Combined signature of nine immune-related genes: a novel risk score for predicting prognosis in hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is one of the most common internal malignancies worldwide and is associated with a poor prognosis. There is an urgent need to identify diagnostic and prognostic biomarkers of HCC pathogenesis and progression. Accordingly, in this study, we analyzed differentially expressed immune-related genes (IRGs) from 329 patients with HCC from The Cancer Genome Atlas datasets. Functional analysis revealed that the IRGs had potential effects on tumor immune processes, such as inflammatory responses and growth factor activity. In the training group, we constructed a nine-IRG formula to predict prognosis in patients with HCC. To validate the protein and mRNA levels of these IRGs, we used the Human Protein Atlas database and quantitative PCR analysis and found that most protein expression levels matched the corresponding mRNA expression levels. Furthermore, we also validated the prognostic value of the new risk model in another independent cohort (n = 277) from a Gene Expression Omnibus dataset (GSE14520). Our data suggested that there was a significant association between our risk model and patient prognosis. Stratification analysis showed that the nine-IRG signature was significantly associated with overall survival in men. Finally, the signature was found to be correlated with various clinicopathological features. Intriguingly, the prognostic index based on the IRGs reflected infiltration by several types of immune cells. In summary, our data provided evidence that the nine-IRG signature could serve as an independent biomarker to predict prognosis in patients with HCC.


Expiratory Time Constant and Sleep Apnea Severity in the Overlap Syndrome.
Lung mechanics in the overlap of COPD and sleep apnea impact the severity of sleep apnea. Specifically, increased lung compliance with hyperinflation protects against sleep apnea, whereas increased airway resistance worsens sleep apnea. We sought to assess whether the expiratory time constant, which reflects lung mechanics, is associated with sleep apnea severity in such patients. Polysomnographies in 34 subjects with the overlap syndrome were reviewed. Three time constants were measured for each of up to 5 stages (wake, NREM stages, and REM). The time constants were derived by fitting time and pressure coordinates on the expiratory portion of a nasal pressure signal along an exponentially decaying equation, and solving for the time constant. Demographics, morphometrics, wake end-tidal CO2, right diaphragmatic arc on a chest radiograph, and the apnea-hypopnea index (AHI) were recorded. The time constant was not associated with age, gender, body mass index, right diaphragmatic arc, or wake end-tidal CO2, and was not significantly different between sleep stages. A mean time constant (TC) was therefore obtained. Subjects with a TC > 0.5 seconds had a greater AHI than those with a TC ≤ 0.5 seconds (median AHI 58 vs. 18, respectively, p = 0.003; Odds ratio of severe sleep apnea 10.6, 95% CI 3.9-51.1, p = 0.005). A larger time constant in the overlap syndrome is associated with increased odds of severe sleep apnea, suggesting a greater importance of airway resistance relative to lung compliance in sleep apnea causation in these subjects.


Intra-articular multifunctional celecoxib loaded hyaluronan nanocapsules for the suppression of inflammation in an osteoarthritic rat model.
Direct intra-articular delivery of drugs to osteoarthritic joints offers the possibility of delivering high drug concentrations at the site of action as well as decreasing long term associated side effects after oral drug delivery. So in the current work, we aimed to improve the osteoarthritic therapeutic efficacy of the non-steroidal anti-inflammatory drug; celecoxib, through the formulation of drug loaded hyaluronan nanocapsules. The proposed formulation aimed to combine the beneficial viscosupplemental properties of hyaluronic acid with the pharmacological, anti-inflammatory, effect of celecoxib in a novel drug carrier for intra-articular delivery. The proposed nanocapsules were prepared by the nanoprecipitation method. Several formulation variables were studied aiming at optimizing the nanocapsules' size, polydispersity index and celecoxib entrapment efficiency %. The optimized hyaluronan nanocapsules formulation showed a size of 254.9 ± 3.06 nm, which is appropriate for the intra-articular delivery of celecoxib, high entrapment efficiency% of 97.98% ± 0.19, and prolonged celecoxib release for almost one week. The transmission electron microscope images revealed spherical shape of the nanocapsules with distinct shell and core structure. The in-vivo evaluation of the anti-osteoarthritic activity of the optimized hyaluronan nanocapsules formulation showed the superiority of the prepared celecoxib nanocapsules compared to celecoxib suspension in a Monoiodoacetate induced osteoarthritic rat model, regarding histological, swelling and immunohistochemical parameters of osteoarthritis.


Total synthesis of (+)-geldanamycin and (-)-o-quinogeldanamycin: asymmetric glycolate aldol reactions and biological evaluation.
The total synthesis of (+)-geldanamycin (GA), following a linear route, has been completed using a demethylative quinone-forming reaction as the last step. Key steps include the use of two new asymmetric boron glycolate aldol reactions. To set the anti-C11,12 hydroxymethoxy functionality, (S,S)-5,6-bis-4-methoxyphenyldioxanone 8 was used. Methylglycolate derived from norephedrine 5 set the C6,7 methoxyurethane stereochemistry. The quinone formation step using nitric acid gave the non-natural o-quino-GA product 55 10:1 over geldanamycin. Other known oxidants gave an unusual azaquinone product 49. o-Quino-GA 55 binds Hsp90 with good affinity but is less cytotoxic compared to GA.


Melanoma Cells Inhibit iNKT Cell Functions via PGE2 and IDO1.
Invariant natural killer T (iNKT) cells are a distinct group of immune cells known for their immunoregulatory and cytotoxic activities, which are crucial in immune surveillance against tumors. They have been extensively investigated as a potential target for adoptive cell immunotherapy. Despite the initial promise of iNKT cell-based immunotherapy as a treatment for melanoma patients, its effective utilization has unfortunately yielded inconsistent outcomes. The primary cause of this failure is the immunosuppressive tumor microenvironment (TME). In this study, we specifically directed our attention towards melanoma cells, as their roles within the TME remain partially understood and require further elucidation. Methods: We conducted co-culture experiments involving melanoma cell lines and iNKT cells. Results: We demonstrated that melanoma cell lines had a significant impact on the proliferation and functions of iNKT cells. Our findings revealed that co-culture with melanoma cell lines led to a significant impairment in the expression of the NKG2D receptor and cytolytic granules in iNKT cells. Moreover, we observed a strong impairment of their cytotoxic capability induced by the presence of melanoma cells. Furthermore, through the use of selective inhibitors targeting IDO1 and COX-2, we successfully demonstrated that the melanoma cell line's ability to impair iNKT cell activation and functions was attributed to the up-regulation of IDO1 expression and PGE2 production.


Spanish Adaptation of the Inventory Brief Child Abuse Potential and the Protective Factors Survey.
Child maltreatment is a public health problem with different consequences depending on the form of abuse. Measuring risk and protective factors has been a fertile ground for research, without involving instruments with sufficient evidence of validity. The aim of the study was to gather evidence of validity and reliability of the Inventory Brief Child Abuse Potential (IBCAP) and Protective Factors Survey (PFS) in the Mexican population. The instruments were translated into Spanish. In a non-probabilistic sample of 200 participants, the 7-factor model for the IBCAP [comparative fit index (CFI) = 0.984; root mean square error of approximation (RMSEA) = 0.067] and the 4-factor model for the PFS (CFI = 0.974; RMSEA = 0.061) were confirmed, showing adequate fit indices. Reliability was estimated and evidence of convergent, divergent, and discriminant validity was collected, controlling for effects of social desirability. We also report interpretability statistics of the scores. We achieved solid progress in the development of instrumentation that allows determining the presence or absence of protective and risk factors for child abuse.


[Evaluation of In vitro Efficacy of Meropenem/Colistin and Meropenem/Fosfomycin Combinations on Multidrug Resistant Gram-Negative Bacilli].
The rate of extensively drug-resistant and pan-resistant gram-negative rods isolated as infectious agents is increasing around the world and in Türkiye. One of the important options in the treatment of these infections is the combined use of antibiotics. Therefore, the aim of this study was to investigate the in vitro effect of meropenem/colistin and meropenem/fosfomycin combinations on carbapenem-resistant gram-negative bacilli isolated as infectious agents. Escherichia coli (n= 6), Klebsiella pneumoniae (n= 10), Pseudomonas aeruginosa (n= 5), and Acinetobacter baumannii (n= 6) isolates were recovered from blood and tracheal aspirate samples of patients hospitalized in our hospital's intensive care unit were included in the study. In the first stage of the combination study, minimal inhibitory concentrations (MIC) were investigated by broth microdilution for meropenem and colistin, and agar dilution methods for fosfomycin. In the second stage of the study, synergy, partial synergy, indifference, and antagonistic effects were investigated with the checkerboard method for the meropenem/colistin combination and the agar dilution method for the meropenem/fosfomycin combination. The checkerboard results were interpreted as follows: fractional inhibitory concentration index (FICI) values ≤ 0.5 synergy, < 0.5-≤ 1 partial synergy, > 1-≤ 4 indifference and FIC values of > 4 antagonism. MIC values obtained in the study were interpreted according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria. Of the 27 isolates studied with the broth microdilution method, 63% were found to be colistin-resistant and 37% susceptible. The MIC values of fosfomycin against Enterobacterales group bacteria were found to be in the range of 2-2048 mg/L. Two of the six E.coli isolates and nine of the 10 K.pneumoniae isolates were found to be resistant to fosfomycin (IV). The MIC values of ≥ 128 mg/L were found in all 11 non-fermentative gram-negative rods with intrinsic resistance to fosfomycin. In the combination of meropenem/ colistin, synergy and partial synergy were observed in 11 (40.7%) of 27 isolates, an indifference effect was observed in 13 (48.2%), and antagonistic effects were observed in three (11.1%) of the isolates. The synergy and partial synergy effects of this combination were 37.5% for Enterobacterales group bacteria, 50% for E.coli, and 30% for K.pneumoniae. Regarding the 11 non-fermentative gram-negative rods included in the study, 83.3% synergy and partial synergy was found in A.baumannii for the meropenem/colistin combination, while no synergy and partial synergistic effect was found in P.aeruginosa. Meropenem/fosfomycin synergy and partial synergy effects were 83.3% (5/6) for E.coli, 100% (8/8) for K.pneumoniae, 100% (6/6) for A.baumannii, and 25% (1/4) for P.aeruginosa. In all of the isolates studied, meropenem/fosfomycin combination was found to be more effective than the meropenem/colistin combination. It would be meaningful to support these data obtained in vitro with clinical efficacy results to be obtained as a result of the application of antibiotics in vivo, taking into account the pharmacokinetic and pharmacodynamic properties of the antibiotics used in this study.


