that the attachment of OCH3 at 3-position (-26.14% to -77.04%) is adverse but that at 5-position is highly favorable (156.96% to 190.70%) for the interactions.


Median dermatology base incomes in senior academia and practice are comparable, but a significant income gap exists at junior levels.
The perception that dermatologists in practice have substantially higher incomes than in academics is often cited as the primary reason people choose to practice outside academic institutions. We sought to compare the incomes of dermatologists in academics versus various practice settings. Data from various surveys of dermatologists from 2002 to 2004 were adjusted for annual inflation to the year 2004 and compared. Benefits and bonuses were not included. The income level of clinical instructors, who are 7.0% of all academic dermatology faculty, were not available for inclusion. Median dermatology faculty income (combined average of assistant, associate, and professor levels) was 192,267 dollars, 12.0% less than the median practice income of 215,303 dollars. There was substantial variation across regions, institutions, and types of nonacademic practice. Median starting incomes for dermatology residency graduates were comparable in practice across multiple data sources (182,116 dollars-200,000 dollars) and private universities (189,336 dollars); however, both were significantly higher than median starting incomes in public universities (83,349 dollars). This study relied on self-reported data. Although all attempts were made to use comparable information, variances in how data were collected and classified may exist. Initial income for those entering practice is equivalent to those entering academia in private universities; however, incomes for both of these groups are 2- to 3-fold higher than those entering academia in public universities. This discrepancy may discourage some recent trainees, some of whom have high debt and high expenses, from entering the field of academic dermatology. Because incomes in academia increase predictably with increasing rank, overall self-reported incomes for established dermatologists in practice and senior academia are comparable.


Investigation of defect-rich CeO2 catalysts for super low-temperature catalytic oxidation and durable styrene removal.
Spherical cerium dioxide (CeO2-S) nanoparticles were successfully prepared using a solvothermal method, and their performances in catalytic oxidation reactions were studied. The CeO2-S catalyst showed superior low-temperature catalytic activity for styrene removal (T90 = 118 °C, GHSV = 18,000 h-1) compared with commercial CeO2. The characterization results showed that there were numerous oxygen defects in CeO2-S that were key to its catalytic performance at low temperatures, high redox properties, and high adsorption capacity for the reaction gases (O2 and styrene). Moreover, the catalytic performance of CeO2-S was highly stable (132 h), and the particles were reusable. FTIR and in-situ DRIFTS results showed that the type of intermediates formed during the oxidation of styrene determined the CeO2 catalytic stability, and the main intermediates were bidentate carbonate species that accumulated on the surface of deactivated CeO2-S and were not thermally stable. Moreover, the soft carbon that also deposited on CeO2-S during the reaction was easily decomposed at higher temperatures. The role of the oxygen vacancies on the CeO2-S catalyst was further revealed by correlating the concentration of oxygen vacancies and the accumulation of coke on the catalyst surface.


Vonoprazan versus proton pump inhibitors in treating post-endoscopic submucosal dissection ulcers and preventing bleeding: Protocol for meta-analysis of randomized controlled trials and observational studies.
Vonoprazan is a potassium-competitive acid blocker (P-CAB). It is often used in Japan for Helicobacter pylori (H pylori) eradication, gastroesophageal reflux disease, and endoscopic submucosal dissection (ESD) ulcers and bleeding. This meta-analysis aims to evaluate whether vonoprazan has better therapeutic effect on ESD-induced ulcers and bleeding than proton pump inhibitors (PPIs) at different length of treatment periods (2, 4, and 8 weeks). This meta-analysis will include both randomized controlled trials (RCTs) and observational studies discussing the effectiveness of vonoprazan and PPIs on ESD-induced ulcers and bleeding. Information of studies will be collected from PubMed, Cochrane Library, ClinicalTrials.gov, and Google Scholar. Studies will be selected according to the eligibility criteria and data will be extracted by 2 people and compared with each other to keep in consistency. Cochrane risk of bias tool will be used to assess RCTs and the Newcastle-Ottawa Quality Assessment Scale will be used to assess the observational studies. Meta-analysis based on the random-effects model will be conducted to compare the differences of ulcers' shrinkage ratios (%) and the odds ratios (OR) of scars' stages and delayed bleeding. Publication bias will be evaluated using funnel plots and Egger's regression test. Heterogeneity will be assessed with the I statistics. Sensitivity analysis will be conducted on follow-up periods. The evidential quality of the findings will be assessed with the Grading of Recommendations Assessment Development and Evaluation (GRADE) profiler. The findings of the present systematic review will be critical for physicians, patients, and policymakers regarding the use of vonoprazan in ESD-induced ulcers. PROSPERO registration number: CRD42018116855.


An introduction to hearing loss and screening procedures for behavioral research.
Hearing loss is a confounding variable that is rarely addressed in behavioral research despite its prevalence across the life span. Currently, the most common method of experimental control over hearing acuity is through self report of perceived impairment. We argue that this technique may lack sensitivity and that researchers should more commonly utilize standardized hearing screening procedures. Distinctive patterns of hearing loss are reviewed with attention to populations that commonly participate in behavioral research. We explain standard techniques for conducting pure tone hearing screening using a conventional portable audiometer and outline a procedure for how researchers can modify a conventional laptop computer for audiometric screening when a standard audiometer is unavailable. We offer a sample hearing screening program that researchers may use toward the development of their own protocol. This program is freely available for download at www .psychonomic.org/archive.


Effects of Dyract AP and released ionic products on periodontal ligament cells and bone marrow cultures.
The aim of this work was to investigate the release of inorganic ionic products from specimens of the polyacid-modified composite resin Dyract AP (DAP) and furthermore, to analyze the biological effect of DAP and the medium extract in human periodontal ligament (PDL) cells and mouse bone marrow cell (BMC) cultures. Ion release from DAP specimens immersed in cell culture medium was analyzed with inductively coupled plasma optical emission spectroscopy (ICP-OES). Cells were cultured with either DAP specimens or with DAP media extract and effects on cell proliferation, osteoblastic gene expression and mineralization capacity were analyzed with direct-contact tests, neutral red (NR) uptake, quantitative real-time PCR and a bone nodule formation assay. ICP-OES analysis of DAP extract demonstrated a significant increase in fluoride, strontium and silica. PDL cells demonstrated normal growth pattern in the direct-contact tests with the material. DAP extracts produced a dose-dependent stimulation of cell proliferation and concomitant inhibition of osteoblast specific markers and nodule formation. The compomer may have possible bioactive properties due to ions leaching out from the filler component.


Molecularly imprinted photoelectrochemical sensing based on ZnO/polypyrrole nanocomposites for acrylamide detection.
A highly sensitive quenching molecular imprinting (MIP) photoelectrochemical (PEC) sensor was proposed to detect acrylamide (AM) by using the photoactive composite of ZnO and polypyrrole (PPy) as the PEC signal probe. ZnO, with high electron mobility, excellent chemical and thermal stability as well as good biocompatibility, was selected as the photoelectrically active material. A polypyrrole film was formed on the nanodisk ZnO by electrochemical polymerization, and the recognition site of AM was left on the surface of the PPy film by elution, enabling the specific detection of AM. The transfer of electrons will be hindered when AM is adsorbed on the ZnO/PPy nanocomposites surface, which results in the decrease of photocurrent signal. The proposed molecularly imprinted PEC sensor exhibits significant detection performance of AM in the range of 10-1 M-2.5 × 10-9 M with a LOD of 2.147 × 10-9 M (S/N = 3). The use of photoelectrochemical technology combined with molecular imprinting technology enables the PEC sensor to have excellent selectivity, superior repeatability, preferable stability, low cost, and easy construction, providing a new method for the detection of AM. The high recovery rate in the detection of real samples of potato chips and biscuits indicates that the proposed PEC sensor has potential in monitoring the emerging food safety risks.


Polymorphisms in the NFkB, TNF-alpha, IL-1beta, and IL-18 pathways are associated with response to anti-TNF therapy in Danish patients with inflammatory bowel disease.
Anti-tumor necrosis factor-α (TNF-α) is used for the treatment of severe cases of IBD, including Crohn's disease (CD) and ulcerative colitis (UC). However, one-third of the patients do not respond to the treatment. We have previously investigated whether single nucleotide polymorphisms (SNPs) in genes involved in inflammation were associated with response to anti-TNF therapy among patients with CD or UC. A new cohort of patients was established for replication of the previous findings and to identify new SNPs associated with anti-TNF response. Fifty-three SNPs assessed previously in cohort 1 (482 CD and 256 UC patients) were genotyped in cohort 2 (587 CD and 458 UC patients). The results were analysed using logistic regression (adjusted for age and gender). Ten SNPs were associated with anti-TNF response either among patients with CD (TNFRSF1A(rs4149570) (OR: 1.92, 95% CI: 1.02-3.60, P = 0.04), IL18(rs187238) (OR: 1.35, 95% CI: 1.00-1.82, P = 0.05), and JAK2(rs12343867) (OR: 1.35, 95% CI: 1.02-1.78, P = 0.03)), UC (TLR2(rs11938228) (OR: 0.55, 95% CI: 0.33-0.92, P = 0.02), TLR4(rs5030728) (OR: 2.23, 95% CI: 1.24-4.01, P = 0.01) and (rs1554973) (OR: 0.49, 95% CI: 0.27-0.90, P = 0.02), NFKBIA(rs696) (OR: 1.45, 95% CI: 1.06-2.00, P = 0.02), and NLRP3(rs4612666) (OR: 0.63, 95% CI: 0.44-0.91, P = 0.01)) or in the combined cohort of patient with CD and UC (IBD) (TLR4(rs5030728) (OR: 1.46, 95% CI: 1.01-2.11, P = 0.04) and (rs1554973)(OR: 0.80, 95% CI: 0.65-0.98, P = 0.03), NFKBIA(rs696) (OR: 1.25, 95% CI: 1.01-1.54, P = 0.04), NLRP3(rs4612666) (OR: 0.73, 95% CI: 0.57-0.95, P = 0.02), IL1RN(rs4251961) (OR: 0.81, 95% CI: 0.66-1.00, P = 0.05), IL18(rs1946518) (OR: 1.24, 95% CI: 1.01-1.53, P = 0.04), and JAK2(rs12343867) (OR: 1.24, 95% CI: 1.01-1.53, P = 0.04)). The results support that polymorphisms in genes involved in the regulation of the NFκB pathway (TLR2, TLR4, and NFKBIA), the TNF-α signalling pathway (TNFRSF1A), and other cytokine pathways (NLRP3, IL1RN, IL18, and JAK2) were associated with response to anti-TNF therapy. Our multi-SNP model predicted response rate of more than 82% (in 9% of the CD patients) and 75% (in 15% of the UC patients), compared to 71% and 64% in all CD and UC patients, respectively. More studies are warranted to predict response for use in the clinic.


