Metastatic neuroendocrine tumor found on screening mammogram.
Tumor metastatic to the breast is uncommon, and a neuroendocrine tumor metastatic to the breast is even more unusual. The breast lesion can be the first manifestation of a nonmammary malignancy. Metastatic neuroendocrine tumors to the breast have been described in the literature in case reports or very small case series. Because of the small number, current treatment recommendations are not well defined. We present a case report of a metastatic neuroendocrine tumor that first presented as a breast lesion on screening mammography. Accurate diagnosis is important for appropriate management, as the treatment for a breast primary neuroendocrine tumor is different than a neuroendocrine tumor metastatic to the breast.


High-Throughput Identification of miR-596 Inducing p53-Mediated Apoptosis in HeLa and HCT116 Cells Using Cell Microarray.
miRNAs play a key role in the regulation of gene networks in mammalian cells. However, little is known about their roles and functions in the apoptosis pathway. Here, we conducted a whole-genome miRNA screening for apoptosis and identified more than 100 miRNAs as apoptosis inducers. To further explain the roles of these mRNAs in apoptosis, a second round of screening was conducted between p53 +/+ and -/- cells. Among the hits, miR-596 was identified as a regulator of p53. The overexpression of miR-596 significantly increased p53 at the protein level, thereby inducing apoptosis. We also demonstrated that Smurf1 was the direct target of miR-596. Previously, Smurf1 was reported to attenuate the level of p53 through binding and stabilizing MDM2, a p53 inhibitor. Consequently, by targeting Smurf1, miR-596 indirectly increased the p53 level in mammalian cells. Moreover, our study demonstrated that miR-596 had other antitumor characteristics, such as inhibiting migration and proliferation. The data from the GEO dataset revealed that the high expression of miR-596 contributed to survival benefits among cancer patients. These results make miR-596 a potential antitumor factor for future biomedical applications.


Remarkable differences in photoluminescence properties between BaF2:Eu3+ microrods and nanorods.
The preparation process and photoluminescent properties of one-dimensional BaF2:Eu3+ nanorods (NRs) and microrods (MRs) were investigated. The results indicate that the samples were NRs with uniform diameters in the range of 30-50 nm, and lengths in the range of 1.2-3 microm when cooled to room temperature naturally. However, the samples were MRs with length of 1.5-3.0 microm and outer diameters of 200-250 nm when cooled to room temperature immediately. Furthermore, the relative intensity of 5D0 --> 7F2 depended on the two structures obtained under different temperatures. This work demonstrates that a MRs may be more favorable than NRs for photoluminescence.


Determination of paramagnetic ferrous gel sensitivity in low energy x-ray beam produced by a miniature accelerator.
The INTRABEAM Carl Zeiss Surgical system (Oberkochen, Germany) is a miniature accelerator producing low energy photons (50 keV maximum). The published dosimetric characterization of the INTRABEAM was based on detectors (radiochromic films or ionization chambers) not allowing measuring the absorbed dose in the first millimeters of the irradiated medium, where the dose is actually prescribed. This study aims at determining with Magnetic Resonance Imaging (MRI) the sensitivity of a paramagnetic gel in order to measure the dose deposit produced with the INTRABEAM from 0 to 20 mm. Although spherical applicators are mostly used with the INTRABEAM system for breast applications, this study focuses on surface applicators that are of interest for cutaneous carcinomas. The irradiations at 12 different dose levels (between 2 Gy and 50 Gy at the gel surface) were performed with the INTRABEAM and a 4 cm surface applicator. The gel used in this study is a new « sensitive » material. In order to compare gel sensitivity at low energy with high energy, gels were irradiated by an 18 MV photon beam produced by a Varian Clinac 2100 CD. T2 weighted multi echo MRI sequences were performed with 16 echo times. The T2 signal versus echo times was fitted with a mono-exponential function with 95% confidence interval. The calibration curve determined at low energy is a linear function (r2 = 0.9893) with a sensitivity of 0.0381 s-1.Gy-1, a similar linear function was obtained at high energy (0.0372 s-1.Gy-1 with r2 = 0.9662). The calibration curve at low energy was used to draw isodose maps from the MR images. The PDD (Percent Depth Dose) determined in the gel is within 5%-1mm of the ionization chamber PDD except for one point. The dosimetric sensitivity of this new paramagnetic ferrous gel was determined with MRI measurements. It allowed measuring the dose distribution specifically in the first millimeters for an irradiation with the INTRABEAM miniature accelerator equipped with a surface applicator.


When is LABA/LAMA Better than LAMA in GOLD Group B or D Patients for Reducing Acute Exacerbations of COPD?
Long-acting β2-agonist (LABA)/long-acting muscarinic-antagonist (LAMA) dual therapy has been found to be more effective than LAMA monotherapy in the treatment of chronic obstructive pulmonary disease (COPD). However, among patients with group B or D COPD, the characteristics of patients for whom LABA/LAMA dual therapy is superior to LAMA monotherapy in minimizing acute exacerbations remain unknown. With data from a prospective COPD cohort, subgroup analyses were conducted to determine whether LABA/LAMA dual therapy was superior to LAMA monotherapy in reducing the rate of acute exacerbations in group B and D COPD patients. Group B and D COPD patients taking LAMA or LABA/LAMA were enrolled according to the 2022 Global initiative for Chronic Obstructive Pulmonary Disease guidelines. A total of 737 patients were included in this study: 600 with group B COPD and 137 with group D COPD. Compared with patients taking LAMA monotherapy, those taking LABA/LAMA had a significantly lower incidence of acute exacerbations over 1 year. In the subgroup of patients ≥70 years old, there was a significantly lower risk of severe COPD exacerbations among group B patients taking LABA/LAMA than among those taking LAMA monotherapy (odds ratio [OR], 0.258; 95% confidence interval [CI], 0.095-0.703). In contrast, in the subgroup of group D patients with COPD Assessment Test scores ≥25, compared with LAMA monotherapy, LABA/LAMA treatment was associated with lower risk of severe COPD exacerbations (OR, 0.115; 95% CI, 0.018-0.749). The combination of LABA and LAMA was found to be superior to LAMA monotherapy, especially for treating older adults with group B COPD, as well as for group D patients with severe symptoms.


Natural products to drugs: natural product derived compounds in clinical trials.
Natural product and natural product-derived compounds that are being evaluated in clinical trials or in registration (current 31 December 2004) have been reviewed. Natural product derived drugs launched in the United States of America, Europe and Japan since 1998 and new natural product templates discovered since 1990 are discussed.


Mental disorder and comorbidity among runaway and homeless adolescents.
To investigate prevalence of mental disorder and comorbidity among homeless and runaway adolescents in small to medium sized cities in four Midwestern states. The study presents lifetime, 12-month prevalence, and comorbidity rates for five mental disorders (conduct disorder, major depressive episode, posttraumatic stress disorder, alcohol abuse, and drug abuse) based on UM-CIDI and DISC-R structured interviews from the baseline interviews of a longitudinal diagnostic study of 428 (187 males; 241 females) homeless and runaway adolescents aged 16-19 years (mean age = 17.4 years, SD = 1.05). The data were collected by full-time street interviewers on the streets and in shelters in eight Midwestern cities of various populations. Separate logistic regression models were used to investigate factors associated with meeting criteria for any disorder and two or more disorders. Lifetime prevalence rates were compared with rates for same-aged respondents from the National Comorbidity Survey (NCS). Homeless and runaway adolescents were six times more likely than same-aged NCS respondents to meet criteria for two or more disorders and were from two to 17 times more likely to meet criteria for individual disorders than. Homeless and runaway adolescents in small and mid-sized Midwestern cities report significant levels of mental disorder and comorbidity that are comparable and often exceed that reported in studies of larger magnet cities.


[Comparative analysis of radical surgical treatment of periampullary tumors].
Retrospective analysis of patients with periampullary tumors undergoing pancreatoduodenectomy. A retrospective review included 48 patients with resectable periampullary tumors. Patients were divided into two groups according to the localization of cancer. Group 1 - pancreatic head tumors (n=27), group 2 - tumors of major duodenal papilla (n=21). Survival was analyzed depending on chemotherapy and vascular resection. All patients underwent standard pancreatoduodenectomy with anastomosis on a single intestinal loop and D2 lymph node dissection. Annual survival rate in patients with pancreatic head tumors was significantly higher compared with patients with tumors of major duodenal papilla (69.1% vs. 95.6%, p<0.05). Moreover, vascular resection (PV/SMV) was significant predictor of survival (p<0.01). There was a noticeable tendency to impaired survival if adjuvant chemotherapy was absent. Pancreatoduodenectomy is preferred for periampullary tumors since this procedure significantly increases life expectancy. Postoperative adjuvant chemotherapy is recommended in all patients regardless histological data because combined approach is associated with improved survival.


Image-guided thermal ablation of benign thyroid nodules.
Benign thyroid nodules are a common disease in the general population. Most often, they are completely asymptomatic and discovered occasionally during routine ultrasound examinations, and do not require any treatment. When thyroid nodules become symptomatic, surgical excision is still considered standard treatment. In the last few years, several experiences in the treatment of benign thyroid nodules through image-guided percutaneous thermal ablation have been reported with encouraging results, so that currently, these treatments are often proposed as first-choice options for patients with symptomatic benign thyroid nodules. In this paper, we discuss the present literature on the topic, focusing on different techniques available for image-guided percutaneous ablation, particularly radiofrequency (RFA), laser (LA), microwave (MWA), and high-intensity-focus ultrasound (HIFU). Little evidence about the efficacy of MWA and HIFU is now available. According to the literature, good results have been obtained with RFA and LA. Regarding RFA, volume reduction after ablative treatment has been found to range from 47 to 84 % at 3-6 months, and from 62 to 93 % at 1 year; LA also seems to be effective in achieving shrinkage of thyroid nodules, with volume reduction from 37 to 81 % at 3-6 months, and from 13 to 82 % at 1-year follow-up. Moreover, applications of advanced image-guidance modality, such as contrast-enhanced ultrasound and virtual navigation with fusion imaging, are discussed.


Incidence of Guillain-Barré Syndrome post COVID-19: a systematic review of case reports and case series.
The purpose of this systematic review was to study the incidence, risk factors and patients subjected to Guillain-Barré syndrome (GBS) after COVID-19. For qualitative assessment and assessing the methodological quality, the Cochrane Handbook for Systematic Reviews of Interventions and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020) checklist were utilized. Data from PubMed, Cochrane, Embase, CINAHIL, Medline, ResearchGate, and Scopus were searched. The relevant studies involved patients with confirmed COVID-19 diagnosis by RT-PCR, and GBS diagnosis based on typical clinical symptoms and/or confirmatory diagnostic results. A total of 12 English relevant articles (6 papers were case reports and 8 were case series with a total of 32 patients) published in a peer-reviewed journal from 2019 to 2021 were included. Following the review methodology, two independent raters were responsible for retrieving, extracting and checking for data eligibility. Demographic characteristics are presented as frequencies and percentages. Based on distribution of values, continuous data were expressed as median and interquartile range (IQR). Out of 32 patients, 26 patients reported neurological symptoms, 6 cases went unnoticed, 7 cases showed involvement of the cranial nerves, 12 cases did not, and 13 cases went unreported. It is too early to draw any conclusions concerning a potential relationship between SARS-CoV-2 infection and GBS. More large-scale observational studies are required to understand the pathogenesis of SARS-CoV-2-associated GBS and to demonstrate a definite causal relationship between GBS and SARS-CoV-2 infection.