Clinical feasibility of radiofrequency ablation using novel adjustable separable electrodes with a multipurpose needle for treating small hepatocellular carcinomas: a prospective single center study.
The novel separable clustered electrode system with two adjustable active tips (ICAEs) and a fine multipurpose needle (MPN) for in situ temperature monitoring and adjuvant agent injection was developed and validated in an animal study. The purpose of this study was to evaluate the technical efficacy and complication of the novel electrode system for patients who have small HCC. In this prospective, single-center clinical trial, ten participants with 14 small (≤ 2 cm, BCLC 0-A) HCCs referred for RFA were enrolled. A novel electrode system consisting of two ICAEs and one MPN with a thermometer and side holes was used for RFA. The RF energy was delivered using a multichannel RF system combining bipolar and switching monopolar modes. Technical success, efficacy, and complications were evaluated on immediate and one-month follow-up CT. Technical success was achieved in 92.9% (13/14) of tumors. One participant withdrew consent after RFA, and technical efficacy was achieved in 91.7% (11/12) of tumors. None showed thermal injury to nontarget organs. All patients were discharged the day after RFA without major complications. The active electrode lengths were adjusted in 60% (6/10) of patients during the procedure to tailor the ablation zone (83.3%, n = 5) or treat two tumors with different sizes (16.7%, n = 1). MPN was capable of continuous temperature monitoring during all ablations (100%, 14/14). RFA using a novel electrode system showed acceptable technical efficacy and safety in patients with small HCCs. Further comparative studies are needed for the investigation of the system's potential benefits compared to conventional electrodes.


Work with embryonic stem cells - legal considerations.
Apparently, there is a broad scope of legal issues affecting the work with embryonic stem cells. I cannot address them all. I would like to focus on two fields of law and discuss, rather in the overview, some salient issues of German constitutional and administrative law framing the scientific research process. Compared to the sophisticated scientific work we discuss here, legal arguments and operations remain blunt and awkward, addressing rather the identity of a society than the fluid frontiers of science and technology.


RNA sequencing identifies gene expression profile changes associated with β-estradiol treatment in U2OS osteosarcoma cells.
This study was conducted to identify gene expression profile changes associated with β-estradiol (E2) treatment in U2OS osteosarcoma cells by high-throughput RNA sequencing (RNA-seq). Two U2OS cell samples treated with E2 (15 μmol/L) and two untreated control U2OS cell samples were subjected to RNA-seq. Differentially expressed genes (DEGs) between the groups were identified, and main biological process enrichment was performed using gene ontology (GO) analysis. A protein-protein interaction (PPI) network was constructed using Cytoscape based on the Human Protein Reference Database. Finally, NFKB1 expression was confirmed by quantitative real-time polymerase chain reaction (qRT-PCR). The map ratios of the four sequenced samples were >65%. In total, 128 upregulated and 92 downregulated DEGs were identified in E2 samples. After GO enrichment, the downregulated DEGs, such as AKT1, were found to be mainly enriched in cell cycle processes, whereas the upregulated DEGs, such as NFKB1, were involved in the regulation of gene expression. Moreover, AKT1 (degree =117) and NFKB1 (degree =72) were key nodes with the highest degrees in the PPI network. Similarly, the results of qRT-PCR confirmed that E2 upregulated NFKB1 expression. The results suggest that E2 upregulates the expression of NFKB1, ATF7IP, and HDAC5, all of which are involved in the regulation of gene expression and transcription, but downregulates that of TCF7L2, ALCAM, and AKT, which are involved in Wnt receptor signaling through β-catenin and morphogenesis in U2OS osteosarcoma cells.


The Partial Least Squares Spline Model for Public Health Surveillance Data.
Factor discovery of public health surveillance data is a crucial problem and extremely challenging from a scientific viewpoint with enormous applications in research studies. In this study, the main focus is to introduce the improved survival regression technique in the presence of multicollinearity, and hence, the partial least squares spline modeling approach is proposed. The proposed method is compared with the benchmark partial least squares Cox regression model in terms of accuracy based on the Akaike information criterion. Further, the optimal model is practiced on a real data set of infant mortality obtained from the Pakistan Demographic and Health Survey. This model is implemented to assess the significant risk factors of infant mortality. The recommended features contain key information about infant survival and could be useful in public health surveillance-related research.


A Mouse Model for Corneal Neovascularization by Alkali Burn.
Corneal neovascularization (CoNV), a pathological form of angiogenesis, involves the growth of blood and lymph vessels into the avascular cornea from the limbus and adversely affects transparency and vision. Alkali burn is one of the most common forms of ocular trauma that leads to CoNV. In this protocol, CoNV is experimentally induced using sodium hydroxide solution in a controlled manner to ensure reproducibility. The alkali burn model is useful for understanding the pathology of CoNV and can be extended to study angiogenesis in general because of the avascularity, transparency, and accessibility of the cornea. In this work, CoNV was analyzed by direct examination under a dissecting microscope and by immunostaining flat-mount corneas using anti-CD31 mAb. Lymphangiogenesis was detected on flat-mount corneas by immunostaining using anti-LYVE-1 mAb. Corneal edema was visualized and quantified using optical coherence tomography (OCT). In summary, this model will help to advance existing neovascularization assays and discover new treatment strategies for pathologic ocular and extraocular angiogenesis.


Internet prescribing.
Prescribing prescription-only medications solely on the basis of a questionnaire filled out on an internet site is merely an updated version of "diagnosis by mail" and has been condemned by all respectable authorities for over 100 years. The Wisconsin Medical Examining Board has disciplined 1 physician for the practice, and authorities in other states have taken similar actions.


[Doppler sonography of the umbilical artery, mode of delivery and perinatal morbidity in prolonged pregnancy].
130 women with postterm pregnancies (281-297 days of gestation) were examined with pulsed Doppler ultrasound of an umbilical artery. The result was not included in clinical decisions. In the group with abnormal flow a high rate of cesarean sections because of fetal distress (53%) was necessary, whereas only 3% were performed in the group with normal flow. In cases with reduced enddiastolic blood flow velocity the fetal outcome was significantly worse compared with cases with normal flow. The sensitivity of pulsed doppler ultrasound in predicting cesarean section for fetal distress was 71%, the specificity 91% (3 days before delivery). The oxytocin challenge test indicated this with a sensitivity of 58% and a specifity of 82%, whereas the nonstress test is not useful in predicting fetal risk in postterm pregnancy.


Neurodevelopmental outcome for extended cold water drowning: a longitudinal case study.
There is little longitudinal data examining outcome of pediatric near-drowning. Most literature tracks status 5 years or less post insult, focusing primarily on gross neurologic status as opposed to more subtle neurocognitive deficits. The present case tracks the neuropsychological profile of a child who was submerged for 66 min, the longest time documented. Acute medical support was aggressive, and recovery was dramatic, being featured in multiple media reports. Although an article published 6 years after the near-drowning described the child as "recovering completely," the longitudinal profile indicates a pronounced pattern of broad cognitive difficulties, particularly notable for global memory impairment. Neuropsychological test results were significant despite the fact that the patient's recent MRI and MEG were within normal limits. This case demonstrates the need for long-term neuropsychological follow-up of pediatric patients with histories of neurologic injury, as gross neurological examination and MRI and MEG scans may not reveal underlying brain dysfunction.


The interaction of Tamm-Horsfall protein with the extracellular matrix.
Tamm-Horsfall protein (THP) is the major glycoprotein component of urine, yet its biological role remains obscure. Recent reports have suggested that a concanavalin A (Con A)-binding fraction of THP from pregnancy urine can bind the cytokines tumour necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1). In order to investigate this claim in relation to THP from normal adult urine we raised monoclonal antibodies to THP and sought THP/TNF-alpha interactions in three separate assay systems. We found no evidence that THP binds to TNF-alpha under physiological conditions, but we observed that it exerts a weak, probably not physiologically relevant, but reproducible inhibitory effect on the toxicity of TNF-alpha for monolayers of L929 cells, even when the cells are pretreated with the THP, and washed before addition of the cytokine. Since our preparations of THP do not interact directly with TNF-alpha we postulated an interaction with the cells themselves, or with their extracellular matrix. The THP was found by ELISA, immunoblotting and immunohistology, to bind to as yet unidentified components of the extracellular matrix in a manner dependent on cations, pH and carbohydrates. These data, considered in the light of the published amino acid sequence and biochemical properties, suggest that THP is a member of a structural glycoprotein family known to modulate cell adhesion.


Identification and characterization of lipopolysaccharide in acetic acid bacteria.
Lipopolysaccharide (LPS), a major component of the cell walls of Gram-negative bacteria, was one of the main components of Coley's vaccine and is known to have strong adjuvanticity. Though it is known that LPS exists in the digestive tract of organisms, the biological significance for the organism has not been clarified. In this study, the correlation between the structure and function of LPS was determined using acetic acid bacteria. These are Gram-negative bacteria consumed in human diets. Extracts were obtained from a strain of acetic acid bacteria which is used for producing vinegar. Determination of the LPS neutralizing activity was carried out by the Limulus test. Tumor necrosis factor (TNF) and nitric oxide (NO) production were then observed after the addition of the extracts to murine monocyte macrophages (RAW264. 7), with or without Polymyxin B. TNF production in peritoneal macrophages derived from LPS-low responsive mice (C3H/HeJ) was studied after the addition of extracts. The extracts were shown to be positive only in LPS-specific Limulus test and were negative in the (1,3)-beta-D-glucan-specific Limulus test. Both extracts induced NO and TNF production in RAW264. 7 cells, but this was inhibited by the presence of Polymyxin B. TNF production was inhibited in peritoneal macrophages from LPS low-responsive mice (C3H/HeJ). LPS with macrophage-activating activity is present in acetic acid bacteria, routinely consumed by humans.


Mmu_circ_003795 regulates osteoblast differentiation and mineralization in MC3T3‑E1 and MDPC23 by targeting COL15A1.
Circular RNAs (circRNAs) are a class of non‑coding RNAs that exhibit important regulatory roles in various biological processes. However, the role of circRNAs and their potential role in osteoblast differentiation and mineralization is unclear. The aim of the present study was to investigate the expression of mmu_circ_003795 and its effect on collagen type XV α 1 chain (COL15A1). First, it was identified that the expression levels of mmu_circ_003795 and osteopontin (OPN) were upregulated in the induced cells. Silencing of mmu_circ_003795 reduced the gene and protein levels of COL15A1 and OPN, whereas the expression level of mmu‑microRNA (miR)‑1249‑5p was upregulated. In addition, after 7 or 14 days of induction, alkaline phosphatase and Alizarin Red‑S staining were decreased in the mmu_circRNA_003795 inhibitory group compared with the negative control group. In conclusion, mmu_circ_003795 may regulate osteoblast differentiation and mineralization in MC3T3‑E1 and MDPC23 cells via mmu‑miR‑1249‑5p by targeting COL15A1.