Developmental Evolution: Downsizing Wings in the Flightless Emu.
The vestigial wings of emus are a striking illustration of morphological evolution. A new study points to reduced activity of an essential signaling pathway as a factor in the evolution of the emu's stunted wings.


Low sports participation is associated with withdrawn and depressed symptoms in urban, school-age children.
The association between sports participation and mental health has not been studied in primary care samples of school-age children, nor in underrepresented minority children. We assessed the relationship between number of sports played and psychiatric symptoms in children ages 6-11 at well-child visits in an urban clinic. Guardians of 206 children (85% Latinx) ages 6-11 completed Child Behavior Checklists (CBCL) in Spanish (66.5%) or English at well-child visits at an urban community health center. We performed linear regression between number of sports played and individual CBCL syndrome scores, and multiple logistic regression with normal (T-score <60) vs. elevated (T-score ≥60) CBCL syndrome scale score as the outcome. We conducted bivariate, multiple logistic regression, and linear regression analyses between low (1 or fewer) vs. high (2 or more) sports participators and subscales of interest. Fewer sports played was associated with higher Withdrawn/Depressed CBCL syndrome scale T-scores (p = 0.019), but not with other CBCL syndrome scale scores nor number of syndrome scale elevations (p = 0.638). Low participators had higher odds of an elevated Withdrawn/Depressed T-score (p = 0.033) than high participators. Our dataset did not contain certain details about sports played, nor information about income and insurance, and our results may not generalize to other populations. Playing fewer sports is associated with higher withdrawn/depressed symptoms in urban, predominantly Latinx, school-age children. Therefore, urban school-age children with low sports participation may be at risk for depression, and sports participation might protect against depressive symptoms in childhood.


Idiopathic granulomatous mastitis: A case report and literature review.
Idiopathic granulomatous mastitis (IGM) is a challenging chronic inflammatory disease in diagnosis with unknown etiology. Although the most appropriate treatment protocol has not yet been identified, prednisolone was used in our patient as an effective and practical choice in the treatment of IGM. Idiopathic granulomatous mastitis (IGM) is a chronic inflammatory disease of the breast and mimics disorders such as breast cancer and breast abscess. Due to the uncommon of this disease, there is no definitive etiology, or treatment. A 38-year-old woman presented with a 3-week history of painful right retro-areolar mass. She had no history of breast trauma and a family history of breast cancer. She had a history of breastfeeding her second child for 12 months in the past year. Diagnostic tests and investigations led to the IGM diagnosis. Therefore, the patient was successfully treated with a course of corticosteroids, but after 2 months, during treatment, she developed Brucellosis. Despite the patient's Brucella infection and treatment with anti-Brucella drugs, prednisolone as an anti-inflammatory corticosteroid therapy was influential in the treatment of IGM.


2-Chloro-1-[4-(2,4-difluoro-benz-yl)piperazin-1-yl]ethanone.
In the title mol-ecule, C(13)H(15)ClF(2)N(2)O, the piperazine ring is in a chair conformation with the 2,4-difluoro-benzyl and chloro-acetyl substituents in equatorial positions.


Statistical Considerations on the Evaluation of Imbalances of Adverse Events in Randomized Clinical Trials.
Adverse events (AEs) data compose the main body of safety data in clinical trials. Medically important imbalances of AEs in large double-blind randomized controlled trials (RCTs) are signals of potential adverse drug reactions. They will be further evaluated for causality and shape the initial label that gives users necessary information on the safe use of the drug. However, causality assessment in premarketing RCTs can be challenging. This article highlights key aspects that need attention and statistical analysis approaches that could be helpful for screening and evaluation of signals generated from imbalances of AEs in moderate or large RCTs.


Adult presentation with a bilobed membranous ventricular septal aneurysm.
Membranous ventricular septum aneurysm (MVSA) is an uncommon cardiac abnormality primarily associated with the spontaneous closure of a small membranous ventricular septal defect in childhood. Diagnosis of an idiopathic MVSA in an adult is exceedingly rare. We report on a man, aged 38 years, with a bilobed MVSA diagnosed by transesophageal echocardiography and gated computed tomography, with separate aneurysm sacs extending into the right atrium and right ventricle.


Glucocorticoids coordinate macrophage metabolism through the regulation of the tricarboxylic acid cycle.
Glucocorticoids (GCs) are one of the most widely prescribed anti-inflammatory drugs. By acting through their cognate receptor, the glucocorticoid receptor (GR), GCs downregulate the expression of pro-inflammatory genes and upregulate the expression of anti-inflammatory genes. Metabolic pathways have recently been identified as key parts of both the inflammatory activation and anti-inflammatory polarization of macrophages, immune cells responsible for acute inflammation and tissue repair. It is currently unknown whether GCs control macrophage metabolism, and if so, to what extent metabolic regulation by GCs confers anti-inflammatory activity. Using transcriptomic and metabolomic profiling of macrophages, we identified GC-controlled pathways involved in metabolism, especially in mitochondrial function. Metabolic analyses revealed that GCs repress glycolysis in inflammatory myeloid cells and promote tricarboxylic acid (TCA) cycle flux, promoting succinate metabolism and preventing intracellular accumulation of succinate. Inhibition of ATP synthase attenuated GC-induced transcriptional changes, likely through stalling of TCA cycle anaplerosis. We further identified a glycolytic regulatory transcription factor, HIF1α, as regulated by GCs, and as a key regulator of GC responsiveness during inflammatory challenge. Our findings link metabolism to gene regulation by GCs in macrophages.


Intestinal Microbiome Inhibits CD8+ T Cells via the Calcineurin-NFAT Axis.
Bacterial sensing activates the calcineurin-NFAT axis, inhibiting CD8+ T cells in colon cancer.


Identification of multiple novel viruses, including a parvovirus and a hepevirus, in feces of red foxes.
Red foxes (Vulpes vulpes) are the most widespread members of the order of Carnivora. Since they often live in (peri)urban areas, they are a potential reservoir of viruses that transmit from wildlife to humans or domestic animals. Here we evaluated the fecal viral microbiome of 13 red foxes by random PCR in combination with next-generation sequencing. Various novel viruses, including a parvovirus, bocavirus, adeno-associated virus, hepevirus, astroviruses, and picobirnaviruses, were identified.


Effect of cardiopulmonary bypass on plasma and erythrocytes oxylipins.
Oxylipins, the oxidative metabolites of polyunsaturated fatty acids (PUFAs), serve as key mediators of oxidative stress, inflammatory responses, and vasoactive reactions in vivo. Our previous work has established that hemodialysis affects both long chain fatty acids (LCFAs) and oxylipins in plasma and erythrocytes to varying degrees, which may be responsible for excess cardiovascular complications in end-stage renal disease. In this study, we aimed to determine changes in blood oxylipins during cardiopulmonary bypass (CPB) in patients undergoing cardiac surgery to identify novel biomarkers and potential metabolites of CPB-related complications. We tested the hypothesis that CPB would differentially affect plasma oxylipins and erythrocytes oxylipins. We conducted a prospective observational study of 12 patients undergoing elective cardiac surgery with expected CPB procedure. We collected venous and arterial blood samples before CPB, 15 and 45 min after the start of CPB, and 60 min after the end of CPB, respectively. Oxylipins profiling in plasma and erythrocytes was achieved using targeted HPLC-MS mass spectrometry. Our results revealed that most venous plasma diols and hydroxy- oxylipins decreased after CPB initiation, with a continuous decline until the termination of CPB. Nevertheless, no statistically significant alterations were detected in erythrocytes oxylipins at all time points. CPB decreases numerous diols and hydroxy oxylipins in blood plasma, whereas no changes in erythrocytes oxylipins are observed during this procedure in patients undergoing cardiac surgery. As lipid mediators primarily responsive to CPB, plasma diols and hydroxy oxylipins may serve as potential key biomarkers for CPB-related complications.


Asymptomatic postendarterectomy dissection of the internal carotid artery detected incidentally on MRI.
A patient who had recently undergone carotid endarterectomy was found to have internal carotid artery dissection on an MRI examination. This is a supposedly rare complication of this frequently performed operation. Since most patients with dissection of the ICA (from whatever cause) are symptomatic when the diagnosis is made, its incidental detection in an asymptomatic patient suggests that this complication may be commoner than generally recognised. We review the ways in which carotid dissection may occur during endarterectomy and the differential diagnosis of the MRI appearances.


Long COVID and possible preventive options.
Most of the people who suffered from COVID-19 fully recovered, but approximately 10-20% of them developed a wide variety of symptoms after they recover from their initial illness. Long COVID can develop at any patient; however, several studies suggest that the development of Long Covid syndrome may be linked to severity of acute illness. Some of the risk factors are hospitalization (with mechanical ventilation), Intensive Care Unit admission, age (over 50 years), gender (female) and comorbidities. Since the precise mechanism of Long COVID has not been clarified, neither the management of Long COVID-19 syndrome has been solved yet. Promising results have been published with vaccines as they effectively reduced the risk of Long COVID; however, other data suggest that vaccination results only partial protection in the post-acute phase of the disease. Recently, the orally effective antiviral agents (Paxlovid, molnupiravir) are preferred for outpatient management, and they highly reduce the progression of mild-to-moderate COVID-19 to severe one, and consequently, might reduce the development of Long COVID. Finally, recently, several clinical trials are in progress with either dietary supplements or drugs with different mechanisms of action. Additional information on the precise mechanisms, risk factors of Long COVID may result in successful preventive and therapeutic management of Long Covid 19 syndrome.