Involvement of elevated ASF1B in the poor prognosis and tumorigenesis in pancreatic cancer.
Anti-silencing function 1B (ASF1B) has been reported to be associated with the occurrence of many kinds of tumors. However, the biological effect and action mechanism of ASF1B in pancreatic cancer (PC) tumorigenesis remain unclear. The expression and prognosis value of ASF1B in PC were analyzed using GEPIA, GEO, and Kaplan-Meier plotter databases. The diagnostic value of ASF1B in PC was determined by receiver operating characteristic curve. The relationship between ASF1B expression and the clinical feathers in PC was investigated based on TCGA. qRT-PCR and western blot analyses were used to measure ASF1B expression in PC cells. Cell proliferation was evaluated by MTT and EdU assays, and apoptosis was examined by TUNEL and caspase-3 activity assays. Western blot analysis was utilized to detect the expression of proliferating cell nuclear antigen (PCNA), cyclin D1, Bax, Bcl-2, and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling proteins. ASF1B was overexpressed in several digestive cancers, including PC. Upregulated ASF1B was correlated with the poor prognosis and clinical features in PC patients. The area under the curve (AUC) value of ASF1B was 0.990. ASF1B was also overexpressed in PC cells. ASF1B silencing inhibited PC cell proliferation, promoted apoptosis, and increased caspase-3 activity, which were accompanied by the reduction of PCNA and cyclin D1 expression and increase of the ratio of Bax/Bcl-2 expression. Additionally, ASF1B silencing suppressed the PI3K/Akt pathway and 740Y-P treatment partially abolished the effects of ASF1B knockdown on PC cells. In conclusion, ASF1B silencing retarded proliferation and promoted apoptosis in PC cells by inactivation of the PI3K/Akt pathway.


[Solid tumours of human primary hepatocellular carcinoma cell-lines in hypothymic mice: a model for biochemical and therapeutic studies (author's transl)].
HBsAg producing cell-lines of human primary hepatocellular carcinomas express a multitude of differentiated hepatocyte functions. They also grow in hypothymic (nude) mice as solid tumours. Here we describe the subcutaneous injection of cell-lines PLC/PRF/5, Hep 3B and Mahlavu (HBsAg negative) into hypothymic mice to produce a high tumour take without prior immunosuppressive treatment. Serial transplantation of tumour fragments into new animals allows the development of large homogeneous experimental groups and a substantial multiplication of tumour cell mass. The transplanted tumours from PLC/PRF/5 and Hep 3B cells continue to synthesize HBsAg and alpha-fetoprotein, and they secrete these proteins into the blood of their hosts. Fibrinogen and alpha 1-antitrypsin can be demonstrated in the cells of these two tumours but not in tumours originating from Mahlavu cells. This model offers experimental conditions to study the function of solid human primary liver cell carcinomas under the influence of an intact organism.


[Therapy of chronic hepatitis (author's transl)].
Therapy of chronic hepatitis as practized today is discussed, including general therapeutic procedures, the so-called "liver-protective substances", and drug therapy of chronic aggressive hepatitis and of liver cirrhosis. A causal treatment of chronic hepatitis is unknown; prognosis however can be improved by treatment with glucocorticoids as demonstrated by controlled clinical trials. A combination with azathioprin does have similarly good results with a decreased frequency of the unwanted side effects of the 2 drugs. The effects of other immunosuppressive drugs and of D-penicillamin cannot yet be evaluated sufficiently at present.


Apparent requirement for CD4+ T cells in primary anti-herpes simplex virus cytotoxic T-lymphocyte induction can be overcome by optimal antigen presentation.
Mice depleted in vivo of either CD4+ or CD8+ T cells were used to define the requirement for interaction between the two T subsets for the induction and maturation of a herpes simplex virus (HSV) cytotoxic T-lymphocyte (CTL) response. Whereas C3H mice generated normal CD8+ CTL in the absence of CD4+ T cells, responses were undetectable in BALB/c mice. However, the role of CD4+ T cells appeared to be to supply helper factors for CTL maturation, as the numbers of CTL precursors in CD4-depleted mice were similar to those in nondepleted animals. Moreover, CTL responses were demonstrable if CD4-depleted primed populations were stimulated with antigen or supplied with a source of helper factors. The optimal means of presenting antigen appeared to be via dendritic cells. Our results indicated that CD8+ cells alone were fully capable of differentiating into CTL provided they were appropriately stimulated with antigen. Possibly, the environment necessary for this to occur in vivo is usually lacking, accounting for the fact that in the mouse, it usually is not possible to demonstrate HSV-specific CTL unless cells are cultured or restimulated in vitro.


Resistance to conventional cardiopulmonary resuscitation in witnessed out-of-hospital cardiac arrest patients with shockable initial cardiac rhythm.
Shockable initial cardiac rhythm is a key predictor of survival after out-of-hospital cardiac arrest (OHCA). However, not all patients with shockable OHCA achieve return of spontaneous circulation (ROSC) via conventional cardiopulmonary resuscitation (CPR). Therefore, we retrospectively analyzed patients with witnessed OHCA and shockable initial cardiac rhythm to identify the resistance factors for conventional CPR. We retrospectively analyzed consecutive patients with witnessed OHCA and shockable initial cardiac rhythm who were admitted to our hospital between October 2009 and October 2014. We then compared the baseline characteristics, pre-hospital clinical course, and causes of the cardiopulmonary arrest among patients who achieved ROSC via conventional CPR and patients who did not achieve ROSC via conventional CPR and underwent extracorporeal CPR (ECPR). A total of 85 patients achieved ROSC via conventional CPR (non-ECPR group) and 40 patients did not achieve ROSC via conventional CPR and underwent ECPR (ECPR group). Among these 125 patients, 113 had known causes for their cardiopulmonary arrest, including 66 cases (53%) of acute myocardial infarction (AMI). There were no significant differences in the causes of arrest between the non-ECPR and ECPR cases. However, among the 66 cases of AMI (43 non-ECPR and 23 ECPR), the rate of non-recanalization during the initial coronary angiography was significantly higher among the ECPR cases (non-ECPR: 58% vs. ECPR: 87%; p=0.03). The major cause of witnessed OHCA with shockable initial cardiac rhythm was AMI, and resistance to conventional CPR was related to continuous myocardial ischemia.


p38 MAPK as a potential therapeutic target for inflammatory osteolysis.
Inflammatory osteolysis is a relatively frequent and incapacitating complication of rheumatoid arthritis and other inflammatory diseases, and is induced by accelerated osteoclast recruitment and activation in bone under the aegis of cytokines produced in the inflammatory environment. The success of antitumor necrosis factor-alpha and interleukin-1 therapy in correcting this condition highlights the central role of these cytokines in this process. Recent years have witnessed a revolution in understanding the molecular mechanism and pathogenesis of this family of diseases. It is now clear that p38 mitogen-activated protein kinase plays an essential role in the production of proinflammatory cytokines and cytokine-induced osteoclastogenesis, thus providing a potential therapeutic target for prevention of pathologic bone loss.


Endothelial Hypoxia-Inducible Factor-1α Promotes Atherosclerosis and Monocyte Recruitment by Upregulating MicroRNA-19a.
Chemokines mediate monocyte adhesion to dysfunctional endothelial cells (ECs) and promote arterial inflammation during atherosclerosis. Hypoxia-inducible factor (HIF)-1α is expressed in various cell types of atherosclerotic lesions and is associated with lesional inflammation. However, the impact of endothelial HIF-1α in atherosclerosis is unclear. HIF-1α was detectable in the nucleus of ECs covering murine and human atherosclerotic lesions. To study the role of endothelial HIF-1α in atherosclerosis, deletion of the Hif1a gene was induced in ECs from apolipoprotein E knockout mice (EC-Hif1a(-/-)) by Tamoxifen injection. The formation of atherosclerotic lesions, the lesional macrophage accumulation, and the expression of CXCL1 in ECs were reduced after partial carotid ligation in EC-Hif1a(-/-) compared with control mice. Moreover, the lesion area and the lesional macrophage accumulation were decreased in the aortas of EC-Hif1a(-/-) mice compared with control mice during diet-induced atherosclerosis. In vitro, mildly oxidized low-density lipoprotein or lysophosphatidic acid 20:4 increased endothelial CXCL1 expression and monocyte adhesion by inducing HIF-1α expression. Moreover, endothelial Hif1a deficiency resulted in downregulation of miR-19a in atherosclerotic arteries determined by microRNA profiling. In vitro, HIF-1α-induced miR-19a expression mediated the upregulation of CXCL1 in mildly oxidized low-density lipoprotein-stimulated ECs. These results indicate that hyperlipidemia upregulates HIF-1α expression in ECs by mildly oxidized low-density lipoprotein-derived unsaturated lysophosphatidic acid. Endothelial HIF-1α promoted atherosclerosis by triggering miR-19a-mediated CXCL1 expression and monocyte adhesion, indicating that inhibition of the endothelial HIF-1α/miR-19a pathway may be a therapeutic option against atherosclerosis.


Realization of Microwave Quantum Circuits Using Hybrid Superconducting-Semiconducting Nanowire Josephson Elements.
We report the realization of quantum microwave circuits using hybrid superconductor-semiconductor Josephson elements comprised of InAs nanowires contacted by NbTiN. Capacitively shunted single elements behave as transmon circuits with electrically tunable transition frequencies. Two-element circuits also exhibit transmonlike behavior near zero applied flux but behave as flux qubits at half the flux quantum, where nonsinusoidal current-phase relations in the elements produce a double-well Josephson potential. These hybrid Josephson elements are promising for applications requiring microwave superconducting circuits operating in a magnetic field.


