The learning curve of thoracoscopic surgery in a single surgeon and successful implementation of uniportal approach.
In some institutions, a recently introduced uniportal approach has replaced the multiportal approach for thoracoscopic major pulmonary resection. This study investigated the effect of this change on the surgical learning curve by examining the perioperative results of a single surgeon. Between April 2012 and August 2020, 376 patients with primary lung cancer underwent thoracoscopic lobectomy with ND2a-1/2 lymphadenectomy in the authors' hospital. Surgery was performed by one of the authors in 189 of these patients, who were thus enrolled in this retrospective study. The surgeries were classified chronologically into five phases and the operative time, rate of intraoperative massive bleeding, and rate of postoperative prolonged air leak (PAL) were then compared. The learning curve (i.e., operative time) was assessed by Spearman's rank correlation test. The perioperative results achieved with the uniportal and multiportal approaches were also compared before and after the patients were matched for their characteristics based on the propensity score. The five phases differed significantly with respect to the operative time and rate of postoperative PAL (P<0.0001, P=0.0061). The correlation between operative time and number of consecutive cases was also significant (r=-0.579, P<0.0001). Superior results in terms of operative time (P<0.0001), duration of postoperative drainage (P<0.0001), and rate of postoperative PAL (P=0.0034) were obtained using a uniportal rather than multiportal approach. The transition from a multiportal to a uniportal approach did not cause a decline in the learning curve of thoracoscopic lobectomy with ND2a-1/2 lymphadenectomy.


Neurodegenerative movement disorders: the contribution of functional imaging.
Functional imaging such as positron emission tomography and single-photon emission computed tomography provide sensitive tools to assess functional brain abnormalities associated with neurodegenerative disease. This review discusses recent findings in this field, with a focus on the detection and characterization of receptor binding and presynaptic dopamine changes in movement disorders. The classical role of positron emission tomography and radioligands such as F-dopa and C-raclopride for investigating abnormalities of the presynaptic and postsynaptic dopaminergic system underlying Parkinson's disease, Parkinsonism and Huntington's disease has recently been made more powerful by the application of statistical mapping to localize changes in dopamine storage capacity and receptor binding across the whole brain at a voxel level. C-raclopride positron emission tomography provides an indirect marker of changes in levels of dopamine in the synaptic cleft. The application of this model in assessing dopamine changes in response to pharmacological, behavioural, motor task and magnetic stimulation in normal individuals and Parkinson's disease patients is reviewed. Recent studies using positron emission tomography and single-photon emission computed tomography to discriminate Parkinson's disease from essential tremor and Parkinsonism, the involvement of non-dopaminergic systems in Parkinson's disease and the role of cell transplantation in Parkinson's disease and Huntington's disease are also discussed. Functional imaging techniques provide insight into the pathophysiology of Parkinson's disease, Parkinsonism, and Huntington's disease and the mechanisms of the progression of these diseases. They also play a role in assessing the efficacy of putative neuroprotective and restorative therapy, such as striatal infusions of neurotrophic factors and implants of fetal cells.


Serotonergic neurons in the ventral nerve cord of Chilopoda - a mandibulate pattern of individually identifiable neurons.
Given the numerous hypotheses concerning arthropod phylogeny, independent data are needed to supplement knowledge based on traditional external morphology and modern molecular sequence information. One promising approach involves comparisons of the structure and development of the nervous system. Along these lines, the morphology of serotonin-immunoreactive neurons in the ventral nerve cord has been investigated in numerous tetraconate taxa (Crustacea and Hexapoda). It has been shown that these neurons can be identified individually due to their comparably low number, characteristic soma position, and neurite morphology, thus making it possible to establish homologies at the single cell level. Within Chilopoda (centipedes), detailed analyses of major branching patterns of serotonin-immunoreactive neurons are missing, but are crucial for developing meaningful conclusions on the homology of single cells. In the present study, we re-investigated the distribution and projection patterns of serotonin-immunoreactive neurons in the ventral nerve cord of three centipede species: Scutigera coleoptrata, Lithobius forficatus, and Scolopendra oraniensis. The centipede serotonergic system in the ventral nerve cord contains defined groups of individually identifiable neurons. An anterior and two posterior immunoreactive neurons per hemiganglion with contralateral projections, a pair of ipsilateral projecting lateral neurons (an autapomorphic character for Chilopoda), as well as a postero-lateral group of an unclear number of cells are present in the ground pattern of Chilopoda. Comparisons to the patterns of serotonin-immunoreactive neurons of tetraconate taxa support the homology of anterior and posterior neurons. Our results thus support a sister group relationship of Myriapoda and Tetraconata and, further, a mandibulate ground pattern of individually identifiable serotonin-immunoreactive neurons in the ventral nerve cord. Medial neurons are not considered to be part of the tetraconate ground pattern, but could favor the 'Miracrustacea hypothesis', uniting Remipedia, Cephalocarida, and Hexapoda.


IRE1α Stands astride Many Paths to Insulin Production.
A new study shows that components of the unfolded protein pathway are needed to help manage the production of vast amounts of insulin by pancreatic β cells in response to glucose stimulation. Read the Research Article.


Infiltrating ductal carcinoma breast with central necrosis closely mimicking ductal carcinoma in situ (comedo type): a case series.
Here we present a series of infiltrative ductal carcinoma breast cases (infiltrative ductal carcinoma with central necrosis) so closely mimicking 'DCIS with central comedo necrosis' that on initial morphological analysis these foci of tumors were labeled as DCIS (high grade, comedo). However on further histological work up and by using immunohistochemistry (IHC) for myoepithelial markers it was later confirmed that these were foci of infiltrative ductal carcinoma breast with central necrosis. This case series gives the realization that a breast carcinoma may be partly or entirely DCIS like yet invasive. In such a dilemma IHC especially for assessment of myoepithelial lining is very useful to differentiate DCIS comedo from invasive carcinoma with central necrosis.


[Prevention of type 2 diabetes in Germany--a challenge for health professionals].
The most efficient way to manage diabetes and its complications is to prevent diabetes. Recent studies have convincingly demonstrated that prevention of diabetes and its complications are possible and cost effective. Life-style interventions and also early pharmacological preventive strategies have yielded a 25-75% diabetes risk reduction and an even more promising reduction in cardiovascular risks. These findings offer the evidence-base for diabetes prevention, but essential is the delivery of intervention into our societies. The challenge, therefore, is the management of prevention and intervention programs considering scientific aspects and practical requirements during implementation. This can only be addressed in a coordinated interdisciplinary setting and across sectors which requires the development of a comprehensive, integrated prevention management program also on an European level. Pharmacies have to play an important role in this concept because of their widespread distribution and the frequency of pharmacy visits of the general population. They should be established as places where patients can continuously offer risk assessment including recommendations on how to prevent the disease. Developing the role of the prevention manager and continuous evaluation and quality control are key factors in performing high quality intervention and care. Community pharmacies could take an active part in this prevention program, its evaluation, and quality assurance. Implementing structured prevention programs will enable nationwide prevention of diabetes mellitus without consuming large resources from health care insurances. This process will be challenging and time consuming, requiring many partners but resulting in a profitable "health" investment.