Non-Hodgkin's Lymphoma of the Anterior Maxilla Mimicking a Chronic Apical Abscess.
Non-Hodgkin lymphomas (NHLs) are malignant neoplasms of the lymphatic system, typically occurring in the fifth through seventh decades of life. Tumors develop from abnormal lymphocyte proliferation and accumulation. Although a majority of NHLs occur in nodal regions, 40% of cases appear in extranodal sites involving the stomach, spleen, Waldeyer's ring, central nervous system, lung, skin, and bone. Extranodal NHL presents a diagnostic challenge because it may mimic endodontic disease when occurring in intraosseous and soft tissue sites. This case report presents misdiagnosis of a diffuse large B-cell lymphoma (DLBCL) of the anterior maxilla in a 72-year-old man with a history of Waldenstrom's macroglobulinemia, where the lesion was thought to be associated with a necrotic pulp and a chronic apical abscess on tooth #7. Clinical findings of a facial sinus tract, a nonresponsive pulp, large periapical radiolucency, and history of trauma were in support of this diagnosis for tooth #7. On encountering vital pulpal tissues during cavity access of tooth #7, a cone-beam computed tomography scan and lesion biopsy were obtained. Through immunohistochemistry and histologic analysis, a diagnosis of DLBCL was made. During evaluation of lesions with suspected endodontic etiology, the clinician should consider all factors of the patient's health history, hereditary risk, and comprehensive clinical testing to attain a differential diagnosis. A nonodontogenic etiology of disease should always be considered unless ruled out otherwise. Atypical presentation or testing may prompt the need for biopsy and interspecialty assessment.


Intervening polyadenylate sequences in RNA transcripts of vesicular stomatitis virus.
Purified and partially resolved vesicular stomatitis virus (VSV) messenger RNA has been annealed to the VSV genomic RNA and visualized in the electron microscope under conditions in which duplex regions have a wider image width than single-stranded RNA. The locations of the intercistronic boundaries between the messages have been mapped on the VSV genome. The contour of the double-stranded regions is occasionally interrupted by looped-out single-stranded RNA. The loops are comprised of post transcriptionally synthesized polyadenylate. Most of these structures are found at the intercistronic boundaries and covalently bridge adjacent message sequences. In this paper, we discuss the possible significance of these loops.


Specific reading difficulty or decompensated heterophoria?
This case report illustrates the importance of both an educational psychology and optometric assessment in the management of reading difficulties. Only after these have been concluded can the aetiology of the reading difficulty be determined and the correct course of treatment instigated.


Does cyberbullying impact youth suicidal behaviors?
Even though several youth fatal suicides have been linked with school victimization, there is lack of evidence on whether cyberbullying victimization causes students to adopt suicidal behaviors. To investigate this issue, I use exogenous state-year variation in cyberbullying laws and information on high school students from the Youth Risk Behavioral Survey within a bivariate probit framework, and complement these estimates with matching techniques. I find that cyberbullying has a strong impact on all suicidal behaviors: it increases suicidal thoughts by 14.5 percentage points and suicide attempts by 8.7 percentage points. Even if the focus is on statewide fatal suicide rates, cyberbullying still leads to significant increases in suicide mortality, with these effects being stronger for men than for women. Since cyberbullying laws have an effect on limiting cyberbullying, investing in cyberbullying-preventing strategies can improve individual health by decreasing suicide attempts, and increase the aggregate health stock by decreasing suicide rates.


Grouping of haemolytic streptococci by monoclonal antibodies: determinant specificity, cross-reactivity and affinity.
Streptococcal group polysaccharide (CHO), A-, A-variant-, B-, C-, D- and G-specific monoclonal antibodies were prepared by the hybridoma technique employing spleen cells of several inbred mouse strains which are either high or low responders to the group A-CHO. The isotypes of these reagents were restricted to the class mu and IgG subclasses gamma 3 and--in small numbers--gamma 1. Two distinct categories of antibodies were identified for all but group D specificity: those which agglutinate suspended bacteria but do not precipitate purified soluble antigen, and those which show both agglutinating and precipitating properties. The group D antibodies described here were only of the latter category. The reactions were inhibitable by haptens in as far as these were known. Cross-reactions were observed in group-A-specific antibodies with E and L polysaccharides. Most G-CHO-specific antibodies cross-reacted with B-CHO. Association constants determined by fluorescence quenching measurements were for binding of complete A and C polysaccharides in the range of 10(6) to greater than 10(8) M-1, and for hapten binding by A-, Av- and C-CHO-specific antibodies in the range of 10(3) to 10(4) M-1. These results support a model of steric arrangements of antigenic determinants on A-variant bacteria and solubilized antigen [42] and allow its extension to streptococcal groups A, B, C and G. This model explains the observed functional differences by postulating single, terminal determinants which interact with the prevailing non-precipitating antibodies and internal repeating determinants which react with precipitins, respectively. No significant differences were found in the reactivity patterns to these streptococcal group antigens between strains of mice in terms of their ability to respond with high or low serum antibody titres to group A-CHO. On the other hand, within high and low responder strains, different kinetics of the optimal timing of fusion after initiation of the secondary immune reaction by boosting was observed. Low responders were most efficiently used for fusion 1.5 days later than high-responder spleen cells. This feature is interpreted to indicate an earlier proliferation of B lymphocytes in high responders, due to either an improved responsiveness to T-lymphocyte help or a reduced reactivity with T suppressor cells in comparison to low-responder B lymphocytes.


Planning helps, behavioral disengagement does not: coping and depression in the spouses of heart transplant candidates.
To describe the coping strategies used by the spouses of cardiac patients who are pursuing heart transplant and to determine whether coping strategies predict depression in these spouses. This is a cross-sectional design with 28 spouses (86% female) of cardiac patients who were being evaluated for heart transplant at a large medical center. Coping styles were measured using the COPE Inventory (Carver CS, Scheier MF, Weintraub JK, J Pers Soc Psychol 1989: 56: 267). Depression was assessed with the Center for Epidemiological Studies Depression Scale (Radloff LS, Appl Psychol Meas 1977: 1: 385). Spouses reported using adaptive coping strategies more than the less adaptive strategies. Increased levels of depression were positively correlated with 'behavioral disengagement' and negatively correlated with 'planning' coping strategies. Most studies find that maladaptive coping styles are associated with psychological distress. Consistent with these findings, we found that behavioral disengagement was associated with increased levels of depression. However, in the present study the more adaptive coping strategy of planning was associated with lower levels of psychological distress. These findings suggest that in the spouses of heart transplant candidates, both maladaptive and adaptive coping strategies may serve as markers of the presence or absence of emotional distress and thus may help in identifying spouses who may benefit from psychological, social work, or nursing interventions.


Brunneroma with duodenojejunal intussusception: a rare cause of gastric outlet obstruction.
Duodenal adenoma presenting with duodenojejunal intussusception is very rare. Only a few have ever been reported. Upon evaluation it may be difficult to rule out malignancy. The final diagnosis may be reached only at surgery and confirmed at histopathology.


Is there evidence that emotional reasoning processing underlies emotional disorders in adults? A systematic review.
The prevalence of emotional disorders has increased in recent times. Emotional Reasoning (ER), which is a transdiagnostic process, occurs when feelings, rather than objective evidence, are used as a source of information to make judgements about the valence of a situation. Differences in ER may explain the existence and maintenance of emotional disorders. The objective is to systematically review the role of ER in the occurrence and severity of emotional disorders. Following PRISMA guidelines, we searched through: PubMed, PsycInfo, Scopus and The Cochrane Library. Search terms were "Emotional Reasoning", "ex-consequentia reasoning", "Affect-as-information"; and "emotional disorders", "anxiety", "depression", "depressive". Nine articles were included. An association was demonstrated between ER and a greater degree of anxious symptomatological severity. In depressive symptomatology, no significant differences were found. One study reported the effect of Cognitive Behavioural Therapy on ER bias, finding no changes after the intervention. Finally, another study evaluated the efficacy of computerised experiential training in reducing ER bias, showing significant differences. There are few studies on ER and its evolution in research has not been uniform over time. Encouragingly, though, research to date suggests that ER is a transdiagnostic process involved in several anxiety disorders. More investigation is needed to dilucidate whether ER also underlies the onset and maintenance of depressive disorders.


Clinicopathological Analysis of Non-B Non-C Hepatocellular Carcinoma Focusing on Cellular Proliferation.
Non-B non-C hepatocellular carcinomas (NBNC-HCCs) are larger than hepatitis virus-related HCCs. We conducted a clinicopathological study of patients who underwent curative NBNC-HCC resection, including proliferative activity assessments, such as nuclear grade and Ki-67 labelling index (LI). Histopathological findings of 197 patients were examined, including 56 NBNC-HCCs, 45 hepatitis B virus (HBV)-related HCCs (HBV-HCC), and 96 hepatitis C virus (HCV)-related HCCs (HCV-HCC). NBNC-HCCs were significantly larger than HCV-HCCs, but not significantly different from HBV-HCCs. Mitotic counts, nuclear grade, and Ki-67 LI of NBNC-HCCs were not significantly different from those of HCV-HCCs, but were significantly lower than those of HBV-HCCs. Recurrence-free survival was significantly better in the NBNC-HCC group than in the HBV-HCC group in cases with mild liver fibrosis. NBNC-HCCs were significantly larger in diameter, but their nuclear grade or Ki-67 LI were not significantly different from those of other HCCs, suggesting that they do not have a higher proliferative activity.


Diving Deep into the Adult Mouse Kidney.
In this issue of Developmental Cell, Ransick et al. (2019) provide a comprehensive anatomically guided single-cell dataset from adult mouse kidney, representing the most detailed analysis of the cellular heterogeneity and lineage relationship of cells in the adult mouse kidney published to date.


