Real-world effectiveness and persistence of reference etanercept versus biosimilar etanercept GP2015 among rheumatoid arthritis patients: A cohort study.
Although several randomized clinical trials have confirmed that there is no difference in efficacy between etanercept and its biosimilar versions in the treatment of rheumatoid arthritis (RA), limited real-world evidence is available. We conducted a cohort study to compare the effectiveness and treatment persistence between the reference etanercept (ETN) and the biosimilar GP2015 in RA patients in a real-life setting. Adults with a diagnosis of RA who initiated treatment with ETN or GP2015, between January 2007 and December 2019, were included. The follow-up period was 52 weeks. The primary outcome was the mean of change in the DAS28-CRP values and the adjusted mean difference from baseline to 52 weeks between ETN and GP2015. Other effectiveness endpoints assessed were the rate of patients who achieved remission or low disease activity (LDA) at week 52, who showed a reduction of DAS28-CRP value greater than or equal to 1.2 from baseline to week 52 and rate of good responder patients (those meeting both effectiveness measures) at week 52. Treatment effectiveness over time (baseline, 26 and 52 weeks) was compared between the ETN and GP2015 groups using mixed effects models. Treatment persistence (probability of maintaining the same treatment over time) was also evaluated and shown using Kaplan-Meier survival curves. A total of 115 RA patients were included (ETN, n = 90; GP2015, n = 25). No differences were observed in the primary outcome: DAS28-CRP score decreased from baseline to week 52 [5.1 to 2.7 (mean of change -2.37) in ETN group and 5.0 to 2.2 (mean of change -2.84) in GP2015 group, p-value = 0.372] and the adjusted mean difference was -0.37 (-1.03 to 0.29). No differences were also observed in the other effectiveness endpoints assessed among patients treated with ETN or GP2015: rate of patients who achieved remission (54.1% vs. 66.7%, p-value = 0.303) and LDA (71.6% vs. 80.9%, p-value = 0.391) at week 52, reduction of DAS28-CRP value greater than or equal to 1.2 from baseline to week 52 (75.6% vs. 80.9%, p-value = 0.613) and rate of good responder patients (58.1% vs. 76.1%, p-value = 0.202). Drug survival was 82% and 80% for ETN and GP2015, respectively (log-rank p-value = 0.804). Etanercept and its biosimilar GP2015 show similar effectiveness and treatment persistence in RA patients in a real-life setting.


Adrenal pheochromocytomas: a broad spectrum of sonographic presentation.
Sonographic findings in 19 patients with proved adrenal pheochromocytomas observed over a 10 year period were evaluated retrospectively. Adrenal tumors were analyzed by number, size, echogenicity, internal echogenicity, and biologic behavior. There were 16 benign and 3 malignant pheochromocytomas, all of which were well marginated or encapsulated and ranged from 1.4 to 11 cm in greatest diameter (mean, 4.8 +/- 2.2 cm). A broad spectrum of sonographic appearances has been noted, including purely solid tumors (68%), complex masses (16%), and cystic lesions (16%). Compared with renal parenchyma as a reference tissue, 10 (77%) of 13 solid pheochromocytomas were isoechoic or hypoechoic, whereas three (23%) were hyperechoic. Six (46%) of the solid tumors were homogeneously echogenic, and seven (54%) were heterogeneous. Ultrasonic discrimination between benign and malignant pheochromocytoma on the basis of acoustic features alone has proved impossible. Abdominal sonography, however, provided evidence of malignancy in all three patients with malignant tumors by disclosing regional or distant metastases. In conclusion, rather than showing a specific uniform ultrasonographic appearance, pheochromocytoma is associated with a broad spectrum of possible sonographic presentations.


End-of-life decisions: Christian perspectives.
While legal rights to make medical treatment decisions at the end of one's life have been recognized by the courts, particular religious traditions put axiological and metaphysical meat on the bare bones of legal rights. Mere legal rights do not capture the full reality, meaning and importance of death. End-of-life decisions reflect not only the meaning we find in dying, but also the meaning we have found in living. The Christian religions bring particular understandings of the vision of life as a gift from God, human responsibility for stewardship of that life, the wholeness of the person, and the importance of the dying process in preparing spiritually for life beyond earthly life, to bear on end-of-life decisions.


Correlation between severity of rheumatoid arthritis and manner and extent of cervical lesion.
Abstract To determine the proper management of treatment for rheumatoid cervical lesions, we investigated the clinical course of the cervical spine in rheumatoid arthritis (RA). The severity of RA was classified into three groups according to the disease subsets advocated by Ochi et al.: the less erosive subset (LES), the more erosive subset (MES), and mutilating disease (MUD). Then the following radiographic assessments were performed on cervical roentogenograms: atlantoaxial subluxation (AAS), vertical subluxation (VS), and subaxial subluxation (SAS). One hundred and seventy-four patients were available for this study. The mean age of the patients was 60.9 years (19-85 years). The average duration from the onset of RA was 19.1 years (10-40 years). Eighty-seven patients were classified as LES, 69 were MES, and 18 were MUD. We found that few patients in the LES group had required an operation on the cervical spine. AAS was seen in about 60% of the MES patients, but few cases had VS or SAS, and most operations were atlantoaxial fusion. All patients in the MUD group had some cervical instabilities. Not only VS but also SAS were seen in more than half of these patients, and many patients had required occipitothoracic fusion.


[Neurodermatitis and psyche].
The clinical term "constitutional eczematoid" (synonyms: neurodermite, eczema flexuarum, atopic dermatitis e. g.) with/without bronchial asthma and/or allergic rhinitis is presented in its multifactorial dimensions from an overlooking point of view. There are different clinical types, the neurodermite --, the prurigo, the seborrheic and the mixed type of atopic dermatitis. The psychic way of behaviour of these patients which is the neurodermite structure of personality is presented thoroughly. This way of behaviour can especially be seen in patients of neurodermite and prurigo type of atopic dermatitis. In about 10% so called extreme case can be stated presenting this abnormal psychic way of behaviour. Wether in patients with atopic dermatitis a genetic caused psycho-dermatosis has to be discussed, cannot be answered, because there is no allround valid conception of ethology and pathogenesis for this multifactorial disease.


B7-H1, which represses EBV-immortalized B cell killing by autologous T and NK cells, is oppositely regulated by c-Myc and EBV latency III program at both mRNA and secretory lysosome levels.
EBV-immortalized B cells induce a complex immune response such that the virus persists as a clinically silent infection for the lifetime of the infected host. B7-H1, also called PD-L1, is a cosignaling molecule of the B7 family that can inhibit activated T cell effectors by interaction with its receptor PD-1. In this work, we have studied the dependence of B7-H1 on NF-κB and c-Myc, the two main transcription factors in EBV latency III proliferating B cells, on various lymphoblastoid and Burkitt lymphoma cell lines, some of them being inducible or not for the EBV latency III program and/or for c-Myc. We found that B7-H1 repressed killing of EBV-immortalized B cells by their autologous T and NK cells. At the mRNA level, NF-κB was a weak inducer whereas c-Myc was a strong repressor of B7-H1 expression, an effect mediated by STAT1 inhibition. At the protein level, B7-H1 molecules were stored in both degradative and unconventional secretory lysosomes. Surface membrane B7-H1 molecules were constitutively internalized and proteolyzed in lysosomes. The EBV latency III program increased the amounts of B7-H1-containing secretory lysosomes and their export to the surface membrane. By repressing actin polymerization, c-Myc blocked secretory lysosome migration and B7-H1 surface membrane export. In addition to B7-H1, various immunoregulatory molecules participating in the immunological synapse are stored in secretory lysosomes. By playing on actin polymerization, c-Myc could thus globally regulate the immunogenicity of transformed B cells, acting on export of secretory lysosomes to plasma membrane.


Increased Expressions of ICAM-2 and ICAM-3 in Pterygium.
Purpose: Pterygium, one of the most common ocular surface diseases, is characterized by inflammatory infiltrates, proliferation, angiogenesis, fibrosis, and extracellular matrix breakdown. The objective of this study was to elucidate the levels of the intercellular adhesion molecule (ICAM)-2, and ICAM-3 gene and protein expressions in pterygium. Methods: A total of 59 patients with pterygium were included in this study. mRNA from pterygial and conjunctival autograft tissues were extracted, and real-time polymerase chain reaction on the BioMark HD dynamic array system was performed for the ICAM-2 and ICAM-3 gene expressions. ICAM-2 and ICAM-3 protein expressions using western blot and immunohistochemistry methods were also investigated in pterygial and conjunctival autograft tissues. Results: ICAM-2 and ICAM-3 gene expressions were markedly augmented in pterygial tissues (P = 0.0018 and P = 0.0023, respectively). Significant increases in protein expressions in pterygial tissues were also detected for ICAM-2 and ICAM-3 (P = 0.0116 and P = 0.0252, respectively). In the immunohistochemical studies, there was a marked increase in ICAM-3 (P = 0.0152), but not in ICAM-2 (P = 0.1041), protein expressions in pterygial tissues. Significant positive correlations between pterygia grading with ICAM-2 protein expression (P = 0.0398) and ICAM-3 immunohistochemical scores (P = 0.0138) were observed. Conclusion: These results demonstrate, for the first time, the expressions of ICAM-2 and ICAM-3 in the pterygium. These findings may help to understand the signal transduction mechanisms in the pterygium formation and provide a new therapy strategy for pterygium treatment.


Impact of chronic hepatitis C on HIV-1 disease progression.
Although there is clear evidence of an accelerated progression of liver fibrosis in HIV-positive patients with chronic hepatitis C virus (HCV) infection, it is unclear whether HCV infection may influence HIV-1 disease progression. We have analyzed the impact of HCV on CD4 counts and plasma HIV RNA in a large group of HIV-positive individuals. Epidemiological data, CD4 counts, and plasma HIV RNA values were recorded from 902 consecutive HIV-1-positive persons who attended our institution since 1998. HCV infection was documented (antibodies and/or HCV RNA) in 72% of the total study population. The higher rates were seen among intravenous drug users (97%) compared to other groups (17% in homosexual men, 23% in patients who acquired HIV heterosexually). In a cross-sectional analysis performed at the first trimester of 2000, the mean CD4 count was lower among HCV-positive than among HCV-negative individuals (518 +/- 282 cells/microL vs. 620 +/- 302 cells/microL; p <.001). The mean plasma HIV RNA was 11,188 +/- 55,301 copies/mL in HCV-positive persons versus 6,352 +/- 32,152 copies/mL in HCV-negative persons (p =.03). Undetectable plasma HIV RNA (<50 copies/mL) was recognized in 54% of HCV-positive persons versus 64% of HCV negative persons (p =.04); a similar proportion of patients in each group was on antiretroviral therapy (90% vs. 93%) or HAART (86% vs. 89%). When comparing data from 1998 and 2000, the CD4 count increased an average of 53 cells/microL (11%) in HCV-positive persons versus 111 (19%) in HIV-negative persons during this 2-year interval (p <.05). Plasma HIV RNA on average declined 606 copies/mL (5%) in HCV-positive persons versus 5,788 copies/mL (54%) in HCV-negative persons (p <.05). A significant association between HCV infection and CD4 counts was recognized in the multivariate analysis, which was independent of gender, age, plasma HIV RNA, use of HAART, and adherence to therapy. In contrast, no significant effect of HCV on HIV RNA was found. Hepatitis C may be associated with a poor immunologic outcome in HIV-infected persons. This worst influence is not explained by a lower rate of antiretroviral therapy among HCV-positive persons nor a much poorer drug adherence in this population. Therefore, hepatitis C may act as a direct cofactor for HIV disease progression. If so, treatment of chronic hepatitis C might indirectly benefit HIV disease.