Fas Promotes T Helper 17 Cell Differentiation and Inhibits T Helper 1 Cell Development by Binding and Sequestering Transcription Factor STAT1.
The death receptor Fas removes activated lymphocytes through apoptosis. Previous transcriptional profiling predicted that Fas positively regulates interleukin-17 (IL-17)-producing T helper 17 (Th17) cells. Here, we demonstrate that Fas promoted the generation and stability of Th17 cells and prevented their differentiation into Th1 cells. Mice with T-cell- and Th17-cell-specific deletion of Fas were protected from induced autoimmunity, and Th17 cell differentiation and stability were impaired. Fas-deficient Th17 cells instead developed a Th1-cell-like transcriptional profile, which a new algorithm predicted to depend on STAT1. Experimentally, Fas indeed bound and sequestered STAT1, and Fas deficiency enhanced IL-6-induced STAT1 activation and nuclear translocation, whereas deficiency of STAT1 reversed the transcriptional changes induced by Fas deficiency. Thus, our computational and experimental approach identified Fas as a regulator of the Th17-to-Th1 cell balance by controlling the availability of opposing STAT1 and STAT3 to have a direct impact on autoimmunity.


Prevalence of wound infections and postoperative complications after total elbow arthroplasty for rheumatoid arthritis: A meta-analysis.
This study aimed to systematically evaluate the prevalence of surgical site wound infections and postoperative complications after total elbow arthroplasty (TEA) in patients with rheumatoid arthritis (RA) for clinical research and application. Embase, PubMed, Cochrane Library, CNKI, VIP, CBM, and Wanfang databases were electronically searched to collect clinical studies on the application of TEA in the treatment of RA from inception to August 2023. Two independent researchers performed literature screening, data extraction, and quality assessment. A meta-analysis was performed using the R 4.3.1 software. Overall, 26 studies with a total of 2374 patients were included. The results of the meta-analysis revealed that after TEA in patients with RA, the prevalence of surgical site wound infections and postoperative complications was 3.37% (95% confidence interval [CI]: 2.68%-4.13%), and 31.63% (95% CI: 24.97%-38.28%), respectively. The prevalence of surgical site wound infections is low, whereas that of postoperative complications is high; thus, the safety of TEA remains debatable. Owing to limitations on the quality and number of included studies, the findings need to be verified in higher-quality studies.


Combining different functions to describe milk, fat, and protein yield in goats using Bayesian multiple-trait random regression models.
We proposed multiple-trait random regression models (MTRRM) combining different functions to describe milk yield (MY) and fat (FP) and protein (PP) percentage in dairy goat genetic evaluation by using Bayesian inference. A total of 3,856 MY, FP, and PP test-day records, measured between 2000 and 2014, from 535 first lactations of Saanen and Alpine goats, including their cross, were used in this study. The initial analyses were performed using the following single-trait random regression models (STRRM): third- and fifth-order Legendre polynomials (Leg3 and Leg5), linear B-splines with 3 and 5 knots, the Ali and Schaeffer function (Ali), and Wilmink function. Heterogeneity of residual variances was modeled considering 3 classes. After the selection of the best STRRM to describe each trait on the basis of the deviance information criterion (DIC) and posterior model probabilities (PMP), the functions were combined to compose the MTRRM. All combined MTRRM presented lower DIC values and higher PMP, showing the superiority of these models when compared to other MTRRM based only on the same function assumed for all traits. Among the combined MTRRM, those considering Ali to describe MY and PP and Leg5 to describe FP (Ali_Leg5_Ali model) presented the best fit. From the Ali_Leg5_Ali model, heritability estimates over time for MY, FP. and PP ranged from 0.25 to 0.54, 0.27 to 0.48, and 0.35 to 0.51, respectively. Genetic correlation between MY and FP, MY and PP, and FP and PP ranged from -0.58 to 0.03, -0.46 to 0.12, and 0.37 to 0.64, respectively. We concluded that combining different functions under a MTRRM approach can be a plausible alternative for joint genetic evaluation of milk yield and milk constituents in goats.


[Treatment of congenital clubfoot with the Ponseti method].
The primary therapy for congenital clubfoot is non-surgical involving manipulation and serial casting. With traditional casting, relatively large numbers of feet require extensive surgery to achieve full correction. The purpose of this study was to evaluate the efficacy of the Ponseti method. Between 1.1.2004 und 31.12.2005, 29 patients with 41 clubfeet were treated with the Ponseti method. Only patients without any prior treatment were included. Classification followed Pirani's score. The number of casts to full correction, tenotomies, number of posteromedial releases, dorsi-, plantarflexion and hindfoot position were documented. The follow-up time was 1-9 months, the average follow-up time was 9.1 months. 39 clubfeet were successfully treated with the Ponseti method. The average Pirani score was 4.9. Percutaneous tenotomies were necessary in 34 of the clubfeet. Average dorsiflexion was 19 degrees and plantarflexion 42 degrees . After failed Ponseti treatment 2 feet were treated with a posteromedial release. With the Ponseti method the need for extensive corrective surgery is greatly reduced. We recommend the Ponseti method as standard therapy in clubfoot management.


Ventilator-Associated Pneumonia and Its Responsible Germs; an Epidemiological Study.
Ventilator-associated pneumonia (VAP) is one of the most common hospital infections and a side effect of lengthy stay in intensive care unit (ICU). Considering the ever-changing pattern of common pathogens in infectious diseases and the raise in prevalence of hospital infections, the present study was designed aiming to determine the prevalence of VAP and its bacterial causes. In this cross-sectional study, the medical profiles of all the patients under mechanical ventilation, who had no symptoms of pneumonia at the time of intubation and developed new infiltration in chest radiography after 48 hours under mechanical ventilation along with at least 2 of the symptoms including fever, hypothermia, leukocytosis, leukopenia, or purulent discharge from the lungs, were evaluated. Demographic data, clinical and laboratory findings, and final outcome of the patients were extracted from the patient's clinical profile and reported using SPSS version 20 and descriptive statistics. 518 patients with the mean age of 62.3 ± 20.8 years were evaluated (50.9% female). Mean time interval between intubation and showing symptoms was 10.89 ± 12.27 days. Purulent discharges (100%), leukocytosis (71.9%), fever (49.1%), hypothermia (12.3%), and leukopenia (8.8%) were the most common clinical and laboratory symptoms and acinetobacter baumannii (31.58%) and klebsiella pneumoniae (29.82%) were the most common germs growing in sputum cultures. 19 (33.3%) cases of pan drug resistance (PDR) and 10 (17.5%) cases of extensive drug resistance (XDR) were seen. Mortality due to VAP was 78.9% and there was no significant correlation between age (p = 0.841), sex (p = 0.473), ICU admission (p = 0.777), duration of hospitalization (p = 0.254), leukocytosis (p = 0.790), leukopenia (p = 0.952), fever (p = 0.171), hypothermia (p = 0.639), type of culture (p = 0.282), and type of antibiotic resistance (p = 0.066) with mortality. Prevalence of VAP and its associated mortality were 11% and 78.9%, respectively. The most common symptoms and signs were purulent discharge, leukocytosis, and fever. Acinetobacter baumannii and klebsiella pneumoniae were the most common germs in sputum cultures with 50% resistance to commonly used antibiotics.


Tendon growth in rabbits.
The longitudinal growth of the Achilles and tibialis anterior tendons in young rabbits was investigated. At 5 weeks of age, sutured marks were placed along the entire length of each tendon from the musculotendinous junction to the portion near the osseous attachment using a microsurgical technique. The distances between the marks were measured using a microscope with a micro ruler. At 16 weeks of age, all distances between the marks had increased. In the Achilles tendon, none of the intermark distances differed significantly. In the tibialis anterior, the retinaculum is situated between the musculotendinous junction and the insertion, and acts as a pulley, so this tendon was divided into 2 zones, one proximal and one distal to the retinaculum, and the intermark distances were measured. There were no significant differences among these distances in proximal, or distal zones, but those in the proximal zone were greater than those in the distal zone (< 0.01). Furthermore, in a separate experiment, the longitudinal growth of the underlying bone in the zone proximal to the retinaculum was found to be greater than that in the distal zone (p < 0.01).


Self-assembled peptide nanofibers raising durable antibody responses against a malaria epitope.
Biomaterials that modulate innate and adaptive immune responses are receiving increasing interest as adjuvants for eliciting protective immunity against a variety of diseases. Previous results have indicated that self-assembling β-sheet peptides, when fused with short peptide epitopes, can act as effective adjuvants and elicit robust and long-lived antibody responses. Here we investigated the mechanism of immunogenicity and the quality of antibody responses raised by a peptide epitope from Plasmodium falciparum circumsporozoite (CS) protein, (NANP)(3),conjugated to the self-assembling peptide domain Q11. The mechanism of adjuvant action was investigated in knockout mice with impaired MyD88, NALP3, TLR-2, or TLR-5 function, and the quality of antibodies raised against (NANP)(3)-Q11 was assessed using a transgenic sporozoite neutralizing (TSN) assay for malaria infection. (NANP)(3)-Q11 self-assembled into nanofibers, and antibody responses lasted up to 40 weeks in C57BL/6 mice. The antibody responses were T cell- and MyD88-dependent. Sera from mice primed with either irradiated sporozoites or a synthetic peptide, (T1BT*)(4)-P3C, and boosted with (NANP)(3)-Q11 showed significant increases in antibody titers and significant inhibition of sporozoite infection in TSN assays. In addition, two different epitopes could be self-assembled together without compromising the strength or duration of the antibody responses raised against either of them, making these materials promising platforms for self-adjuvanting multi-antigenic immunotherapies.


What is bioethics without Christianity?
The author uses the essays in this issue as a springboard for making three points. First, he argues that most, if not all, current institutional versions of Christianity have failed to provide a meaningful framework for the spiritual life. Second, he argues that there is no ethics other than Judeo-Christian ethics and that there can be no bioethics other than Judeo-Christian bioethics. Finally, he argues that the overriding issue we face is not whether to address bioethical issues from a Christian perspective or from a non-Christian perspective, but rather whether we shall address biological and medical issues from an ethical or a scientific-technological perspective.


Surgical management of dentigerous cyst and keratocystic odontogenic tumor in children: a conservative approach and 7-year follow-up.
Dentigerous cyst (DC) is one of the most common odontogenic cysts of the jaws and rarely recurs. On the other hand, keratocystic odontogenic tumor (KCOT), formerly known as odontogenic keratocyst (OKC), is considered a benign unicystic or multicystic intraosseous neoplasm and one of the most aggressive odontogenic lesions presenting relatively high recurrence rate and a tendency to invade adjacent tissue. Two cases of these odontogenic lesions occurring in children are presented. They were very similar in clinical and radiographic characteristics, and both were treated by marsupialization. The treatment was chosen in order to preserve the associated permanent teeth with complementary orthodontic treatment to direct eruption of the associated permanent teeth. At 7-years of follow-up, none of the cases showed recurrence.