Evaluating of Gene Expression Alteration after Garlic Consumption, Analyzing through Bioinformatics Approach.
Molecular study of garlic as a popular food ingredient could better understand its health benefits such as immunological effects. For this aim, effects of garlic on the spleen and possible side effects including oxidative stress increment, the molecular mechanism is investigated through network analysis of differentially expressed genes in the treatment of garlic. Protein-protein interaction (PPI) network analysis of spleen gene expression profile of Mus musculus (8-week old male C57BL/6J mice) in garlic treatments from a microarray study with the code of GSE10344 was analyzed via GEO2R software. Furthermore, Cytoscape V 3.7.1 was applied to construct and analyze a network of up- and down-regulated genes. The differentially expressed genes (DEGs) were analyzed via the CluePedia plugin of Cytoscape to determine expression patterns. After the identification of central nodes, an action map was created. A total of 77 DEGs were achieved which were including 40 up-regulated and 37 Down-regulated. The centrality analysis of the network indicated that Vcan, Lamb1, and Ltbp1 are hubs and Glra1, Wdr17, Nefl, and Becn1 are bottlenecks. Mutual regulatory connections between hubs and Alb and App (as two non-queried hubs) were determined. The findings indicate that garlic effect on the spleen and its mechanism may be involved mostly with App dysregulation.


New restriction endonuclease CviRI cleaves DNA at TG/CA sequences.
A new type II restriction endonuclease, CviRI, was isolated from virus XZ-6E infected chlorella cells. CviRI is the first restriction endonuclease to recognize the sequence 5'-TGCA-3' and cleaves DNA between the G and C residues to produce blunt-end termini. Methylation of the adenine or cytosine in 5'-TGCA-3' sequences prevents CviRI cleavage. Due to its sequence specificity, CviRI may be especially useful for detecting mutant alleles of many heritable human genetic diseases.


T Cell Profile was Altered in Pulmonary Tuberculosis Patients with Type 2 Diabetes.
BACKGROUND Studies have suggested that type 2 diabetes (T2D) increases the risk of active pulmonary tuberculosis (TB) infection. T2D might exacerbate TB severity and adversely impact the treatment of TB patients by suppressing the immune response of TB. However, how the immune cell profiles are changed in Chinese TB patients with coincident of T2D compared with TB patients without T2D is still unclear. MATERIAL AND METHODS To explore the immune cell profile alteration in TB patients with T2D, we collected blood samples from 46 TB patients with or without T2D and measured the profiles of T cell subsets. RESULTS We found TB patients with coincident of T2D had higher percentages of Th2 and Th17 cells after TB antigens stimulation, while they had unchanged Th1 cells and decreased CD8+ cytotoxic T cells compared to TB patients without T2D. However, no significant difference in baseline percentages of these T cells subsets was observed. CONCLUSIONS T2D has important impacts on regulating anti-TB immunity by increasing Th2 and Th17 cell differentiation, but reducing the activity of CD8+ T cells. Our study supports the need to perform longitudinal studies to evaluate the roles of immunological interaction between T2D and TB in TB development.


Clinical, endocrinological, and molecular features of four Korean cases of cytochrome P450 oxidoreductase deficiency.
Cytochrome P450 oxidoreductase (POR) deficiency is a rare autosomal recessive disorder caused by mutations in the POR gene encoding an electron donor for all microsomal P450 enzymes. It is characterized by adrenal insufficiency, ambiguous genitalia, maternal virilization during pregnancy, and skeletal dysplasia. In this study, we investigated the clinical, hormonal, and molecular characteristics of patients with POR deficiency in Korea. This study included four patients with POR deficiency confirmed by biochemical and molecular analysis of POR. Clinical and biochemical findings were reviewed retrospectively. Mutation analysis of POR was performed by Sanger sequencing after polymerase chain reaction amplification of all coding exons and the exon-intron boundaries. All patients presented with adrenal insufficiency and ambiguous genitalia regardless of their genetic sex. Two patients harbored homozygous p.R457H mutations in POR and presented with adrenal insufficiency and genital ambiguity without skeletal phenotypes. The other two patients with compound heterozygous mutations of c.[1329_1330insC];[1370G>A] (p.[I444Hfs*6];[R457H]) manifested skeletal abnormalities, such as craniosynostosis and radiohumeral synostosis, suggesting Antley-Bixler syndrome. They also had multiple congenital anomalies involving heart, kidney, and hearing ability. All patients were treated with physiologic doses of oral hydrocortisone. We report the cases of 4 patients with POR deficiency identified by mutation analysis of POR. Although the study involved a small number of patients, the POR p.R457H mutation was the most common, suggesting founder effect in Korea. POR deficiency is rare and can be misdiagnosed as 21-hydroxylase or 17α-hydroxylase/17,20-lyase deficiency. Therefore, molecular analysis is critical for confirmatory diagnosis.


Modification of phospholipase C-gamma-induced Ca2+ signal generation by 2-aminoethoxydiphenyl borate.
The mechanisms by which Ca(2+)-store-release channels and Ca(2+)-entry channels are coupled to receptor activation are poorly understood. Modification of Ca(2+) signals by 2-aminoethoxydiphenyl borate (2-APB), suggests the agent may target entry channels or the machinery controlling their activation. In DT40 B-cells and Jurkat T-cells, complete Ca(2+) store release was induced by 2-APB (EC(50) 10-20 microM). At 75 microM, 2-APB emptied stores completely in both lymphocyte lines, but had no such effect on other cells. In DT40 cells, 2-APB mimicked B-cell receptor (BCR) cross-linking, but no effect was observed in mutant DT40 lines devoid of inositol 1,4,5-trisphosphate (InsP(3)) receptors (InsP(3)Rs) or phospholipase C-gamma2 (PLC-gamma2). Like the BCR, 2-APB activated transfected TRPC3 (canonical transient receptor potential) channels, which acted as sensors for PLC-gamma2-generated diacylglycerol in DT40 cells. The action of 2-APB on InsP(3)Rs and TRPC3 channels was prevented by PLC-inhibition, and required PLC-gamma2 catalytic activity. However, unlike BCR activation, no increased InsP(3) level could be measured in response to 2-APB. Also, calyculin A-induced cytoskeletal reorganization prevented 2-APB-induced InsP(3)R and TRPC3-channel activation, but not that induced by the BCR. 2-APB still activated TRPC3 channels in DT40 cells with fully depleted Ca(2+) stores, indicating its action was not via Ca(2+) release. Significantly, 2-APB-induced InsP(3)R and TRPC3 activation was prevented in DT40 knockout cells devoid of the BCR- and PLC-gamma2-coupled adaptor/kinases, Syk, Lyn, Btk or BLNK. The results suggest that 2-APB activates Ca(2+) signals in lymphocytes by initiating and enhancing coupling between components of the BCR-PLC-gamma2 complex and both Ca(2+)-entry and Ca(2+)-release channels.