A population-based study of US women's preferred versus usual sources of reproductive health care.
We characterized US women's preferred and usual sources of reproductive health care. Data were drawn from the Women's Health Care Experiences and Preferences Study, an Internet survey of 1078 women aged 18-55 years randomly sampled from a national probability panel. We described and compared women's preferred and usual sources of care (women's health specialists including obstetricians-gynecologists and family-planning clinics, primary care, other) for Papanicolaou/pelvic examination, contraception, and sexually transmitted infection (STI) services using χ(2), logistic regression, and kappa statistics. Among women reporting health service utilization (n = 984, 92% overall; 77% Papanicolaou/pelvic; 33% contraception; 8% STI), women's health specialists were the most used sources of care for Papanicolaou/pelvic (68%), contraception (74%), and STI (75%) services. Women's health specialists were also the most preferred care sources for Papanicolaou/pelvic (68%), contraception (49%), and STI (35%) services, whereas the remainder of women preferred primary care/other sources or not to get care. Differences in preferred and usual care sources were noted across sociodemographic groups, including insurance status and income level (P < .05). Preference for women's health specialists was the strongest predictor of women's health specialist utilization for Papanicolaou/pelvic (adjusted odds ratio, 48.8; 95% confidence interval, 25.9-91.8; P < .001) and contraceptive (adjusted odds ratio, 194.5; 95% confidence interval, 42.3-894.6; P < .001) services. Agreement between preferred and usual-care sources was high for Papanicolaou/pelvic (85%, kappa, 0.63) and contraception (86%; kappa, 0.64) services; disagreement (range, 15-22%) was associated with insurance, employment, income, race, and religion (P < .05). Women's preferences for and use of women's health specialists for reproductive health care has implications for efforts to define the role of obstetricians-gynecologists and family planning clinics in current health systems.


Characterization of nasal obstruction in the allergic guinea pig using the forced oscillation method.
This is the first report to evaluate changes in nasal resistance in a preclinical animal model using the forced oscillation method. The method involves characterizing pressure-flow relationships of the respiratory system due to external oscillatory forces. First, we evaluated changes in nasal resistance using an established small-animal rhinometric technique. In these studies, aerosolized ovalbumin (3%) administered to the nasal cavity of ovalbumin-sensitized guinea pigs increased nasal resistance at 30 min by 99 +/- 14%. The histamine H1 antagonists, chlorpheniramine (1 mg/kg i.v.) and pyrilamine (1 mg/kg i.v.), blocked the increase in nasal resistance due to ovalbumin provocation (50 +/- 17% and 39 +/- 11% over baseline, respectively). The alpha-adrenergic agonist phenylpropanolamine (3 mg/ kg i.v.) had no effect on the nasal actions of ovalbumin. In separate studies, nasal resistance was measured at 2 Hz by forced oscillation and ovalbumin (3%) increased nasal resistance by 91 +/- 14%. Chlorpheniramine (1 mg/kg i.v.) significantly attenuated the increase in nasal resistance due to ovalbumin. Finally, changes in nasal resistance for each treatment group were evaluated at frequencies of 1 - 18 Hz. Area under the curve analysis demonstrated that chlorpheniramine blocked the nasal obstructive effect of ovalbumin. In contrast, a pharmacologically active dose of phenylpropanolamine (3 mg/kg i.v.) did not produce decongestant activity. The current data are inconsistent with the well-established clinical efficacy of alpha-adrenergic agonists as nasal decongestants. Consequently, we suggest that allergic nasal obstruction in the guinea pig may not be the best preclinical approach to assess the nasal decongestant activity of vasoconstrictor alpha-adrenergic agonists. Additionally, our studies demonstrate the utility of the forced oscillation technique in assessing changes in nasal resistance in small laboratory animals.


Development of an efficient strategy for the synthesis of the ETB receptor antagonist BQ-788 and some related analogues.
BQ-788 [N-cis-2,6-dimethylpiperidine-1-carbonyl-L-gamma-methylleucyl-D-1-methoxycarbonyltryptophanyl-D-norleucine sodium salt] is a very potent and selective ETB receptor antagonist. The formation of the highly hindered trisubstituted urea functionality in the peptide chain and the carbamination on the indole nitrogen of the tryptophan side chain are major challenges in the synthesis of this particular antagonist. Furthermore, the high cost of the unnatural amino acids in the sequence of BQ-788 and its reported synthesis render this pseudopeptide very expensive to produce. In order to improve the yield and to reduce the number of steps compared to previous reported syntheses, we developed an efficient strategy involving a novel one-pot procedure for the synthesis of a highly hindered trisubstituted urea. Under very mild conditions, the urea was obtained by using triphosgene and sodium iodide. This strategy allowed us to synthesize BQ-788 in seven steps with an overall yield of 53%. We also generalized the use of this powerful methodology by creating some new structural analogues of the cis-2,6-dimethylpiperidine moiety by replacing it with other bulky secondary amines. We evaluated the antagonist properties of those three new analogues of BQ-788 in two bioassays in vitro. These new antagonists were less potent than BQ-788 in an ETB rich preparation and inactive in an ETA rich preparation.


Identification of cancer-type specific expression patterns for active aldehyde dehydrogenase (ALDH) isoforms in ALDEFLUOR assay.
Aldehyde dehydrogenases (ALDHs) defend intracellular homeostasis by catalyzing the conversion of toxic aldehydes into non-toxic carboxylic acids, which is of particular importance to the self-renewal of stem cells and cancer stem cells. The widely used ALDEFLUOR assay was initially designed to indicate the activity of ALDH1A1 in leukemia and has been demonstrated to detect the enzyme activity of several other ALDH isoforms in various cancer types in recent years. However, it is still elusive which isoforms, among the 19 ALDH isoforms in human genome, are the potential contributors in catalyzing ALDEFLUOR assay in different cancers. In the current study, we performed a screening via overexpressing each ALDH isoform to assess their ability of catalyzing ALDEFLUOR assay. Our results demonstrate that nine isoforms are active in ALDEFLUOR assay, whose overexpression significantly increases ALDH-positive (ALDH+) population. Further analysis of the expression of these active isoforms in various cancers reveals cancer-type specific expression patterns, suggesting that different cancer types may exhibit ALDEFLUOR activity through expression of specific active ALDH isoforms. This study strongly indicates that a detailed elucidation of the functions for each active ALDH isoform in CSCs is necessary and important for a profound understanding of the underlying mechanisms of ALDH-associated stemness.


Macrophages regulate gastrointestinal motility through complement component 1q.
Peristaltic movement of the intestine propels food down the length of the gastrointestinal tract to promote nutrient absorption. Interactions between intestinal macrophages and the enteric nervous system regulate gastrointestinal motility, yet we have an incomplete understanding of the molecular mediators of this crosstalk. Here, we identify complement component 1q (C1q) as a macrophage product that regulates gut motility. Macrophages were the predominant source of C1q in the mouse intestine and most extraintestinal tissues. Although C1q mediates the complement-mediated killing of bacteria in the bloodstream, we found that C1q was not essential for the immune defense of the intestine. Instead, C1q-expressing macrophages were located in the intestinal submucosal and myenteric plexuses where they were closely associated with enteric neurons and expressed surface markers characteristic of nerve-adjacent macrophages in other tissues. Mice with a macrophage-specific deletion of C1qa showed changes in enteric neuronal gene expression, increased neurogenic activity of peristalsis, and accelerated intestinal transit. Our findings identify C1q as a key regulator of gastrointestinal motility and provide enhanced insight into the crosstalk between macrophages and the enteric nervous system.


Aerobic granular sludge: Cultivation parameters and removal mechanisms.
Aerobic granular sludge (AGS) has been the focus of many investigations, and the main parameters responsible for AGS formation are hydrodynamic shear force, short periods and feast-famine cycles. However, some other parameters are associated with AGS maintenance after long periods of operation. This review evaluates the parameters responsible for AGS formation and maintenance and some reference values are proposed. In addition, some discussions are addressed about the main metabolic pathways that AGS uses for the removal of some compounds, such as nutrients, organic matter, dyes, recalcitrant compounds, among others. Finally, the main microbial groups present in the AGS and their respective functions are discussed. It is also highlighted that many parameters that are taken as reference currently for AGS cultivation and maintenance can be optimized for energy savings, implementation costs, among others, as well as a greater recovery of resources during wastewater treatment, within the scope of the biorefinery concept.


Meal-induced peptide tyrosine tyrosine inhibition of pancreatic secretion in the rat.
In the present studies we examined the distribution, release, and biological actions of peptide tyrosine tyrosine (PYY) in the rat. The concentration and distribution of PYY was highest in the ileum and colon as determined by both radioimmunoassay of rat tissue extracts and immunocytochemistry. An ultrastructural comparison of rat and dog colonic PYY cells revealed a bipolar distribution of peptide-containing secretory granules in both species. Serum PYY and pancreatic exocrine secretory responses were monitored after presentation of a meal to meal-trained rats (n = 12). A significant increase in PYY concentrations was not observed until 120 min after meal presentation, a delayed response similar to that previously observed in the dog. PYY responses were also observed in rats after perfusion of the intestine at the level of the duodenum and ileum with an 80 mOsm micellar solution of sodium oleate. Duodenal instillations of the fatty acids resulted in a maximum PYY response after 120 min, whereas rats subject to ileal perfusion of fat exhibited maximum PYY release within the first hour. In other experiments, infusion of exogenous PYY at 100 pmol.kg-1.h-1, which reproduced plasma PYY levels observed after a meal and perfusion of the gut with fat, significantly inhibited CCK-stimulated bile pancreatic volume (P less than 0.02), protein (P less than 0.01), and amylase (P less than 0.01) output. These studies demonstrate a bipolar distribution of PYY-containing secretory granules in cells of the jejunal, ileal, and colonic mucosa, and show that PYY is released in response to a meal in amounts sufficient to inhibit cholecystokinin-stimulated pancreatic secretion. Evidence is presented that PYY may mediate the delayed inhibition of pancreatic secretion that is observed in the rat after ingestion of a meal.