Structural basis for dimerization and RNA binding of avian infectious bronchitis virus nsp9.
The potential for infection by coronaviruses (CoVs) has become a serious concern with the recent emergence of Middle East respiratory syndrome and severe acute respiratory syndrome (SARS) in the human population. CoVs encode two large polyproteins, which are then processed into 15-16 nonstructural proteins (nsps) that make significant contributions to viral replication and transcription by assembling the RNA replicase complex. Among them, nsp9 plays an essential role in viral replication by forming a homodimer that binds single-stranded RNA. Thus, disrupting nsp9 dimerization is a potential anti-CoV therapy. However, different nsp9 dimer forms have been reported for alpha- and beta-CoVs, and no structural information is available for gamma-CoVs. Here we determined the crystal structure of nsp9 from the avian infectious bronchitis virus (IBV), a representative gamma-CoV that affects the economy of the poultry industry because it can infect domestic fowl. IBV nsp9 forms a homodimer via interactions across a hydrophobic interface, which consists of two parallel alpha helices near the carboxy terminus of the protein. The IBV nsp9 dimer resembles that of SARS-CoV nsp9, indicating that this type of dimerization is conserved among all CoVs. This makes disruption of the dimeric interface an excellent strategy for developing anti-CoV therapies. To facilitate this effort, we characterized the roles of six conserved residues on this interface using site-directed mutagenesis and a multitude of biochemical and biophysical methods. We found that three residues are critical for nsp9 dimerization and its abitlity to bind RNA.


Quality assessment and antiplasmodial activity of West African Cochlospermum species.
The present study focuses on development of phytochemical methods for quality assessment of two West-African Cochlospermum species (Cochlospermum planchonii and Cochlospermum tinctorium) traditionally used for malaria treatment in Burkina Faso. Antimalarial activity of preparations from dried rhizomes (decoction) was tested against the chloroquine-sensitive Plasmodium strain 3D7 using the histidine-rich protein II (HRP2) drug susceptibility assay and compared with extract preparations using organic solvents of different polarity. Two main apocarotenoids were isolated from rhizomes of C. planchonii and unambiguously identified as dihydrocochloxanthine and cochloxanthine by spectroscopic methods. Comparative HPLC analyses of thirty-nine (39) samples from markets and from collections in natural habitats of both species showed a high variability in the accumulation of cochloxanthines and related carotenoids which were proven to be characteristic for rhizomes of both species and generally absent in leaves. Furthermore, content of total phenolics and antioxidant activities (DPPH and FRAP) as well as haemolytic activity of various extracts was tested. The HPLC method presented here was validated and provides a good separation of both compounds including 10 minor carotenoids. Extracts from both species and pure cochloxanthine offered pronounced antioxidant activities and weak haemolytic activity while, in contrast, dihydrocochloxanthine had a strong haemolytic effect at the highest concentration analysed. However, cochloxanthine as well as dihydrocochloxanthine showed erythroprotective effects against the haemolytic activity of the reference saponin. Moderate antiplasmodial activity between 16 and 63 μg/ml were observed with all tested extracts, and lower IC50 values were obtained with pure dihydrocochloxanthine (IC50=6.9 μg/ml), cochloxanthine (IC50=6.8 μg/ml), the DCM fraction (IC50=2.4 μg/ml) and the ethyl acetate fraction (IC50=11.5μg/ml) derived from a methanolic extract of C. planchonii. This study shows a major variability of carotenoid content and antiplasmodial activity of both C. planchonii and C. tinctorium. The high haemolytic activity of dihydrocochloxanthine (at 100 μg/ml) should be considered as a selection criterion for choosing species phenotypes for treatment.


ASM LabCap's contributions to disease surveillance and the International Health Regulations (2005).
The revised International Health Regulations [IHR(2005)], which requires the Member States of the World Health Organization (WHO) to develop core capacities to detect, assess, report, and respond to public health threats, is bringing new challenges for national and international surveillance systems. As more countries move toward implementation and/or strengthening of their infectious disease surveillance programs, the strengthening of clinical microbiology laboratories becomes increasingly important because they serve as the first line responders to detect new and emerging microbial threats, re-emerging infectious diseases, the spread of antibiotic resistance, and the possibility of bioterrorism. In fact, IHR(2005) Core Capacity #8, "Laboratory", requires that laboratory services be a part of every phase of alert and response.Public health laboratories in many resource-constrained countries require financial and technical assistance to build their capacity. In recognition of this, in 2006, the American Society for Microbiology (ASM) established an International Laboratory Capacity Building Program, LabCap, housed under the ASM International Board. ASM LabCap utilizes ASM's vast resources and its membership's expertise-40,000 microbiologists worldwide-to strengthen clinical and public health laboratory systems in low and low-middle income countries. ASM LabCap's program activities align with HR(2005) by building the capability of resource-constrained countries to develop quality-assured, laboratory-based information which is critical to disease surveillance and the rapid detection of disease outbreaks, whether they stem from natural, deliberate or accidental causes.ASM LabCap helps build laboratory capacity under a cooperative agreement with the U.S. Centers for Disease Control and Prevention (CDC) and under a sub-contract with the Program for Appropriate Technology in Health (PATH) funded by the United States Agency for International Development (USAID). Successful activities of ASM LabCap have occurred throughout Africa, Asia, Central America and the Caribbean. In addition, ASM LabCap coordinates efforts with international agencies such as the WHO in order to maximize resources and ensure a unified response, with the intended goal to help build integrated disease surveillance and response capabilities worldwide in compliance with HR(2005)'s requirements.


Living With "Man's Fate" Away From Home.
Edward Nilges is a former software consultant who came from Chicago to Hong Kong in 2005, and has since worked as a teacher. Having been residing in Hong Kong for all these years, Edward fell ill with cancer and its complications. He choose to receive medical treatment in Hong Kong, where both the dominant culture and medical system were foreign to him. Here, he gives an account of his physical, psychological, social and existential experience, in quest of meaning away from home, while his physician discusses the clinician's perspective.


Empiric antimicrobial therapy for febrile granulocytopenic cancer patients. Lessons from four EORTC trials.
The experience from four EORTC trials on antimicrobial therapy for febrile granulocytopenic cancer patients (GCP) is reviewed. A general conclusion from these trials is that studies of the management of infection in GCP should include sufficient numbers of eligible patients to allow for evaluation of bacteremic patients at highest risk of death. The need for large collaborative studies stems directly from these considerations.


Liquid nitrogen preservation of standard inoculum: gas-phase storage.
Liquid nitrogen storage was the most satisfactory of several methods tested for supplying standard Streptomyces viridoflavus inoculum for laboratory and pilot plant experimentation. Shake-flask cultures were subdivided into sterile cotton-plugged ampoules and stored in the gas space of a liquid nitrogen refrigerator. There were no detectable changes in viability or in candidin-producing capacity over a 12-month test period. The procedure also proved satisfactory with all other organisms tested.


Cross-correlation corrected friction in (generalized) Langevin models.
We propose a route for parameterizing isotropic (generalized) Langevin [(G)LE] thermostats with the aim to correct the dynamics of coarse-grained (CG) models with pairwise conservative interactions. The approach is based on the Mori-Zwanzig formalism and derives the memory kernels from Q-projected time correlation functions. Bottom-up informed (GLE and LE) thermostats for a CG star-polymer melt are investigated, and it is demonstrated that the inclusion of memory in the CG simulation leads to predictions of polymer diffusion in quantitative agreement with fine-grained simulations. Interestingly, memory effects are observed in the diffusive regime. We demonstrate that previously neglected cross-correlations between the "irrelevant" and the CG degree of freedom are important and lie at the origin of shortcomings in previous CG simulations.


Phase II trial of Baker's antifol in metastatic sarcoma.
Iv Baker's antifol (BAF) (250 mg/m2/day X 3 consecutive days) was administered to 34 patients with metastatic sarcoma. All patients had received extensive prior therapy including prior chemotherapy and had progressive disease at the start of the study. Liver and renal functions were normal in all patients. Of 29 patients evaluable for response, 25 demonstrated progressive disease and four had stable disease for periods of from 1 to 6 months. No objective responses were observed. The other five patients died from 3 to 12 days after initiation of therapy. Toxicity included myelosuppression of significant degree in nine patients, gastrointestinal effects of nausea and vomiting in seven, stomatitis in three, and dermatitis in four. Most toxicity was mild to moderate, although one drug-related death due to marked myelosuppression was seen. In conclusion, BAF is considered to be insignificantly active in the secondary treatment of metastatic sarcomas at the dose and schedule studied.


Malakoplakia after kidney transplantation: Case report and literature review.
Malakoplakia is a granulomatous disease associated with an infectious etiology, usually involving the urinary tract. It reveals itself as a recurrent urinary tract infection (r-UTI), and in some cases, it is associated with impairment of renal function. Immunosuppression is one of its main associated factors, and it has been increasingly described in patients with solid organ transplantation (SOT), mainly kidney transplantation. Macroscopically, it can form masses and sometimes it may be confused with neoplasia, which is why histological findings are fundamental for the diagnosis. Here, we present a case of bladder malakoplakia, manifested by r-UTI from Escherichia coli in a patient with renal transplantation, refractory to long-term antibiotic treatment and reduction in immunosuppression, which resolved after surgical management. We also summarize the clinical characteristics of malakoplakia and compare them with previous reports in the literature on SOT.


Crosstalk among the proteome, lysine phosphorylation, and acetylation in romidepsin-treated colon cancer cells.
Romidepsin (FK228) is one of the most promising histone-deacetylase inhibitors due to its potent antitumor activity, and has been used as a practical option for cancer therapy. However, FK228-induced changes in protein modifications and the crosstalk between different modifications has not been reported. To better understand the underlying mechanisms of FK228-related cancer therapy, we investigated the acetylome, phosphorylation, and crosstalk between modification datasets in colon cancer cells treated with FK228 by using stable-isotope labeling with amino acids in cell culture and affinity enrichment, followed by high-resolution liquid chromatography tandem mass spectrometry analysis. In total, 2728 protein groups, 1175 lysine-acetylation sites, and 4119 lysine-phosphorylation sites were quantified. When the quantification ratio thresholds were set to > 2.0 and < 0.5, respectively, a total of 115 and 38 lysine-acetylation sites in 85 and 32 proteins were quantified as increased and decreased targets, respectively, and 889 and 370 lysine-phosphorylation sites in 599 and 289 proteins were quantified as increased and decreased targets, respectively. Furthermore, we identified 274 proteins exhibiting both acetylation and phosphorylation modifications. These findings indicated possible involvement of these proteins in FK228-related treatment of colon cancer, and provided insight for further analysis of their biological function.