Insights into acid dissociation of HCl and HBr with internal electric fields.
The electric field experienced by an acid molecule in the acid-water cluster depends on its local environment comprising of surrounding water molecules. A critical field of about 193 and 163 MV cm-1 is required for the dissociation of HCl and HBr, respectively, and is associated with the arrangement of water molecules around the acid. The critical field required for dissociation of isolated HCl and HBr is 510 and 462 MV cm-1, respectively. Hence the solvation of the proton and the halide anion by water molecules substantially lowers the critical electric field by about 300 MV cm-1, relative to vacuum.


Neighborhoods and child abuse: Multiple informant perspectives.
Using data from the nationally representative longitudinal Future of Families and Child Wellbeing Study, the current study sought to examine associations between neighborhood disorder and physical characteristics of the neighborhood at child age three with the likelihood of experiencing physical and psychological abuse and neglect at age five. Negative binomial regression and zero inflated negative binomial regression models were used to estimate the associations. Resident perceptions of neighborhood disorder and outside observation of neighborhood physical characteristics were both found to be independently related to the likelihood of physical assault. Resident perceptions were related to psychological aggression. A more positive perception of the neighborhood environment for children (lack of neighborhood disorder) and physical characteristics of the neighborhood were protective against maltreatment. These relationships were not significant for neglect. Neighborhood environment is a crucial contributor to maltreatment risk. Findings from the present study showed that multiple perceptions of neighborhood quality were associated with lower risk for child physical assault and psychological aggression. Mothers' perceptions of a more positive neighborhood environment were associated with significantly lower physical assault and psychological aggression scores.


Poorly differentiated carcinoma arising in the setting of erythema ab igne.
Erythema ab igne (EAI) is a reticulated, erythematous, or hyperpigmented dermatosis that is caused by chronic exposure to infrared radiation. Chronic lesions of EAI have significant potential for malignant transformation. We report a case of poorly differentiated carcinoma arising within a patch of long-standing EAI on the lower extremity of a 92-year-old female. This case highlights the importance of recognizing EAI early and counseling patients to avoid further exposure to the offending infrared source to reduce the risk of malignant transformation. EAI has been associated with several different types of cutaneous neoplasms including the Merkel cell carcinoma, squamous cell carcinoma, and cutaneous marginal zone lymphoma.


[Rotavirus infections in childhood: studies using a molecular biology method (gene electrophoresis)].
During a 15-month period all children below 16 years admitted to the Children's Hospital in St. Gallen with acute diarrheal disease were studied for rotavirus (RV) infection. Stool samples from control patients without gastrointestinal disease were investigated for RV shedding in order to detect RV carriers or asymptomatically infected children. RV was detected by electrophoresis of RV genomic dsRNA in 154 children. 119 (58%) of 205 patients hospitalized because of diarrhea were RV associated, 25 children became symptomatically ill during their hospitalization, and in 10 (1%) of 954 control patients RV could be found. During the winter 1983/1984 two epidemic peaks of RV associated diarrhea were noted, whereas in the summer period RV related disease occurred only sporadically. The peak incidence of RV infection was in the age group between 10 and 12 months. After the 3rd year of life RV infection only rarely required hospitalization. During this study period 8 different genomic RNA patterns of RV were found. The number of patients within these 8 RV types, however, is too small to allow definite correlations between epidemiological or clinical features and selected electrophorotypes. The possibility to perform refined epidemiological and clinical analyses of RV infection by genomic dsRNA electrophoresis offers important advantages when compared to other RV detection systems. In addition, this method has proven to be fast, simple and reliable.


Systems Biology Approaches-based Biomarkers Discovery for Acute Aortic Dissection.
Acute aortic dissection (AAD) faces great challenges in early diagnosis and effective drug treatment. Recent developments in systems biology approaches allow high-throughput screening of novel diagnostic biomarkers and potential therapeutic targets. In this review, we summarize the currently available AAD biomarkers identified in the context of genomic, transcriptomic, proteomic, and metabolic profiles, and highlight the benefits of using a combination of these findings for a better understanding of the molecular nature of this life-threatening disease. This review also provides a reference for future studies that employ a comprehensive, multiple-level approach at the single-cell level to decipher the underlying molecular pathophysiology of AAD.


Identification and quantitation of equine serum and secretory immunoglobulin A.
Immunoglobulin A (IgA) was demonstrated in equine serum and secretions. This immunoglobulin had a molecular weight extending from 150,000 to 700,000 and reacted with specific antihuman alpha-chain antiserum. Antigenic determinants specific for secretory IgA were demonstrated and found to be absent on serum IgA. Antigen binding activity was detected in IgA from tears. Purified IgA was antigenically distinct from equine IgG, IgM, IgG(T), and aggregating immunoglobulin. Quantitative studies demonstrated that IgA was the predominant immunoglobulin in tears and milk but not in colostrum. The electrophoretic mobility, size, presence of secretory component, and reaction with specific antihuman alpha-chain antiserum demonstrates that this immunoglobulin is the equine homologue of human IgA.


Snapshot hyperspectral imaging of intracellular lasers.
Intracellular lasers are emerging as powerful biosensors for multiplexed tracking and precision sensing of cells and their microenvironment. This sensing capacity is enabled by quantifying their narrow-linewidth emission spectra, which is presently challenging to do at high speeds. In this work, we demonstrate rapid snapshot hyperspectral imaging of intracellular lasers. Using integral field mapping with a microlens array and a diffraction grating, we obtain images of the spatial and spectral intensity distribution from a single camera acquisition. We demonstrate widefield hyperspectral imaging over a 3 × 3 mm2 field of view and volumetric imaging over 250 × 250 × 800 µm3 (XYZ) volumes with a lateral (XY) resolution of 5 µm, axial (Z) resolution of 10 µm, and a spectral resolution of less than 0.8 nm. We evaluate the performance and outline the challenges and strengths of snapshot methods in the context of characterizing the emission from intracellular lasers. This method offers new opportunities for a diverse range of applications, including high-throughput and long-term biosensing with intracellular lasers.