Decrease of beta-receptors in asthmatic and rhinitic patients.
The number of beta-receptors was determined in 60 atopic patients: 30 asthmatics with sensitization to domestic inhalant allergens and 30 rhinitic patients with sensitization to pollen and/or Dermatophagoides antigens. A L-iodocyanopindolol radio-active marker was used. Our control population (20 healthy individuals) showed 908 +/- 396 receptors/cell. The rhinitic individuals showed a 24% decrease in receptors in relation to the control population. On the other hand, within the asthmatic patients there existed 2 differentiated groups: inactive asthmatics whose receptors were found to be within the normal limits and active asthmatics with a 36% decrease in receptors in relation to the healthy individuals (673 receptors/cell) establishing a significant statistical difference (p less than 0.005). As a consequence these data seem to support Szentivanyi's B-adrenoreceptor theory.


Modelling hen harrier dynamics to inform human-wildlife conflict resolution: a spatially-realistic, individual-based approach.
Individual-based models have gained popularity in ecology, and enable simultaneous incorporation of spatial explicitness and population dynamic processes to understand spatio-temporal patterns of populations. We introduce an individual-based model for understanding and predicting spatial hen harrier (Circus cyaneus) population dynamics in Great Britain. The model uses a landscape with habitat, prey and game management indices. The hen harrier population was initialised according to empirical census estimates for 1988/89 and simulated until 2030, and predictions for 1998, 2004 and 2010 were compared to empirical census estimates for respective years. The model produced a good qualitative match to overall trends between 1989 and 2010. Parameter explorations revealed relatively high elasticity in particular to demographic parameters such as juvenile male mortality. This highlights the need for robust parameter estimates from empirical research. There are clearly challenges for replication of real-world population trends, but this model provides a useful tool for increasing understanding of drivers of hen harrier dynamics and focusing research efforts in order to inform conflict management decisions.


Impact of different malocclusion types on the vertical mandibular asymmetry in young adult sample.
The aim of this study was to investigate the vertical mandibular asymmetry in a group of adult patients with different types of malocclusions, based on Angle's dental classification. A sample of 102 patients (age range 19-28) who went for routine orthodontic treatment in the institution were divided into four groups: Class I, 26 patients; Class II/1, 30 patients; Class III, 23 patients; and control group (CG) with normal occlusion, 23 patients. Condylar asymmetry index (CAI), ramal asymmetry index (RAI), condylar-plus-ramal asymmetry index values were measured for all patients on panoramic radiographs. Data were analyzed using Kruskal-Wallis and Mann-Whitney U-test at the 95% confidence level (P < 0.05). The results of the analysis showed that different occlusal types significantly affected the vertical symmetry of the mandible at the condylar level. Class I and Class II/1 malocclusion groups showed a significant difference in CAI values relative to the CG (P < 0.05, P < 0.001). No statistically significant difference was found between the CG and Class III malocclusion group (P > 0.05). Comparisons between Class II/1 and Class I malocclusions revealed a significant difference in CAI values (P < 0.01). Both Class II/1 and Class I malocclusions patients had significantly higher CAI values compared to CG and Class III group. CAI value was significantly higher in Class II/1 malocclusion compared to Class I malocclusion. Both these malocclusions could act as a predisposing factor for having asymmetric condyles if left untreated.


Pharmacokinetics and safety of deferasirox in subjects with chronic kidney disease undergoing haemodialysis.
Treatment of chronic kidney disease (CKD) includes parenteral iron therapy, and these infusions can lead to iron overload. Secondary iron overload is typically treated with iron chelators, of which deferasirox is one of the most promising. However, it has not been studied in patients with CKD and iron overload. A pilot study was conducted to evaluate the pharmacokinetics and safety of deferasirox in eight haemodialysis-dependent patients, who were receiving intravenous iron for treatment of anaemia of CKD. Deferasirox was administered at two doses (10 mg/kg and 15 mg/kg), either acute (once daily for 2 days) or steady-state (once daily for 2 weeks). A dose of 10 mg/kg in either protocol was not sufficient to achieve a plasma concentration in the therapeutic range (acute peak 14.1 and steady-state 22.8 μmol/L), while 15 mg/kg in either protocol maintained plasma concentration well above this range (acute peak 216 and steady-state 171 μmol/L). Plasma concentration observed at 15 mg/kg was well above that expected for this dose (40-50 μmol/L), although no adverse clinical events were observed. This study highlights the need to profile drugs such as deferasirox in specific patient groups, such as those with CKD and iron overload.


The Genetics of Primary Familial Brain Calcification: A Literature Review.
Primary familial brain calcification (PFBC), also known as Fahr's disease, is a rare inherited disorder characterized by bilateral calcification in the basal ganglia according to neuroimaging. Other brain regions, such as the thalamus, cerebellum, and subcortical white matter, can also be affected. Among the diverse clinical phenotypes, the most common manifestations are movement disorders, cognitive deficits, and psychiatric disturbances. Although patients with PFBC always exhibit brain calcification, nearly one-third of cases remain clinically asymptomatic. Due to advances in the genetics of PFBC, the diagnostic criteria of PFBC may need to be modified. Hitherto, seven genes have been associated with PFBC, including four dominant inherited genes (SLC20A2, PDGFRB, PDGFB, and XPR1) and three recessive inherited genes (MYORG, JAM2, and CMPK2). Nevertheless, around 50% of patients with PFBC do not have pathogenic variants in these genes, and further PFBC-associated genes are waiting to be identified. The function of currently known genes suggests that PFBC could be caused by the dysfunction of the neurovascular unit, the dysregulation of phosphate homeostasis, or mitochondrial dysfunction. An improved understanding of the underlying pathogenic mechanisms for PFBC may facilitate the development of novel therapies.


Heterogeneity of responses to orthostatic stress in homozygous twins.
Early analysis into the role of genetics on cardiovascular regulation has been accomplished by comparing blood pressure and heart rate in homozygous twins during unstressed, resting physiological conditions. However, many variables, including cognitive and environmental factors, contribute to the regulation of cardiovascular hemodynamics. Therefore, the purpose of this study was to determine the hemodynamic response of identical twins to an orthostatic stress, ranging from supine rest to presyncope. Heart rate, arterial blood pressure, middle cerebral artery blood velocity, an index of cerebrovascular resistance, cardiac output, total peripheral resistance, and end-tidal carbon dioxide were measured in 16 healthy monozygotic twin pairs. Five minutes of supine resting baseline data were collected, followed by 5 min of 60 degrees head-up tilt. After 5 min of head-up tilt, lower body negative pressure was applied in increments of 10 mmHg every 3 min until the onset of presyncope, at which time the subject was returned to the supine position for a 5-min recovery period. The data indicate that cardiovascular regulation under orthostatic stress demonstrates a significant degree of variance between identical twins, despite similar orthostatic tolerance. As the level of stress increases, so does the difference in the cardiovascular response within a twin pair. The elevated variance with increasing stress may be due to an increase in the role of environmental factors, as the influential role of genetics nears a functional limit. Therefore, although orthostatic tolerance times were very similar between identical twins, the mechanism involved in sustaining cardiovascular function during increasing stress was different.


MicroRNAs as Novel Biomarkers for the Diagnosis and Prognosis of Mild and Severe Traumatic Brain Injury.
Traumatic brain injury (TBI) is the leading cause of death and disability in people younger than 45 in Western countries. Despite many studies, no reliable biomarkers have been found to assess TBI severity and predict recovery. MicroRNA (miRNA) profiling has become widely used to identify biomarkers and therapeutic targets. Through use of the TaqMan Array Human MicroRNA A+B Cards, the expression of 754 miRNAs was analyzed in serum of five mild TBI (mTBI) patients with extra-cranial injury (EC), five severe TBI (sTBI) patients with EC, and five healthy volunteers (HV) at 1 day and 15 days post-injury. The aim was to find candidate biomarkers able to discriminate between mTBI and sTBI. Following this, it was possible to select 10 miRNAs for further study in an enlarged validation cohort of 120 patients by using single TaqMan assays at the following time-points: T0-1 h, T4-12 h, T48-72 h, and 15 days from the injury. Analysis revealed two miRNAs (miR-425-5p and miR-502) that were significantly downregulated (p < 0.05) in mTBI at early time-points and are ideal candidates for diagnosis of mTBI, and two miRNAs (miR-21 and miR-335) that were significantly upregulated (p < 0.01) and are valid biomarkers for the diagnosis of sTBI. In addition, miR-425-5p was a strong predictor of 6-month outcome at T0-1 h and T4-12 h, while miR-21 was predictive of the outcome at T4-12 h. The panel of selected miRNAs shows promise as biomarkers to discriminate mTBI from sTBI. In addition, the selected miRNAs represent new potential therapeutic targets.


Modified In Vivo Matrix Gel Plug Assay for Angiogenesis Studies.
Several models have been developed to investigate angiogenesis in vivo. However, most of these models are complex and expensive, require specialized equipment, or are hard to perform for subsequent quantitative analysis. Here we present a modified matrix gel plug assay to evaluate angiogenesis in vivo. In this protocol, vascular cells were mixed with matrix gel in the presence or absence of pro-angiogenic or anti-angiogenic reagents, and then subcutaneously injected into the back of recipient mice. After 7 days, phosphate buffer saline containing dextran-FITC is injected via the tail vein and circulated in vessels for 30 min. Matrix gel plugs are collected and embedded with tissue embedding gel, then 12 µm sections are cut for fluorescence detection without staining. In this assay, dextran-FITC with high molecular weight (~150,000 Da) can be used to indicate functional vessels for detecting their length, while dextran-FITC with low molecular weight (~4,400 Da) can be used to indicate the permeability of neo-vessels. In conclusion, this protocol can provide a reliable and convenient method for the quantitative study of angiogenesis in vivo.


Durkheim's theories of deviance and suicide: a feminist reconsideration.
In The division of labor in society, Durkheim conceptualizes deviance as an essentially asocial phenomenon, and he conceptualizes "woman" as an essentially asocial being. Both theories contradict Durkkheim's characteristic social determinism, and both encounter, in Suicide, two further contradictions. First, Suicide demonstrates conclusively that relatively asocial individuals, women, are actually much less prone to deviance than relatively social individuals, men. Second, Suicide introduces the theory that deviance is an essentially social phenomenon that is produced by pathological social forces or "currents" rather than by "excessive individualization" and "insufficient socialization." Durkkheim's second theory of deviance thus simultaneously rescues his theory of the social nature of men and his theory of the asocial nature of women.


Pectus excavatum in two littermate dogs.
One male and 1 female, 8-week-old, schnauzer littermates were presented with moderate and mild pectus excavatum, respectively. External application of a coaptation splint to the ventral aspect of the thorax was used for correction of the sternal deformity in the male; conservative treatment was used in the female.