Differences in the growth properties of Zika virus foetal brain isolate and related epidemic strains in vitro.
Zika virus (ZIKV) has recently emerged into new areas in the Americas and Asia, causing an epidemic characterized by severe congenital infections. While ZIKV infection is usually asymptomatic or causes mild symptoms, it has now caused a high rate of foetal brain and ocular abnormalities. The underlying reasons for the varying severity of disease outcomes is poorly understood. In this study, we compared the infectivity and replication of three disease-associated Zika viruses of Asian lineage, as well as the prototypic ZIKV strain from Africa. The recent foetal brain isolate FB-GWUH-2016 demonstrated enhanced infectivity and replication over the serum-origin isolates from French Polynesia and Martinique, suggesting differences in the pathogenic properties.


Medical management for adults with Prader-Willi syndrome.
Prader-Willi syndrome (PWS) is a genetic disorder characterized by morbid obesity resulting from insatiable appetite. Complications like diabetes mellitus or other cardiovascular diseases typically occur during lifetime. Lifestyle advice and education as well as limited caloric intake are the major concepts in assistance of PWS patients. A 12.9-month follow-up study, which included 8 formerly genetically diagnosed PWS patients, was conducted. Physical and laboratory examinations were done at the beginning and at the end of the follow-up. Improved medical care and lifestyle advice were given. The participants lived in an assisted living environment with a fixed daily schedule and limited caloric intake. The group of patients consisted of manifest diabetics (n=6) as well as nondiabetics (n=2). Therapeutic concepts were simplified in 2 patients by switching from insulin to oral antidiabetics. The reduction in body weight was moderate, but attributable to a loss of fat mass. A significant reduction in blood cholesterol and triglyceride content was achieved along the observational period as well as a significant reduction of glycosylated hemoglobin (HbA1c) in the group of diabetic PWS patients. Systolic blood pressure improved during the study. A combination of an assisted living environment following conservative treatments as well as consistent patient care improved the daily and medical situation of PWS patients. Weight loss and, as a consequence, improvements in terms of metabolic condition and blood pressure were observed. A combination of medical and daily routine management should be established in PWS patients to improve their quality of life.


The present situation of paragonimiasis in endemic area in Phitsanulok Province.
A cross-sectional survey and evaluation of paragonimiasis situation from endemic area in Phitsanulok Province was studied. Studies on the species and prevalence of parasites which infected people in Noen Maprang, Phitsanulok Province were also conducted during October 1999-March 2000. The sputum specimens were collected and examined to identify Paragonimus heterotremus eggs. In addition fecal samples were collected and examined for parasites by the formalin-ethyl acetate concentration technique. P. heterotremus eggs were detected in 2 out of 391 sputum specimens; a prevalence of 0.51%. A total of 584 stool specimens were obtained and examined. It was found that the prevalence of parasitic infection was 36.30%. Opisthorchis viverrini infection was the most prevalent (10.78%), followed by Strongyloides stercoralis (9.59%), hookworm (8.22%), Echinostoma spp (2.23%), minute intestinal flukes (1.54%), Taenia species (1.37%), Enterobius vermicularis (0.68%), Entamoeba coli (1.03%) and Giardia lamblia (0.86%). The prevalent rate of paragonimiasis in this endemic area in Phitsanulok Province has decreased during the past decade. However, there were other important parasite infections, especially opisthorchiasis and strongylodiasis and these should be studied further.


Stages of abstraction and exemplar memorization in pigeon category learning.
It has been proposed that human category learning consists of an early abstraction-based stage followed by a later exemplar-memorization stage. To investigate whether similar processing stages extend to category learning in a nonverbal species, we applied a prototype-exception paradigm to investigating pigeon category learning. Five birds and 8 humans learned six-dimensional perceptual categories constructed to include prototypes, typical items, and exceptions. We evaluated the birds' and humans' categorization strategies at different points during learning. Early on in both species, prototype performance improved rapidly as exception performance remained below chance, indicating an initial mastery of the categories' general structure. Later on, exception performance improved selectively and dramatically, indicating exception-item resolution and exemplar memorization. Abstraction- and exemplar-based formal models reinforced these interpretations. The results suggest a psychological transition in pigeon category learning from abstraction- to exemplar-based processing similar to that found in humans.


[Pancreatic hormones and hormonal regulation of insulin secretion].
Endocrine pancreas producing insulin, glucagon, somatostatin and pancreatic polypeptide is under the influence of different types of regulation; among them the regulatory role of enteropancreatic axis plays an important role. Incretin effect of glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide 1 (GLP-1) is significantly involved in the insulin secretion which is modulated by many other hormones. Diabetes mellitus, similarly to disturbances of other hormones, can cause impaired regulation of insulin and other pancreatic hormones.


Effect of heat-inactivated kefir-isolated Lactobacillus kefiranofaciens M1 on preventing an allergic airway response in mice.
In this study, we assessed the anti-asthmatic effects of heat-inactivated Lactobacillus kefiranofaciens M1 (HI-M1) and its fermented milk using different feeding procedures and at various dosage levels. The possible mechanisms whereby HI-M1 has anti-allergic asthmatic effects were also evaluated. Ovalbumin (OVA)-allergic asthma mice that have been orally administrated the HI-M1 samples showed strong inhibition of production of T helper cell (Th) 2 cytokines, pro-inflammatory cytokines, and Th17 cytokines in splenocytes and bronchoalveolar fluid compared to control mice. An increase in regulatory T cell population in splenocytes in the allergic asthma mice after oral administration of H1-M1 was also observed. In addition, all of the features of the asthmatic phenotype, including specific IgE production, airway inflammation, and development of airway hyperresponsiveness, were depressed in a dose-dependent manner by treatment. These findings support the possibility that oral feeding of H1-M1 may be an effective way of alleviating asthmatic symptoms in humans.


Genetic diversity of respiratory syncytial virus isolated during an epidemic period from children of northeastern Brazil.
Outbreaks of human respiratory syncytial virus (HRSV) are the leading cause of serious acute lower respiratory viral disease in many countries in different continents. Data on clinical and epidemiological aspects of HRSV infections in this country have been reported, but there is lack of data regarding the molecular epidemiology of this virus in Salvador. The genetic variability of HRSV isolated during an outbreak in Salvador, Brazil (1999) has been analysed. Partial sequences of the G protein gene of 13 isolates from antigenic group A and 4 isolates from antigenic group B of HRSV were determined. Nucleotide sequences of C-terminal G gene were compared to sequences of HRSV isolates from countries of South America and from the rest of the world available at the GenBank. Brazilian group A and B isolates were clustered into previously characterised genotypes: GA5, GA2, GA7, and GB3, SAB3, respectively. This is the first study of GA7 and SAB3 genotypes circulation in South American countries. It is interesting to point out that viruses isolated in Salvador appear to be closer related with those from Montevideo-Uruguay and Buenos Aires, Argentina strains, suggesting circulation of similar strains among different South American countries in different seasons. Moreover, viruses closely related genetically circulated in the same year in Salvador and distant places such as Mozambique, supporting the previous suggestion on the complexity of HRSV strain circulation patterns, and the high capability of HRSV spreading world-wide.


Preoperative assessment of hilar cholangiocarcinoma by multidetector row computed tomography.
Hilar cholangiocarcinoma is the one of the most difficult carcinomas to diagnose because of the localization of the main tumor at the hepatic hilus, and because of the complex anatomy of the biliary, artery, and portal systems. To perform a curative operation, it is important to evaluate the extent of carcinoma and the resectability. Hilar cholangiocarcinoma often extends along the axis of the bile duct. Percutaneous transhepatic cholangiogaraphy (PTC) and/or endoscopic retrograde cholangiography (ERC) are usually performed to diagnose the extent of the hilar cholangiocarcinoma. However, computed tomography (CT) was thought not to be useful because its resolution is poor. Now that multidetector row CT (MDCT) and high-performance imaging systems are available, the diagnostic strategy for hilar cholangiocarcinoma has changed. In this study, we analyzed the preoperative diagnostic imaging of 24 consecutive patients whose hilar cholangiocarcinoma was confirmed by histopathological examination. All patients were submitted to 16-channel MDCT, except for those with an allergy to iodine contrast medium. The data obtained from MDCT were analyzed and checked by both radiologists and surgeons, using multiplanar reconstruction (MPR) images. The accuracy of diagnosis of horizontal spreading was 80.9% and that of vertical spreading was 100%. However, the sensitivity for lymph node metastasis was insufficient. Based on the data from MDCT and other examinations, all patients underwent surgery. Curative operation was performed in 15 patients (62.5%). Our results indicate that 16-channel MDCT is reliable for the diagnosis of hilar cholangiocarcinoma, especially prior to bile duct drainage. Thus, it is important to perform MDCT when patients with obstructive jaundice are encountered.


Amplification of Circularly Polarized Luminescence through Triplet-Triplet Annihilation-Based Photon Upconversion.
Amplification of circularly polarized luminescence (CPL) is demonstrated in a triplet-triplet annihilation-based photon upconversion (TTA-UC) system. When chiral binaphthyldiamine acceptors are sensitized with an achiral Pt(II) octaethylporphine (PtOEP) in solution, upconverted circularly polarized luminescence (UC-CPL) were observed for the first time, in which the positive or negative circularly polarized emission could be obtained respectively, following the molecular chirality of the acceptors (R/S). More interestingly, one order of magnitude amplification of the dissymmetry factor glum in UC-CPL was obtained in comparison with the normal promoted CPL. The multistep photophysical process of TTA-UC including triplet-triplet energy transfer (TTET) and triplet-triplet annihilation (TTA) have been suggested to enhance the UC-CPL, which provided a new strategy to design CPL materials with a higher dissymmetry factor.