Thromboelastography on-the-go: Evaluation of the TEG 6s device during ground and high-altitude Aeromedical Evacuation with extracorporeal life support.
Coagulation monitoring capabilities during transport are limited. Thromboelastography (TEG) is a whole-blood clotting test measuring clot formation, stabilization, and fibrinolysis and is traditionally performed in a laboratory. We evaluated a new point-of-care TEG analyzer, TEG 6s (Haemonetics, Braintree, MA), in a large animal model of combat-relevant trauma managed with extracorporeal life support during ground and high-altitude aeromedical evacuation. The objective was to compare TEG 6s used during transport versus the predicate device, TEG 5000, used in the laboratory. We hypothesized that TEG 6s would be comparable with TEG 5000 during dynamically changing transport conditions. Thromboelastography parameters (R, K, angle, MA, LY30) derived by TEG 6s and TEG 5000 were compared during transport of 8 swine. TEG 6s was transported with animals during ground transport and flight. TEG 5000 was stationary in an adjacent building. TEG 6s activated clotting time (ACT) was compared with a Hemochron Junior ACT analyzer (Accriva Diagnostics, San Diego, CA). Statistics were performed using SAS 9.4 with Deming regressions, Spearman correlations, and average differences compared. Correlation between devices was stronger at sea-level (R, r = 0.7413; K, r = 0.7115; angle, r = 0.7192; MA, r = 0.8386; LY30, r = 0.9099) than during high-altitude transport (R, r = 0.4787; K, r = 0.4007; angle, r = 0.3706; MA, r = 0.6573; LY30, r = 0.8481). Method agreement was comparable during stationary operation (R, r = 0.7978; K, r = 0.7974; angle, r = 0.7574; MA, r = 0.7841; LY30, r = 0.9140) versus ground transport (R, r = 0.7927; K, r = 0.6246; angle, r = 0.6967; MA, r = 0.9163; LY30, r = 0.8603). TEG 6s ACT trended higher than Hemochron ACT when subjects were heparinized (average difference, 1,442 ± 1,703 seconds) without a methodological difference by Deming regression. Mobile TEG 6s during ground and altitude transport is feasible and provides unprecedented information to guide coagulation management. Future studies should assess the precision and accuracy of TEG 6s during transport of critically ill.


Prostate cancer outcome: epidemiology and biostatistics.
Substantial gaps exist in our ability to accurately predict prognosis, and these gaps limit our understanding of the complex mechanisms that contribute to the greatest cancer epidemic of our time, prostate cancer. This review addresses contemporary epidemiologic and biostatistical issues in prostate cancer. It covers the science of outcome prediction and biomarker evaluation, recognition of the need to combine biomarkers to improve the accuracy of our outcome estimates and an analysis of current outcome assessment methods, including the TNM staging system and multivariate regression models. The simplicity and intuitive ease of the current TNM staging system must be balanced against its serious limitations in predictive accuracy and its loss of clinical utility. Statistical regression methods are required as we move to the new era of personalized medicine. We must implement statistical approaches that integrate the new molecular biomarkers with existing prognostic biomarkers to accurately predict which patients require treatment and to determine the optimal therapy.


Invasive amebiasis in men who have sex with men, Australia.
Entamoeba histolytica is a pathogenic ameba that has recently been recognized as an emerging pathogen in men who have sex with men (MSM) in Asia-Pacific countries where it is not endemic, i.e., Japan, Taiwan, and Republic of Korea. We report locally acquired invasive amebiasis in Sydney, Australia, exclusively in MSM.


Intra- and Interlaboratory Agreement in Assessing the In Vitro Activity of Micafungin against Common and Rare Candida Species with the EUCAST, CLSI, and Etest Methods.
The emergence of resistant strains among common and rare Candida species necessitates continuous monitoring of the in vitro susceptibilities of those isolates. We therefore assessed the in vitro activities of micafungin against 1,099 molecularly identified isolates belonging to 5 common and 20 rare Candida species by the EUCAST, CLSI, and Etest methods, assessing both the intralaboratory agreement and the interlaboratory agreement for two centers. The median micafungin EUCAST MICs were as follows, from the lowest to the highest: for Candida albicans, 0.004 mg/liter; for C. glabrata, 0.016 mg/liter; for C. tropicalis, 0.031 mg/liter; for C. krusei, 0.125 mg/liter; for C. parapsilosis, 2 mg/liter. Among rare Candida species, high MICs were found for C. guilliermondii, C. lipolytica, C. orthopsilosis, C. metapsilosis, and C. fermentati. No resistant isolates were found by the CLSI method, whereas resistance rates of 1 to 2% were found by the EUCAST method. Overall, the EUCAST method resulted in MICs 1 to 2 dilutions higher than those found by the CLSI and Etest methods. The intra- and interlaboratory agreement between methods was >92%, except for the interlaboratory agreement between the EUCAST and CLSI methods (81%), where 17 to 31% of the differences were >2 2-fold dilutions for C. albicans, C. glabrata, C. tropicalis, and other rare Candida species and <6% for C. parapsilosis and C. krusei For the other interlaboratory comparisons, the EUCAST method resulted in higher MICs than the Etest method for all species, but <7% of these differences were >2 2-fold dilutions. Overall, the CLSI method resulted in lower MICs than the Etest method, with 11% of all isolates demonstrating >2 2-fold-dilution differences (6 to 20% for C. albicans, C. tropicalis, and rare Candida species; <5% for C. glabrata, C. krusei, and C. parapsilosis) and smaller differences found after 24 h. Despite these differences, categorical agreement was excellent (>97%), with only 1 to 2% very major errors between the EUCAST method and the other two methods.