Classification of schizophrenia by intersubject correlation in functional connectome.
Functional connectomes have been suggested as fingerprinting for individual identification. Accordingly, we hypothesized that subjects in the same phenotypic group have similar functional connectome features, which could help to discriminate schizophrenia (SCH) patients from healthy controls (HCs) and from depression patients. To this end, we included resting-state functional magnetic resonance imaging data of SCH, depression patients, and HCs from three centers. We first investigated the characteristics of connectome similarity between individuals, and found higher similarity between subjects belonging to the same group (i.e., SCH-SCH) than different groups (i.e., HC-SCH). These findings suggest that the average connectome within group (termed as group-specific functional connectome [GFC]) may help in individual classification. Consistently, significant accuracy (75-77%) and area under curve (81-86%) were found in discriminating SCH from HC or depression patients by GFC-based leave-one-out cross-validation. Cross-center classification further suggests a good generalizability of the GFC classification. We additionally included normal aging data (255 young and 242 old subjects with different scanning sequences) to show factors could be improved for better classification performance, and the findings emphasized the importance of increasing sample size but not temporal resolution during scanning. In conclusion, our findings suggest that the average functional connectome across subjects contained group-specific biological features and may be helpful in clinical diagnosis for schizophrenia.


A meta-analysis of PDE-gene polymorphism and cerebral infarction risk.
Previous studies identified that phosphodiesterase 4D (PDE4D) gene polymorphism might be associated with cerebral infarction or ischemic stroke, and hemorrhagic stroke in human populations. However, as yet, no meta-analysis has revealed any detailed association. We retrospectively reviewed studies regarding the relationship of PDE4D gene polymorphism with ischemic stroke (IS) published during the period January 2003 to September 2012. According to the inclusion criteria, 9 of 105 initial studies were included in the subsequent analysis. The PubMed, Embase and CNKI of China were searched to identify the relevant studies. A total of 186 young patients with IS were included for the meta-analysis and 232 matched control subjects were enrolled and results were presented. The association of PDE4D gene polymorphism with IS in various populations was examined. The results suggested that single nucleotide polymorphism (SNP), SNP 83 in PDE4D gene was significantly related with susceptibility to IS. The meta-analysis also showed that PDE4D gene was associated with an enhanced risk of IS. The meta-analysis suggested that PDE4D SNP 87 constitutes an independent risk factor for IS development. To the best of our knowledge, the present meta-analysis reveals a number of possible associations between PDE4D gene polymorphism and IS.


Effects of Experience Abroad and Language Proficiency on Self-Efficacy Beliefs in Language Learning.
Experience abroad has been recognized as one of the best investments for second or foreign language learning. A lot of research has examined its impact on language learning from linguistic as well as non-linguistic perspectives. Nonetheless, literature on the relationships between and among experience abroad, language proficiency, and self-efficacy beliefs in language learning seems to still be cursory and thus the present study chose to focus on these aspects in more detail. To do so, 259 Korean English as a foreign language students answered the Questionnaire of English Self-Efficacy as well as completed a background questionnaire. Statistical analyses identified two underlying factors of self-efficacy beliefs-production and comprehension-that helped analyze the data from a new perspective. Using this two-factor structure of self-efficacy, it was found that the combination of experience abroad and English proficiency were indeed related to these self-efficacy factors. In addition, the results indicate that students may have benefitted most in self-efficacy formation in production and comprehension aspects when they have four to six months of experience abroad.


Percutaneous absorption of aromatic amines in rubber industry workers: impact of impaired skin and skin barrier creams.
Several aromatic amines (AA) could cause bladder cancer and are an occupational hygiene problem in the workplace. However, little is known about the percutaneous absorption of chemicals via impaired skin and about the efficacy of skin protection measures to reduce internal exposure. To determine the impact of skin status and of skin protection measures on the internal exposure to AA in workers manufacturing rubber products. 51 workers occupationally exposed to aniline and o-toluidine were examined. The workplace conditions, risk factors for skin and the use of personal protective equipment were assessed by means of a self-administered questionnaire. The skin of hands and forearms was clinically examined. Exposure to aniline and o-toluidine was assessed by ambient air and biological monitoring (analyses of urine samples and of haemoglobin adducts). Haemoglobin-AA-adduct levels in workers with erythema (73%) were significantly higher (p<0.04) than in workers with healthy skin (mean values: aniline 1150.4 ng/l vs 951.7 ng/l, o-toluidine 417.9 ng/l vs 118.3 ng/l). The multiple linear regression analysis showed that wearing gloves significantly reduced the internal exposure. A frequent use of skin barrier creams leads to a higher internal exposure of AA (p<0.03). However, the use of skincare creams at the workplace was associated with a reduced internal exposure (p<0.03). From these findings we assume that internal exposure of the workers resulted primarily from the percutaneous uptake. The study demonstrates a significantly higher internal exposure to AA in workers with impaired skin compared with workers with healthy skin. Daily wearing of gloves efficiently reduced internal exposure. However, an increased use of skin barrier creams enhances the percutaneous uptake of AA. Skincare creams seem to support skin regeneration and lead to reduced percutaneous uptake.


Fournier's Gangrene in a Two Year Old Child: A Case Report.
Necrotizing fasciitis of the perineum and external genitalia is a life-threatening infective gangrene, primarily seen in adults. It may be seen at any age but it is relatively uncommon in children. Here, we report a case of Fournier's gangrene in a two year old male child who was treated aggressively with broad spectrum antibiotics and early surgical debridement with hemodynamic stabilization. Even though no obvious precipitating cause was identified, hygiene was thought to be the inciting factor. Early surgical debridement with appropriate antibiotics and aggressive supportive care gave good results.


Using RNA-Seq to Explore the Repair Mechanism of the Three Methods and Three-Acupoint Technique on DRGs in Sciatic Nerve Injured Rats.
To study the effects of the three methods and three-acupoint technique on DRG gene expression in SNI model rats and to elucidate the molecular mechanism of the three methods and three-acupoint technique on promoting recovery in peripheral nerve injury. 27 male SD rats were randomly divided into three groups: a Sham group, the SNI group, and the Tuina group. The Tuina group was treated with a tuina manipulation simulator to simulate massage on points, controlling for both quality and quantity. Point-pressing, plucking, and kneading methods were administered quantitatively at Yinmen (BL37), Chengshan (BL57), and Yanglingquan (GB34) points on the affected side once a day, beginning 7 days after modeling. Intervention was applied once a day for 10 days, then 1 day of rest, followed by 10 more days of intervention, totally equaling 20 times of intervention. The effect of the three methods and three-point technique on the recovery of injured rats was evaluated using behavior analysis. RNA sequencing (RNA-Seq) analysis of differentially expressed genes in DRGs of the three groups of rats was also performed. GO and KEGG enrichment was analyzed and verified using real-time PCR. RNA-Seq combined with database information showed that the number of differentially expressed genes in DRG was the largest in the Tuina group compared with the SNI group, totaling 226. GO function is enriched in the positive regulation of cell processes, ion binding, protein binding, neuron, response to pressure, response to metal ions, neuron projection, and other biological processes. GO function is also enriched in the Wnt, IL-17, and MAPK signaling pathways in the KEGG database. PCR results were consistent with those of RNA sequencing, suggesting that the results of transcriptome sequencing were reliable. The three methods and three-acupoint technique can promote the recovery of SNI model rats by altering the gene sequence in DRGs.


Association between Serum Essential Metal Elements and the Risk of Schizophrenia in China.
Numerous essential metal elements (EMEs) are necessary to maintain the proper function of human body. In this case-control study, we investigated the associations of 11 EMEs [Calcium (Ca), potassium (K), magnesium (Mg), sodium (Na), manganese (Mn), selenium (Se), cobalt (Co), Molybdenum (Mo), copper (Cu), zinc (Zn), and iron (Fe)] in serum with the risk of schizophrenia. We recruited first-episode and drug-naïve schizophrenic patients (cases = 99) and age-sex-matched normal subjects (controls = 99) from Tangshan, Hebei Province, China. The 11 EMEs in serum from cases and controls were quantified by inductively coupled plasma atomic emission spectrometry and inductively coupled plasma mass spectrometry. We observed that a higher level of Mn (OR = 2.390; 95%CI: 1.504-3.796) and lower levels of Ca (OR = 0.939; 95%CI: 0.890-0.990), Mg (OR = 0.806; 95%CI: 0.669-0.972), Na (OR = 0.995; 95%CI: 0.993-0.998), and Se (OR = 0.954; 95%CI: 0.937-0.972) were associated with an elevated risk of schizophrenia. Dose-response relationships between serum EME concentrations and the risk of schizophrenia were observed in most of the schizophrenia-associated EMEs. Moreover, the serum concentrations of these schizophrenia-associated EMEs in patients were correlated with the severity of their clinical symptoms. Significant correlations were found between EMEs and biomarkers associated with schizophrenia related to metabolic and oxidative stress. This study suggested that the concentration and profile of EMEs were different between schizophrenic patients and normal controls and revealed potential metabolisms associated with EMEs and schizophrenia, suggesting EMEs might act as biomarkers of schizophrenia to improve the current situation of diagnosis and treatment.


Use of Norcuron in the course of different surgical interactions.
Norcuron has been used for intubation and short-term relaxation in 21 cases and for maintaining neuromuscular blockade during major operations of 48 patients suffering from severe clinical conditions. The drug assured in all cases relaxation for the required period and longer operations could also be performed, if required, with the repetition of doses. According to the observations Norcuron proved to be a muscle relaxant of medium duration of action which may be combined with drugs commonly used for premedication, as well as with narcotics introducing and maintaining anaesthesia. The special advantage of the drug is that virtually it does not influence the circulatory parameters and its action may be reliably antagonized.