Mediators and autopathogenic effector cells in proteoglycan-induced arthritic and clinically asymptomatic BALB/c mice.
Proteoglycan (aggrecan)-induced arthritis is an autoimmune inflammatory animal model produced in genetically susceptible BALB/c mice. This animal model shows many similarities to human rheumatoid arthritis as indicated by clinical assessments, histopathological studies, and immunological parameters. The systemic immunization of mice with a select group of cartilage proteoglycans provokes immune responses to the immunizing antigen and then the production of cross-reactive antibodies to self proteoglycans. This is followed by an explosive proliferation of autoreactive T cells, especially in joint draining lymph nodes, accompanied by local (joint) inflammatory events. In the current experiments we found that lymphocytes from arthritic, or potentially arthritic but yet clinically asymptomatic animals, produced more IL-2 than those T cells obtained from animals immunized with nonarthritogenic PGs. In addition, synoviocytes isolated from prearthritic or arthritic animals produced several-fold more interleukin-1 beta (IL-1 beta) than cells from normal animals. Flow cytometric analysis indicated an autoantigen (mouse PG)-specific selective proliferation of surface Ig+/CD45R+ cells in prearthritic stages followed by the proliferation of predominantly T helper (CD4+) cells during and after the development of arthritis.


Laccase-derived lignin compounds boost cellulose oxidative enzymes AA9.
The discovery of lignin as activator for the redox enzyme lytic polysaccharide monooxygenases (LPMOs) for the oxidation of cell-wall polysaccharides opens a new scenario for investigation of the interplay between different lignocellulose-degrading enzymes. The lignin-active enzymes in one hand, and the carbohydrate active in the other, are linked through a variety of electrons carrier molecules either derived from lignin or enzymatically transferred. Likewise, in nature, many lignocellulose-degrading organisms are expressing those enzymes simultaneously, and we wanted to test if a major commercial available lignin oxidase enzyme, i.e., laccase could benefit and synergize the activity of the LPMOs by depolymerizing the insoluble lignin. In this work, two fungal laccases together with a mediator (ABTS) were used to isolate low-molecular-weight lignin from lignocellulosic biomass. The isolated lignins were used as electron donors for activation of LPMOs. A direct correlation between the low-molecular-weight lignin isolated with laccases and an increased activity of a cellulolytic cocktail containing LPMO was found when pure cellulose was hydrolyzed. We then tried to implement existing commercial cellulases cocktail with laccase enzymes, but under the conditions tested, the co-incubation of laccases with LPMOs showed a substrate competition towards oxygen inhibiting the LPMO. In addition, we found that laccase treatment may cause other modifications to pure cellulose, rendering the material more recalcitrant for enzymatic saccharification. Laccase-mediated system was able to depolymerize lignin from pre-treated and native sugarcane bagasse and wheat straw, and the released phenolic molecules were able to donate electrons to LPMO enzymes boosting the overall enzymatic hydrolysis of cellulose. Likewise, other poly-phenol oxidase, we might have just started showing possible pros or cons in applying several oxidase enzymes for a simultaneous degradation of cellulose and lignin, and we found that the competition towards oxygen and their different consumption rates must be taken into account for any possible co-application.


Sequential changes of parathyroid hormone related protein (PTHrP) in articular cartilage during progression of inflammatory and degenerative arthritis.
To investigate immunolocalisation of parathyroid hormone related protein (PTHrP) in two sequential models of experimental cartilage damage (inflammatory and degenerative) in order to elucidate differences in chondrocyte response to the disease. Immunohistochemistry with a polyclonal rabbit antiserum to the N-terminal domain of PTHrP was used to detect this protein in two different rabbit models sharing progressive cartilage damage: antigen induced arthritis (AIA) and osteoarthritis (OA) secondary to partial medial meniscectomy. Cartilage specimens from early (2 days in AIA; 8 weeks in experimental OA) and late (3 weeks in AIA; 52 weeks in OA) disease were compared. Cell and matrix PTHrP staining in early AIA and OA was similar to that in controls. Late AIA cartilage showed a significant decrease in PTHrP positive cells and in the cartilage matrix. In contrast, at late OA stages, distinct PTHrP positivity was detected in proliferating cell clones, as assessed by proliferating cell nuclear antigen staining around cartilage damaged areas. PTHrP staining of hyaline articular cartilage shows a different pattern during progression of each type of arthritis: an overall decrease associated with the inflammatory disease, and an increase in the proliferating chondrocyte clones with degenerative arthritis.


Early changes of rheumatoid arthritis in the hand and wrist.
The radiographic diagnosis of rheumatoid arthritis can be suggested long before bone and joint destruction. Soft tissue swelling at the ulnar styloid is classical, but soft tissue swelling also occurs at the PIP and MCP joints. Joint space widening, loss of the lateral fat planes of the wrist, and radial carpal narrowing can all be seen prior to bony change. The earliest bony change is loss of the cortical white line on the radial aspect of the fourth and fifth metacarpal heads.


Bryozoan framework composition in the oddly shaped reefs from Abrolhos Bank, Brazil, southwestern Atlantic: taxonomy and ecology.
Bryozoans are a key group of sessile invertebrates in some reef frameworks but are typically neglected in environmental monitoring programs. Abrolhos Bank (Brazil) is the largest reef complex in the South Atlantic Ocean, encompassing several reef landscapes over an area of 46,000 km2. A transition takes place across the shelf from mangroves to soft sediments, coastal shallow reefs to a volcanic archipelago - surrounded by fringing reefs - and unique mushroom-shaped biogenic structures, with mesophotic pinnacle reefs, rhodolith beds, sink-holes and shelf break deep environments. The taxonomic composition of the bryozoan fauna was studied in 11 core samples taken from shallow to mesophotic mid-shelf reefs (4-25 m deep) on Abrolhos Bank by divers using a submersible drill. Of the 20 bryozoan species sampled, 17 are new records for Abrolhos Bank and seven species are new to science: Crassimarginatella winstonae n. sp., Parasmittina distincta n. sp., Parasmittina abrolhosensis n. sp., Hemismittoidea asymmetrica n. sp., Stylopoma variabilis n. sp., Stylopoma hastata n. sp., and Plesiocleidochasma acuminata n. sp. (described by Ramalho, Taylor Moraes). The most conspicuous species is Celleporaria atlantica. These results increase to 48 the total number of bryozoan species known in this region and reinforce the importance of this group as one of the main components apart from crustose coralline algae and corals of the reef framework-building community of Abrolhos Bank.


Fibroblast growth factor 21 (FGF21) inhibits macrophage-mediated inflammation by activating Nrf2 and suppressing the NF-κB signaling pathway.
Our previous report has shown that FGF21 has anti-inflammatory properties in a collagen-induced arthritis (CIA) model. In this study, the underlying molecular mechanisms of action were also investigated using RAW 264.7 cells, a murine monocyte-macrophage. RAW 264.7 cells were pre-incubated with various concentrations (2000, 500, 100ng/ml) of FGF21 and stimulated with LPS to induce oxidative stress and inflammation. The result of flow cytometry showed that β-Klotho, FGF21 specific receptor, was expressed in murine splenic macrophages and RAW 264.7. In vitro, FGF21 reduced the expression of TNF-α, IL-1β, IL-6 and IFN-γ and increased the level of IL-10 in a dose-dependent manner in LPS-stimulated RAW 264.7 macrophages. FGF21 also suppressed profound elevation of ROS production and oxidative stress, as evidenced by an increase of the MDA level and depletion of the intracellular GSH level, and restored the activities of antioxidant enzymes SOD and GSH-Px in LPS-stimulated RAW 264.7 macrophages. Moreover, FGF21 inhibited LPS-induced nuclear factor-κB (NF-κB) activation, including degradation of I-κB and nuclear translocation of p65. In addition, the result of Western blot and real-time PCR showed that FGF21 induced heme oxygenase-1 (HO-1) expression and increased the nuclear transcription factor-E2-related factor 2 (Nrf2) levels in a dose-dependent manner in LPS-stimulated RAW 264.7 macrophages. In conclusion, the results suggest that macrophages are the targets for the anti-inflammatory effects of FGF21, and FGF21 exerted an anti-inflammatory effect mainly via enhancing Nrf2-mediated anti-oxidant capacity and suppressing NF-κB signaling pathway.


Effects of mechanical vibration on DNA and proteoglycan syntheses in cultured articular chondrocytes.
Abstract The objective of this study was to determine the effects of mechanical vibration loading on DNA and proteoglycan syntheses in cultured rabbit articular chondrocytes. Chondrocyte culture plates were placed in a vibratory apparatus and subjected to a mechanical vibratory load at various frequencies and periods during culture. Mechanical vibration was applied at a sinusoidal waveform of 1.4 G-acceleration with frequencies of 200, 300, 400, 800, and 1600 Hz. (3)H-thymidine and H2 (35)SO4 incorporation were used to detect radiolabeled DNA and proteoglycan syntheses, respectively. A frequency of 300 Hz showed a time-dependent augmentation of DNA synthesis and gave a maximal increase on day 3 with periodic vibration (8 h per day), and at 72 h or longer with continuous vibration. It also promoted proteoglycan synthesis in long-term cul-ture (from 3 to 15 days) by periodic vibration. However, frequencies above 400 Hz suppressed biosynthesis. These results suggest that mechanical vibration at certain frequencies may modulate the biosynthetic response of articular chondrocytes.


Na(+)/Ca(2+) exchanger 2 is neuroprotective by exporting Ca(2+) during a transient focal cerebral ischemia in the mouse.
Na(+)/Ca(2+) exchanger (NCX), by mediating Na(+) and Ca(2+) fluxes bi-directionally, assumes a role in controlling the Ca(2+) homeostasis in the ischemic brain. It has been suggested that the three isoforms of NCX (NCX1, 2 and 3) may be differentially involved in permanent cerebral ischemia. However, the role of NCX2 has not been defined in ischemic reperfusion injury after a transient focal cerebral ischemia. Furthermore, it is not known whether NCX2 imports or exports intracellular Ca(2+) ([Ca(2+)](i)) following ischemia and reperfusion. To define the role of NCX2 in ischemia and reperfusion, we examined mice lacking NCX2, in vivo and in vitro. After an in vitro ischemia, a significantly slower recovery in population spike amplitudes, a sustained elevation of [Ca(2+)](i) and an increased membrane depolarization were developed in the NCX2-deficient hippocampus. Moreover, a transient focal cerebral ischemia in vivo produced a larger infarction and more cell death in the NCX2-deficient mouse brain. In particular, in the wild type brain, NCX2-expressing neurons were largely spared from cell death after ischemia. Our results suggest that NCX2 exports Ca(2+) in ischemia and thus protects neuronal cells from death by reducing [Ca(2+)](i) in the adult mouse brain.