Depolarization of mitochondria in endothelial cells promotes cerebral artery vasodilation by activation of nitric oxide synthase.
Mitochondrial depolarization after ATP-sensitive potassium channel activation has been shown to induce cerebral vasodilation by the generation of calcium sparks in smooth muscle. It is unclear, however, whether mitochondrial depolarization in endothelial cells is capable of promoting vasodilation by releasing vasoactive factors. Therefore, we studied the effect of endothelial mitochondrial depolarization by mitochondrial ATP-sensitive potassium channel activators, BMS-191095 (BMS) and diazoxide, on endothelium-dependent vasodilation. Diameter studies in isolated rat cerebral arteries showed BMS- and diazoxide-induced vasodilations that were diminished by endothelial denudation. Mitochondrial depolarization-induced vasodilation was reduced by inhibition of mitochondrial ATP-sensitive potassium channels, phosphoinositide-3 kinase, or nitric oxide synthase. Scavenging of reactive oxygen species, however, diminished vasodilation induced by diazoxide, but not by BMS. Fluorescence studies in cultured rat brain microvascular endothelial cells showed that BMS elicited mitochondrial depolarization and enhanced nitric oxide production; diazoxide exhibited largely similar effects, but unlike BMS, increased mitochondrial reactive oxygen species production. Measurements of intracellular calcium ([Ca(2+)]i) in cultured rat brain microvascular endothelial cells and arteries showed that both diazoxide and BMS increased endothelial [Ca(2+)]i. Western blot analyses revealed increased phosphorylation of protein kinase B and endothelial nitric oxide synthase (eNOS) by BMS and diazoxide. Increased phosphorylation of eNOS by diazoxide was abolished by phosphoinositide-3 kinase inhibition. Electron spin resonance spectroscopy confirmed vascular nitric oxide generation in response to diazoxide and BMS. Pharmacological depolarization of endothelial mitochondria promotes activation of eNOS by dual pathways involving increased [Ca(2+)]i as well as by phosphoinositide-3 kinase-protein kinase B-induced eNOS phosphorylation. Both mitochondrial reactive oxygen species-dependent and -independent mechanisms mediate activation of eNOS by endothelial mitochondrial depolarization.


Oxygen-laden mesenchymal stem cells enhance the effect of gastric cancer chemotherapy in vitro.
Hypoxia is an important factor that results in failure of chemotherapy for the majority of solid tumor types, particularly for gastric cancer. In the present study, mesenchymal stem cells (MSCs), which have the ability to migrate to cancer tissues were used as a vehicle to supply oxygen to gastric cancer. The hemoglobin genes were transfected into MSCs as MSC-hemo groups. Subsequently, MSC-hemo groups were induced by isopropyl-b-D-thiogalactopyranoside and hemin to express hemoglobin. The hemoglobin was detected by western blotting method. Following this, the MSC-hemo groups were placed in an atmosphere containing 100% oxygen and were used to investigate the effect of the function of the oxygen-laden MSC-hemo group on gastric cancer chemotherapy with an MTT assay. As a first approach to investigate the possibility of MSCs as a vehicle to supply oxygen to anoxic cancer types, including gastric, liver, breast cancer, the results indicated that the oxygen-laden MSC-hemo group significantly enhanced the effect of chemotherapeutic treatments on gastric cancer cells. Utilizing MSCs as a svehicle to supply oxygen to the solid tumor may be a novel method to improve the hypoxia conditions of tumor tissues and improve the effect of chemotherapy on tumor cells.


Z-Score Reference Ranges for Angular M-Mode Displacement at 22-40 Weeks' Gestation.
To construct Z-score reference ranges for fetal mitral and tricuspid annular plane systolic excursions (MAPSE and TAPSE), using angular M-mode (AM) and conventional M-mode (CM). A prospective cross-sectional investigation was conducted on 261 normal singleton fetuses from 22 to 40 weeks' gestation. TAPSE and MAPSE were measured by AM and CM. Reference ranges of TAPSE and MAPSE derived from AM and CM were determined against gestational age (GA) and heart area (HA), using regression analyses of the mean and standard deviation. TAPSE and MAPSE showed positive correlations with GA and HA. A cubic regression was the best-fitted model for the mean of MAPSE and TAPSE based on HA, while a linear regression model was established for the mean based on GA. Z-scores and 95% reference intervals for predicting MAPSE and TAPSE were established. Strong correlations were found between AM and CM, whereas CM underestimated AM (mean error: MAPSE 0.25 ± 0.18 mm; TAPSE 0.35 ± 0.2 mm). Normal data and the Z-scores of fetal MAPSE and TAPSE were provided against GA and HA, which can be useful for quantitative assessment of fetal cardiac dysfunction, particularly in cases of intrauterine growth restriction.


Antitumor effect of human pancreatic cancer cells transduced with cytokine genes which activate Th1 helper T cells.
We have examined antitumor effect of human pancreatic carcinoma cells (AsPC-1) retrovirally transduced with interleukin-12 (IL-12), IL-15 or IL-18 gene in nude mice. The tumor growth of IL-12-expressing AsPC-1 cells was significantly retarded and that of IL-15-expressing cells was also impeded compared with that of wild-type cells, although their in vitro cell growth remained unchanged. However, the expression of IL-18 in AsPC-1 cells did not generate any antitumor effect since the tumor growth of the transduced cells was the same as that of wild-type cells. Thus, the differential actions of these cytokines on non-T cells can generate a variety of antitumor effect in nude mice, although their actions on T cells lineage favor the stimulation of Th1-type helper T cells.


Cell-penetrating peptides improve pharmacokinetics and pharmacodynamics of anticancer drugs.
This review concentrates on the research concerning conjugates of anticancer drugs with versatile cell-penetrating peptides (CPPs). For a better insight into the relationship between the components of the constructs, it starts with the characteristic of the peptides and considers its following aspects: mechanisms of cellular internalization, interaction with cancer-modified membranes, selectivity against tumor tissue. Also, CPPs with anticancer activity have been distinguished and summarized with their mechanisms of action. With respect to the conjugates, the preclinical studies (in vitro, in vivo) indicated that they possess several merits in comparison to the parent drugs. They concerned not only better cellular internalization but also other improvements in pharmacokinetics (e.g. access to the brain tissue) and pharmacodynamics (e.g. overcoming drug resistance). The anticancer activity of the conjugates was usually superior to that of the unconjugated drug. Certain anticancer CPPs and conjugates entered clinical trials.


Correlation between Nurr1 expression and drug resistance in the brain of rats with epilepsy.
To investigate the correlation between nuclear receptor related 1 (Nurr1) expression and drug resistance in the brain of rats with epilepsy. A total of 60 adult male Sprague-Dawley rats were selected, and the animal model of epilepsy was established by electrical stimulation. These rats were randomly divided into the control group and the drug-resistant group. The model of drug-resistant epilepsy was screened with phenytoin (PHT) and phenobarbital (PB); the hippocampus and temporal lobe cortex tissues were isolated from rats; the messenger ribonucleic acid (mRNA) and protein levels of Nurr1 in the hippocampus and cortex tissues of the two groups of rats were detected by reverse transcription polymerase chain reaction (RT-PCR), Western blotting and immunohistochemistry, respectively. The budding tissue marker growth-associated protein-43 (GAP43) in hippocampus tissues were labeled by immunofluorescence staining; the mRNA and protein levels of indicators related to drug-resistant epilepsy, including leukemia-associated phenotype (LAP), multi-drug resistance protein (MRP), P-glycoprotein (P-gp) and monocyte chemoattractant protein-1 (MCP-1), were further detected. Pearson correlation analysis was used to analyze the correlations of the protein level of Nurr1 with drug-resistant indicators. The mRNA and protein levels of Nurr1 in hippocampus tissues of the drug-resistant group were significantly increased compared with those of the control group (p < 0.05). In temporal lobe cortex tissues, there was no significant difference in the mRNA level of Nurr1 between the control group and the drug-resistant group (p > 0.05). The immunohistochemistry results showed that the fluorescence intensity of GAP3 in hippocampus tissues of the drug-resistant group was significantly higher than that of the control group. The mRNA and protein levels of epilepsy-related indicators, LAP, MRP, P-gp and MCP-1 in hippocampus tissues of drug-resistant group were significantly up-regulated compared with those of the control group (p < 0.05). Pearson correlation analysis indicated that the protein level of Nurr1 in hippocampus tissues was positively correlated with those of LAP, MRP, P-gp and MCP-1 in the corresponding regions (p < 0.05). Nurr1 enhances the drug resistance of epilepsy in rats by up-regulating the expression of proteins related to drug resistance.