Concanavalin A-activated suppressor cell activity in peripheral blood lymphocytes of urologic cancer patients.
Concanavalin A (Con A)-inducible suppressor cell activity in peripheral blood lymphocytes (PBL) of urologic cancer patients and of appropriate controls with benign urologic disorders was measured concurrently. Although the proliferative responses to Con A of the cancer patients were significantly lower than those of controls, no difference in Con A-induced suppressor cell activity was demonstrated between cancer patients and controls when tested under a variety of conditions. Moreover, regression analysis revealed no correlation between the proliferative response to Con A and suppressor cell activity in either cancer patients or controls. The results indicated that Con A-inducible suppressor cell activity was unaltered in urologic cancer patients and suggested that suppressor cells of the type that can be activated by Con A were not involved in the general immunologic impairment frequently associated with urologic cancer.


Historical Datasets Support Genomic Selection Models for the Prediction of Cotton Fiber Quality Phenotypes Across Multiple Environments.
Genomic selection (GS) has successfully been used in plant breeding to improve selection efficiency and reduce breeding time and cost. However, there has not been a study to evaluate GS prediction models that may be used for predicting cotton breeding lines across multiple environments. In this study, we evaluated the performance of Bayes Ridge Regression, BayesA, BayesB, BayesC and Reproducing Kernel Hilbert Spaces regression models. We then extended the single-site GS model to accommodate genotype × environment interaction (G×E) in order to assess the merits of multi- over single-environment models in a practical breeding and selection context in cotton, a crop for which this has not previously been evaluated. Our study was based on a population of 215 upland cotton (Gossypium hirsutum) breeding lines which were evaluated for fiber length and strength at multiple locations in Australia and genotyped with 13,330 single nucleotide polymorphic (SNP) markers. BayesB, which assumes unique variance for each marker and a proportion of markers to have large effects, while most other markers have zero effect, was the preferred model. GS accuracy for fiber length based on a single-site model varied across sites, ranging from 0.27 to 0.77 (mean = 0.38), while that of fiber strength ranged from 0.19 to 0.58 (mean = 0.35) using randomly selected sub-populations as the training population. Prediction accuracies from the M×E model were higher than those for single-site and across-site models, with an average accuracy of 0.71 and 0.59 for fiber length and strength, respectively. The use of the M×E model could therefore identify which breeding lines have effects that are stable across environments and which ones are responsible for G×E and so reduce the amount of phenotypic screening required in cotton breeding programs to identify adaptable genotypes.


Developing Thermal Regulating and Electromagnetic Shielding Nacre-Inspired Graphene-Conjugated Conducting Polymer Film via Apparent Wiedemann-Franz Law.
In this work, we observed size-dependent behavior of filler on both the thermal and electrical conductivities of nacre-like graphene-conjugated conducting polymer films and demonstrated the display of apparent Wiedemann-Franz law and tunability of Lorenz constant in such films. The maximum thermal and electrical conductivities of as-fabricated films can reach over 73 W·m-1·K-1 and 1200 S·cm-1, respectively. Furthermore, the maximum value of electromagnetic interference shielding reaches 54 dB with SSE/t over 16000 dB·cm2·g-1. These films can not only show high-quality electromagnetic interference shielding performance with small thickness and low filler ratio but also achieve simultaneous thermal management during electromagnetic shielding. The findings in this work offer new insight into designing flexible graphene-conjugated polymers with customizable thermal and electrical properties in the broad fields of thermal management systems, electromagnetic defense systems, and flexible electronic systems.


Towards the validation of quantitative contrast sensitivity as a clinical endpoint: correlations with vision-related quality of life in bilateral AMD.
To investigate if active learning of contrast sensitivity (CS) in bilateral age-related macular degeneration (AMD) correlates better than visual acuity (VA) with vision-related quality of life (VRQoL) using factor analysis-calibrated National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25). Prospective cross-sectional observational study in 93 patients (186 eyes) with bilateral AMD. CS was measured in one eye at a time with the quantitative CS function (qCSF) method (Adaptive Sensory Technology). Same-day VRQoL was assessed with factor analysis-calibrated NEI VFQ-25 visual function and socioemotional scales. Mixed-effects multiple linear regression analyses evaluated the associations of the qCSF outcomes and VA with the NEI VFQ-25 scales. A subgroup analysis on patients with AMD with VA more than 20/25 in both eyes was performed. Compared with VA, CS outcomes were associated with larger effect on both visual function scale (standardised beta coefficients (β*) for area under the logarithm of CSF (AULCSF) curve and CS thresholds at 1.5, 3 and 6 cycles per degree (cpd): β*=0.50, 0.48, 0.52, 0.46, all p<0.001, respectively, vs β*=-0.45 for VA, all p<0.001) and socioemotional scale (β* for AULCSF and CS threshold at 6 cpd: β*=0.44, 0.44 vs β*=-0.42 for VA, all p<0.001). In patients with AMD with VA more than 20/25 in both eyes (N=20), both VFQ-25 scales and all CS outcomes were significantly reduced. qCSF-measured CS strongly correlates with patient-reported VRQoL in bilateral AMD, even stronger than VA does. This study further validates qCSF-measured CS as a promising functional endpoint for future clinical trials in AMD.


Concentration and fate of persistent organochlorine pesticides in estuarine sediments using headspace solid-phase microextraction.
The concentration and fate of persistent organochlorine pesticides (OCPs) in estuarine surface sediments in Erh-jen and Lan-yang rivers, Taiwan were investigated using headspace solid-phase microextraction (HSSPME) method to evaluate the possible pollution potential and guideline for OCP concentrations in Taiwan. The HSSPME method exhibits a good analytical performance with low detection limits for OCP determination in sediment. In addition, results obtained using the developed HSSPME method were in good agreement with those obtained using Soxhlet extraction in a certified sample. The developed analytical method was further applied to the determination of concentrations of OCP residues in surface sediments from the estuaries of the selected rivers in Taiwan. A total of 20 surface sediments from each river was collected from 10 sampling stations. The total OCP concentrations in sediments from Erh-jen River ranged from 0.17 to 5.04 ng/g-dw with the mean values of 0.25-1.24 ng/g-dw for HCHs, 0.10-0.89 ng/g-dw for cyclodienes and 0.16-0.64 ng/g-dw for DDTs. The concentrations of OCPs in sediments from Lan-yang River were in the range 0.37-0.9 ng/g-dw with an average of lower than 0.5 ng/g-dw. HCHs and DDTs were abundant in the estuarine sediments from the selected rivers. Results obtained in this study show that the origin of OCPs in the surface sediments from Erh-jen River is a combination of erosion of the weathered soils and long-range atmospheric transport, while the OCP concentrations found in Lan-yang River could be regarded as the background levels of OCPs in Taiwan.


Disentangling the effects of race and SES on arthritis-related symptoms, coping, and well-being in African American and White women.
This study examined both unique and interactive effects of race and socioeconomic status (SES) on arthritis-related symptoms, coping, and well-being in African American and White women. Participants included 77 African American and 98 White women, aged 45 to 90, who completed structured, face-to-face interviews. A series of 2 x 2 MANCOVAs examined race (African American, White) and SES (high/low education or high/low occupational status) differences in arthritis-related symptoms, coping, and well-being. African Americans used more religious coping, wishful-thinking, seeking social support, and emotional expression than Whites. Individuals with low SES reported worse arthritis-related symptoms, poorer well-being, and greater use of coping strategies that tend to be maladaptive. Race x SES interactions revealed higher depressive symptoms in African Americans with low versus high education and coping differences in African Americans with low versus high occupational status; however differences in depressive symptoms and coping based on SES were not evident for Whites. Results demonstrate unique and interactive race and SES differences for arthritis-related symptoms, coping, and well-being showing the complexity of race and SES in the realm of physical and mental health.


Renal cortical thickness and PON1 activity both decrease in chronic renal failure.
Chronic renal failure (CRF) is associated with a tendency to atherosclerosis due to the enhanced oxidative stress and insufficient antioxidant enzyme activities such as superoxide dismutase (SOD), catalase (CAT) and paraoxonase (PON 1), together with abnormalities in lipid parameters. We determined the in vitro susceptibility of low-density lipoprotein (LDL) to oxidation and PON1 activities in patients with chronic renal insufficiency to see how PON1 affected the progression of the disease and whether hemodialysis influenced these parameters. Thirty-seven patients (21 men, 16 women, mean age 43.9 +/- 16) with CRF were included, 23 were receiving hemodialysis treatment. Exclusion criteria were diabetes mellitus and acute coronary disease. Eighteen healthy subjects (9 men and 9 women, mean age 39.9 +/- 10.5) volunteered to participate as controls. All patients were evaluated by renal ultrasound (USG) and two-dimensional echography, and their lipid profiles, PON1 activity, basal and Cu-induced LDL oxidation were determined. PON1 activities of patients were lower than controls (14.4 +/- 11 vs 30.9 +/- 19 U/L, p < 0.05) while basal ox-LDL levels determined by the thiobarbituric acid reactive substances (TBARS) method were higher (0.6 +/- 0.4 vs 0.4+/- 0.2 nmol/mg LDL protein, p<0.01). There was no significant difference between the groups treated with hemodialysis or not. There was a positive correlation between renal cortical thickness and HDL levels (r=0.47, p=0.006) and PON1 activity (r=0.45, p=0.01). Our data showed that HDL cholesterol levels and PON1 activities were both lower in patients, indicating depletion of the protective antioxidant capacity. PON1 activities and phenotypes were no different in patients with coronary disease and others so it does not appear to be a significant indicator of coronary artery disease in patients with CRF.


Trichomonas vaginalis infection among women receiving gynaecological care at an Alabama HIV Clinic.
Trichomoniasis vaginalis is a risk factor for the acquisition and transmission of HIV. The objective of this study was to determine the prevalence of T vaginalis (using culture) among HIV-infected women receiving gynaecological care at an university HIV clinic in Alabama in addition to predictors of infection. Electronic medical record review of women presenting to the clinic for gynaecological care during 2006-2012 was performed. Demographic and sexual history data was abstracted in addition to absolute CD4 cell count, HIV-1 viral load and sexually transmitted infection (STI) (including T vaginalis) testing results. Analysis was conducted using Stata V.12. T vaginalis was prevalent in 17.4% (83/478) of HIV-infected women; other STIs were less prevalent. Among these women, 384 presented for routine STI screening, of which 12% (46/384) were T vaginalis-infected. Younger age, African-American race, lifetime history of tobacco and drug abuse, lack of HIV therapy, HIV-1 viral load >400 copies/ml, and report of seeking gynaecological care for reasons other than routine STI screening (ie, having symptoms) were significant predictors of T vaginalis in univariate analysis. Age, African American race, and report of seeking gynaecological care for reasons other than routine STI screening remained associated with T vaginalis in multivariable analysis. T vaginalis remains highly prevalent among HIV-infected women, a proportion of which may be asymptomatic. If left undiagnosed and untreated, these women may be more likely to transmit HIV. Increased emphasis on screening for high risk sexual behaviours, testing for T vaginalis, and risk reduction counselling is necessary for all HIV-infected women.