Recombination and heterologous expression of allophycocyanin gene in the chloroplast of Chlamydomonas reinhardtii.
Heterogeneous expression of multiple genes in the nucleus of transgenic plants requires the introduction of an individual gene and the subsequent backcross to reconstitute multi-subunit proteins or metabolic pathways. In order to accomplish the expression of multiple genes in a single transformation event, we inserted both large and small subunits of allophycocyanin gene (apcA and apcB) into Chlamydomonas reinhardtii chloroplast expression vector, resulting in papc-S. The constructed vector was then introduced into the chloroplast of C. reinhardtii by micro-particle bombardment. Polymerase chain reaction and Southern blot analysis revealed that the two genes had integrated into the chloroplast genome. Western blot and enzyme-linked immunosorbent assay showed that the two genes from the prokaryotic cyanobacteria could be correctly expressed in the chloroplasts of C. reinhardtii. The expressed foreign protein in transformants accounted for about 2%-3% of total soluble proteins. These findings pave the way to the reconstitution of multi-subunit proteins or metabolic pathways in transgenic C. reinhardtii chloroplasts in a single transformation event.


Expression of Tn and sialyl-Tn antigens in endometrial cancer: its relationship with tumor-produced cyclooxygenase-2, tumor-infiltrated lymphocytes and patient prognosis.
Although many tumors arising from epithelial tissues produce mucins, little is known regarding the biological significance of mucins in cancer. Recent researches have revealed that mucins produced by cancer cells play a critical role in the initial induction of cyclooxygenase (COX)-2 in the tumor microenvironment. Moreover, the consequence of abnormal glycosylation and overexpression of mucins includes suppression of the host-immune function. The expression of Tn/sialyl-Tn (s-Tn) antigen and its impact on COX-2 expression by tumor cells and infiltration of CD8+ T-cell into the cancer cell nest (nest CD8) in endometrial cancer was evaluated. Tissue specimens from 70 endometrial cancer patients who had undergone a curative resection were evaluated for Tn/s-Tn antigen, COX-2 and CD8 by immunohistochemistry. The overexpression of Tn and s-Tn antigen was significantly correlated with COX-2 overexpression (p <0.005 and p <0.001, respectively). There was a significant association between s-Tn overexpression and low infiltration of nest CD8 (p<0.05). Strong expression of s-Tn antigen was significantly associated with poor prognosis (p < 0. 005). Among several prognostic factors, s- Tn expression remained the strong independent predictor of survival by multivariate analysis (p<0.05). These results suggested that tumor-produced mucins, which were associated with COX-2 induction and immunosuppression, provided additional prognostic information in endometrial cancer patients.


Assessment of Hepatic Impairment and Implications for Pharmacokinetics of Substance Use Treatment.
Although the liver is the primary site of metabolism and biliary excretion for many medications, data are limited on the liver's pharmacokinetic abilities in cirrhosis. Cirrhosis develops through collagen deposition, eventually culminating in end-stage liver disease that compromises hepatic drug metabolism. Consequently, the US Food and Drug Administration (FDA) recommends evaluating the pharmacokinetics of medications in subjects with hepatic impairment if hepatic metabolism constitutes more than 20% of their elimination or if they have a narrow therapeutic range. A variety of noninvasive indices and radiologic procedures can be employed to assess hepatic drug metabolism and excretion. The Child-Pugh score is the most commonly used scale for assessing hepatic impairment among drugs submitted for US FDA approval. The score, originally developed to guide operative mortality in patients undergoing hepatic resection, has not been modified since its inception 5 decades ago. Furthermore, the score was not originally intended to be a guide for potential dose modification in patients with hepatic impairment. These reasons, in combination with the availability of a variety of new imaging modalities and an enhanced understanding of hepatic biology, should foster the development of novel methods to assess the effect of hepatic impairment on liver drug metabolism.


Fungal infections in pediatric intensive care units.
Pediatric fungal infections are associated with significant morbidity and mortality. Few adequately powered antifungal trials have been performed in neonates and children. Neonatologists and pediatricians are reliant on adult trials when managing candidemia. Recent guidelines from the Infectious Diseases Society of America recommend fluconazole or an echinocandin for empiric therapy in suitable candidates, with a preference for an echinocandin in patients with moderate-to severe disease, recent azole exposure, or high risk of C. glabrata or C. krusei infection.


Comparing Clinical Outcomes of a Pharmacist-Managed Diabetes Clinic to Usual Physician-Based Care.
This study analyzed the impact of a pharmacist-managed diabetes clinic on clinical outcomes compared to usual care received from primary care providers (PCPs). This comparison may more definitively demonstrate the value of pharmacist management of chronic disease states. Retrospective observational cohort study conducted in patients referred to a pharmacist-managed pharmacotherapy (PT) clinic from July 2009 to October 2014. For the primary outcome, the absolute change in A1c during the usual care phase was +1.53% (95% confidence interval [CI]: 1.10-1.96, P < .0001) versus an absolute change of -1.63% (95% CI: -1.28 to -1.97, P < .0001) in the intervention phase. For secondary outcomes, diabetes-related hospitalizations (10 vs 6, P = .104) and emergency room (ER) visits (27 vs 8, P = .049) decreased in the intervention phase compared to the usual care phase. The rate of diabetes-related interventions made per patient per year in the usual care phase was 2.7 versus 11.1 in the intervention phase ( P < .0001). Patients referred to the PT clinic had worsening blood glucose control prior to referral, and their control improved after referral to the clinic. Furthermore, there was an improvement in all diabetes-related outcomes in the intervention phase compared to the usual care phase.


Temporal bone pneumatization in otosclerosis.
To determine whether there is a difference in the pneumatization of temporal bones with otosclerosis versus normal temporal bones. A retrospective study of 46 ears from 24 adult patients with otosclerosis and 64 ears from 47 adult patients in a control group. The study group included temporal bone CT scans available from patients with otosclerosis. The control group consisted of patients who had temporal bone CTs for reasons likely unrelated to a history of middle ear disease. Data were obtained with a virtual reality system that allows three-dimensional manipulation and analysis. The temporal bone pneumatization for the otosclerosis group was 4.82 +/- 2.27 cm(3) vs 6.06 +/- 2.71 cm(3) for the control group. Two-sample t test analysis revealed no statistical significance (P = 0.059) between pneumatization in the control vs otosclerosis groups. There is no difference in temporal bone pneumatization between patients with otosclerosis and a control population. Therefore, temporal bone pneumatization by itself is not an adequate explanation for the apparent protective effect of otosclerosis against otitis media.


Cardiovascular parameters to assess the severity of acute pulmonary embolism with computed tomography.
Computed tomographic pulmonary angiography (CTPA) has been established as a first-line test in the acute pulmonary embolism (APE) diagnostic algorithm, but the assessment of the severity of APE by this method remains to be explored. To retrospectively evaluate right ventricular (RV) dysfunction and severity in patients with APE without underlying cardiopulmonary disease using helical computed tomography (CT). Seventy-three patients (35 men and 38 women) were divided into two groups according to the clinical findings: severe APE (n=22) and non-severe APE (n=51). Pulmonary artery CT obstruction index was calculated according to the location and degree of clots in the pulmonary arteries. Cardiovascular parameters including RV short axis and left ventricular (LV) short axis, RV short axis to LV short axis (RV/LV) ratio, main pulmonary artery, azygos vein, and superior vena cava diameters were measured. Leftward bowing of the interventricular septum, reflux of contrast medium into the inferior vena cava and azygos vein, and bronchial artery dilatation were also recorded. The results were analyzed by Mann-Whitney U test, chi(2) test, Spearman's rank correlation coefficient, and the area under the receiver operating characteristic curve (A(z)). CT obstruction index in patients with severe APE (median 43%) was higher than that of patients with non-severe APE (median 20%). Comparison of cardiovascular parameters between patients with severe and non-severe pulmonary embolism showed significant differences in RV short axis, LV short axis, RV/LV ratio, RV wall thickness, main pulmonary artery diameter, azygos vein diameter, leftward bowing of the interventricular septum, and bronchial artery dilatation. The correlation between CT obstruction indexes and cardiovascular parameters was significant. Spearman's rank correlation coefficient was highest between RV/LV ratio and CT obstruction index. A(z) values were significantly higher than 0.5 for CT obstruction index, LV short axis, RV/LV ratio, main pulmonary artery diameter, and azygos vein diameter. These results suggest that CTPA is a practical and accurate means for evaluating RV dysfunction of pulmonary embolism in patients without any underlying cardiopulmonary disease and can discriminate between severe and non-severe APE.


Usefulness of Age-Stratified N-Terminal Prohormone of Brain Natriuretic Peptide for Diagnosing Kawasaki Disease.
N-terminal prohormone of brain natriuretic peptide (NT-proBNP) was recently reported as a biomarker for diagnosing Kawasaki disease (KD). The basal NT-proBNP level, however, gradually decreases with age. We investigated the usefulness of an age-stratified cutoff value of NT-proBNP for diagnosing KD. All the patients enrolled in this study visited Chonnam National University Hospital between December 2007 and March 2016. The KD groups consisted of 214 patients with complete KD and 129 patients with incomplete KD. The control group included 62 children with simple febrile illness but without heart disease. Laboratory data including NT-proBNP level were evaluated. Each group was divided into subgroups according to patient age (<6 months, 6-12 months, 12-24 months, and >24 months), and different cutoff values of NT-proBNP were calculated. The cutoff values of NT-proBNP used to diagnose total KD and incomplete KD were 762 and 762 pg/mL (<6 months), 310 and 310 pg/mL (6-12 months), 326 and 326 pg/mL (12-24 months), and 208 and 137 pg/mL (>24 months), respectively. In conclusion, age-stratified NT-proBNP is a useful biomarker for the differential diagnosis of KD in patients with a simple febrile illness.


Large scale NaLaMo2O8 nanospindles: synthesis, characterization, and luminescence properties.
Large scale tetragonal NaLaMo2O8 nanocrystallines with spindle morphology have been prepared through a facile method by low-temperature hydrothermal treatment of Na2MoO4, LaCl3, and EDTA in an ethanolamine/water mixed solution. The products were characterized by X-ray powder diffraction, field-emission scanning electron microscopy, high-resolution transmission electron microscopy, and photoluminescence spectroscopy. Results indicate that High-quality, and uniform nanospindles with a mean length of 260 nm and a mean width of 100 nm can be easily obtained. Furthermore, EDTA and EA (ethanolamine) were found to have great influence on the formation of NaLaMo2O8 spindlelike nanostructures. The room temperature PL spectrum of the products shows a relatively strong emission peak at 365 nm.