Thalamic input to representations of the teeth, tongue, and face in somatosensory area 3b of macaque monkeys.
Representations of the parts of the oral cavity and face in somatosensory area 3b of macaque monkeys were identified with microelectrode recordings and injected with different neuroanatomical tracers to reveal patterns of thalamic projections to tongue, teeth, and other representations in primary somatosensory cortex. The locations of injection sites and resulting labeled neurons were further determined by relating sections processed to reveal tracers to those processed for myeloarchitecture in the cortex and multiple architectural stains in the thalamus. The ventroposterior medial subnucleus (VPM) for touch was identified as separate from the ventroposterior medial parvicellular nucleus (VPMpc) for taste by differential expression of several types of proteins. Our results revealed somatotopically matched projections from VPM to the part of 3b representing intra-oral structures and the face. Retrogradely labeled cells resulting from injections in area 3b were also found in other thalamic nuclei including: anterior pulvinar (Pa), ventroposterior inferior (VPI), ventroposterior superior (VPS), ventroposterior lateral (VPL), ventral lateral (VL), center median (CM), central lateral (CL), and medial dorsal (MD). None of our injections, including those into the representation of the tongue, labeled neurons in VPMpc, the thalamic taste nucleus. Thus, area 3b does not appear to be involved in processing taste information from the thalamus. This result stands in contrast to those reported for New World monkeys.


Nuclear medicine in the 1990s: a quantitative physiological approach.
This paper describes the potential advantages to medical diagnosis and treatment that might be obtained from the wider application of positron emission tomography as a clinical tool. Developments along the lines suggested here will require a radical change in thinking from both clinicians and the medically related scientific community in the UK and some enlightened and resourceful funding from a mixture of charitable, industrial and government sources. If these ideas are to be pursued successfully, then the work must start now on a much wider scale than is presently perceived in the UK, and close collaboration between physicists, engineers, chemists, biochemists, clinicians and industrialists is needed. Furthermore, it is imperative that the scientific developments now underway in silicon technology, parallel data processors, biochemical and pharmacological processes and even high-temperature superconductors be kept under close and constant review by those associated with the technological advancements of medicine, so that the value of such developments is rapidly transferred to applications to medicine. This must include closer relationships between academic medicine and science than is the general rule in the UK at present. In conclusion, the scenario presented here includes the installation of regional cyclotron facilities to provide a large number of institutions in the UK with positron-emitter labelled radiopharmaceuticals. Additionally, agents labelled with radionuclides from in-house generators and other already existing higher-energy cyclotrons will provide a versatile and valuable range of radiopharmaceuticals for the study of human disease. These developments must be supported by the manufacture of lower-cost positron camera systems, as suggested here, connected to high-data-rate parallel processors to provide images of body function and to determine the effects brought about by disease. These images may then be processed using algorithms based on kinetic models of the body systems to provide information about the basic biochemical and physiological processes of the body. Such a development could have a profound effect on our knowledge of human disease and on our ability to control and treat it successfully.


Optimal parameters for eliciting cardio-acceleration by electrical stimulation of the ventromedial hypothalamus.
The ventromedial hypothalamus of the unrestrained cat was stimulated electrically through permanent electrodes. The stimulation parameters, amplitude, duration and frequency of the square wave pulses were combined to produce a 20% increase of the resting heart rate value. The total electric charge for each parametric combination was calculated. The charge per stimulation (10 s) varied from about 1 to 100 micro-coulombs, depending on the parametric combination used. The response could therefore not be expressed as a function of the charge but depended on the individual parametric combinations. The relation among the stimulation parameters and the total amount of electric charge of the pulses was estimated by the correlation technique. The results suggested that about 60% of the variation in the electric charge resulting in the constant response was due to the variation of the pulse repetition frequency. The optimal parameters for eliciting cardio-acceleration in the cat by stimulation of the ventromedial hypothalamus seem to be pulse durations between 0.1 and 0.5 ms and pulse repetition frequencies below 100 P/s, with pulse amplitude as the dependent variable.


The Role of EGFR, Hepatocyte Growth Factor Receptor (c-Met), c-ErbB2 (HER2-neu) and Clinicopathological Parameters in the Pathogenesis and Prognosis of Chordoma.
Chordoma is a rare malignant bone tumor with a poor outcome. Although radiotherapy and gamma knife surgery have been used for treatment, providing a cure for the tumor is not easy, because of the frequent recurrences. Molecular targeted therapy against tyrosine kinases has been effective in the treatment of malignancies such as breast and lung cancers and brain tumors. We aimed to analyse the histopathological features of chordomas and the immunoexpression profiles of the three receptor tyrosine kinases of EGFR, c-Met and c-Erb-B2 in chordomas. We have correlated these results with recurrence and overall survival status of the patients. We studied 49 chordoma patients in order to evaluate the histopathological features and immunohistochemical stainings by EGFR, c-Met and c-ErbB2 antibodies. Of the 49 patients, follow up data was available for 40 patients. Clinical data of the patients were correlated with histopathological features and survival analysis was performed. The immunostaining rate by EGFR and c-Met was 73.5% and 12.2% respectively. None of the cases showed immunoreactivity by c-ErbB2 (0%). Of the 40 cases, 17 cases showed recurrences. EGFR expression was detected in 14 recurrent (14/17) and 17 non-recurrent cases (17/23). Four of the 17 recurrent cases (4/17) were positive by c-Met, while none of the non-recurrent cases (0/23) were positive by this antibody. Significantly, all cases with positive c-Met expression showed recurrences (p < 0.05). Our study indicates that EGFR expression is detected in the majority of chordoma cases. c-Met expression can be used as a prognostic indicator for chordoma.


The Relationship of Brain Amyloid Load and APOE Status to Regional Cortical Thinning and Cognition in the ADNI Cohort.
Both amyloid (Aβ) load and APOE4 allele are associated with neurodegenerative changes in Alzheimer's disease (AD) prone regions and with risk for cognitive impairment. To evaluate the unique and independent contribution of APOE4 allele status (E4+∖E4-), Aβ status (Amy+∖Amy-), and combined APOE4 and Aβ status on regional cortical thickness (CoTh) and cognition among participants diagnosed as cognitively normal (CN, n = 251), early mild cognitive impairment (EMCI, n = 207), late mild cognitive impairment (LMCI, n = 196), and mild AD (n = 162) from the ADNI. A series of two-way ANCOVAs with post-hoc Tukey HSD tests, controlling independently for Aβ and APOE4 status and age were examined. Among LMCI and AD participants, cortical thinning was widespread in association with Amy+ status, whereas in association with E4+ status only in the inferior temporal and medial orbito-frontal regions. Among CN and EMCI participants, E4+ status, but not Amy+ status, was independently associated with increased CoTh, especially in limbic regions [e.g., in the entorhinal cortex, CoTh was 0.123 mm greater (p = 0.002) among E4+ than E4-participants]. Among CN and EMCI, both E4+ and Amy+ status were independently associated with cognitive impairment, which was greatest among those with combined E4 + and Amy+ status. Decreased CoTh is independently associated with Amy+ status in many brain regions, but with E4+ status in very restricted number of brain regions. Among CN and EMCI participants, E4 + status is associated with increased CoTh, in medial and inferior temporal regions, although cognitive impairment at this state is independently associated with Amy+ and E4 + status. These findings imply a unique pathophysiological mechanism for E4 + status in AD and its progression.


Trends in Complications and Outcomes in Patients Aged 65 Years and Younger Undergoing Total Hip Arthroplasty: Data From the American Joint Replacement Registry.
This study sought to determine common complications and the rates of readmission and revision in total hip arthroplasty patients younger than 65 years. Using the American Joint Replacement Registry, we conducted a retrospective review of all THAs in patients aged 18 to 65 years from 2012 to 2020. We excluded patients aged older than 65 years, revisions, oncologic etiology, conversion from prior surgery, and nonelective cases. Primary outcomes included cumulative revision rate, 90-day readmission rate, and reason for revision. The Kaplan-Meier method and univariate analysis were used. Five thousand one hundred fifty-three patients were included. The average age was 56.7 years (SD 7.8 years), 51% were female, 85% were White, and 89% had a Charlson Comorbidity Index of 0 (1 = 7%, >2 = 4%). The mean follow-up was 39.57 months. Fifty-three patients (1.0%) underwent revision. Seventy-four patients (1.4%) were readmitted within 90 days. Revision was more common in Black patients (P = 0.023). Survivorship was 99% (95% confidence interval, 98.7 to 99.3) and 99% (95% confidence interval, 98.5 to 99.3) at 5 and 8 years, respectively. Infection (21%), instability (15%), periprosthetic fracture (15%), and aseptic loosening (9%) were the most common indications for revision. Total hip arthroplasty performed in young and presumed active patients had a 99% survivorship at 8 years. A long-term follow-up is needed to evaluate survival trends in this growing population.


Paradoxical effects of sublethal exposure to the naturally derived insecticide spinosad in the dengue vector mosquito, Aedes aegypti.
Recent studies have indicated that spinosad, a mixture of two tetracyclic macrolide compounds produced during the fermentation of a soil actinomycete, may be suitable for controlling a number of medically important mosquito species, including the dengue vector, Aedes aegypti L. The authors determined the effects of a 1 h exposure to a 50% lethal concentration (LC(50)) of spinosad in the larval stage on the wing length, longevity and reproductive capacity of the adult survivors. The LC(50) of spinosad for a wild-caught population of Ae. aegypti from Chiapas, southern Mexico, was estimated to be 0.06 mg AI L(-1) in late third instars. Paradoxically, the female survivors of exposure to this concentration were significantly larger (as determined by wing length) laid more eggs, but were slightly less fertile than control females. This was probably due to elimination of the smaller and more susceptible fraction of mosquito larvae from the experimental population following spinosad treatment. Male survivors, in contrast, were significantly smaller than controls. No significant differences were detected in the adult longevity of treated and control insects of either sex. The increase in reproductive capacity of spinosad-treated females did not compensate for mortality in the larval stage and would be unlikely to result in population increase in this mosquito under the conditions that were employed. Sustained-release formulations would likely assist in minimizing the occurrence of sublethal concentrations of this naturally derived product in mosquito breeding sites.