Microneurosurgical treatment under the guidance of neuroendoscopy for an intracranial optic nerve Schwannoma: A case report.
Optic Schwannoma is rarely observed clinically as optic nerve had anatomically impossibility for the location of Schwannoma. However, several reports described the established cases of optic Schwannoma, of which the locations were in orbit or within optic canal. The occurrence of optic Schwannoma intracranially has been not reported. A 60-year-old female complained of visual impairment in the right eye and the frequent headache and the dizziness over 2 years with unknown reasons. The result of magnetic resonance imaging (MRI) showed a round, well-circumscribed, heterogeneously enhancing signal with cystic change displayed on the right suprasellar cistern. Intracranial optic Schwannomas. The patient accepted microneurosurgery assisted by endoscopy. We observed a gray and yellow lesion located near the right anterior clinoid process with a mid-sized cyst. And there was a vague boundary between the tumor and the right optic nerve which was compressed by the tumor. Optic chiasm and left optic nerve were also compressed. Meanwhile, the tumor had also adhesion to the right anterior cerebral artery (ACA). After the tumor was totally resected, the patient had satisfactory recovery. We reported an intracranial optic Schwannoma removal with the lateral supraorbital keyhole approach assisted by neuroendoscopy. Intracranial optic Schwannoma was rarely seen clinically. Neuroendoscopy imaging suggested the close relationship between the tumor and ACA, supporting vasculature-origin hypothesis for the optic Schwannoma.


Safety and efficacy of BAY 81-8973 for surgery in previously treated patients with haemophilia A: results of the LEOPOLD clinical trial programme.
BAY 81-8973 is a recombinant factor VIII (rFVIII) with the same amino acid sequence as Bayer's sucrose-formulated rFVIII (rFVIII-FS) but manufactured with certain more advanced technologies. To describe surgery outcomes with BAY 81-8973 in the LEOPOLD trials. Male patients with severe haemophilia A and no inhibitors aged 12-65 years with ≥150 exposure days (EDs) to FVIII (LEOPOLD I and II), or aged ≤12 years with ≥50 EDs to FVIII (LEOPOLD Kids), received BAY 81-8973 based on dosing recommendations for rFVIII-FS according to surgical requirements. Haemostasis-related complications, investigator/surgeon assessment of haemostasis, blood loss, need for transfusion and use of BAY 81-8973 were determined. In LEOPOLD I and II, 11 patients (mean age, 35.3 years) underwent 13 major surgeries. In LEOPOLD Kids, one patient (aged 6 years) underwent one major surgery. Thirty-two adult and paediatric patients underwent 46 minor surgeries. Haemostasis was rated good or excellent in all major and minor surgeries. Blood loss during surgery did not exceed expected amounts; blood transfusions were required in three of the 14 major surgeries. For major surgeries in LEOPOLD I and II, patients received a presurgical 50-IU kg(-1) dose of BAY 81-8973; median nominal dose on day of surgery was 7000 IU (107.5 IU kg(-1) ). Total BAY 81-8973 dose was 2500 IU (108.7 IU kg(-1) ) on the day of the only major surgery in LEOPOLD Kids. No haemostasis-related complications were reported. Haemostatic control with BAY 81-8973 during all surgeries in the LEOPOLD trials was good or excellent, with no haemostasis-related complications.


Size effect on oral absorption in polymer-functionalized mesoporous carbon nanoparticles.
In this manuscript, the effect of the particle size of polymer-functionalized mesoporous carbon (MPP) nanoparticles on enhancing oral absorption of a water-insoluble drug is first investigated. The insoluble drug, fenofibrate (Fen), was selected as the model drug loaded in the MPP nanoparticles. MPP nanoparticles with different particle sizes were designed for improving the oral bioavailability of drugs, in which the branched polyethyleneimine (PEI) and polyacrylic acid (PAA) were modified on the surfaces of mesoporous carbon nanoparticles (MCNs) with amide bonds. In addition, PEI-functionalized carbon quantum dots (PCA) and radioisotope 125I were applied to label the MPP nanoparticles to trace in the vivo process. According to the data, the MPP nanoparticles could markedly improve the dissolution rate and oral bioavailability of Fen. Interestingly, the MPP nanoparticle size had a notable effect on Fen oral absorption, and intermediate sized MPP nanoparticles were expected to be more ideal oral drug carriers. The nanoparticles were safe and easily excreted. These findings present the prospect of MPP nanoparticles for oral application, and guides the rational design of an oral delivery system with respect to particle size.


A physiological pharmacokinetic model for morphine disposition in the pregnant rat.
A physiological model was used to examine the disposition of morphine in the pregnant rat. In the model was incorporated an expression of both a linear and a nonlinear binding term of morphine to the maternal muscular tissue. Furthermore, the experimental data suggested that a diffusion-limited transport of morphine occurred across the placenta. Morphine showed a relatively high partition into the maternal kidney and muscle tissues. The concentration of morphine in the foetus was about 1.5 times higher than that of the maternal plasma, whereas the foetal brain concentration was about 4 times higher than that of the maternal plasma. The influence on morphine disposition by changes in both the tissue binding of the maternal muscle and the placental plasma flow was explored by model simulations. Due to the diffusion-limited transport of morphine across the placenta, a change in the placental plasma flow would only have an effect on the concentration-time profile of morphine in the foetal tissues if the plasma flow approached and became less than the diffusion clearance across the placenta. An increase in the partition of morphine into the maternal muscle produced an increase in the terminal half-life in all tissues including the foetus.


Patient-reported experience with hypoglossal nerve stimulation in the treatment of obstructive sleep apnea.
Breathing-synchronized hypoglossal nerve stimulation (HNS) is routinely used as an alternative treatment for patients with obstructive sleep apnea (OSA). Significant and clinically relevant improvements in disease severity and OSA symptoms such as daytime sleepiness as well as overall quality of life have been reported in randomized-controlled trials and large real-world cohort studies. However, so far, few data exist on patient-reported experience with the treatment. A structured survey with 22 questions was constructed using five-level Likert scales (1 = no agreement, 5 = complete agreement) to evaluate patient experience with HNS and perception of the treatment in the domains "Overall experience with therapy," "Experience with treatment process," and "Side-effects from treatment." Additional data were collected on current symptom status, measured with Epworth sleepiness scale (ESS) questionnaire, and OSA disease history. Multiple linear regression analysis was conducted to test associations of medical variables and response behavior. Correlations between variables and domains, as well as individual items, were assessed using Spearman rank test. A total of 75 patients from Germany who were treated with breathing-synchronized HNS were enrolled (mean age 57.3 years, 78% male), and 71 questionnaires with complete data were included for analysis. Two-thirds of participants (67%) had a history of OSA history for 5 years or longer. Of all patients, 76% had normalized OSA symptoms at time of the study (ESS: 6.4 ± 5.0) and 98% reported using stimulation therapy every night. Regression analysis revealed an association of current symptoms measured with ESS and response behavior. Hence, patients with normalized daytime sleepiness reported significantly more positive experience across all domains assessed, compared to patients with residual daytime sleepiness. Overall, only 2% of participants reported side effects that made them reduce or discontinue stimulation therapy. The rate of reported side effects was associated with current symptom control under therapy. Overall patient-reported experience with breathing-synchronized HNS therapy was positive and high satisfaction with the treatment process was observed. Side effects occurred, but rarely affected subjective use of the therapy or satisfaction. Subjective experience and perception are influenced by residual daytime sleepiness with stimulation therapy.


Cingulate seizures and recent treatment strategies.
Cingulate epilepsy manifests with a broad range of semiologic features and seizure types. Key clinical features may elucidate ictal involvement of certain subregions of the cingulate gyrus. Ictal and interictal electroencephalogram findings in cingulate epilepsy vary and are often poorly localized, adding to the diagnostic challenge of identifying the seizure onset zone for presurgical cases, particularly in the absence of a lesion on imaging. Recent advances in multimodal imaging techniques may contribute to ictal localization and further our understanding of neural and epileptic pathways involving the cingulate gyrus. Beyond medication and surgical resection, new techniques including stereotactic laser ablation, responsive neurostimulation, and deep brain stimulation offer additional approaches for the treatment of cingulate epilepsy.


Monoclonal antibodies against the leptospiral immunoglobulin-like proteins A and B conserved regions.
Leptospirosis is an infectious disease caused by pathogenic spirochetes of the genus Leptospira that affects humans and a wide variety of animals. Recently the genomes of Leptospira interrogans, Leptospira borgpetersenii and Leptospira biflexa species were sequenced allowing the identification of new virulence factors involved in survival and pathogenesis of bacteria. LigA and LigB are surface-exposed bacterial adhesins whose expression is correlated with the virulence of Leptospira strains. In this study, we produced and characterized five monoclonal antibodies (MAbs) against a recombinant fragment of LigB (rLigBrep) with approximately 54kDa that comprise the portions of LigA and LigB (domains 2-7). The 5 MAbs obtained were of the IgG1 (2) and IgG2b (3) isotypes and their affinity constants for rLigBrep ranged from 7×10(7) M(-1) to 4×10(8) M(-1). The MAbs were able to react with the native antigen on the L. interrogans, L. borgpetersenii and Leptospira noguchii surfaces by indirect immunofluorescence, immunoblotting and immunoelectron microscopy. These results demonstrate that the MAbs anti-rLigBrep can be useful to complement genetic studies and to aid studies aiming understanding the role of Lig proteins in Leptospira pathogenesis and the development of Lig-based vaccines and improved diagnostic tests for leptospirosis.


The utility of full-thickness skin grafts (FTSGs) for auricular reconstruction.
Full-thickness skin grafts (FTSGs) are a common repair option on the external ear, but there are few large case series examining graft sublocations, dimensions, and outcomes. We sought to report our experience with FTSGs for repair of postsurgical defects of the external ear. We conducted a retrospective review of all FTSGs on the ear performed by 2 surgeons (J. C., 2000-2014; B. C. L., 2007-2014) after clearance by Mohs micrographic surgery at a single institution. A total of 1519 FTSGs on the ear were performed between June 2000 and March 2014. The most common sublocations were the superior helix (38.8%), the crura of the antihelix or scapha (18.9%), and the back of ear/back of helix (15.4%). The overall complication rate was 1.6%, and the most common complication was graft failure (1.2%). Data were collected retrospectively from a single institution. Follow-up beyond 3 months was limited. A standardized assessment tool for aesthetic outcomes was not performed. By taking advantage of predictable "pincushioning" and combining with local flaps or cartilage grafts, FTSGs can provide more volumetric replacement than previously described. They reliably preserve the height and complex topography of the ear with a low complication rate.