Screw head plugs increase the fatigue strength of stainless steel, but not of titanium, locking plates.
Screw plugs have been reported to increase the fatigue strength of stainless steel locking plates. The objective of this study was to examine and compare this effect between stainless steel and titanium locking plates. Custom-designed locking plates with identical structures were fabricated from stainless steel and a titanium alloy. Three types of plates were compared: type I unplugged plates; type II plugged plates with a 4 Nm torque; and type III plugged plates with a 12 Nm torque. The stiffness, yield strength, and fatigue strength of the plates were investigated through a four-point bending test. Failure analyses were performed subsequently. For stainless steel, type II and type III plates had significantly higher fatigue strength than type I plates. For titanium, there were no significant differences between the fatigue strengths of the three types of plates. Failure analyses showed local plastic deformations at the threads of screw plugs in type II and type III stainless steel plates but not in titanium plates. The screw plugs could increase the fatigue strength of stainless steel plates but not of titanium plates. Therefore, leaving screw holes open around fracture sites is recommended in titanium plates.Cite this article: L-W. Hung, C-K. Chao, J-R. Huang, J. Lin. Screw head plugs increase the fatigue strength of stainless steel, but not of titanium, locking plates. Bone Joint Res 2018;7:629-635. DOI: 10.1302/2046-3758.712.BJR-2018-0083.R1.


Influence of watershed system management on herbicide concentrations in Mississippi Delta oxbow lakes.
The Mississippi Delta Management Systems Evaluation Area (MD-MSEA) project was established in 1994 in three small watersheds (202 to 1,497 ha) that drain into oxbow lakes (Beasley, Deep Hollow, and Thighman). The primary research objective was to assess the implications of management practices on water quality. Monthly monitoring of herbicide concentrations in lake water was conducted from 2000 to 2003. Water samples were analyzed for atrazine, cyanazine, fluometuron, metolachlor, and atrazine metabolites. Herbicide concentrations observed in the lake water reflected cropping systems of the watershed, e.g., atrazine and metolachlor concentrations were associated with the level of corn and sorghum production, whereas cyanazine and fluometuron was associated with the level of glyphosate-sensitive cotton production. The dynamics of herbicide appearance and dissipation in lake samples were strongly influenced by herbicide use, lake hydrology, rainfall pattern, and land management practices. The highest maximum concentrations of atrazine (7.1 to 23.4 microg L(-1)) and metolachlor (0.7 to 14.9 microg L(-1)) were observed in Thighman Lake where significant quantities of corn were grown. Introduction of s-metolachlor and use of glyphosate-resistant cotton coincided with reduced concentration of metolachlor in lake water. Cyanazine was observed in two lakes with the highest levels (1.6 to 5.5 microg L(-1)) in 2000 and lower concentrations in 2001 and 2002 (<0.4 microg L(-1)). Reduced concentrations of fluometuron in Beasley Lake were associated with greater use of glyphosate-resistant cotton and correspondingly less need for soil-applied fluometuron herbicide. In contrast, increased levels of fluometuron were observed in lake water after Deep Hollow was converted from conservation tillage to conventional tillage, presumably due to greater runoff associated with conventional tillage. These studies indicate that herbicide concentrations observed in these three watersheds were related to crop and soil management practices.


The effect of antibiotic therapy on the faecal excretion of Salmonella typhimurium by experimentally infected chickens.
Chickens in groups of 40 were infected orally with a nalidixic acid-resistant mutant of Salmonella typhimurium and then fed continuously on diets containing ampicillin, chloramphenicol, furazolidone, neomycin, oxytetracycline, polymixin, spectinomycin, streptomycin or a mixture of trimethoprim and sulphadiazine. The amount of S. typhimurium excreted in their faeces was estimated at intervals by culture on brilliant green agar containing sodium nalidixate, both direct and after enrichment in selenite broth; the amount of Escherichia coli excreted was estimated by culture on MacConkey agar. The feeding of diets containing 500 mg./kg. of ampicillin, furazolidone, neomycin, polymixin, spectinomycin or streptomycin or 100 mg./kg. of trimethoprim and 500 mg./kg. of sulphadiazine for 46 days reduced to a varying degree the amount of S. typhimurium and E. coli excreted, the greatest reduction in S. typhimurium being brought about by the last treatment. The effect was less obvious when the concentration of the antibiotics in the food was decreased fivefold. An important reason for the very limited effect of some of the antibiotics was the emergence of antibiotic-resistant populations of S. typhimurium and E. coli. High concentrations of antibiotic-resistant organisms also arose in the faeces of the chickens fed diets containing tetracyclines and chloramphenicol, treatments which had no apparent effect on the amount of S. typhimurium and E. coli excreted. Much of the antibiotic resistance encountered was determined by R factors, a particular R factor usually being found in the E. coli populations of individual chickens before it was found in their S. typhimurium populations. No S. typhimurium or E. coli were isolated that possessed R factors determining resistance to polymixin, furazolidone or trimethoprim. No S. typhimurium or E. coli were isolated that were polymixin-resistant and no S. typhimurium that were furazolidone-resistant. The few trimethoprim-resistant S. typhimurium isolated were thymine-dependent. The feeding of diets containing the higher concentrations of trimethoprim/sulphadiazine, neomycin, furazolidone or ampicillin for 9 days reduced the amount of S. typhimurium excreted. After the withdrawal of these diets, the amount of S. typhimurium excreted increased to the numbers found in chickens given ordinary diets throughout; the chickens that had been given trimethoprim/sulphadiazine or furazolidone did not remain faecal excreters of S. typhimurium longer than the chickens that had been given ordinary diets. Similar results were obtained with trimethoprim/sulphadiazine when the start of the 9-day treatment period was delayed for an extra 9 days or when it was extended to 18 days.