Dependence of protein-induced lipid bilayer deformations on protein shape.
Membrane proteins typically deform the surrounding lipid bilayer membrane, which can play an important role in the function, regulation, and organization of membrane proteins. Membrane elasticity theory provides a beautiful description of protein-induced lipid bilayer deformations, in which all physical parameters can be directly determined from experiments. While analytic solutions of protein-induced elastic bilayer deformations are most easily developed for proteins with approximately circular cross sections, structural biology has shown that membrane proteins come in a variety of distinct shapes, with often considerable deviations from a circular cross section. We develop here a boundary value method (BVM) that permits the construction of analytic solutions of protein-induced elastic bilayer deformations for protein shapes with arbitrarily large deviations from a circular cross section, for constant as well as variable boundary conditions along the bilayer-protein interface. We apply this BVM to protein-induced lipid bilayer thickness deformations. Our BVM reproduces available analytic solutions for proteins with circular cross section and yields, for proteins with noncircular cross section, excellent agreement with numerical, finite element solutions. On this basis, we formulate a simple analytic approximation of the bilayer thickness deformation energy associated with general protein shapes and show that, for modest deviations from rotational symmetry, this analytic approximation is in good agreement with BVM solutions. Using the BVM, we survey the dependence of protein-induced elastic bilayer thickness deformations on protein shape, and thus explore how the coupling of protein shape and bilayer thickness deformations affects protein oligomerization and transitions in protein conformational state.


Serological viral testing of cadaveric cornea donors.
Cornea graft recipients are exposed to viral transmission from the donor. Cadaveric donor serum is often of poor quality and frequently yields falsely positive results in serological assays that may result in the graft being needlessly discarded. We examined the influence of the time of blood collection after death, and the macroscopic aspect of serum, on serological test results in cadaveric cornea donors. Five hundred sixty-five consecutive cadaveric cornea donors were systematically tested for serological markers of human immunodeficiency virus type 1 and 2, human T-cell leukemia virus type 1, hepatitis B and hepatitis C viruses (HCV). We studied the influence of the macroscopic aspect of the donor's serum and the time of blood collection after death on the results of serological testing and on the subsequent decision to use or discard the graft. Twenty-one and a half percent of corneas were rejected on the basis of virological test results. We found significant relationships between the macroscopic aspect of serum at the time of testing and: (i) a positive, equivocal or discrepant result of immunoassays, for all markers except anti-HCV antibodies, (ii) non acceptance of cornea grafts, and (iii) the time of blood sampling after death. The macroscopic aspect of postmortem blood samples is the best predictor of the specificity of serological testing in cornea donors. Serological results should be interpreted with care when serum is macroscopically abnormal, and cadaveric donors should not be sampled more than 12 hr after death.


[Cavitating pleomorphic carcinoma of the lung; report of a case].
We report a case of a previously healthy 76-year-old male with cavitating pleomorphic carcinoma of the lung. He was admitted because of an abnormal lung shadow on chest X-ray. Computed tomography (CT) showed a well-demarcated nodular shadow within thin-walled cavity in the right upper lobe. Because the lesion was revealed as adenocarcinoma by transbronchial lung biopsy, right upper lobectomy was performed. By histopathologic examination of the resected specimen, the nodule contained a component of spindle cell features and the cavity wall was composed of adenocarcinoma. The final diagnosis was pleomorphic carcinoma. Postoperative course has been uneventful for 12 months after surgery.


Nephron-sparing surgery for renal angiomyolipoma.
Renal angiomyolipoma (RAML) is a benign tumor composed of varying amounts of mature adipose tissue, smooth muscle and thick-walled blood vessels. RAML tend to grow over time requiring active intervention due to serious associated complications, such as hemorrhage and pain. Although RAML is an ideal tumor for organ preservation, data concerning efficacy of nephron-sparing surgery (NSS) are sparse. The aim of the study was to evaluate the efficacy of NSS in RAML with regard to renal function, tumor recurrence and surgical feasibility. Charts of patients with pathologically confirmed RAML were reviewed and data recorded: tumor size, associated symptoms, intraoperative blood loss, serum creatinine, follow-up data with regard to tumor recurrence and long-term renal function. A total of 28 patients were identified with RAML who underwent NSS because of tumor size > 4 cm, pain and/or to rule out malignancy due to radiographic features of uncertain interpretation. The median follow-up of all patients is 58 (3-114) months; median age was 55.6 (34-78) years, 24 patients were women, 4 patients were men. None of the patients developed a local recurrence. Median size of enucleated tumors was 5.5 (2.5-15) cm; indication for NSS was symptomatic tumor with hemorrhage in 4 patients (16%), prophylaxis of hemorrhage in 5 patients (20%) and radiographic features suspicious for malignancy in 16 patients (64%). In those cases, unenhanced and enhanced CT scans exhibit a hyperdense and a hypodense lesion as compared to the adjacent normal renal cortex, respectively. There were no intraoperative complications, median blood loss was 320 (50-1200) ml, none of the patients required blood transfusions. Post-operative course was uneventful in 26 patients (96%), 2 patients (7.1%) developed a urinary fistula managed by an endoluminal stent. Pre-operative serum creatinine was 0.9 (0.7-1.3) mg/dl, post-operative creatinine was 1.23 (0.7-1.5) mg/dl and serum creatinine at last follow-up was 0.95 (0.7-1.2) mg/dl. NSS can be performed with a high success rate in RAML when surgical management is indicated. Long-term follow-up reveals no local tumor recurrences and stable renal function even in patients with a solitary kidney.


Generic Interpretable Reaction Condition Predictions with Open Reaction Condition Datasets and Unsupervised Learning of Reaction Center.
Effective synthesis planning powered by deep learning (DL) can significantly accelerate the discovery of new drugs and materials. However, most DL-assisted synthesis planning methods offer either none or very limited capability to recommend suitable reaction conditions (RCs) for their reaction predictions. Currently, the prediction of RCs with a DL framework is hindered by several factors, including: (a) lack of a standardized dataset for benchmarking, (b) lack of a general prediction model with powerful representation, and (c) lack of interpretability. To address these issues, we first created 2 standardized RC datasets covering a broad range of reaction classes and then proposed a powerful and interpretable Transformer-based RC predictor named Parrot. Through careful design of the model architecture, pretraining method, and training strategy, Parrot improved the overall top-3 prediction accuracy on catalysis, solvents, and other reagents by as much as 13.44%, compared to the best previous model on a newly curated dataset. Additionally, the mean absolute error of the predicted temperatures was reduced by about 4 °C. Furthermore, Parrot manifests strong generalization capacity with superior cross-chemical-space prediction accuracy. Attention analysis indicates that Parrot effectively captures crucial chemical information and exhibits a high level of interpretability in the prediction of RCs. The proposed model Parrot exemplifies how modern neural network architecture when appropriately pretrained can be versatile in making reliable, generalizable, and interpretable recommendation for RCs even when the underlying training dataset may still be limited in diversity.


Deubiquitinase Inhibitor Auranofin Attenuated Cardiac Hypertrophy by Blocking NF-κB Activation.
Cardiac hypertrophy is a major outcome and compensatory response of the cardiovascular system to hemodynamic and additional stress responses that ultimately lead to heart failure. Auranofin (Aur) has been used for treating rheumatic arthritis for several decades. Aur is a 19S proteasome-associated deubiquitinase inhibitor, and inhibition of the proteasome is speculated to reverse cardiac hypertrophy. However, the role of the deubiquitinases, especially 19S proteasome-associated deubiquitinases, in the regulation of cardiac remodeling remains poorly understood. The present study investigated the role of Aur in cardiac hypertrophy both in vitro and in vivo. Male Sprague-Dawley rats underwent abdominal aortic constriction to induce left ventricular hypertrophy. The neonatal rat primary myocardial cell hypertrophy model was induced by Ang II. Echocardiography, hematoxylin-eosin staining, Masson's trichrome staining, immunochemistry, western blot analysis, a cell viability assay, and enzyme-linked immunosorbent assay were performed. Aur significantly reduced the abdominal aortic constriction that led to left ventricular hypertrophy, reduced heart cavity expansion, and functional disorder, and thereby reduced fetal gene expression and attenuated cardiac fibrosis. Furthermore, Aur caused marked accumulation of ubiquitinated proteins and IκBα, as well as inactivation of NF-κB. This phenomenon was confirmed in the neonatal rat primary myocardial cell hypertrophy model. The present study indicated that Aur blocks the development of left ventricular hypertrophy induced by abdominal aortic constriction. This phenomenon might be attributed to inhibition of the 19S proteasome-associated deubiquitinase that can lead to aggregation of IκBα and inactivation of the NF-κB pathway. Thus, Aur could be a potential anti-cardiac hypertrophy agent.


Conservation of structure and location of Rhizobium meliloti and Klebsiella pneumoniae nifB genes.
Using transposon Tn5-mediated mutagenesis, an essential Rhizobium meliloti nitrogen fixation (nif) gene was identified and located directly downstream of the regulatory gene nifA. Maxicell and DNA sequence analysis demonstrated that the new gene is transcribed in the same direction as nifA and codes for a 54-kilodalton protein. In Klebsiella pneumoniae, the nifBQ operon is located directly downstream of a gene which is structurally and functionally homologous to the R. meliloti nifA gene. The DNA sequences of the K. pneumoniae nifB and nifQ genes (which code for 51- and 20-kilodalton proteins, respectively) were determined. The DNA sequence of the newly identified R. meliloti gene was approximately 50% homologous to the K. pneumoniae nifB gene. R. meliloti does not contain a gene homologous to nifQ directly downstream of nifB. The R. meliloti nifB product shares approximately 40% amino acid homology with the K. pneumoniae nifB product, and 10 of the 12 cysteine residues of the R. meliloti nifB product are conserved with 10 of the 17 cysteine residues of the K. pneumoniae nifB product.


Expression of Nicotiana glutinosa ribonucleases in Escherichia coli.
We previously isolated from Nicotiana glutinosa leaves three distinct cDNA clones, NGR1, NGR2, and NGR3, encoding a wound-inducible RNase NW, and putative RNases NGR2 and NGR3, respectively. In this study, we produced RNases NW and NGR3 in Escherichia coli and purified them to homogeneity. RNase NGR3 had non-absolute specificity toward polynucleotides, although RNase NW preferentially cleaved polyinosinic acid (Poly I). Both RNases NW and NGR3 were more active toward diribonucleoside monophosphates ApG, CpU, and GpU. Furthermore, kinetic parameters for RNase NW (Km, 0.778 mM and kcat, 1938 min(-1)) and RNase NGR3 (Km, 0.548 mM and kcat, 408 min(-1)) were calculated using GpU as a substrate.