Bumetanide and cerebrospinal fluid acid-base variables during acute CO2 elevation.
The purpose of this study was to investigate the effects of bumetanide, an inhibitor of NaCl cotransport on cisternal cerebral spinal fluid (CSF) acid-base balance during acute respiratory acidosis (ARA). We measured blood and CSF acid-base variables in two groups (N = 7 in each) of anesthetized paralyzed and mechanically ventilated dogs with bilateral ligation of renal pedicles (to eliminate saluresis). After baseline samples were obtained (-1 h) bumetanide (0.5 mg/kg) was administered intravenously within 15 min (group 2); group 1 received equal volume of diluted saline. ARA was induced 1 h later (0 h) and was maintained for 5 h. In both groups PaCO2 was maintained between 55 to 60 mm Hg. Mean cisternal CSF PCO2 was 42.8 +/- 2.6, and 43.8 +/- 2.5 mm Hg, respectively in group 1 and group 2 and rose approximately 20 mm Hg during ARA. In group 1, CSF [HCO3-] was 22.0 +/- 1.0, 24.8 +/- 0.6, and 25.4 +/- 1.6 mEq/L, respectively at 0, 2 1/2, and 5 h; respective values for group 2 were 22.9 +/- 1.5, 24.7 +/- 1.4, and 26.1 +/- 1.3 mEq/L. Comparing the two groups, respective values were not significantly different from each other. Similarly, between the two groups changes in CSF [Na(+)-Cl-] during ARA were not significantly different from each other. Based on our results we conclude that at the dose used in the present study bumetanide does not change ionic composition and acid-base balance of cisternal CSF when compared to controls. Because changes in CSF [Na(+)-Cl-] during ARA were similar in both groups, any inhibition of Cl- influx into CSF by bumetanide should have been proportional to that of Na+.


The potential and sustainable strategy for swine wastewater treatment: Resource recovery.
Swine wastewater is highly polluted with complex and harmful substances that require effective treatment to minimize environmental damage. There are three commonly used biological technologies for treating swine wastewater: conventional biological technology (CBT), microbial electrochemical technology (MET), and microalgae technology (MT). However, there is a lack of comparison among these technologies and a lack of understanding of their unique advantages and efficient operation strategies. This review aims to compare and contrast the characteristics, influencing factors, improvement methods, and microbial mechanisms of each technology. CBT is cost-effective but has low resource recovery efficiency, while MET and MT have the highest potential for resource recovery. However, all three technologies are affected by various factors and toxic substances such as heavy metals and antibiotics. Improved methods include exogenous/endogenous enhancement, series reactor operation, algal-bacterial symbiosis system construction, etc. Though MET is limited by construction costs, CBT and MT have practical applications. While swine wastewater treatment processes have developed automatic control systems, the application need further promotion. Furthermore, key functional microorganisms involved in CBT's pollutant removal or transformation have been detected, as have related genes. The unique electroactive microbial cooperation mode and symbiotic mode of MET and MT were also revealed, respectively. Importantly, the future research should focus on broadening the scope and scale of engineering applications, preventing and controlling emerging pollutants, improving automated management level, focusing on microbial synergistic metabolism, enhancing resource recovery performance, and building a circular economy based on low-cost and resource utilization.


Atlantoaxial Instability.
Atlantoaxial instability is a congenital neurologic condition predominantly affecting toy breed dogs. Neurologic signs of a cranial cervical myelopathy typically present at a young age and can range from cervical pain (hyperesthesia) to paralysis. Diagnosis is often based on survey radiographs, although advanced diagnostic imaging can facilitate surgical planning, allow evaluation of spinal cord parenchyma, and rule out concurrent neurologic conditions. Treatment options consist of medical or surgical management, with surgical management being preferable in patients with neurologic deficits or those with unresolved cervical pain despite medical management. The prognosis for surgery is generally favorable.


Differential inhibition of F0F1-ATPase-catalysed reactions in bovine-heart submitochondrial particles by organotin compounds.
Preincubation of coupled submitochondrial particles with low concentrations of triorganotin compounds results in complete inhibition of the oligomycin-sensitive ATPase activity without any significant effect on the rate of succinate-driven ATP synthesis. The residual ATP synthetic activity is inhibited by oligomycin and uncouplers. The differential inhibition of ATP synthesis and hydrolysis by the triorganotin compounds examined suggests that the two processes are not 'mirror images' of each other, but that they occur through different routes and that the F1F0-ATPase is at least bifunctional.


An alternative approach for controlling bacterial pathogens in liquid and solid poultry waste using Calcium hypochlorite Ca(OCl)2 disinfectant-based silver nanoparticles.
Inappropriate handling of poultry waste from the beginning to the end of the production cycle could lead to health and environmental hazards. The purpose of this study was to assess the current state of poultry waste management practices as well as to evaluate the efficacy of disinfectants (VIRKON S, Quaternary ammonium compound (QAC), Calcium hypochlorite [Ca(OCl)2], and nanomaterials (nano-silver particles (Ag NPs), and Ca(OCl)2-Ag NPs composite) on pathogenic bacteria for use in the disinfection of waste collection areas within poultry operation systems. Two hundred and ten samples were gathered from variant waste types for isolation and identification of pathogenic bacteria. Then, the efficacy of some disinfectants against fifty strains of isolated bacteria was evaluated using a broth micro-dilution assay. Results showed the most predominant bacterial isolates from wastes were E. coli (33.69%), Salmonella spp. (26.09%), followed by K. pneumonae (15.22%) and L. monocytogenes (14.13%). Ca(OCl)2-Ag NPs had a microbial lethal effect against all pathogenic bacteria (100%) that were isolated from liquid and solid waste. In conclusion, poultry manure waste is collected and dumped on the agricultural land around those chicken farms without any treatment. The Ca(OCl)2-Ag NPs composite was lethal to all pathogenic microbes isolated from waste and their collected areas at 1.0 mg/L concentration.


Chenodeoxycholic and deoxycholic acids induced positive inotropic and negative chronotropic effects on rat heart.
Bile acids are endogenous amphiphilic steroids from the metabolites of cholesterol. Studies showed that they might contribute to the pathogenesis of cardiopathy in cholestatic liver diseases. Chenodeoxycholic acid (CDCA) and deoxycholic acid (DCA) is associated with colon cancer, gallstones, and gastrointestinal disorders. However, little information is available regarding their cardiac effects. Here, we reported that CDCA (100 μM) and DCA (100 μM) significantly increased the left ventricular developed pressure of the isolated rat hearts to 122.3 ± 5.6% and 145.1 ± 13.7%, and the maximal rate of the pressure development rising and descending (± dP/dtmax) to 103.4 ± 17.6% and 124.4 ± 37.7% of the basal levels, respectively. They decreased the heart rate and prolonged the RR, QRS, and QT intervals of Langendorff-perfused hearts in a concentration-dependent manner. Moreover, CDCA and DCA increased the developed tension of left ventricular muscle and the cytosolic Ca2+ concentrations in left ventricular myocytes; these functions positively coordinated with their inotropic effects on hearts. Additionally, CDCA (150 μM) and DCA (100 μM) decreased the sinoatrial node beating rate to 80.6 ± 3.0% and 79.7 ± 0.9% of the basal rate (334.2 ± 10.7 bpm), respectively. These results were consistent with their chronotropic effects. In conclusion, CDCA and DCA induced positive inotropic effects by elevating the Ca2+ in left ventricular myocytes. They exerted negative chronotropic effects by lowering the pace of the sinoatrial node in rat heart. These results indicated that the potential role of bile acids in cardiopathy related to cholestasis.


Hepatitis C virus testing in primary biliary cirrhosis.
We retrospectively investigated anti-HCV prevalence in a series of 160 consecutive patients with primary biliary cirrhosis who presented between 1980 and 1989. Of these, 19 (12%) were positive for anti-HCV by C-100 ELISA. Serum IgG levels were significantly higher in anti-HCV-positive patients and correlated to optical density values. A serum sample was again collected from all the patients from the same series who were seen in 1990 for follow-up, after a median period of 32 months. Anti-HCV positivity was found to be substantially unchanged in this subgroup of patients when the freshly drawn blood samples were retested with C-100 ELISA, while it increased from 10% to 17% when second generation ELISA was used. Three of the C-100 ELISA positive samples were C-100 RIBA reactive, and six of the second generation ELISA positive samples were 4-RIBA reactive. The HCV genome was not detected in any of the seven anti-HCV C-100 ELISA and second generation ELISA positive sera which were studied by polymerase chain reaction, including four cases confirmed by 4-RIBA. Life expectancy, as determined by survival analysis, did not differ significantly between anti-HCV-positive and -negative patients. These findings suggest that anti-HCV positivity does not influence the clinical presentation and course of primary biliary cirrhosis.


Pathologic features and expression of insulin-like growth factor-2 in adrenocortical neoplasms.
We analyzed a series of adrenocortical neoplasms to compare the clinicopathologic features and the expression of insulin-like growth factor-2 (IGF-2) in adrenocortical adenomas and carcinomas. IGF-2 is a growth factor commonly expressed in many tumors including adrenal cortical and medullary neoplasms. Formalin-fixed paraffin-embedded tissues from 64 adrenocortical adenomas and 67 adrenocortical carcinomas were analyzed. The carcinomas were histologically graded from 1 to 4 based on mitotic activity and necrosis. Tumor weight, size, and follow-up information were obtained by chart review. Expression of IGF-2 was detected by immunohistochemistry with the avidin-biotin-peroxidase complex method and a monoclonal antibody against IGF-2. Adrenocortical carcinomas were larger (mean: 13.1 cm, 787 g) than adenomas (mean: 4.2 cm, 52 g) (p < 0.001). Inpatients with adrenocortical carcinomas, high tumor grade (3 or 4) (p = 0.01) was associated with decreased survival. Expression of IGF-2 was higher in adrenocortical carcinomas than in adenomas (p < 0.001). These results show that tumor size and weight along with expression of IGF-2 protein are useful features to assist in distinguishing between adrenocortical adenomas and carcinomas, and that high tumor grade is a predictor of survival in adrenocortical carcinomas. However, single immunohistochemical markers such as IGF-2 or single histopathologic features cannot by themselves separate adrenocortical adenomas from carcinomas, and a combination of clinical, gross, and microscopic features are needed to establish the diagnosis in difficult cases.