Determination of fluoxetine enantiomers in rat plasma by pre-column fluorescence derivatization and column-switching high-performance liquid chromatography.
A column-switching HPLC method employing both octadecylsilica (ODS) and chiral columns with fluorescence detection was developed for the determination of enantiomer of fluoxetine (FLX), an antidepressant drug, in rat plasma. Racemic FLX was derivatized with a fluorescent reagent, 4-(N-chloroformylmethyl-N-methyl)amino-7-nitro-2,1,3-benzoxadiazole (NBD-COCl) or 4-(N-chloroformylmethyl-N-methyl)amino-7-N,N-dimethylaminosulfonyl-2,1,3-benzoxadiazole (DBD-COCl) and the enantiomeric separation of the resultant derivatives was examined on an amylose-based chiral column (CHIRALPAK AD-RH) in the reversed-phase mode. The derivative with NBD-COCl (NBD-FLX) showed a sufficient separation factor (a) and resolution (Rs) compared with that with DBD-COCl. Thus, FLX was derivatized with NBD-COCl and the resultant NBD-FLX was first quantified on the ODS column and then introduced to the CHIRALPAK AD-RH column via a six-port switching valve to examine the enantiomeric ratio. The intra- and inter-day accuracy (97.6-112.7%) and precision (1.47-10.60%) were satisfactory in the range 10-1000 nM FLX and the limit of quantification was approximately 10 nM. The absolute recoveries of FLX with hexane from rat plasma were in the range 87.5-92.2% (n = 3). The method was applied to determine FLX enantiomers in the plasma of rats administered FLX orally, and it was shown that the R-isomer was eliminated faster than the S-isomer.


The utility of outpatient commitment: Reduced-risks of victimization and crime perpetration.
Outpatient civil commitment (OCC) provisions, community treatment orders (CTOs) in Australia and Commonwealth nations, are part of mental health law worldwide. This study considers whether and by what means OCC provides statutorily required "needed-treatment" addressing two aspects of its legal mandate to protect the safety of self (exclusive of deliberate-self-harm) and others. Over a 12.4-year period, records of hospitalized-psychiatric-patients, 11,424 with CTO-assignment and 16,161 without CTO-assignment were linked to police-records. Imminent-safety-threats included perpetrations and victimizations by homicides, rapes, assaults/abductions, and robberies. "Need for treatment" determinations were validated independently by Health of the Nations Scale (HoNOS) severity-score-profiles. Logistic regressions, with propensity-score- adjustment and control for 46 potential confounding-factors, were used to evaluate the association of CTO-assignment with occurrence-risk of perpetrations and victimizations. CTO-assignment was associated with reduced safety-risk: 17% in initial-perpetrations, 11% in initial-victimizations, and 22% for repeat-perpetrations. Each ten-community-treatment-days in interaction with CTO-assignment was associated with a 3.4% reduced-perpetration-risk. CTO-initiated-re-hospitalization was associated with a 13% reduced-initial-perpetration-risk, a 17% reduced-initial-victimization-risk, and a 22% reduced-repeat-victimization-risk. All risk-estimates appear to be the unique contributions of the CTO, CTO-initiated-re-hospitalization, or the provision of ten-community-treatment-days-i.e. after accounting for the influence of prior crimes and victimizations, ethnic-bias, neighborhood disadvantage and other between-group differences in the analysis. CTO assignment's association with reduced criminal-victimization and perpetration-risk, in conjunction with requiring participation in needed-treatment via re-hospitalization and community-service, adds support to the conclusion that OCC is to some extent fulfilling its legal objectives related to protecting safety of self (exclusive of deliberate-self-harm), and others.


Hiatal Hernia Repair: Current Evidence for Use of Absorbable Mesh to Reinforce Hiatal Closure.
There continues to be debate regarding the best surgical technique for the treatment of paraesophageal hernias. While laparoscopic and robotic approaches are widely employed around the world, the benefits of mesh use to reinforce hiatal closure are still not well established. The goal of this manuscript is to describe the currently available results with biologic and bioabsorbable meshes for treatment of paraesophageal hernias, particularly with reference to the rate of recurrence. A systematic review of the literature was conducted to identify studies describing treatment of hiatal hernias with biologic or bioabsorbable mesh. The available studies were categorized as comparative (when authors compared results with a different patient cohort undergoing suture repair of the hiatus without mesh reinforcement) and non-comparative, and organized by levels of evidence. We identified two randomized control trials, a long-term follow-up to one of the trials, a prospective case control study, one retrospective case control study, two meta-analyses of the above-mentioned studies, as well as 11 non-comparative studies, which included two prospective, 10 retrospective, and two case series. Most studies involved the use of different biologic meshes, while bioabsorbable mesh use was only described in four of the retrospective studies mentioned. The results are variable, however, most authors found a benefit from hiatal closure reinforcement with mesh. The available literature lacks definitive evidence to support the use of biologic or bioabsorbable materials to reinforce hiatal closure in the cure of paraesophageal hernias. Further studies are needed to assess newer materials and longer-term effects of existing products.


Ideglira is Associated With Improved Short-Term Clinical Outcomes and Cost Savings Compared with Insulin Glargine U100 Plus Insulin Aspart in the U.S.
In the DUAL (Dual Action of Liraglutide and Insulin Degludec in Type 2 Diabetes) VII trial, IDegLira (a combination of insulin degludec and liraglutide) was compared with insulin glargine U100 plus insulin aspart. Both treatment approaches achieved similar glycemic control, but there were differences in hypoglycemia, changes in body weight, and injection frequency. The aim of the present analysis was to assess the short-term cost effectiveness of IDegLira versus insulin glargine U100 plus insulin aspart for treatment of patients with type 2 diabetes mellitus not meeting glycemic targets on basal insulin in the U.S. A cost-utility model was developed to evaluate the clinical and economic outcomes associated with the 2 treatments over a 1-year time horizon, capturing the impact on quality of life of hypoglycemic events, body mass index, and injection frequency. Costs were captured from a healthcare payer perspective in 2017 U.S. dollars ($). IDegLira was associated with improved quality of life by 0.12 quality-adjusted life years compared with insulin glargine U100 plus insulin aspart. The key drivers of this difference were reduced injection frequency and hypoglycemic events avoided. IDegLira was associated with increased annual drug costs, but this was entirely offset by reduced needle costs and reduced costs of self-monitoring of blood glucose testing. IDegLira was associated with total annual cost savings of $743 per patient. IDegLira was found to improve quality-adjusted life expectancy and reduce costs when compared with insulin glargine U100 plus insulin aspart for treatment of patients with type 2 diabetes not achieving glycemic control on basal insulin in the U.S. ADA = American Diabetes Association; BMI = body mass index; CI = confidence interval; DUAL = Dual Action of Liraglutide and Insulin Degludec in Type 2 Diabetes; GLP-1 = glucagon-like peptide-1; HbA1c = glycated hemoglobin; ICER = incremental cost-effectiveness ratio; IU = international units; QALY = quality-adjusted life year; SMBG = self-monitoring of blood glucose.


Expression of CheA fragments which define domains encoding kinase, phosphotransfer, and CheY binding activities.
The histidine protein kinase CheA is a central component of the Escherichia coli chemotaxis system. The autophosphorylation activity of CheA is controlled by membrane-bound chemoreceptors and by the CheW coupling protein. CheA phosphorylates the CheY and CheB proteins which respectively control the direction of flagellar rotation and the level of receptor adaptation, thereby regulating the cells' chemotactic response. Genes encoding three polypeptide fragments of CheA were constructed and expressed in order to better define the functional organization of the wild-type protein. These fragments allowed the identification of regions of the protein responsible for CheY binding, phosphotransfer, and kinase activity. The kinase domain was expressed as a 30-kDa polypeptide corresponding to the central portion of the wild-type protein which contains sequences homologous to other histidine kinases. It was able to phosphorylate a 15-kDa amino-terminal phosphotransfer domain which was separately expressed and purified. This latter domain is capable of phosphotransfer to CheY despite the fact that it lacks the ability to stably bind CheY. CheY was immobilized to a dextran matrix through a single cysteine residue which was introduced into the protein at a position far removed from the active site. A stable binding site for CheY was mapped to a segment between the site of autophosphorylation and the kinase domain by using surface plasmon resonance to detect binding to the immobilized CheY. The region of the kinase which tightly binds the unphosphorylated substrate may play an important role in regulating the specificity of the signal transducing system.


Influence of antihypertensive drugs on aortic and coronary effects of Ang-(1-7) in pressure-overloaded rats.
This study investigated the influence of antihypertensive drugs, such as angiotensin-converting enzyme inhibitors (ACEIs), AT1 receptor blockers (ARBs), voltage-gated L-type calcium channel blockers, and mineralocorticoid receptor antagonists (MRAs), on the effects of angiotensin-(1-7) [Ang-(1-7)] on aorta and coronary arteries from pressure-overloaded rats. Pressure overload was induced by abdominal aortic banding (AB). To evaluate the role of antihypertensive drugs on the effect of Ang-(1-7), AB male Wistar rats weighing 250-300 g were treated with vehicle or low doses (5 mg·kg-1·day-1, gavage) of losartan, captopril, amlodipine, or spironolactone. Isolated aortic rings and isolated perfused hearts under constant flow were used to evaluate the effect of Ang-(1-7) in thoracic aorta and coronary arteries, respectively. Ang-(1-7) induced a significant relaxation in the aorta of sham animals, but this effect was reduced in the aortas of AB rats. Chronic treatments with losartan, captopril or amlodipine, but not with spironolactone, restored the Ang-(1-7)-induced aorta relaxation in AB rats. The coronary vasodilatation evoked by Ang-(1-7) in sham rats was blunted in hypertrophic rats. Only the treatment with losartan restored the coronary vasodilatory effect of Ang-(1-7) in AB rat hearts. These data support a beneficial vascular effect of an association of Ang-(1-7) and some antihypertensive drugs. Thus, this association may have potential as a new therapeutic strategy for cardiovascular diseases.


DNA radiolysis by fast neutrons. II. Oxygen, thiols and ionic strength effects.
Plasmid DNA was irradiated with fast neutrons, and the protection by cysteamine against strand breakage (ssb and dsb) was evaluated in the presence and absence of oxygen. In the absence of cysteamine no radiosensitizing effect of oxygen was observed. In anoxia the protection factors, PF(ssb) and PF(dsb) of 1 mM cysteamine (in 50 mM potassium phosphate solution) were lower than the PFs observed with gamma-irradiation. The results agree with the radical repair model, in which the thiol competes with the oxygen produced inside the anoxic neutron-irradiated system, according to the 'oxygen-in-the-track' hypothesis. At low ionic strength in air-saturated solutions, positively charged cysteamine protects more efficiently than negatively charged thiolactate. The dependence of the PFs on the charge of the thiol can be explained by the condensation of counter-ions and depletion of co-ions around DNA, predicted by Manning's theory. Based on the same theory, we propose here an explanation of the ionic strength or by thiolactate at low ionic strength is largely due to scavenging of OH. radicals in the bulk solution. At low ionic strength the PF(ssb) of cysteamine is higher for neutrons than for gamma-irradiation. This might suggest different primary lesions for the two types of irradiation.