Scanning electron microscopy of Trichomonas vaginalis.
By scanning electron microscopy (SEM), T. vaginalis surface appeared pleated with crater-like depressions. All the flagella appeared to start off in a single bundle from a shallow depression with a prominent rim. The side carrying the undulating membrane is extensively ruffled having a mulberry-like appearance to which flocculent material was frequently adherent. T. vaginalis nutrition appeared to proceed through pseudopodia-like extensions and phagocytosis by a constant deep invagination at the anterior pole which seems to be a cytostome. The mulberry-like surface may serve adhesion of T. vaginalis to the host cells and probably increases the surface area for exchange of nutrients, metabolites and parasite-derived factors.


Sporadic hypothyroidism-related hypokalemic paralysis: Diagnosis in a resource-poor setting.
Hypothyroidism and distal renal tubular acidosis causing hypokalemic paralysis (HP) have been described only in four female patients. HP as the initial manifestation of uncomplicated diabetes has been reported only in three young males. We report two middle-aged patients presenting with gradual-onset areflexic quadriparesis and neck flop, associated with urinary potassium losses, and recovering over 3 days. The male patient with alcohol abuse had urine pH >5.5 and hyperchloremic metabolic acidosis due to renal tubular acidosis and hypothyroidism. The second, a hypertensive female, had metabolic alkalosis, hypomagnesemia, and diabetes mellitus diagnosed at admission. Both these patients improved with intravenous and oral potassium supplementation.


[Surveillance system on drug abuse: Interest of the French national OPPIDUM program of French addictovigilance network].
It is important to assess drug abuse liability in 'real life' using different surveillance systems. OPPIDUM ('Observation of illegal drugs and misuse of psychotropic medications') surveillance system anonymously collects information on drug abuse and dependence observed in patients recruited in specialized care centers dedicated to drug dependence. The aim of this article is to demonstrate the utility of OPPIDUM system using 2015 data. OPPIDUM is a cross-sectional survey repeated each year since 1995. In 2015, 5003 patients described the modality of use of 10,159 psychoactive drugs. Among them, 77% received an opiate maintenance treatment: 68% methadone (half of them consumed capsule form) and 27% buprenorphine (39% consumed generic form). Brand-name buprenorphine is more often injected than generic buprenorphine (10% vs. 2%) and among methadone consumers 7% of methadone capsule consumers have illegally obtained methadone (vs. 9% for syrup form). The proportion of medications among psychoactive drugs injected is important (42%), with morphine representing 21% of the total psychoactive drugs injected and buprenorphine, 16%. OPPIDUM highlighted emergent behaviors of abuse with some analgesic opioids (like tramadol, oxycodone or fentanyl), pregabalin, or quetiapine. OPPIDUM highlighted variations of drugs use regarding geographic approaches or by drug dependence care centers (like in harm reduction centers). OPPIDUM clearly demonstrated that collection of valid and useful data on drug abuse is possible, these data have an interest at regional, national and international levels.


detectIR: a novel program for detecting perfect and imperfect inverted repeats using complex numbers and vector calculation.
Inverted repeats are present in abundance in both prokaryotic and eukaryotic genomes and can form DNA secondary structures--hairpins and cruciforms that are involved in many important biological processes. Bioinformatics tools for efficient and accurate detection of inverted repeats are desirable, because existing tools are often less accurate and time consuming, sometimes incapable of dealing with genome-scale input data. Here, we present a MATLAB-based program called detectIR for the perfect and imperfect inverted repeat detection that utilizes complex numbers and vector calculation and allows genome-scale data inputs. A novel algorithm is adopted in detectIR to convert the conventional sequence string comparison in inverted repeat detection into vector calculation of complex numbers, allowing non-complementary pairs (mismatches) in the pairing stem and a non-palindromic spacer (loop or gaps) in the middle of inverted repeats. Compared with existing popular tools, our program performs with significantly higher accuracy and efficiency. Using genome sequence data from HIV-1, Arabidopsis thaliana, Homo sapiens and Zea mays for comparison, detectIR can find lots of inverted repeats missed by existing tools whose outputs often contain many invalid cases. detectIR is open source and its source code is freely available at: https://sourceforge.net/projects/detectir.


Targeting CD47 and Autophagy Elicited Enhanced Antitumor Effects in Non-Small Cell Lung Cancer.
CD47-specific antibodies and fusion proteins that block CD47-SIRPα signaling are employed as antitumor agents for several cancers. Here, we investigated the synergistic antitumor effect of simultaneously targeting CD47 and autophagy in non-small cell lung cancer (NSCLC). SIRPαD1-Fc, a novel CD47-targeting fusion protein, was generated and was found to increase the phagocytic and cytotoxic activities of macrophages against NSCLC cells. During this process, autophagy was markedly triggered, which was characterized by the three main stages of autophagic flux, including formation and accumulation of autophagosomes, fusion of autophagosomes with lysosomes, and degradation of autophagosomes in lysosomes. Meanwhile, reactive oxygen species and inactivation of mTOR were shown to be involved in autophagy initiation in SIRPαD1-Fc-treated cells, indicating a probable mechanism for autophagy activation after targeting CD47 by SIRPαD1-Fc. Inhibition of autophagy enhanced macrophage-mediated phagocytosis and cytotoxicity against SIRPαD1-Fc-treated NSCLC cells. In addition, simultaneously targeting both CD47 and autophagy in NSCLC xenograft models elicited enhanced antitumor effects, with recruitment of macrophages, activated caspase-3, and overproduction of ROS at the tumor site. Our data elucidated the cytoprotective role of autophagy in CD47-targeted therapy and highlighted the potential approach for NSCLC treatment by simultaneously targeting CD47 and autophagy. Cancer Immunol Res; 5(5); 363-75. ©2017 AACRSee related Spotlight by Kaufman, p. 355.


Insulin reverses impaired alveolar fluid clearance in ARDS by inhibiting LPS-induced autophagy and inflammatory.
Until now, acute respiratory distress syndrome (ARDS) has been a difficult clinical condition with a high mortality and morbidity rate, and is characterized by a build-up of alveolar fluid and impaired clearance. The underlying mechanism is not yet fully understood and no effective medications available. Autophagy activation is associated with ARDS caused by different pathogenic factors. It represents a new direction of prevention and treatment of ARDS to restrain autophagy to a reasonable level through pharmacological and molecular genetic methods. Na, K-ATPase is the main gradient driver of pulmonary water clearance in ARDS and could be degraded by the autophagy-lysosome pathway to affect its abundance and enzyme activity. As a normal growth hormone in human body, insulin has been widely used in clinical for a long time. To investigate the association of insulin with Na, K-ATPase, autophagy and inflammatory markers in LPS-treated C57BL/6 mice by survival assessment, proteomic analysis, histologic examination, inflammatory cell counting, myeloperoxidase, TNF-α and IL-1β activity analysis etc. This was also verified on mouse alveolar epithelial type II (AT II) and A549 cells by transmission electron microscopy. We found that insulin restored the expression of Na, K-ATPase, inhibited the activation of autophagy and reduced the release of inflammatory factors caused by alveolar epithelial damage. The regulation mechanism of insulin on Na, K-ATPase by inhibiting autophagy function may provide new drug targets for the treatment of ARDS.


Outcome and recurrence rate of diabetic foot ulcers treated by a total contact cast: short-term follow-up.
Foot ulcers in patients with diabetes present an increasing burden to healthcare. Total contact cast (TCC) is a well established treatment option for many of these ulcers, but little seems to be known about the final outcome once healing has been reached. The study examined healing and final outcome after TCC treatment among patients with diabetes. During a 22-month period, 15 consecutive patients with a total of 17 ulcers started treatment with a TCC. Three patients (three ulcers) were lost to follow-up (FU). Average FU was 91 weeks. The patients were followed with emphasis on healing, complications during FU, footwear, compliance, and frequency of visits. All ulcers healed, some after additional surgery. During FU, control visits were performed at an average of one visit every 4.7 weeks. Notwithstanding this, a high frequency of ulcer recurrence and/or other complications was noticed. Only four patients out of 12 remained without any new (ulcer) problem during FU. TCC proved to be a very efficient tool to heal neuropathic foot ulcers, but the recurrence rate and frequency of other complications remained very high. These data show how difficult it is to achieve reliable (secondary) preventive general foot care, and to prescribe and manufacture reliable footwear.


TET Upregulation Leads to 5-Hydroxymethylation Enrichment in Hepatoblastoma.
Hepatoblastoma is an embryonal liver tumor carrying few genetic alterations. We previously disclosed in hepatoblastomas a genome-wide methylation dysfunction, characterized by hypermethylation at specific CpG islands, in addition to a low-level hypomethylation pattern in non-repetitive intergenic sequences, in comparison to non-tumoral liver tissues, shedding light into a crucial role for epigenetic dysregulation in this type of cancer. To explore the underlying mechanisms possibly related to aberrant epigenetic modifications, we evaluated the expression profile of a set of genes engaged in the epigenetic machinery related to DNA methylation (DNMT1, DNMT3A, DNMT3B, DNMT3L, UHRF1, TET1, TET2, and TET3), as well as the 5-hydroxymethylcytosine (5hmC) global level. We observed in hepatoblastomas a general disrupted expression of these genes from the epigenetic machinery, mainly UHRF1, TET1, and TET2 upregulation, in association with an enrichment of 5hmC content. Our findings support a model of active demethylation by TETs in hepatoblastoma, probably during early stages of liver development, which in combination with UHRF1 overexpression would lead to DNA hypomethylation and an increase in overall 5hmC content. Furthermore, our data suggest that decreased 5hmC content might be associated with poor survival rate, highlighting a pivotal role of epigenetics in hepatoblastoma development and progression.


The Impact of Transcription Factor Prospero Homeobox 1 on the Regulation of Thyroid Cancer Malignancy.
Transcription factor Prospero homeobox 1 (PROX1) is continuously expressed in the lymphatic endothelial cells, playing an essential role in their differentiation. Many reports have shown that PROX1 is implicated in cancer development and acts as an oncoprotein or suppressor in a tissue-dependent manner. Additionally, the PROX1 expression in many types of tumors has prognostic significance and is associated with patient outcomes. In our previous experimental studies, we showed that PROX1 is present in the thyroid cancer (THC) cells of different origins and has a high impact on follicular thyroid cancer (FTC) phenotypes, regulating migration, invasion, focal adhesion, cytoskeleton reorganization, and angiogenesis. Herein, we discuss the PROX1 transcript and protein structures, the expression pattern of PROX1 in THC specimens, and its epigenetic regulation. Next, we emphasize the biological processes and genes regulated by PROX1 in CGTH-W-1 cells, derived from squamous cell carcinoma of the thyroid gland. Finally, we discuss the interaction of PROX1 with other lymphatic factors. In our review, we aimed to highlight the importance of vascular molecules in cancer development and provide an update on the functionality of PROX1 in THC biology regulation.