Correlation between anorectocele with the anterior anal canal and anorectal junction anatomy using echodefecography.
The aim of this prospective study was to evaluate the relationship between the pathogenesis of anorectocele and the anatomy of the anal canal and anorectal junction using echodefecography. The study was conducted on a total of 100 women with obstructed defecation, mean age 46.6 years, who underwent echodefecography. Patients were classified based on rectocele status into group I, without rectocele (n = 32); group II, grade I rectocele (n = 11); group III, grade II (n = 27); and group IV, grade III (n = 30). We identified the layers of the anterior anorectal wall and measured anterior external sphincter length, posterior external sphincter and puborectalis length, gap between anterior external sphincter and anorectal junction, anorectal wall thickness in 3 locations: (1) proximal to anterior external anal sphincter; (2) anterior anorectal junction; (3) 1.0 cm proximal to anorectal junction. The anterior part of the external anal sphincter was significantly longer in group I (18.91 ± 0.38 mm) than in group III (16.94 ± 0.45 mm) (p < 0.05), and the length in group I was similar to that in group II (18.56 ± 0.44 mm) (p = 0.6223). The gap was significantly shorter in group I (21.24 ± 0.97 mm) than in group III (25.04 ± 0.82 mm) and group IV (23.82 ± 0.80 mm) (p < 0.05). The length of the anterior part of the external anal sphincter as a percentage of the length of the posterior external anal sphincter together with the puborectalis muscle was a mean of 57.39 ± 2.13% in group I, 56.01 ± 1.581% in group II, 47.77 ± 1.48% in group III, and 50.45 ± 1.61% in group IV, with a significantly higher percentage in group I than in groups III (p = 0.0126) and IV (p = 0.0007). No significant differences were identified between any of the groups regarding anorectal wall thickness at any of the 3 selected locations (p > 0.05). The muscularis propria layer of the rectal wall was not identified in 2 patients in group I (6.25%), 3 patients in group II (11.11%), and 3 patients in group III (10.00%), and 6 in group IV (8.82%), with no significant differences among groups. The pathogenesis of anorectocele may be associated with a shorter anterior part of the external anal sphincter and consequently a longer gap.


Helioxanthin suppresses the cross talk of COX-2/PGE2 and EGFR/ERK pathway to inhibit Arecoline-induced Oral Cancer Cell (T28) proliferation and blocks tumor growth in xenografted nude mice.
Helioxanthin, an active compound from Taiwania cryptomerioides Hayata, has been shown to have various biological activities. However, their anticancer effect in oral squamous cell carcinoma has not been well established yet. Helioxanthin inhibited the proliferation of oral squamous cell carcinoma cells in a dose-dependent manner by inducing G2/M phase arrest. Similarly, helioxanthin inhibited cyclooxygenase-2, (COX-2), phosphorylated EGFR, and extracellular-signal-regulated kinases (ERK) protein level and further reduced the nuclear accumulation of phosphorylated epidermal growth factor receptor (pEGFR) and activator protein-1(AP-1) family protein, c-fos. Moreover, helioxanthin at the dose of 20 and 30 mg kg-1 for 15 days reduced the tumor growth in animal model. This study demonstrated that Helioxanthin exerts its anticancer activity against oral cancer cells by downregulating EGFR/ERK/c-fos signaling pathway to inhibit COX-2 level and by activating cyclin-dependent kinase inhibitor (p27) to further induce G2/M cell cycle arrest. This helioxanthin may serve as a novel candidate for oral cancer prevention. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 2045-2056, 2016.


Vitellogenesis stimulated by thoracic ganglion implants into destalked immature spider crabs, Libinia emarginata.
Since destalked immature female Libinia emarginata fail to molt to maturity (Hinsch, 1972) and implants of thoracic ganglion of adult females into young females of Potamon dehaani caused a doubling of ovarian weight and differentiation of yolk granules (Otsu, 1963), the effects of the thoracic ganglion implantation on sexual maturation in Libinia was investigated. Destalked immature Libinia with a maximum carapace length of 4-5 cm received two implants of adult female thoracic ganglion at 10-day intervals. All of the surviving experimental animals and destalked controls molted to immaturity. Most of the experimental animals failed to complete a successful molt and few survived longer than 3-4 days. The experimental animals that survived for over a week showed signs of yolk deposition not observed in the destalked controls. Eggs in several stages of vitellogenesis were scattered throughout the gonad in the animal showing the most pronounced effect. This was not observed in any of the destalked controls.


Dyslipidemia independent of body mass in antipsychotic-treated patients under real-life conditions.
Antipsychotic (AP) treatment, in particular with some second-generation drugs, is associated with weight gain and other metabolic side effects. However, the relationship between drug-induced weight gain and dyslipidemia is not well understood. We investigated how cardiometabolic risk factors were related to body mass during treatment with different APs under real-life conditions. This cross-sectional naturalistic study included 242 subjects with severe mental disorders who were on monotherapy with olanzapine (OLZ) or clozapine (CLZ) (n = 80), monotherapy with other APs (n = 80), or unmedicated (n = 82). Groups were adjusted for age and compared for prevalence of the metabolic syndrome and its components. Groups were further adjusted for body mass and compared for mean values of blood pressure, lipids, and fasting glucose. There was no significant intergroup difference in the prevalence of metabolic syndrome, obesity, hypertension, or hyperglycemia. Despite similar body mass index, OLZ/CLZ-treated subjects had significantly higher prevalence of dyslipidemia (high triglyceride and low HDL cholesterol levels) than unmedicated subjects. They also had higher mean values of triglycerides (P = 0.003) and lower mean values of HDL cholesterol (P < 0.001). Patients treated with other APs had intermediate values. Intergroup differences in body mass index were minimal in this naturalistic setting, probably because of awareness of this treatment hazard among clinicians. However, independently of body mass, dyslipidemia was significantly associated with AP treatment, in particular with OLZ and CLZ. These findings indicate a primary effect of APs on lipid regulation, important in understanding their mechanism of action, and with clinical implications.


Glycosylated prolactin in the murine pituitary: detection by a novel assay and alteration of concentrations by physiological and pharmacological stimuli.
In both rat and mouse pituitary extracts, we detected concanavalin A-binding prolactin immunoreactivity by a lectin-binding radioimmunoassay developed recently. The activity increased in response to estradiol benzoate treatment and lactation, stimuli that augment prolactin secretion, and decreased in response to acute nursing and perphenzine administration, stimuli that cause massive release of prolactin. Western blot analysis revealed a prolactin-immunoreactive band 2,000-3,000 greater in Mr than the main prolactin band that bound to 125I-labeled concanavalin A. These results suggest the existence in the murine adenohypophysis of a glycosylated form of prolactin, which seems to be released under certain physiological states.


Pediatric Quality of Life Inventory (PedsQL) in Fragile X Syndrome.
To date, health related quality of life (QoL) has not been systematically evaluated in youth with fragile X syndrome (FXS), the most common single gene cause of autism and the most common inherited form of developmental disability. We describe QoL data gathered using the Pediatric Quality of Life Inventory (PedsQL) completed online by 364 parents of youth with FXS. Parents consistently reported across all gender and age groups that their children experienced the highest QoL in Physical functioning and the lowest QoL in Cognitive functioning. Overall, older children with FXS had increase QoL ratings in the domains of School and Cognitive function.


A real-world comparison of in-person vs. virtual contraceptive care trainings for clinicians and support staff.
To conduct an exploratory analysis comparing in-person vs. virtual training programs about contraceptive care among clinicians and staff at 14 healthcare agencies in Washington state. Survey data from in-person trainings were collected between July 2019 and March 2020 and from virtual trainings between June 2020 and January 2021. changes in contraceptive knowledge, understanding of contraceptive counseling and care, and participant engagement and experience with the training. Post-survey response rates for in-person trainings were 82% for clinicians and 72% for support staff while post-survey response rates for virtual trainings were 48% for clinicians and 43% for staff. Average knowledge scores for in-person clinician trainings increased from 63% prior to training to 80% post-training (p < 0.05), knowledge scores for virtual clinician trainings increased from 72% to 86% (p < 0.05), and the pre-to-post change in scores between training modalities was similar (p > 0.05 for the score difference). Average knowledge scores among in-person support staff trainings increased from 63% to 84% (p < 0.05), scores among virtual support staff trainings increased from 68% to 87% (p < 0.05) and, again, the pre-to-post change in scores between training modalities was similar (p > 0.05 for the score difference). Only minimal differences in survey scores between modalities were observed on most measures of participant engagement and experience with the trainings (p > 0.05 for most score differences). These exploratory results suggest that in-person and virtual contraceptive care trainings yielded comparable results among both clinicians and support staff. Results from this post-hoc analysis of survey data suggest a general equivalency of effectiveness between in-person trainings and virtual trainings, although in-person trainings may be more satisfying or engaging for participants. Further work and research is needed to inform strategies for making virtual trainings more engaging and satisfying for participants.


MMDAE-HGSOC: A novel method for high-grade serous ovarian cancer molecular subtypes classification based on multi-modal deep autoencoder.
High-grade serous ovarian cancer (HGSOC) is a type of ovarian cancer developed from serous tubal intraepithelial carcinoma. The intrinsic differences among molecular subtypes are closely associated with prognosis and pathological characteristics. At present, multi-omics data integration methods include early integration and late integration. Most existing HGSOC molecular subtypes classification methods are based on the early integration of multi-omics data. The mutual interference among multi-omics data is ignored, which affects the effectiveness of feature learning. High-dimensional multi-omics data contains genes unassociated with HGSOC molecular subtypes, resulting in redundant information, which is not conducive to model training. In this paper, we propose a multi-modal deep autoencoder learning method, MMDAE-HGSOC. MiRNA expression, DNA methylation, and copy number variation (CNV) are integrated with mRNA expression data to construct a multi-omics feature space. The multi-modal deep autoencoder network is used to learn the high-level feature representation of multi-omics data. The superposition LASSO (S-LASSO) regression algorithm is proposed to fully obtain the associated genes of HGSOC molecular subtypes. The experimental results show that MMDAE-HGSOC is superior to the existing classification methods. Finally, we analyze the enrichment gene ontology (GO) terms and biological pathways of these significant genes, which are discovered during the gene selection process.