Localization of the domains involved in ligand binding and activation of the glucose-dependent insulinotropic polypeptide receptor.
The receptors for the two structurally related insulinotropic hormones Glucose-dependent Insulinotropic Polypeptide (GIP) and Glucagon-Like Peptide-1 (GLP-1) share approximately 40% sequence identity and demonstrate complete specificity for their endogenous ligands, while utilizing similar second messenger pathways. In the current study chimeric GIP-GLP-1 receptors were prepared, and the effect of domain-exchange on ligand binding and adenylyl cyclase activation examined. A chimera (CH-2) consisting of the first 132 amino acids of the external N-terminal (NT) domain bound 125I-GIP with high affinity (27.77 +/- 11.85 nM). However, for receptor coupling to cAMP production it was necessary to extend the NT into the first transmembrane (TM-1) region (CH-3: IC50 = 9.04 +/- 1.07 nM; EC50 = 17.1 +/- 3.5 nM). A chimera which included part of TM-3 (CH-4) demonstrated binding and signalling (IC50 = 8.33 +/- 0.14 nM; EC50 = 467.5 +/- 173.6 pM) similar to the wild type receptor (IC50 = 1.33 +/- 0.19 nM; EC50 = 497.9 +/- 211.7 pM). Surprisingly constructs CH-2 and CH-3, while devoid of detectable 125I-GLP-1 binding, were capable of eliciting GLP-1-specific cAMP production (EC50s CH-2 = 81.4 +/- 19.6 nM; CH-3 = 5.99 +/- 0.68 nM) suggesting that receptor activation is not completely dependent on high affinity receptor binding. These data clearly demonstrate that the NT domain of the GIP receptor acts as the ligand-specific binding domain and that the first transmembrane domain is important for receptor activation.


An unusual trigeminal neurinoma.
We report a large trigeminal neurinoma in an 18-month-old child involving the Gasserian ganglion and all three divisions in a plexiform pattern. The tumour in the ophthalmic division extended all the way to the supraorbital nerve. The child presented with proptosis which had been observed since she was 4 months of age. There was a family history of neurofibromatosis.


Limitations of the Mycobacterium tuberculosis reference genome H37Rv in the detection of virulence-related loci.
The genome sequence of Mycobacterium tuberculosis strain H37Rv is an important and valuable reference point in the study of M. tuberculosis phylogeny, molecular epidemiology, and drug-resistance mutations. However, it is becoming apparent that use of H37Rv as a sole reference genome in analysing clinical isolates presents some limitations to fully investigating M. tuberculosis virulence. Here, we examine the presence of single locus variants and the absence of entire genes in H37Rv with respect to strains that are responsible for cases and outbreaks of tuberculosis. We discuss how these polymorphisms may affect phenotypic properties of H37Rv including pathogenicity. Based on our observations and those of other researchers, we propose that use of a single reference genome, H37Rv, is not sufficient for the detection and characterisation of M. tuberculosis virulence-related loci. We recommend incorporation of genome sequences of other reference strains, in particular, direct clinical isolates, in such analyses in addition to H37Rv.


Particle size effect on millimeter-wave absorption, rotation, and ellipticity of gallium-substituted epsilon iron oxide.
Various applications employ millimeter waves. For example, the carrier frequencies of vehicle radar in advanced driver assistance systems are 76-81 GHz millimeter waves. Here, we investigate the particle size effect on millimeter-wave absorption of gallium-substituted epsilon iron oxide ε-Ga x Fe2-x O3 with x = 0.44 ± 0.01. Samples were composed of nanoparticles with sizes of 16.9(1) nm, 28.8(2) nm, and 41.4(1) nm. Millimeter wave absorption, Faraday rotation, and Faraday ellipticity were measured by terahertz time-domain spectroscopy. This series exhibits millimeter-wave absorption at 78.7, 78.2, and 77.7 GHz without an external magnetic field. The millimeter-wave absorption increases from 4.6 dB to 9.4 dB as the particle size increases. In the magnetized sample, the Faraday rotation angle increases from 9.1° to 18.4°, while the Faraday ellipticity increases from 0.27 to 0.52. The particle size effect can be explained by the change in the ratio of the surface and core of the nanoparticles. The present study should contribute to the realization of high-performance millimeter-wave absorbers.


[Learning clinical skills].
The purpose of this study was to analyse the learning environment of medical students in a medical ward and on the basis of this study to make specific suggestions as to how the students' clinical stay in a ward can be optimized. These suggestions were implemented and the effect evaluated. This is a qualitative study. Through observations and interviews with students and staff in the ward the learning environment was analysed. After that an evaluation of the implemented project was carried out in a questionnaire to the ward and in interviews with the persons involved in the project. The result of the study concerning analysis and improvement of the students' stay can briefly be summarized as follows: The students' position in the unit can be characterized as that of an observer rather than as an active working participant in the ward. With this there is a risk that the medical student's trainee stay in a ward will turn into a "work-experience placement", the primary purpose of which will be for the medical student just to dip into the profession. This has consequences for the students' learning process in securing that the students acquire the necessary practical qualifications and acquire essential personal qualifications, such as self-dependence and abilities in decision-making and working under pressure. The study shows that doctors and students agree on the aim of the students' trainee stay: To involve the students in a working partnership in order to obtain the best learning experience. The study concludes that it is difficult to change well-established routines despite good intentions of all parties involved. Therefore, the study rises the question on how new routines are established in the educational culture of medicine.


Screening Glaucoma With Red-free Fundus Photography Using Deep Learning Classifier and Polar Transformation.
PRéCIS:: The novel proposed algorithm using deep learning classifier and polar transformation technique can be an economical as well as an effective tool for early detection of glaucomatous RNFL defect. The main purpose of this study was to develop novel software to determine whether there is a retinal nerve fiber layer (RNFL) defect in a given fundus image using deep learning classifier and, if there is, where it presents. In the deep learning classifier, the bottleneck features were extracted, followed by application of the softmax classifier, which outputted the glaucoma probability. For localization of RNFL defect, an image processing algorithm was implemented as follows: (1) the given image was normalized to enhance the contrast; (2) the region of interest (ROI) was set as the circumferential area surrounding the optic disc (internal diameter: 2 disc diameters, external diameter: 3 disc diameter), and converted to a polar image; (3) blood vessels were removed and the average curvatures were calculated. If the local maximum curvature was greater than the cut-off value, the sector was considered to be an RNFL defect.The images of 100 normal healthy controls and 100 open-angle glaucoma patients were enrolled. Maximum curvatures and area under receiver operating characteristic curve were compared to determine the diagnostic validity. There were no significant differences in age or sex (P=0.275, P=0.479, respectively) between the 2 groups. In the glaucoma group, the mean deviation was -4.9±5.4 dB. There was a significant difference of maximum curvature (14.37±5.13 in control group, 20.67±10.56 in glaucoma group, P<0.001). Area under receiver operating characteristic curve was 0.939 in deep learning classifier and 0.711 in maximum curvature. The proposed software can be an effective tool for automated detection of RNFL defect.


In situ expression of B7 and CD28 receptor families in skin lesions of patients with lupus erythematosus.
To examine the expression of costimulatory molecules of the B7 and CD28 receptor families in active skin lesions of patients with systemic lupus erythematosus (SLE), subacute cutaneous lupus erythematosus (SCLE), and chronic discoid lupus erythematosus (CDLE). The in situ expression of B7-1, B7-2, BB-1, and CD28 was studied by immunohistochemistry, and B7-1 and B7-2 RNA expression was examined by reverse transcription-polymerase chain reaction. Only in lesional skin from SLE, SCLE, and CDLE patients did dermal and epidermal antigen-presenting cells (APC) express B7-1 and B7-2, particularly when in apposition to CD28+ T cells. These B7-1+ and B7-2+ APC bound CTLA-4 fusion protein. In lesional (but not in nonlesional) skin, keratinocytes expressed BB-1. The majority of infiltrating T cells were CD28+. B7-1 and B7-2 RNA were expressed in lesional skin from SLE, SCLE, and CDLE patients; when dermis was separated from epidermis, only faint B7-1 and B7-2 RNA signals were detectable in the epidermis, indicating that dermal but not epidermal cells were the major source of B7-1 and B7-2 RNA. During treatment, both B7-1 and B7-2 protein and RNA expression were reduced. These in situ findings suggest that costimulation via the B7-CD28 pathway may be important for the generation and/or propagation of T cell activity in skin lesions of humans with lupus erythematosus. Thus, the manipulation of this pathway (e.g., by CTLA-4 fusion protein) could be an important target for the development of future therapies for LE.


Effect of two types of hospital feeding gift packs on duration of breast-feeding among adolescent mothers.
Two hundred forty-four adolescent mothers under 18 years of age were surveyed during a 15-month period, and 53% elected to breast-feed. A subset of 60 primiparous breast-feeding adolescents were enrolled in an investigator-blind, randomized, prospective study to compare the effects on breast-feeding duration of a standard hospital discharge feeding gift pack containing formula and a specially designed study pack that was free of infant formula. Thirty-five percent of the 60 women breast-fed less than 1 month; 22% nursed longer than 1 month but less than 2 months; and 43% breast-fed more than 2 months. There was no significant difference in breast-feeding duration among mothers by gift pack group, although those who received the study gift pack rated it higher in usefulness (p less than (0.025). The provision of infant formula samples did not appear to have a deleterious effect on the duration of breast-feeding among a population of adolescent mothers.


Postdrome symptoms in pediatric migraine: A questionnaire retrospective study by phone in 100 patients.
Background No study dedicated to postdrome symptoms of migraine attacks is available in children and adolescents. Objective To study the resolution phase of the migraine attack in children and adolescents. Methods 100 children and adolescents with ICHD-3 beta migraine without and/or with typical aura were included. Each patient, and one of her/his parents, were interviewed by phone about the postdrome phrase of their last six months' migraine attacks. They were specifically instructed to distinguish symptoms that had begun before and went on after migraine headache cessation (referred to as persistent symptoms), and symptoms whose onset was strictly after headache cessation (referred to as true postdromes). Results 91% of patients reported persistent symptoms, with a mean of 2.9 and a median of 2; asthenia, cognitive difficulties, pallor, cognitive slowing, anorexia, somnolence, and nausea were the most frequently reported. They lasted less than 12 h in 71% of patients. True postdromes were reported by 82% of patients, with a mean of 2.6 and a median of 2; thirst, somnolence, visual disturbances, food craving, paraesthesias, and ocular pain being the most frequently reported. They lasted less than 12 h in 94% of patients. Conclusions This study showed that children and adolescents with migraine had both frequent persistent symptoms and true postdromes. Both were notably different from those reported in adults.