Two Dimensional Host-Guest Metal-Organic Framework Sensor with High Selectivity and Sensitivity to Picric Acid.
A dye-sensitized metal-organic framework, TMU-5S, was synthesized based on introducing the laser dye Rhodamine B into the porous framework TMU-5. TMU-5S was investigated as a ratiometric fluorescent sensor for the detection of explosive nitro aromatic compounds and showed four times greater selectivity to picric acid than any state-of-the-art luminescent-based sensor. Moreover, it can selectively discriminate picric acid concentrations in the presence of other nitro aromatics and volatile organic compounds. Our findings indicate that using this sensor in two dimensions leads to a greatly reduced environmental interference response and thus creates exceptional sensitivity toward explosive molecules with a fast response.


Importance of the gastrointestinal life cycle of Bacillus for probiotic functionality.
Bacillus spp. are widely used in animal production for their probiotic properties. In many animal species, feed supplementation with specific Bacillus strains can provide numerous benefits including improvement in digestibility, the gut microbiota and immune modulation, and growth performance. Bacilli are fed to animals as spores that can sustain the harsh feed processing and long storage. However, the spores are metabolically quiescent and it is widely accepted that probiotics should be in a metabolically active state to perform certain probiotic functions like secretion of antimicrobial compounds and enzymes, synthesis of short chain fatty acids, and competition for essential nutrients. These functions should become active in the host gastrointestinal tract (GIT) soon after digestion of spores in order to contribute to microbiota and host metabolism. Considering that bacterial spores are metabolically dormant and many health benefits are provided by vegetative cells, it is of particular interest to discuss the life cycle of Bacillus in animal GIT. This review aims to capture the main characteristics of spores and vegetative cells and to discuss the latest knowledge in the life cycle of beneficial Bacillus in various intestinal environments. Furthermore, we review how the life cycle may influence probiotic functions of Bacillus and their benefits for human and animal health.


[The levels of stable organic pollutants in the breast milk of women living in the Irkutsk region].
The concentrations of stable organic chlorine pollutants (SOCP) in the breast milk of women living in Irkutsk, Baikalsk, and the settlement of Kachug are lower than those in the increased SOCP-burdened areas of the Irkutsk Region (the town of Usolye-Sibirskoye, settlements on the shore of the Baikal Lake) and comparable with those in Russia and industrially developed countries of the world. The content of SOPC is much lower than those in the developing countries where this pesticide continues to be applied. The breast milk levels of OCP, TEQ (polychlorinated dibento-para-dioxines and polychlorinated dibenzofurans) in all towns and individual indicator polychlorinated biphenyls (PCB) in Irkutsk significantly decreased as compared with those in the 1980s. However, in Kachug and Baikalsk, the concentrations of PCB practically unchanged and the level of some congeners increased. The absence of changes in the content of PCB in Kachug and Baikalsk may be associated with no decrease in environmental pollution in the Irkutsk Region. Altered breast concentrations of SOCPs caused a reduction in their intake in babies.


Psychological status, syndromatic measures, and compliance with nasal CPAP therapy for sleep apnea.
38 male patients with obstructive sleep apnea were asked to complete 2 weeks of rating symptoms, physical examination, diagnostic polysomnography, and MMPI testing prior to being placed on nasal continuous positive airway pressure (CPAP) therapy. Six months later, 26 (72.2%) of the 36 subjects available for follow-up showed continued compliance. A regression analysis conducted with those 28 subjects who completed all pretreatment measures showed that continued therapy was predicted by such pretreatment measures as patients' body mass index, ratings of daytime sleepiness and nocturnal sleep quality, and MMPI Depression and Hypochondriasis scale scores (R2 = 0.63). Eventual compliers had a higher Body Mass Index, reported less daytime sleepiness and better nocturnal sleep quality, and scored lower on the MMPI D and Hs scales prior to treatment than did the noncompliers. A linear discriminant function analysis with analog cross-validation showed these five predictors would identify approximately 80% of eventual noncompliers and 97% of those who display compliance. It was concluded that subjective report and personality measures may be useful in predicting long-term use. Additional studies are needed to assess the clinical significance of the noted MMPI scale elevations among sleep apnea patients in general and among those patients who display eventual noncompliance.


A 3.0 micros room temperature excited state lifetime of a bistridentate RuII-polypyridine complex for rod-like molecular arrays.
A bistridentate RuII-polypyridine complex [Ru(bqp)2]2+ (bqp = 2,6-bis(8'-quinolinyl)pyridine) has been prepared, which has a coordination geometry much closer to a perfect octahedron than the typical Ru(terpyridine)2-type complex. Thus, the complex displays a 3.0 mus lifetime of the lowest excited metal-to-ligand charge transfer (3MLCT) state at room temperature. This is, to the best of our knowledge, the longest MLCT state lifetime reported for a RuII-polypyridyl complex at room temperature. The structure allows for the future construction of rod-like, isomer-free molecular arrays by substitution of donor and acceptor moieties on the central pyridine units. This makes it a promising photosensitizer for applications in molecular devices for artificial photosynthesis and molecular electronics.


Levels of blood CD1c+ mDC1 and CD1chi mDC1 subpopulation reflect disease activity in noninfectious uveitis.
Myeloid dendritic cells (mDCs) play an important role in autoimmune diseases. However, the role of blood CD1c(+) myeloid dendritic cells 1 (mDC1s), the subset of human blood mDCs, is not well understood in noninfectious uveitis. Fresh peripheral blood samples from human noninfectious uveitis patients (n = 32) and healthy controls (HCs) (n = 64) were stained with FITC-Lineage 1 (Lin1), PERCP-HLADR, and PE-CD1c antibodies. The levels of mDC1 were quantified by using flow cytometric analysis. Longitudinal data from patients (n = 16) were analyzed to correlate the levels of mDC1 with disease activity. Blood CD1c(+) mDC1 and its subpopulation, CD1c(hi) mDC1, were increased in uveitis patients compared with HCs. Longitudinal data demonstrated that both the CD1c(+) mDC1 and CD1c(hi) mDC1 subpopulation reflected a dynamic change in clinical uveitis activity: CD1c expression was increased in active uveitis but decreased when uveitis became inactive. Given these observations, an alteration in blood CD1c(+) mDC1 and the CD1c(hi) mDC1 subpopulation could be a potential biomarker to monitor clinical uveitis activity within patients.


Degradation of Mg-6Zn alloy stents does not influence the healing of the common bile duct in vivo.
To investigate the effects of Mg-6Zn alloy on the healing of the common bile duct (CBD), Mg-6Zn alloy stents were implanted into the CBDs of rabbits. Stainless steel stents were transplanted into a second group of rabbits to serve as a control. Computed tomography (CT) scanning was performed and weight loss was recorded to evaluate the in vivo degradation process. Hematoxylin and eosin staining and immunohistochemical analyses were performed to determine the expressions of transforming growth factor (TGF)-β, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) and evaluate CBD healing. The Mg-6Zn stents maintained ~82 and ~50% of the original length, and ~90 and ~43% of the original CT value at 1 and 2 weeks post-operatively, respectively. The residual weights of the Mg-6Zn stents were ~89, ~42 and ~9% of the original weights at 1, 2 and 3 weeks post-operatively, respectively. At 3 weeks post-surgery, the CBD was completely healed, with no wounds observed in the 3 groups. VEGF expression in the Mg-6Zn stent group was lower than that in the stainless steel stent group at 3 weeks post-surgery (P=0.002). No significant differences were observed between the mean expressions of the TGF-β1 and bFGF genes at 1 and 2 weeks post-surgery. The results of the present study suggest that degradation of the Mg-6Zn alloy may not affect healing of the CBD.


Plexcitonic Quasi-Bound States in the Continuum.
Enhancing light-matter interactions is fundamental to the advancement of nanophotonics and optoelectronics. Yet, light diffraction on dielectric platforms and energy loss on plasmonic metallic systems present an undesirable trade-off between coherent energy exchange and incoherent energy damping. Through judicious structural design, both light confinement and energy loss issues could be potentially and simultaneously addressed by creating bound states in the continuum (BICs) where light is ideally decoupled from the radiative continuum. Herein, the authors present a general framework based on the two-coupled resonances to first conceptualize and then numerically demonstrate a type of quasi-BICs that can be achieved through the interference between two bare resonance modes and is characterized by the considerably narrowed spectral line shape even on lossy metallic nanostructures. The ubiquity of the proposed framework further allows the paradigm to be extended for the realization of plexcitonic quasi-BICs on the same metallic systems. Owing to the topological nature, both plasmonic and plexcitonic quasi-BICs display strong mode robustness against parameters variation, thereby providing an attractive platform to unlock the potential of the coupled plasmon-exciton systems for manipulation of the photophysical properties of condensed phases.


Analysis of the S. pombe Meiotic Proteome Reveals a Switch from Anabolic to Catabolic Processes and Extensive Post-transcriptional Regulation.
Meiotic progression in S. pombe is regulated by stage-specific gene expression and translation, changes in RNA stability, expression of anti-sense transcripts, and targeted proteolysis of regulatory proteins. We have used SILAC labeling to examine the relative levels of proteins in diploid S. pombe cells during meiosis. Among the 3,268 proteins quantified at all time points, the levels of 880 proteins changed at least 2-fold; the majority of proteins showed stepwise increases or decreases during the meiotic divisions, while some changed transiently. Overall, we observed reductions in proteins involved in anabolism and increases in proteins involved in catabolism. We also observed increases in the levels of proteins of the ESCRT-III complex and revealed a role for ESCRT-III components in chromosome segregation and spore formation. Correlation with studies of meiotic gene expression and ribosome occupancy reveals that many of the changes in steady-state protein levels are post-transcriptional.


Confirmed and Suspected Foreign Body Injuries in Children during 2008-2013: A Hospital-Based Single Center Study in Oulu University Hospital.
Foreign body injuries are common in children. Most of them are not serious but they can be fatal. A suspected foreign body injury in a child results in a high rate of hospitalizations, exposure to radiation, and need for intervention. This study aimed to analyze the current epidemiology of in-hospital or out of hospital treated foreign object injuries and suspected foreign body injuries in children. All children <16 years of age (N = 152) who suffered or were suspected to suffer (N = 63) from a foreign body injury and were treated in a pediatric trauma unit of Oulu University Hospital, Oulu, Finland, over a 6-year study period (2008-2013) were included. A comprehensive chart review was completed in order to evaluate injury history, age at the time of trauma, treatment and characteristics of the foreign objects. The majority (57.9%, N = 88) of the injuries were found in children <3 years of age. There was a male predominance (60.5%, N = 92). The most common anatomical site where the foreign body was found was the nose (28.9%, N = 44), followed by the esophagus (20.4%, N = 31) and the eye (11.2%, N = 17). Foreign objects were also found in the lower airways (10.5%, N = 16), ear (10.5%, N = 16), bowel (9.9%, N = 15), throat (3.9%, N = 6), stomach (3.9%, N = 6), and urethra (0.7%, N = 1). Various household items were the most common foreign bodies (33.6%, N = 51). Toys in particular caused 22.4% (N = 34) of the injuries. In-hospital intervention was necessary for 38.5% of the patients (N = 58). Intervention was needed in 39.7% (N = 25/63) of the patients who were suspected to suffer from foreign body but did not. There were no fatalities. Foreign body injuries treated at the pediatric trauma unit were most common in the youngest children (<3 years of age). Majority (61.8%, N = 94) of the patients were treated non-operatively, without any in-hospital intervention.