Experience with pineal region tumours in childhood.
Sixty-one children with pineal region tumours were managed at the Hospital for Sick Children during the period 1950-1982. Histologic verification of these tumours was possible in forty-six children. Although germ cell tumours were the commonest form, germinomas only made up one third of the pineal region tumours. Since 1967, an aggressive approach has been adopted in the management of pineal region tumours at the Hospital for Sick Children with thirty-four patients having direct surgery on their pineal region mass out of a total of forty-one patients with such tumours. The operative mortality for pineal tumour surgery has steadily fallen so that the operative mortality between 1975 and 1982 was 4.3% and there have been no operative deaths since 1977 among the thirteen patients with pineal region tumours who have been operatively treated. Pineal tumours are operable lesions which should be removed if they are benign. Histologic confirmation should be obtained if they are malignant in order to provide for rational management of these lesions.


Gradual funnel photon trapping enhanced InAs/GaSb type-II superlattice infrared detector.
InAs/GaSb type-II superlattice materials have attracted in the field of infrared detection due to their high quality, uniformity and stability. The performance of InAs/GaSb type-II superlattice detector is limited by dark noise and light response. This work reports a gradual funnel photon trapping (GFPT) structure enabling the light trapping in the T2SL detector absorption area. The GFPT detector exhibits an efficient broadband responsivity enhancement of 30% and a darker current noise reduction of 3 times. It has excellent passivated by atomic layer deposition and achieves a high detectivity of 1.51 × 1011 cm Hz1/2 at 78 K.


Resolution of the abraham-minkowski dilemma.
The dilemma of identifying the correct form for the momentum of light in a medium has run for a century and has been informed by many distinguished contributions, both theoretical and experimental. We show that both the Abraham and Minkowski forms of the momentum density are correct, with the former being the kinetic momentum and the latter the canonical momentum. This identification allows us to explain why the experiments supporting each of the rival momenta gave the results that they did. The inclusion of dispersion and absorption provides an interesting subtlety, but does not change our conclusion.


Innate immune receptor genetic polymorphisms in pouchitis: is CARD15 a susceptibility factor?
Pouchitis is a frequent complication after ileal pouch-anal anastamosis (IPAA) for ulcerative colitis (UC). The aim of this study was to determine whether genetic polymorphisms in the innate immune receptors toll-like receptor (TLR)4 and caspase activation and recruitment domain family member 15 (CARD15) genes are associated with pouchitis. From a retrospectively ascertained cohort of patients with UC 5 to 12 years after IPAA (n = 101), subjects were classified into 3 groups: no pouchitis (n = 52); 1 to 2 episodes per year (n = 11), and more than 2 episodes per year (n = 38). Single nucleotide polymorphisms in the tlr4 gene (D299G, T399I) were determined by a real-time polymerase chain reaction-based fluorogenic probe technique; and card15 polymorphisms (L1007fsinsC, R702W, G908R) were determined by pyrosequencing. Pouchitis affected 49% (49/101) of the study population. No correlation between pouchitis and the presence of TLR4 polymorphisms was found. The percentage of patients who harbored CARD15 mutations was significantly higher in patients with pouchitis than in patients without pouchitis (18% versus 8%; P < 0.05); 24% of pouchitis patients with more than 2 episodes per year harbored CARD15 mutations (P < 0.01 compared with the no pouchitis group). The CARD15 insertion mutation L1007fsinsC was present in 14% of patients with pouchitis and in 0% without pouchitis (P < 0.05). All patients who carried L1007fsinsC developed more than 2 episodes per year. CARD15 polymorphisms are seen in greater frequency in patients with pouchitis after IPAA for UC. These findings, if borne out in prospective analyses, suggest that CARD15 mutations, particularly L1007fsinsC, may predispose to the development of pouchitis after IPAA for UC.


Inhibition of Yeast-to-Hypha Transition and Virulence of Candida albicans by 2-Alkylaminoquinoline Derivatives.
A rapid increase in Candida albicans infection and drug resistance has caused an emergent need for new clinical strategies against this fungal pathogen. In this study, we evaluated the inhibitory activity of a series of 2-alkylaminoquinoline derivatives against C. albicans isolates. A total of 28 compounds were assessed for their efficacy in inhibiting the yeast-to-hypha transition, which is considered one of the key virulence factors in C. albicans Several compounds showed strong activity to decrease the morphological transition and virulence of C. albicans cells. The two leading compounds, compound 1 (2-[piperidin-1-yl]quinolone) and compound 12 (6-methyl-2-[piperidin-1-yl]quinoline), remarkably attenuated C. albicans hyphal formation and cytotoxicity in a dose-dependent manner, but they showed no toxicity to either C. albicans cells or human cells. Intriguingly, compound 12 showed an excellent ability to inhibit C. albicans infection in the mouse oral mucosal infection model. This leading compound also interfered with the expression levels of hypha-specific genes in the cyclic AMP-protein kinase A and mitogen-activated protein kinase signaling pathways. Our findings suggest that 2-alkylaminoquinoline derivatives could potentially be developed as novel therapeutic agents against C. albicans infection due to their interference with the yeast-to-hypha transition.


Rare Presentation of Neurofibromatosis and Turner Syndrome in a Pediatric Patient.
Neurofibromatosis type 1 (NF1) is classically defined by the presence of multiple café-au-lait macules as one of the diagnostic criteria. Turner syndrome (TS) can also present with café-au-lait macules along with short stature. Our patient is the fifth reported with both NF1 and TS and the first who has been on growth hormone for short stature associated with TS.


Haematological and biochemical measurements in healthy, adult, free-ranging golden jackals (Canis aureus syriacus) held in captivity.
Blood from 31 healthy, free-ranging golden jackals held in captivity for seven days was collected while they were anaesthetised. Haematological and serum biochemical measurements were analysed and the 95 per cent confidence interval for each variable was compared with the reference value for domestic dogs. The measurements of their red blood cells were within the reference interval for dogs, but the jackals had higher white blood cell counts and eosinophil counts than dogs. The male jackals had a higher haematocrit, red blood cell count, mean corpuscular volume and mean corpuscular haemoglobin concentration, and a lower red blood cell distribution width than the female jackals. High activities of muscle enzymes were detected in many of the jackals, in several of which the activity of creatine kinase exceeded 5000 U/l; these were considered abnormal.