Facts and values: on the acceptability of risks in children's sport using the example of rugby - a narrative review.
A clash of values has been identified between those who assert that:1. all childhood injuries, regardless of origin, are inherently undesirable and should be prevented and;2. those who believe that some measure of injury to children is an acceptable compromise for the physical benefits associated with physical activity and the development of abilities to appraise and deal with risks.A debate regarding whether the tackles and collisions permitted in schools' rugby represent acceptable risks, and what steps should be taken if they do not, exemplifies the issue.Questions regarding the magnitude of injury risks in sport are issues of fact and can be quantified via the results of injury surveillance studies. Risks are neither high nor low in isolation; they are relatively high or low with reference to other activities or across groups participating in an activity. Issues of the acceptability of a given degree of risk are value dependent. Research regarding perceptions of risk reveals wide variations in the degree of risk people view as acceptable. Factors impacting on risk perception include whether the risks are well known and understood, whether they are 'dread' risks and the degree to which people undertake the risks voluntarily and feel they have control over them.Based on the evidence currently available, the risks to children playing rugby do not appear to be inordinately high compared with those in a range of other childhood sports and activities, but better comparative information is urgently needed. Further evidence, however, should not necessarily be expected to result in the resolution of acceptable risk debates-pre-existing values shape our perspectives on whether new evidence is relevant, valid and reliable.


Maternity blues in Athens, Greece: a study during the first 3 days after delivery.
Although maternity blues have been studied in many countries worldwide the factors that influence the occurrence of this clinical entity are not well understood. The purpose of this study was to investigate the prevalence, time course and symptomatology of maternity blues in a Greek urban environment as well as the relation of maternity blues with certain clinical and sociodemographic factors. A study of a sample of 402 women that were recruited during the first day after delivery. Each woman completed the Kennerley's Blues Questionnaire on a daily basis for the first 3 days of puerpartum. Clinical and sociodemographic data were obtained through questionnaires and personal interview. 179 (44.5%) women experienced severe maternity blues during the first 3 days after delivery. Delivery by caesarian section (P=0.006), stressful events during pregnancy (P=0.02), depressive feelings the last month prior to delivery (P=0.002), anxiety on the day of delivery (P=0.001) and hypochondriasis (P=0.001) were the factors that were found to relate significantly to maternity blues. The women's emotional condition prior and after delivery, delivery via caesarotomy, as well as fears concerning somatic health had strong impact on the occurrence of maternity blues.


Pathological haemodynamics of a middle cerebral artery stenosis validated by computational fluid dynamics.
Intracranial arterial stenosis (ICAS) is one of the important causes of ischaemic stroke. However, the treatment for ICAS is not optimised, including medical therapies, because the mechanisms are diverse. The authors report a case of severe middle cerebral arterial stenosis accompanied by a floating thrombus, which caused artery-to-artery cerebral emboli. The patient was successfully treated with multiple antithrombotics including an anticoagulant, and the thrombus disappeared. Local haemodynamics around the middle cerebral arterial stenosis was analysed by computational fluid dynamics (CFD) using the patient-specific model. CFD analysis demonstrated that thrombus formation occurred at the poststenotic area with severe stagnant flow, which was judged by both wall shear stress and shear rate less than the specific thresholds. These findings suggest that CFD may be useful to diagnose the risk of stagnant flow-induced thrombosis and to predict the effectiveness of anticoagulant agents to prevent distal embolisms in ICAS.


Pestalotiopsis-Like Species Causing Gray Blight Disease on Camellia sinensis in China.
Gray blight of tea, caused by several Pestalotiopsis-like species, is one of the most destructive foliar diseases in tea cultivation yet the characteristics of these pathogens have not been confirmed until now. With morphological and multigene phylogenetic analyses, we have identified the gray blight fungi as Pseudopestalotiopsis camelliae-sinensis, Neopestalotiopsis clavispora, and Pestalotiopsis camelliae. Phylogenetic analyses derived from the combined internal transcribed spacer, β-tubulin, and translation elongation factor 1-α gene regions successfully resolved most of the Pestalotiopsis-like species used in this study with high bootstrap supports and revealed three major clusters representing these three species. Differences in colony appearance and conidia morphology (shape, size, septation, color and length of median cells, and length and number of apical and basal appendages) were consistent with the phylogenetic grouping. Pathogenicity tests validated that all three species isolated from tea leaves were causal agents of gray blight disease on tea plant (Camellia sinensis). This is the first description of the characteristics of the three species Pseudopestalotiopsis camelliae-sinensis, N. clavispora, and Pestalotiopsis camelliae as causal agents of tea gray blight disease in China.


The role of plasma fibronectin in platelet adhesion to collagen.
Human washed platelets were eluted from columns of Sepharose 4B linked to different preparations of collagen in order to evaluate cell adhesion. Collagen preparations characterized by low and high affinity toward platelets were identified. In our experiments, fibronectin purified from human plasma modified platelet adhesiveness, though not dramatically. When washed platelets, resuspended in a buffer containing fibronectin, were filtered on a low-affinity collagen-Sepharose, a significant increase in their adhesion occurred. A similar modification could be observed when platelets were allowed to adhere to the same collagen-Sepharose preconditioned with fibronectin. The effect of fibronectin was otherwise negligible when the high-affinity collagen was used for the experiments.


Ability of thrombocytes to acquire HLA specificity from plasma.
Thrombocytes from HLA-A1 and HLA-A2 negative donors were incubated with plasma obtained from respective HLA-positive donors. The plasma-treated thrombocytes were shown to acquire HLA specificity of the plasma as demonstrated by their ability to absorb lymphocytotoxic activity of monospecific anti-HLA sera. The data are consistent with the hypothesis that the expression of HLA antigens in cells of hematopoietic origin diminishes in the course of differentiation and maturation and that the expression of HLA antigens on thrombocytes is primarily due to absorption of these antigens from plasma.


The amino-terminal region of pp60c-src has a modulatory role and contains multiple sites of tyrosine phosphorylation.
The c-src gene product from either platelet-derived growth factor treated cells or from polyomavirus-infected cells migrates anomalously on gels, displays enhanced kinase activity, and contains additional sites of tyrosine phosphorylation within its amino-terminus. To probe the importance of these post-translational modifications, each of the five amino-terminal tyrosine residues (residues 90, 92, 131, 136, and 149) was altered to phenylalanine using site-directed mutagenesis. Except for the 136F variant, the mutants displayed enhanced kinase activity, albeit at a low level shown insufficient to induce focus formation in NIH3T3 cells. Mutagenesis of residues adjacent to tyrosines 90 and 92 also resulted in variants with enhanced kinase activity indicating that the region and not the tyrosines per se, may be involved in regulating this activity. Fingerprinting analysis demonstrated that the enhanced kinase activity brought about by these mutations occurred through a mechanism which appears to be independent of the phosphorylation state of Tyr 416 and possibly Tyr 527. Upon treatment of cells with vanadate both amino-terminal variants and transforming mutants of pp60c-src displayed a slower migrating form, designated p60+. Hence, the appearance of these p60+ proteins may be elicited either by mutations that enhance the transforming activity of pp60c-src or by perturbations within the amino-terminal region of the enzyme. The retarded mobility of p60+ was shown to be due in part to additional tyrosine phosphorylations residing at its amino-terminus. The demonstration that p60+ could be resolved into multiple bands and that amino-terminal fragments containing phosphorylated tyrosine residues were obtained regardless of which of the five tyrosines in the region was altered to phenylalanine indicates that there are multiple sites of tyrosine phosphorylation within the amino-terminal region of pp60c-src.


The Impact of Anti-rheumatic Drugs on the Seroprevalence of Anti-SARS-CoV-2 Antibodies in a Cohort of Patients With Inflammatory Arthritis: The MAINSTREAM Study.
Given the high occurrence of asymptomatic subsets, the true prevalence of SARS-CoV-2 infection in rheumatic patients is still underestimated. This study aims to evaluate the seroprevalence of SARS-CoV-2 antibodies in rheumatic musculoskeletal diseases (RMD) patients receiving immunomodulatory drugs. All consecutive patients with rheumatoid arthritis or spondyloarthritis receiving disease-modifying antirheumatic drugs (DMARDs) evaluated between 4th May and 16th June 2020 were included. All participants were tested for anti-SARS-CoV-2 antibodies (IgG, IgM, IgA) by ELISA and were questioned about previous COVID-19 symptoms and clinical course. Results were compared with healthy population from the same region and with a control group of healthy subjects diagnosed with confirmed COVID-19. The study population includes 358 patients. The overall prevalence of anti-SARS-CoV-2 antibodies (18.4%) was higher than prevalence rate based on swab-positivity (1.12%) or clinically suspected cases (10.6%), but consistent with seroprevalence observed in the healthy population. Among seropositive patients 58% were asymptomatic. Mean anti-SARS-CoV-2 titer was comparable with the control group. No differences in seroprevalence were observed according to age, sex, rheumatic disease and treatment with conventional, biologic or targeted synthetic DMARDs, whereas glucocorticoids and comorbidities resulted in higher seroprevalence rate. The results of this study are reassuring about the low impact of RMDs and immunomodulatory therapies on the risk and clinical course of COVID-19 and on humoral immune response to SARS-CoV-2 infection.


PDLIM2 acts as a cancer suppressor gene in non-small cell lung cancer via the down regulation of NF-κB signaling.
PDZ and LIM domain containing protein 2 (PDLIM2) has been identified as a vital tumor-associated gene that is aberrantly expressed in various types of tumors. Yet, the involvement of PDLIM2 in non-small cell lung cancer (NSCLC) is currently undetermined. The design of the current study was to evaluate whether PDLIM2 plays a role in NSCLC. We found that PDLIM2 expression was commonly decreased in NSCLC tissues. Moreover, low expression of PDLIM2 was also detected in NSCLC cell lines and demethylation treatment restored PDLIM2 expression. The re-expression of PDLIM2 impeded the proliferative, colony-forming, and invasive capabilities of NCLCL cells. In contrast, depletion of PDLIM2 markedly enhanced the malignant behaviors of NSCLC cells. Notably, PDLIM2 overexpression downregulated the expression of nuclear factor (NF)-κB p65 subunit and repressed NF-κB transcription reporter activity in NSCLC cells. The overexpression of p65 significantly reversed PDLIM2-mediated antitumor effects in NSCLC cells. Additionally, the Xenograft tumor formation assay revealed that the overexpression of PDLIM2 markedly restricted the tumor growth of NSCLC in vivo. Overall, our study confirms that PDLIM2 acts as a tumor-inhibitor in NSCLC through the inactivation of NF-κB, suggesting PDLIM2 as a candidate therapeutic target for NSCLC.