[Bacterial diversity of different successional stage forest soils in Dinghushan].
The aim of the present study was to investigate the soil bacterial diversity of pine forest (PF), pine-broadleaf mixed forest (MF) and monsoon evergreen broadleaf forest (MEBF), the typical forest types that represent early, middle and late successional stage forests in Dinghushan, respectively. The results obtained will also provide information for further examination of the relationship between the soil bacterial diversity and ecological function of the forests. Three total DNA samples were extracted directly from soil samples collected from PF, MF and MEBF, and then the 16S rDNA sequences were PCR amplified and the libraries were constructed, respectively. For each of the three libraries constructed, 150 positive clones were picked randomly and the inserted 16S rDNA were sequenced. The soil bacterial diversity of the forests was analyzed by Mothur based on the sequences obtained. A total of 122, 118 and 120 valid 16S rDNA sequences were obtained from PF, MF and MEBF, which represented 70, 64 and 72 operational taxonomic units (OTUs, definition at a level of 97% similarity), respectively. Bacteria belonging to 8 phyla were identified. Among them, Acidobacteria accounted for 53.3%, 67.8% and 60%, while Proteobacteria took up 29.5%, 20.3% and 32.5% in PF, MF and MEBF, respectively. The other bacterial phyla identified each accounted for less than 10%. The bacterial community structure differed significantly at species level among three soil samples (P < 0.05) with the percentages of the shared OTUs between any two soil samples lower than 25%. MEBF had the highest Chao index (414.2), Shannon index (3.90) and the lowest Simpson dominance index (0.0249). The soil bacterial community structure differed significantly at species level among PF, MF and MEBF in Dinghushan, while they have a similar structure at phyla or class levels with Acidobacteria predominated followed by Proteobacteria.


Low-field magnetic stimulation improved cuprizone-induced depression-like symptoms and demyelination in female mice.
Depression is a common and disabling comorbidity of multiple sclerosis (MS), with currently no clear guidelines for treatment. Low-field magnetic stimulation (LFMS), a novel non-invasive neuromodulation intervention, has been previously demonstrated to rapidly alleviate mood disorders. The aim of the present study was to investigate the effects of LFMS on depression-like behaviors and demyelination in a well-established mouse model of MS. C57BL/6 female mice were fed a 0.2% cuprizone (CPZ) diet for 3 or 6 weeks to induce acute demyelination. During this time, the mice were treated with either sham or LFMS for 20 min/day, 5 days/week. After 3 or 6 weeks of treatment, behavior was assessed with the open field task, Y-maze and the forced swim test. The prefrontal cortex and hippocampus were then collected to perform immunohistochemistry and western blot analysis to verify myelination status. The CPZ diet did not cause significant locomotor deficits; however, working memory, measured using the Y maze, depression-like behavior and adaptive learning, assayed using the forced swim test, were significantly impaired in these animals. LFMS treatment demonstrated a significant antidepressant-like effect and markedly attenuated the CPZ-induced demyelination in the prefrontal cortex after 3- and 6-weeks of treatment, as observed by changes in myelin basic protein immunostaining and western blot analysis. Therefore, the results of the present study indicated that LFMS may be a promising therapy for demyelinating diseases due to the improvement of depressive symptoms via regulation of myelination in cortical areas.


Endoscopic harvesting of autogenous fascia lata.
To describe a technique of endoscopic harvesting of autogenous fascia lata. A retrospective, noncomparative clinical study to evaluate the technique of videoendoscope assistance in harvesting autogenous fascia lata was conducted during a 1-year period in 2002. A small incision approximately 2 cm long is made over the lateral aspect of the thigh, either as a low or high approach. A sheathed 4-mm rigid 0- or 30-degree endoscope is used to visualize the length of the fascia lata along both its superficial aspect and its undersurface. Standard endoscopic brow lifting instruments are then used to dissect a length of fascia under direct visualization. Three patients underwent harvesting of autogenous fascia lata under endoscopic visualization (2 high-thigh and 1 low-thigh technique). Adequate lengths of fascia lata, approximately 12 cm long, were harvested and no complications occurred. The endoscope was particularly useful in identifying the anatomical structures adjacent to the fascia. The technique was easy to use, but took twice as long as traditional harvesting techniques. Videoendoscopy allows complete visualization of anatomical structures during harvesting of autogenous fascia lata. It highlights the anatomy for teaching and provides an alternative approach to conventional harvesting methods.


Description of Standardized Planes and Angles for Percutaneous Supra-acetabular Screw Placement.
Percutaneous screw fixation for pelvic fractures has become a minimally invasive alternative to an open operation. The complex anatomy of the pelvis renders this procedure challenging. The objective of this study was to assess standardized angles and dimensions of safety zones within a 3 D computed tomography model for optimal supra-acetabular screw placement. Computed tomography scans of 107 patients that suffered major trauma without showing any bone injury of the pelvis were collected. Using a software-based analysis, raw computed tomography data were transformed into 3 D models to set standardized landmarks and determine the possible insertion corridor. Screws not exceeding a length of 97 mm in females and 106.4 mm in males were, in 95% of the evaluated cases, insertable without cortical bone penetration. The safety zone was 6.6 mm for females and 7.9 mm for males. Screws not exceeding these diameters were safely insertable in 95% of the cases. For the midsagittal plane, the angle was 36.4 ± 5.1 on the left and 34.7 ± 2.9 on the right (p = 0.008). For the anterior pelvic plane, the angle was 31.3 ± 4.5° on the left and 34.0 ± 4.8° on the right (p = 0.008). Percutaneous fixation using supra-acetabular screws is a promising method to treat simple supra-acetabular fractures. These results may improve its safe utilization and could facilitate its broader clinical application.


Changes in ischemic heart disease mortality at the global level and their associations with natural disasters: A 28-year ecological trend study in 193 countries.
Natural disasters are believed to be associated with cardiovascular disease. This study aimed to explore the changes in mortality due to ischemic heart disease (IHD) and their associations with natural disasters at the global level. Country-specific data on the impact of natural disasters, rates of mortality due to IHD and years of life lost (YLL) and socioeconomic variables were obtained for 193 countries for the period from 1990 to 2017. An ecological trend study was conducted to estimate the changes in the IHD mortality and YLL rates and their associations with natural disasters (occurrence, casualties and total damage). Correlation analyses and multivariate linear regression were used. Significant changes were found in the IHD mortality and YLL rates and the occurrence of disasters between the two equal periods (1990 to 2003 and 2004 to 2017) (p<0.001). The bivariate Pearson correlation test revealed that the trend in the occurrence of natural disasters was positively correlated with trends in the IHD mortality and YLL rates among females and all individuals (p<0.05) and was marginally correlated among males. Multiple linear regression revealed an independent association between the occurrence of natural disasters and the IHD mortality rate among males, females and all individuals (standardized coefficients = 0.163, 0.357 and 0.241, p<0.05), and similar associations were found for the YLL rate (standardized coefficients = 0.194, 0.233 and 0.189, p<0.05). Our study demonstrated significant changes in the IHD mortality and YLL rates at the global level and their independent associations with natural disasters. Both males and females were vulnerable to natural disasters. These results provide evidence that can be used to support policy making and resource allocation when responding to disasters and developing strategies to reduce the burden of IHD.


Physical activity of Korean cancer survivors is associated with age and sex.
This study aimed to assess adherence to physical activity guidelines in cancer survivors and to investigate related factors. The cross-sectional data of 39,845 community-dwelling participants aged ≥ 20 years (1,254 cancer survivors) in the Korea National Health and Nutrition Examination Survey were analyzed. The age- and sex-stratified prevalence for meeting exercise guidelines was obtained. The correlates of meeting exercise recommendations were evaluated by using complex-sample logistic regression models. Overall, 36.2% and 20.5% of cancer survivors met the recommendations for aerobic and resistance exercises, respectively. Cancer survivors and noncancer controls had similar low adherence to exercise recommendations in most age and sex groups, except young female cancer survivors (20 to 49 years old) who showed higher engagement in aerobic exercise than female noncancer controls in the same age group. Old cancer survivors (≥ 65 years) were less likely to engage in recommended levels of aerobic exercise than young cancer survivors (odds ratio [OR], 0.44; 95% confidence interval [CI], 0.24 to 0.79). Female cancer survivors were less likely to meet resistance exercise guidelines than male cancer survivors (OR, 0.32; 95% CI, 0.21 to 0.50). In addition, cancer survivors with current smoking status and cardiovascular disease were less likely to meet aerobic exercise recommendations. The prevalence of meeting exercise guidelines are low in Korean cancer survivors and varied by age and sex. Old age is associated with an insufficient level of aerobic exercise, and female sex is associated with low participation in resistance exercise.


[The rattlesnake is not more dangerous than the viper].
The article consists of a comparison of the effects of snakebites inflicted by North American rattlesnakes and those of European vipers, based on a review of series of snake bite victims reported in the literature since 1980. The two groups of snakebites were found to manifest close similarity, even regarding the currently low fatality rates. Whereas local reactions seem to be more extensive after rattlesnake bites, circulatory symptoms including severe hypotension appear to be more common after viper bites. It is concluded that the two groups of snakes may be regarded as equally dangerous.