Zebrafish as tools for drug discovery.
The zebrafish has become a prominent vertebrate model for disease and has already contributed to several examples of successful phenotype-based drug discovery. For the zebrafish to become useful in drug development more broadly, key hurdles must be overcome, including a more comprehensive elucidation of the similarities and differences between human and zebrafish biology. Recent studies have begun to establish the capabilities and limitations of zebrafish for disease modelling, drug screening, target identification, pharmacology, and toxicology. As our understanding increases and as the technologies for manipulating zebrafish improve, it is hoped that the zebrafish will have a key role in accelerating the emergence of precision medicine.


VEGFR-3 signaling restrains the neuron-macrophage crosstalk during neurotropic viral infection.
Upon recognizing danger signals produced by virally infected neurons, macrophages in the central nervous system (CNS) secrete multiple inflammatory cytokines to accelerate neuron apoptosis. The understanding is limited about which key effectors regulate macrophage-neuron crosstalk upon infection. We have used neurotropic-virus-infected murine models to identify that vascular endothelial growth factor receptor 3 (VEGFR-3) is upregulated in the CNS macrophages and that virally infected neurons secrete the ligand VEGF-C. When cultured with VEGF-C-containing supernatants from virally infected neurons, VEGFR-3+ macrophages suppress tumor necrosis factor α (TNF-α) secretion to reduce neuron apoptosis. Vegfr-3ΔLBD/ΔLBD (deletion of ligand-binding domain in myeloid cells) mice or mice treated with the VEGFR-3 kinase inhibitor exacerbate the severity of encephalitis, TNF-α production, and neuron apoptosis post Japanese encephalitis virus (JEV) infection. Activating VEGFR-3 or blocking TNF-α can reduce encephalitis and neuronal damage upon JEV infection. Altogether, we show that the inducible VEGF-C/VEGFR-3 module generates protective crosstalk between neurons and macrophages to alleviate CNS viral infection.


An efficient nickel hydrogen oxidation catalyst for hydroxide exchange membrane fuel cells.
The hydroxide exchange membrane fuel cell (HEMFC) is a promising energy conversion technology but is limited by the need for platinum group metal (PGM) electrocatalysts, especially for the hydrogen oxidation reaction (HOR). Here we report a Ni-based HOR catalyst that exhibits an electrochemical surface area-normalized exchange current density of 70 μA cm-2, the highest among PGM-free catalysts. The catalyst comprises Ni nanoparticles embedded in a nitrogen-doped carbon support. According to X-ray and ultraviolet photoelectron spectroscopy as well as H2 chemisorption data, the electronic interaction between the Ni nanoparticles and the support leads to balanced hydrogen and hydroxide binding energies, which are the likely origin of the catalyst's high activity. PGM-free HEMFCs employing this Ni-based HOR catalyst give a peak power density of 488 mW cm-2, up to 6.4 times higher than previous best-performing analogous HEMFCs. This work demonstrates the feasibility of efficient PGM-free HEMFCs.


Fine-needle aspiration versus core needle biopsy for diagnosis of thyroid malignancy and neoplasm: a matched cohort study.
To compare the diagnostic performances of fine-needle aspiration (FNA) and core needle biopsy (CNB) in the diagnosis of thyroid malignancy and neoplasm in patients who underwent surgery for thyroid nodules. This retrospective study was approved by the institutional review board, and the need to obtain informed consent was waived. 3192 patients who underwent FNA (n = 3048) or CNB (n = 144) for diagnosis of thyroid nodules and then proceeded with surgery were included. Surgical pathologic diagnosis was the reference standard. Diagnostic performances of FNA and CNB to predict malignancy and neoplasm were compared. Propensity score matching was used to match patients with FNA with those with CNB because there were significant differences in the number of nodules and nodule characteristics between the FNA and CNB groups. Before matching, the sensitivity and accuracy of FNA were significantly higher or comparable with those of CNB, and the specificity, negative predictive value and positive predictive value were comparable. After matching, the diagnostic performances were similar, with the exception of specificity for predicting neoplasm being higher with CNB than with FNA. FNA showed comparable diagnostic performance to CNB; therefore, there may be no benefit in performing CNB to diagnose papillary thyroid carcinoma and neoplasm. • Diagnostic performances of FNA and CNB for thyroid malignancy and neoplasm were compared. • FNA showed comparable performances to CNB both before and after statistical matching. • There may be no benefit in performing CNB, given the comparable performances.


TRIM31 is upregulated in hepatocellular carcinoma and promotes disease progression by inducing ubiquitination of TSC1-TSC2 complex.
Tripartite motif (TRIM) 31 is a member of the tripartite motif-containing protein family, and TRIM family proteins are involved in a broad range of biological and pathological processes. However, the role of TRIM31 in hepatocellular carcinoma (HCC) progression is not known. Here we demonstrated that TRIM31 expression was significantly upregulated in liver cancer tissues compared with paired distal non-cancerous liver tissues from HCC patients, and its overexpression was significantly correlated with advanced disease status. Both gain and loss of function assay verified that TRIM31 promoted the malignant behaviors of HCC cells through overactivation of mammalian target of rapamycin complex1 (mTORC1) pathway. We further demonstrated that TRIM31 exerted its oncogenic effect by directly interacting with the tuberous sclerosis complex (TSC) 1 and TSC2 complex, the upstream suppressor of mTORC1 pathway, and promoting the E3 ligase-mediated K48-linked ubiquitination and degradation of this complex. In conclusion, this study demonstrated TRIM31 could promote HCC progression by targeting TSC1-TSC2 complex for degradation and further overactivating mTORC1 pathway. Thus, it revealed a novel molecular mechanism of HCC progression and indicated a potential therapeutic strategy against HCC by targeting TRIM31.


Relations with parents and with peers, temperament, and trajectories of depressed mood during early adolescence.
The present study examined (a) whether groups of children can be empirically identified with distinct longitudinal profiles of depressed mood from late childhood through early adolescence, (b) to what extent these different longitudinal depression profiles are predicted by problematic relations with parents, same-sex peers, and other-sex peers, and (c) what role individuals' temperamental characteristics play in this context. Based on a sample of 414 early adolescents (197 girls), four groups were identified with distinct longitudinal profiles of depressed mood between ages 11 and 14: One group with consistently low levels of depressed mood, another with consistently moderate levels of depressed mood, a third group whose depressed mood increased sharply from late childhood through early adolescence, and a fourth group who already showed clinical-range levels of depressed mood during late childhood and whose depressive feelings increased even slightly more thereafter. Subsequent analyses revealed that rejection by same-sex peers was related to the odds of following an increasing trajectory of depressed mood, but only for girls with a highly reactive temperament. A problematic relationship with parents increased the odds of an elevated trajectory of depressed mood regardless of individual temperament. The theoretical and practical implications of these findings are discussed.


The Protective Role of the Autonomic Nervous System in Intergenerational Cycles of Neglect.
Offspring of parents who experienced childhood neglect are at increased risk for developing internalizing problems. Empirical evidence suggests this link is principally mediated through parenting behavior. However, such intergenerational cycles of adversity are found to be disrupted in many families. Parasympathetic nervous system functioning is well documented to mediate individuals' emotion regulation biologically. Respiratory sinus arrhythmia (RSA) is a validated biomarker for parasympathetic activity. The goal of the current study was to investigate the moderating role of parent RSA reactivity in the effect of parents' childhood neglect on their children's internalizing problems, through parental acceptance. Physiological and survey data were collected from 145 dyads (94% mothers; Youth Mage = 12.9, Youth SDage = 0.85). Results suggest that the effect of parents' childhood neglect on their child's internalizing problems was conditional on parents' RSA reactivity. Specifically, higher levels of parents' neglect were only linked to increased risk for youth internalizing problems if parents exhibited a lack of RSA withdrawal. Further, this moderating effect was found to be mediated through parental acceptance. Findings suggest understanding intergenerational consequences of child maltreatment contexts should include consideration of bioregulatory factors.


[Preliminary treatment of congenital hip dislocation using physical therapy based on neurophysiology].
Adductor tightness is a typical symptom in CDH. In cases of subluxation and complete dislocation even a rigid abduction contracture can occur, preventing reduction and favouring redislocation. The contracture of the hip joint is the result of neurophysiological disorders, which can be treated by an exercise program on a neurophysiological basis. 62 children with 73 severely contracted and 5 hypotonic hip dislocations have been treated by the so-called "Vojta-program" before reduction. In a prospective study over 5 years this kind of treatment has been very successful: the incidence of necrosis of the femoral head could be reduced to 4%, long-lasting traction was not necessary anymore and the rigid hip joints required open reduction only in 2 cases.


PABP prevents the untimely decay of select mRNA populations in human cells.
Gene expression is tightly regulated at the levels of both mRNA translation and stability. The poly(A)-binding protein (PABP) is thought to play a role in regulating these processes by binding the mRNA 3' poly(A) tail and interacting with both the translation and mRNA deadenylation machineries. In this study, we directly investigate the impact of PABP on translation and stability of endogenous mRNAs in human cells. Remarkably, our transcriptome-wide analysis only detects marginal mRNA translation changes in PABP-depleted cells. In contrast, rapidly depleting PABP alters mRNA abundance and stability, albeit non-uniformly. Otherwise stable transcripts, including those encoding proteins with constitutive functions, are destabilized in PABP-depleted cells. In contrast, many unstable mRNAs, including those encoding proteins with regulatory functions, decay at similar rates in presence or absence of PABP. Moreover, PABP depletion-induced cell death can partially be suppressed by disrupting the mRNA decapping and 5'-3' decay machinery. Finally, we provide evidence that the LSM1-7 complex promotes decay of "stable" mRNAs in PABP-depleted cells. Taken together, these findings suggest that PABP plays an important role in preventing the untimely decay of select mRNA populations.