Oxidized LDL attenuates apoptosis in monocytic cells by activating ERK signaling.
Low concentrations of oxidized low density lipoprotein (OxLDL) are cytoprotective for phagocytes, although the underlying mechanisms remain unclear. We investigated signaling pathways used by OxLDL to attenuate apoptosis in monocytic cells. OxLDL at 25-50 mug/ml inhibited staurosporine-induced apoptosis in THP-1 cells and mouse peritoneal macrophages, and it was cytoprotective in human primary monocytes upon serum withdrawal. Attenuated cell demise was reversed by blocking extracellular signal-regulated kinase (ERK) signaling. Translocation of cytochrome c to the cytosol was attenuated by OxLDL, which again demanded ERK signaling. Analysis of Bcl-2 family proteins revealed phosphorylation of Bad at serine 112 as well as ERK-dependent inhibition of Mcl-1 degradation. Although the formation of reactive oxygen species (ROS) is an established signal generated by OxLDL, ROS scavengers did not interfere with cell protection by OxLDL. Thus, activation of the ERK signaling pathway by OxLDL is important to protect phagocytes from apoptosis.


Using video-oriented instructions to speed up sequence comparison.
This document presents an implementation of the well-known Smith-Waterman algorithm for comparison of proteic and nucleic sequences, using specialized video instructions. These instructions, SIMD-like in their design, make possible parallelization of the algorithm at the instruction level. Benchmarks on an ULTRA SPARC running at 167 MHz show a speed-up factor of two compared to the same algorithm implemented with integer instructions on the same machine. Performance reaches over 18 million matrix cells per second on a single processor, giving to our knowledge the fastest implementation of the Smith-Waterman algorithm on a workstation. The accelerated procedure was introduced in LASSAP--a LArge Scale Sequence compArison Package software developed at INRIA--which handles parallelism at higher level. On a SUN Enterprise 6000 server with 12 processors, a speed of nearly 200 million matrix cells per second has been obtained. A sequence of length 300 amino acids is scanned against SWISSPROT R33 (1,8531,385 residues) in 29 s. This procedure is not restricted to databank scanning. It applies to all cases handled by LASSAP (intra- and inter-bank comparisons, Z-score computation, etc.


[Intestinal absorption of different combinations of active compounds from Gegenqinlian decoction by rat single pass intestinal perfusion in situ].
The aim is to study the intestinal absorption of different combinations of active compounds out of Gegenqinlian decoction. Rat single pass intestinal perfusion model with jugular vein cannulated was used. Samples were obtained continuously from the outlet perfusate and the mesenteric vein. The levels of puerarin, daidzin, liquilitin, baicalin, wogonoside, jatrorrhizine, berberine and palmatine were determined by LC-MS/MS and their permeability coefficients were calculated. The results showed that Glycyrrhiza could promote the absorption of the active ingredients in Pueraria which is the monarch herb; meanwhile, Pueraria also played a role in promoting the absorption of liquilitin. Based on the Gegenqinlian decoction and the different combinations experiments, the results concerning the absorption of baicalin and wogonoside were as follows. For baicalin, Pueraria and Glycyrrhiza could promote its absorption and the effect of Pueraria was more obvious. For wogonoside, Pueraria could also promote its absorption, while Glycyrrhiza played a opposite role. Pueraria and Glycyrrhiza both played a part in promoting the absorption of jateorhizine, berberine and palmatine, the effective compounds in Coptis.


Predictors of short-term and long-term incontinence after robot-assisted radical prostatectomy.
Purpose To determine retrospectively the prognostic factors for urinary incontinence following robot-assisted radical prostatectomy (RARP). Methods Altogether, 180 patients with localized prostate cancer underwent RARP (same surgeon). Preoperative physical status, disease characteristics, laboratory findings, and surgical technique were recorded and the patients checked 1, 6, 12, and 24 months after RARP regarding their contribution to predicting post-prostatectomy urinary incontinence (PPI). Results Overall, 114 (63.3%) patients had PPI 1 month after RARP and 19 patients (16.0%) at 24 months. Univariate analysis showed that age was a significant factor for predicting PPI at 1 month. PPI predictors at 24 months were age, body mass index, preoperative serum albumin level, previous transurethral resection of the prostate, total operative time, and bladder neck sparing. Multivariate analysis indicated that age and total operative time were significant predictors. Conclusion Older age and longer operative time were highly relevant to short- and long-term PPI occurrence after RARP.


Evaluation of shading of fish farming ponds as a larval control measure against Anopheles sundaicus Rodenwaldt (Diptera:Culicidae).
Larval density of Anopheles sundaicus in shaded and unshaded fish farming ponds was monitored at a coastal village in North Sumatra, Indonesia. The average density in the experimentally shaded ponds with Nipa leaves was reduced to < 1/10. Disappearance of algae and decline of water temperature also were observed, but the salinity did not change. The larval density was lower in ponds with Tilapia sp than without fish, but that in ponds with Ophiocephalus sp was not significantly lower. Dominant insects collected by dipping were Agrionidae and Libellulidae (Odonata), Corixidae, Notonectidae and Nepidae (Hemiptera), and Dytiscidae (Coleoptera). Density of nymphs of both Odonata and Notonectidae was higher in unshaded ponds. Taking into account longevity of the materials, and easiness in construction and applicability, shading by Nipa leaves was an easy and effective larval control measure against A. sundaicus in non-operating small fish farming ponds if leaves were renewed once in every two months.


Changes in CO2 responsiveness and in autoregulation of the cerebral circulation during and after halothane-induced hypotension.
CO2 responsiveness of the cerebral circulation has been measured in baboons before, during, and after halothane-induced hypotension. At a systolic blood pressure (BP) of 60 mmHg, C02 responsiveness was abolished, but was maintained at higher levels of BP. After hypotension, CO2 responsiveness returned to control values. Autoregulation to BP increases induced by intravenous noradrenaline was impaired when cerebral perfusion pressure during the hypotensive period had been below 30-40 mmHg. It is concluded that at levels of halothane-induced hypotension commonly employed clinically, CO2 responsiveness of the cerebral circulation may be absent. The return of CO2 responsiveness in the post-hypotensive phase argues in favour of controlled hyperventilation after neurosurgery which has involved induced hypotension.


Assessment of parental discipline in daily life.
The use of ecological momentary assessment (EMA) for studying parenting has been rare. We examined the psychometric properties and structural validity of an EMA Parenting Scale based on 32 mothers' reports of their parenting over a period of 10 consecutive days, and explored the acceptance of the scale and compliance with the procedure. The results suggested that the EMA Parenting Scale was well accepted for the assessment of daily parenting, and that it consistently captured the overreactive and lax dimensions of parenting across different episodes of child misbehavior. Moreover, multilevel analyses suggested that the scale was sensitive to change across different parenting episodes, and that it reliably assessed the dimensions at both the personal and situational levels.


Regional Anesthetic Use in Trans-Hiatal Esophagectomy. Are They Worth Consideration? A Case Series.
Esophagectomy traditionally has high levels of perioperative morbidity and mortality due to surgical techniques and case complexity. While thoracic epidural analgesia (TEA) is considered first-line for postoperative analgesia after esophagectomy, complications can arise related to its sympathectomy and mobility impairment. Additionally, it has been shown that postoperative outcomes are improved with early extubation following esophagectomy. Our aim is to describe the impact of transversus abdominis plane (TAP) blocks on extubation rates following esophagectomy when uncoupled from TEA. This is a case series of 42 patients who underwent trans-hiatal esophagectomy between 2019 and 2022 who received a TAP block without TEA. The primary outcomes of interest were the rates of extubation within the operating room (OR) and reintubation. Secondary outcomes included: intensive care unit (ICU) and hospital length of stay (LOS), opioid pain medication use, post-operative hypotension, fluid administration, postoperative pain scores, development of anastomotic leak, and 30-day readmission. The mean age at operation was 63 years and 97.6% of patients were represented by American Society of Anesthesia (ASA) physical status class III or IV. Thirty-four (81%) patients immediately extubated postoperatively. Nine patients (21.4%) underwent reintubation during their hospital course. Only seven patients (16.7%) required vasopressors postoperatively. The median LOS was five days in the ICU and 10 days in the hospital. TAP block alone was found to be equivalent to TAP with additional regional blocks (TAP+) on the basis of immediate extubation, reintubation, ICU and hospital LOS, and reported postoperative pain. The results of this study demonstrated immediate extubation is possible using TAP blocks while limiting post-operative hypotension and fluid administration. This was shown despite the elevated comorbidity burden of this study's population. Overall, this study supports the use of TAP blocks as a possible alternative for primary analgesia in patients undergoing trans-hiatal esophagectomy. This study includes participants who were retrospectively registered. IRB# 037.HPB.2018.R.


[Cotrimoxazole plus rifampicin in the treatment of staphylococcal osteoarticular infection].
To evaluate the efficacy and safety of cotrimoxazol plus rifampicin in staphylococcal osteoarticular infection. Open, non-comparative study of adult hospitalized patients with documented staphylococcal bone infection. From Feb 1989 to Dec 1993 28 episodes of staphylococcal bone infection were treated in 14 men and 13 women; the mean age was 48 +/- 21 years (range, 11-84). They received cotrimoxazol (7 mg/kg/day of trimethoprim) plus rifampicin (600-1200 mg/day), both orally, every 8 to 12 h with a mean duration of treatment of 34.2 +/- 8.2 days (range, 21 to 55 days). This antibiotic regimen was initiated at the same time that appropriate surgery for each specific condition was undertaken. Diagnoses were postsurgical osteomyelitis (10 cases), infected total hip prostheses (4 cases, one with 2 episodes), osteomyelitis secondary to external pin fixation (5 cases), soft tissue infections linked to orthopedic implants (3 cases), two cases of metatarsal osteomyelitis (one diabetic foot and one patient with polineuropathy), and one case each of chronic osteomyelitis of femur, hematogenous lumbar spondylitis and posttraumatic osteomyelitis. Four patients had bacteremia. The duration of the infection, prior to surgery was less than one month in 12 episodes, 1 month to 2 years in 14, and in 2 cases, of 10 and 13 years, respectively. In 23 episodes the causal agent was Staphylococcus aureus and in 5 cases it was coagulase-negative staphylococci. Patients had received previous parenteral therapy with other antimicrobials during 2-40 days (X: 18.6 +/- 10.2 days). All patients but one had resolution of the infection and are currently asymptomatic 6 months to 5 years posttreatment in the 21 evaluable cases (X: 38 +/- 13.1 months). Five patients had adverse effects secondary to the antibiotic combination and in three these were severe enough to discontinue the antimicrobials. In no case of the 11 patients with post-treatment control cultures were staphylococci recovered from the wound. The combination of cotrimoxazole plus rifampicin, both given orally, was highly effective in this selected group of patients. This combination should be considered as a useful alternative therapy of staphylococcal bone infection and deserves further study.