Comparison of Direct and Less Invasive Techniques for the Treatment of Severe Aorto-Iliac Occlusive Disease.
Severe aorto-iliac occlusive disease (AIOD) is traditionally treated with aorto-bifemoral bypass (ABF) or aorto-unifemoral bypass (AUF). However, cross-femoral bypass (CFB) and hybrid femoral endarterectomy and patch angioplasty with iliac stenting (EPS) have gained popularity as less invasive options. We sought to compare 1-year survival, primary patency, and major amputation rates between open surgical (ABF and AUF) and 2 less invasive reconstruction techniques (CFB and EPS) using a large, multicenter cohort. This is a retrospective cohort study of patients who underwent either ABF/AUF or CFB/EPS for AIOD between 2006 and 2013 in the Society for Vascular Surgery Vascular Quality Initiative registry. Baseline patient and periprocedural variables were compared. Propensity score matching (PSM) was performed to predict the likelihood of more invasive repair. Kaplan-Meier analysis and Cox models were performed for 1-year survival, primary patency, and major amputation. 1872 patients underwent procedures for AIOD, including 1,133 ABF/AUF and 739 CFB/EPS, during the study period. Indication was critical limb ischemia in 47.3% (n = 886). Median follow-up time was 305 days (range, 10-406). After PSM, the matched cohort included 1,094 ABF/AUF and 711 CFB/EPS patients. Multivariate analysis revealed that patient factors and procedure indication were significant predictors of 1-year mortality and major amputation, but not procedure type. ABF/AUF was associated with improved primary patency over CFB/EPS at 1 year (94.1% ± 1.1% vs. 92.3% ± 1.5%, hazard ratio 0.65, 95% confidence interval 0.45-0.94; P = 0.02). In a propensity-matched cohort from a multicenter vascular surgery registry, a direct approach to AIOD (ABF/AUF) demonstrated better 1-year primary patency than commonly used less invasive strategies. However, treatment approach was not a predictor of 1-year survival or limb salvage, suggesting that patient factors and procedure indication have a greater impact on outcome.


Ascomycetous yeasts associated with naturally occurring fruits in a tropical rain forest.
Fruits from twenty different species of angiosperms were collected during the period from November, 1991 to January, 1992. Two hundred and two strains of yeasts and yeast-like fungi were isolated, of which 74% showed ascomycetic affinity. Candida was the predominant genus, followed by (in descending order of occurrence): Cryptococcus, Kloeckera, Sporobolomyces, Pichia, Hanseniaspora and Bullera. Black yeasts and other strains showing basidiomycetic affinity were also isolated. The genus Candida represented the highest number of identified species and the greatest variety of associated substrates. Among the ascomycetes and their anamorphs, 38 species were identified, with Kloeckera apiculata being the most frequent among the isolates and the one which occurred in the largest variety of substrates. Some of the biotypes designated as Candida sp. A, B, C, D, E, F, G, H, I, and Pichia sp. did not correspond to the standard species description found in the literature, and may represent new species. The strains of yeasts isolated in this study were characterized and incorporated into the Tropical Culture Collection of the Fundaao Tropical de Pesquisas e Tecnologia Andŕe Tosello, Campinas, São Paulo.


Detection of Cytomegalovirus in Liver Tissue by Polymerase Chain Reaction in Infants With Neonatal Cholestasis.
Cytomegalovirus (CMV) is associated with neonatal cholestasis (NC). Diagnosis of CMV infection is most often based on either positive blood CMV IgM or CMV blood polymerase chain reaction (PCR). Isolation of CMV in liver tissues in patients with NC has rarely been reported. This study was undertaken to see if CMV is present in liver tissues of patients with NC and evaluate the correlation between positive CMV PCR in liver tissue with the serology and blood PCR. This study was conducted in 31 infants with NC from June 2015 to December 2016. All patients underwent blood CMV IgM, blood CMV PCR and liver CMV PCR. Prevalence of CMV in NC based on positive liver CMV PCR was calculated. Sensitivity and specificity of the serologic markers and blood CMV PCR to identify CMV infection in the liver was determined. CMV IgM was positive in 13 (42%) patients, CMV IgG was positive in 26 (84%) patients and blood CMV PCR was positive in 23 (74%) patients. Liver CMV PCR was positive in 16 (52%) patients. Fifteen (48%) patients had biliary atresia (BA), 10 (32%) patients had neonatal hepatitis, 5 (16%) had paucity of bile ducts and 1 (3%) had ascending cholangitis. Of the 16 patients with positive liver CMV PCR, 8 (50%) had BA, 4 (25%) had neonatal hepatitis, 3 (19%) had paucity of bile ducts and 1 (6%) had ascending cholangitis. Sensitivity of blood CMV IgM in relation to liver CMV PCR was 69% and specificity was 61%. Sensitivity of blood CMV PCR was 61% and specificity was 71% when compared with liver CMV PCR. CMV is present in the liver tissues of more than half the patients with NC. Serology or blood CMV PCR is apparently not an accurate marker of CMV in the liver tissue. Also, CMV infection in children seems to be associated equally with BA or non-BA neonatal hepatitis.


Diagnosis of giant cell arteritis.
GCA is the most common form of primary systemic vasculitis affecting older people. It is considered a clinical emergency because it can lead to irreversible blindness in around 20% of untreated cases. High doses of glucocorticoids should be initiated promptly to prevent disease-related complications; however, glucocorticoids therapy usually results in significant toxicity. Therefore, correct diagnosis is crucial. For many years, temporal artery biopsy has been considered the diagnostic 'gold standard' for GCA, but it has many limitations (including low sensitivity). US has proven to be effective for diagnosing GCA and can reliably replace temporal artery biopsy in particular clinical settings. In cases of suspected GCA with large-vessel involvement, other imaging modalities can be used for diagnosis (e.g. CT and PET). Here we review the current evidence for each diagnostic modality and propose an algorithm to diagnose cranial-GCA in a setting with rapid access to high quality US.


New Antibacterial Phenone Derivatives Asperphenone A-C from Mangrove-Derived Fungus Aspergillus sp. YHZ-1.
Marine fungi are a promising source of novel bioactive natural products with diverse structure. In our search for new bioactive natural products from marine fungi, three new phenone derivatives, asperphenone A-C (1-3), have been isolated from the ethyl acetate extract of the fermentation broth of the mangrove-derived fungus, Aspergillus sp. YHZ-1. The chemical structures of these natural products were elucidated on the basis of mass spectrometry, one- and two-dimensional NMR spectroscopic analysis and asperphenone A and B were confirmed by single-crystal X-ray crystallography. Compounds 1 and 2 exhibited weak antibacterial activity against four Gram-positive bacteria, Staphylococcus aureus CMCC(B) 26003, Streptococcus pyogenes ATCC19615, Bacillus subtilis CICC 10283 and Micrococcus luteus, with the MIC values higher than 32.0 µM.


Occult Pneumothorax in Blunt Thoracic Trauma: Clinical Characteristics and Results of Delayed Tube Thoracostomy in a Level 1 Trauma Center.
Occult pneumothorax in blunt trauma patients is often diagnosed only after computed tomography because supine chest X-ray (CXR) is preferred as an initial evaluation. However, improperly managed preexisting occult pneumothorax could threaten the vitality of patients. Therefore, this study aimed to evaluate the incidence, characteristics, risk factors, and outcomes of occult pneumothorax in a single trauma center. From 2020 to 2022, patients who were admitted to the level 1 trauma center were retrospectively investigated. Inclusion criteria focused on blunt chest trauma. Variables including demographic factors, image findings, injury-related factors, tube thoracostomy timing, and treatment results were evaluated. Of the 1621 patients, 187 who met the criteria were enrolled in the study: 32 with overt pneumothorax and 81 with occult pneumothorax. Among all of the pneumothorax cases, the proportion of occult pneumothorax was 71.7% (81/113), and its incidence in all admitted trauma victims was 5.0% (81/1621). Subcutaneous emphysema and rib fractures on supine CXR were risk factors for occult pneumothorax. Six patients underwent delayed tube thoracostomy; however, none had serious complications. Given that occult pneumothorax is common in patients with blunt chest trauma, treatment plans should be established that consider the possibility of pneumothorax. However, the prognosis is generally good, and follow-up is an alternative.


Effects of ERalpha overexpression on female reproduction in mice.
Recently, we generated transgenic mice in which ERalpha can be inducibly overexpressed in reproductive tissues (ERalpha overexpressors). These mice were used to test the hypothesis that prenatal and postnatal ERalpha overexpression reduces female fertility. To do so, litter sizes, ovulation, follicle numbers, uterine histology, implantation sites, and hormone levels were compared in ERalpha overexpressors and controls. The data indicate that ERalpha overexpressors have reduced fertility compared to controls and that the reduced fertility is not due to reduced ovulatory capacity, altered levels of estradiol, FSH, and LH, or impaired follicular growth. ERalpha overexpressors, however, had a higher number of apoptotic cells in the endometrial epithelium and a reduced number of implantation sites compared to controls. Thus, the increased number of apoptotic cells and reduced number of implantation sites observed in ERalpha overexpressing uteri compared to controls may, in part, account for the reduced litter size produced by ERalpha overexpressing females.


Turning point: A new global COVID-19 wave or a signal of the beginning of the end of the global COVID-19 pandemic?
A new variant named Omicron (B.1.1.529), first identified in South Africa, has become of considerable interest to the World Health Organization. This variant differs from the other known major variants, as it carries a large number of unusual mutations, particularly in the spinous process protein and receptor binding domains. Some specific mutation sites make it vaccine resistant, highly infectious, and highly pathogenic. The world fears that the Omicron variant could be even more harmful than the previous major variant, given that it has emerged amid fierce competition to trigger a new global pandemic peak as infections in South Africa rise. However, some epidemiological evidence has emerged that the Omicron variant may produce milder patient symptoms. We speculate if the virulence of the Omicron variant will diminish as transmissibility increases, thereby signaling the beginning of the end for the global COVID-19 pandemic. Based on this view, we make recommendations for COVID-19 mitigation in the present and future. However, it will take a few weeks to determine the true threat posed by the Omicron variant and we need to be fully prepared for future outbreaks, regardless of their severity.


Ovarian cancer stem-like side-population cells are tumourigenic and chemoresistant.
Ovarian cancer is the most lethal gynaecological malignancy. Although ovarian cancer patients often respond initially to chemotherapy, they usually develop chemoresistance. We hypothesised that a small portion of ovarian cancer cells have stem-like cell properties that contribute to tumourigenesis and drug resistance. Flow cytometry and Hoechst 33342 efflux isolated side-population (SP) cells from ascites derived from ovarian cancer patients and from mice inoculated with human ovarian cancer cell lines. The SP cells were examined for stem cell markers OCT4, NANOG, STELLAR, and ABCG2/BCRP1 by immunocytochemistry and RT-PCR. The SP cells and non-SP cells were studied for tumourigenesis and chemoresistance in vitro and in vivo. The SP cells expressed ABCG2/BCRP1, OCT4, STELLAR, and NANOG, detected by immunocytochemistry and RT-PCR. ABCG2/BCRP1 expression was higher in SP than in non-SP cells. Xenogeneic mice inoculated with SP cells yielded more tumours than did mice inoculated with non-SP cells. In parallel, SP cell culture resulted in extensive cell proliferation, which was markedly more than in non-SP cells. SP cells resisted chemotherapy compared with non-SP cells, both in vivo and in vitro. Ovarian cancer SP cells are tumourigenic and chemoresistant. ABCG2/BCRP1 has an important role in chemoresistance, which has implications for new therapeutic approaches.