Myasthenia gravis: difference between thymoma-associated antibodies and cross-striational skeletal muscle antibodies.
Serum from 20 of 137 patients (15%) with myasthenia gravis (MG) contained antibodies to a citric acid extract (CAE) of skeletal muscle. A thymoma was found in all 19 of these patients who were thymectomized. There was no evidence of thymoma in patients who did not have CAE antibodies. Serum from 40 of the same 137 patients (30%) contained antibodies that gave a cross-striational immunofluorescent pattern in skeletal muscle. This pattern was seen with serum from 16 of the 20 thymoma patients, but also with serum from 24 patients without thymoma. The cross-striation antibodies were not absorbed by CAE coated on to tanned sheep erythrocytes. Accordingly, antibodies detected in the two tests have different specificities.


Osteonecrosis of the femoral head: using CT, MRI and gross specimen to characterize the location, shape and size of the lesion.
To investigate the accuracy of using CT and MRI to characterize lesions of osteonecrosis of the femoral head (ONFH). Coronal CT and MRI scans were performed on 30 femoral head specimens collected from 23 patients who had undertaken hip arthroplasty owing to ONFH. The results were compared with findings from coronal sectional gross specimens. Two radiologists independently measured the volume of necrotic lesions from CT and MR images using computer software, and the results were averaged. The volume of specimens' necrotic lesion was measured using the water displacement method. There was a high degree of consistency between CT, MRI and the coronal sectional gross specimen on the location, shape and spatial structure of lesions. Differences of the lesion volume measured from CT and MR images were not statistically significant between two radiologists. The necrotic lesion volumes measured from CT and MR images and gross specimens were 22.07 ±5.35, 22.21 ± 5.15 and 21.12 ±4.96 cm(3), respectively, and the differences were not statistically significant (F = 0.396; p = 0.674). For patients with ONFH in Association Research Circulation Osseous stage III or above, CT and MRI can accurately display the characterization of lesion. The size and location of necrotic lesions are major factors associated with femoral head collapse. CT is superior to MRI in identifying subchondral fracture. CT can help diagnose and predict the prognosis of ONFH.


Impact of aspirin on clinical outcomes for African American men with prostate cancer undergoing radiation.
Preclinical and clinical studies have suggested that aspirin (ASA) may exhibit antineoplastic activity. Particularly in prostate cancer, several reports have suggested that ASA plays a role in improved outcomes. Therefore, we studied the role of ASA in a uniquely African American population, which is known to harbor more aggressive and biologically different disease compared to the general population. We identified 289 African American men with prostate cancer who were treated with definitive radiation therapy to a dose of ≥7560 cGy. The median follow-up was 76 months. Kaplan-Meier analysis was used to analyze biochemical failure-free survival (bFFS), distant progression-free survival (DMPFS), and prostate cancer-specific survival (PCSS). Multivariate Cox regression was used to analyze the impact of covariates on all endpoints. There were 147 men who were ASA+ and 142 who were ASA-. The 7-year bFFS was 80.9% for ASA+ men and 70.3% for ASA- men (p = 0.03). On multivariate analysis, ASA use was associated with a significant reduction in biochemical recurrences (hazard ratio [HR] 0.56, 95% confidence interval [CI] 0.34-0.93, p = 0.03). The 7-year DMPFS was 98.4% for ASA+ and 91.8% for ASA- men (p = 0.04). On multivariate analysis, ASA use was associated with a decreased risk of distant metastases (HR 0.23, 95% CI 0.06-0.91, p = 0.04). The 7-year PCSS was 99.3% for ASA+ and 96.9% for ASA- men (p = 0.07). In this study, ASA use was associated with improved biochemical outcomes and reduced distant metastases. This indicates that ASA appears to play an important antineoplastic role in African American men.


[Immunological markers of alimentary-induced hyperlipidemia in Wistar rats].
Changes in plasma levels of the main groups of cytokines and adipokines may correlate with the severity of metabolic disorders in hyperlipidemia and obesity. The aim of the study was to assess the significance of ghrelin, leptin, their ratio (L/Gh), and the cytokine profile as biomarkers at dietary-induced hyperlipidemia. Material and methods. We used 48 female Wistar rats with an initial body weight of 123±1 g, which were divided into 6 groups. Group 1 (control) received a balanced semi-synthetic diet according to AIN93; group 2 - diet with excess fat (30% by weight); group 3 - a diet with the addition of 20% fructose solution instead of drinking water, group 4 - a diet with excess fat and fructose, group 5 - a diet with added cholesterol (0.5%), group 6 - a diet with cholesterol and fructose. On the 64th day of the experiment, the mass of internal organs was determined; the levels of cytokines and adipokines in blood plasma were measured by multiplex immunoassay. Results and discussion. A decrease in the level of leptin was found in group 5 compared with the control and with groups 2, 4 and 6 groups (p<0.05). The lowest level of ghrelin was found in group 2 (p<0.05) against the background of high concentrations of leptin. Significant correlations were found between L/Gh and the total mass of animals (r=0.321; р=0.034), the relative mass of adipose tissue (r=0.439; р=0.003) and with the relative mass of the spleen (r=-0.460; р=0.003). In group 2, at the maximum L/Gh ratio, a significantly higher weight of adipose tissue was found, whereas in groups 3 and 5, at the lowest L/Gh ratio, the relative amount of total fat was the lowest. L/Gh ratio correlated with the level of monocyte chemotactic protein-1 (MCP-1), RANTES, IL-18 and macrophage colony-stimulating factor (M-CSF). The concentrations of IL-17, IL-18, IL-4, IL-5, MIP-3a, IFN-γ, M-CSF and RANTES in the experimental groups were reduced compared with the control, with the most pronounced effect in group 5 together with the lowest L/Gh ratio. Conclusion. The presence of a significant correlation between L/Gh ratio and changes in the weight of rats' body, spleen, adipose tissue, as well as levels of cytokines involved in inflammation regulation, confirms the importance of L/Gh ratio as a biomarker in an in vivo model of dyslipidemia.


The Usefulness of Nap Sleep Recording During Routine Electroencephalography: An Audit Study.
A measure to increase the electroencephalogram (EEG) outcome includes a short period of nap sleep during a routine standard EEG with the aim of increasing its sensitivity to interictal abnormalities or provoking seizures. As part of an ongoing auditing of our EEG data, we aimed to investigate the contribution of nap sleep during routine outpatient department based EEGs requested for a variety of reasons. EEG data at the Department of Clinical Physiology at Sultan Qaboos University Hospital, Oman, from July 2006 to December 2007 and from January 2009 to December 2010 (total 42 months) were reviewed. The EEGs were for patients older than 13-years referred for possible epilepsy, blackouts, headache, head trauma, and other non-specified attacks. The recording period was between 20 to 40 minutes. Abnormalities were identified during waking and nap sleep periods. A total of 2 547 EEGs were reviewed and 744 were abnormal (29.2%). Of those abnormal EEGs, nap sleep was obtained in 258 (34.7%) EEGs, and 39 (15.1%) showed abnormalities during nap sleep. Nineteen out of the 39 (48.7%) EEGs were abnormal during awake and nap sleep; and 20 (51.3%) were abnormal during nap sleep, which represented only 2.7% of the total abnormal EEGs (n = 744). The contribution of the short nap sleep to the pickup rate of interictal abnormalities in EEG was minimal. We recommend the EEG service to include one cycle of spontaneous sleep EEG directed at patients with a history suggestive of epilepsy if their awake EEGs are normal.


Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis treatment and follow-up of patients with localised colon cancer.
The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of localised colon cancer was published in 2020. It was decided by both the ESMO and the Japanese Society of Medical Oncology (JSMO) to convene a special virtual guidelines meeting in March 2021 to adapt the ESMO 2020 guidelines to take into account the ethnic differences associated with the treatment of localised colon cancer in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with localised colon cancer representing the oncological societies of Japan (JSMO), China (CSCO), India (ISMPO), Korea (KSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence and was independent of the current treatment practices and drug availability and reimbursement situations in the different Asian countries.


Locally invasive tumors arising from hyperplasia of the retinal pigment epithelium.
Focal hyperplasia of the retinal pigment epithelium (RPE) is a common fundus condition that is generally stationary, with little or no tendency to enlarge or spawn neoplasms. The purpose of this report is to describe the unusual clinical features of two similar cases in which a nodular tumor of the RPE was documented to arise from a small focus of hyperplasia of the RPE. Clinical and cytopathologic observations of two patients. Both patients were observed for approximately 25 years with an unusual progressive fundus tumor that originally arose from a small, flat, irregular focus of hyperplasia of the RPE. The originally observed pigmented lesion was attributed to toxoplasmosis in one patient and laser treatment for central serous chorioretinopathy in the other. In both patients, the tumor enlarged, invaded through the full-thickness sensory retina, and produced a characteristic retinal perforation with apposition of the mass to the vitreous. In both instances, fine-needle aspiration biopsy showed scant pigmented cells, but a definite diagnosis was not made. However, clinical observations in both patients suggested that these tumors were acquired neoplasms that arose from small foci of hyperplasia of the RPE. Focal hyperplasia of the RPE can give rise to unusual invasive tumors that invade and replace the overlying sensory retina. These tumors have unique clinical features that differentiate them from uveal melanoma and other pigmented fundus lesions.


[Clinical characteristics and the factors relevant to peritoneal transport function in patients with continuous ambulatory peritoneal dialysis].
To observe the clinical characteristics with different peritoneal transport type in patients with continuous ambulatory peritoneal dialysis (CAPD), and to investigate the factors associated with peritoneal transport function. Methods: The clinical data of 158 CAPD patients were analyzed retrospectively. According to peritoneal equilibration test, a method for evaluation of the peritoneal transport function, the patients were divided into 2 groups: a high average and high peritoneal transport group (Group A, n=84) and a low average and low peritoneal transport group (Group B, n=74). The demographics, clinical biochemical indexes and the incidence of cardiovascular complications were compared between the 2 groups. Logistic regression analysis was used to find the factors relevant to peritoneal transport function. Results: The level of serum albumin (ALB) in the Group B was significantly higher than that in the Group A (P<0.05). The 4 h dialysate/plasma creatinine (D/Pcr), high-sensitivity C-reactive protein (hs-CRP), body mass index (BMI), and the rates of cardiovascular complications in the Group A were significantly higher than those in the Group B (P<0.05). Correlation analysis showed that the D/Pcr was positively correlated with the BMI, serum hs-CRP and cardiovascular complications (r=0.179, 0.373 and 0.426, respectively, P<0.05), while it was negatively correlated with ALB (r=-0.393, P<0.01). Logistic regression analysis showed that the high BMI (OR=1.178, P<0.05), cardiovascular complications (OR=5.035, P<0.01), and the low serum ALB (OR=0.852, P<0.01) were the risk factors for high peritoneal transport. Conclusion: The serum ALB level, BMI and the cardiovascular complications are associated with high peritoneal transport, which are useful markers for predicting the peritoneal transport function before peritoneal dialysis.