Laparoscopic distal pancreatectomy with splenic preservation for serous cystadenoma: a case report and literature review.
A minimally invasive approach can be beneficial in a spleen-preserving distal pancreatectomy. This article reports a 71-year-old woman who presented to her internist with hypertension and persistent hypokalemia. A computed tomography scan to rule out a functional adrenal mass incidentally revealed a 4 cm x 3 cm x 2 cm serous cystadenoma of the distal pancreas and normal adrenal glands. The patient was referred to the general surgery service for resection of the distal pancreatic lesion. A laparoscopic spleen-preserving distal pancreatectomy was performed. The lesion was completely excised, and the pathology revealed serous cystadenoma with focal fibrosis and atrophic acini. The postoperative advantages of this approach were the early return of bowel function, minimal narcotic requirements, and early resumption of normal activities. This case illustrates the advantages of minimally invasive surgery in the performance of a spleen-preserving distal pancreatectomy.


A comparison of family medicine clerkship student performance across multiple teaching sites.
Family medicine clerkships are frequently conducted in decentralized settings. Concerns have been raised regarding the educational consistency of such rotations. In this study, we assess learning across multiple training sites, as reflected by measures of student performance. The study population was 77 students assigned to six clusters of family medicine clerkship training sites during the 1993-1994 academic year. Learning, as measured by faculty evaluations, objective structured clinical examination (OSCE) performance, and Society of Teachers of Family Medicine (STFM) predoctoral examination performance, was compared for student cohorts assigned to each of the teaching site clusters using analysis of variance. No differences in OSCE or STFM examination performance were found across the teaching site clusters. Greater variation in faculty evaluation across sites was apparent, and when the academic and private practice teaching sites were compared with the HMO and community clinics teaching sites, this variation achieved statistical significance. As measured by OSCE and STFM examination performance, student learning did not vary across multiple training sites. However, greater variability was found in faculty evaluations of student performance. Sources of this variation might include differing levels of student-faculty interactions across sites or subjectivity inherent to the faculty evaluation process.


Dancing During Labor: Social Media Trend or Future Practice?
Over the past 30 years, medical interventions in pregnancy and childbirth have increased. Some pregnant women seek less invasive and nonpharmacological options to manage discomforts during labor. While exercise during pregnancy is recommended, less is known about exercise, specifically dancing, during labor. While anecdotal evidence is supportive, little is known about the implications of exercise and dance during the first stage of labor for pain reduction and labor progression. Some movements common in dance, such as expanding hip circles that loosen and relax muscles of the pelvic floor, may be beneficial to women during labor. Available evidence suggests that dancing during the first stage of labor may decrease duration and intensity of pain and increase patient satisfaction, but further study is warranted. Ultimately, before assessing the implications of dance during labor, a feasibility study should be conducted to determine pregnant women's willingness to participate in a prospective or randomized controlled trial.


An Encoder-Decoder Architecture within a Classical Signal-Processing Framework for Real-Time Barcode Segmentation.
In this work, two methods are proposed for solving the problem of one-dimensional barcode segmentation in images, with an emphasis on augmented reality (AR) applications. These methods take the partial discrete Radon transform as a building block. The first proposed method uses overlapping tiles for obtaining good angle precision while maintaining good spatial precision. The second one uses an encoder-decoder structure inspired by state-of-the-art convolutional neural networks for segmentation while maintaining a classical processing framework, thus not requiring training. It is shown that the second method's processing time is lower than the video acquisition time with a 1024 × 1024 input on a CPU, which had not been previously achieved. The accuracy it obtained on datasets widely used by the scientific community was almost on par with that obtained using the most-recent state-of-the-art methods using deep learning. Beyond the challenges of those datasets, the method proposed is particularly well suited to image sequences taken with short exposure and exhibiting motion blur and lens blur, which are expected in a real-world AR scenario. Two implementations of the proposed methods are made available to the scientific community: one for easy prototyping and one optimised for parallel implementation, which can be run on desktop and mobile phone CPUs.


Model of nitric oxide diffusion in an arteriole: impact of hemoglobin-based blood substitutes.
Administration of hemoglobin-based oxygen carriers (HBOCs) frequently results in vasoconstriction that is primarily attributed to the scavenging of endothelium-derived nitric oxide (NO) by cell-free hemoglobin. The ensuing pressor response could be caused by the high NO reactivity of HBOC in the vascular lumen and/or the extravasation of hemoglobin molecules. There is a need for quantitative understanding of the NO interaction with HBOC in the blood vessels. We developed a detailed mathematical model of NO diffusion and reaction in the presence of an HBOC for an arteriolar-size vessel. The HBOC reactivity with NO and degree of extravasation was studied in the range of 2-58 x 10(6) M(-1) x s(-1) and 0-100%, respectively. The model predictions showed that the addition of HBOC reduced the smooth muscle (SM) NO concentration in the activation range (12-28 nM) for soluble guanylate cyclase, a major determinant of SM contraction. The SM NO concentration was significantly reduced when the extravasation of HBOC molecules was considered. The myoglobin present in the parenchymal cells scavenges NO, which reduces the SM NO concentration.


Soluble interleukin-2 receptors in the serum of patients with chronic renal failure.
The levels of soluble form of the interleukin-2 receptor (sIL-2R) were evaluated in the peripheral blood of 29 patients with chronic renal failure (CRF) using enzyme-linked immunosorbent assay. All patients had undergone hemodialysis and the mean (+/- S.D.) BUN was before hemodialysis was 80.9 +/- 22.4 mg/100 ml. The mean level of sIL-2R was 1146 +/- 258 U/ml, which was significantly higher than the level (288 +/- 118 U/ml) in 12 individuals with a normal BUN level (p = 0.01). In patients with CRF, the elevated sIL-2R level was not influenced by hemodialysis, and not correlated with creatinine or beta 2-microglobulin levels. The kidneys may play an important role in the catabolism of serum sIL-2R. The elevated sIL-2R level may be related to compromised immunoregulation in CRF.


Prognostic value of thymidine phosphorylase/platelet-derived endothelial cell growth factor in advanced colorectal cancer after surgery: evaluation with a new monoclonal antibody.
Thymidine phosphorylase (TP) is an essential enzyme for activation of 5-fluorouracil and its derivatives and identical to platelet-derived endothelial cell growth factor. In colorectal cancer (CRC), previous studies evaluating the relationship between TP expression and clinicopathologic features have yielded inconsistent results. These studies used monoclonal antibody 654-1, which stained CRC cells weakly. Now, a new monoclonal antibody, 1C6-203, more sensitive than 654-1, is available. This study included 80 patients whose CRCs were classified into stages II to IV and completely resected surgically in our institute. TP expression in CRC was evaluated by using immunohistochemical staining with 1C6-203. Relationships between TP expression and clinicopathologic variables that might have affected the patients' prognosis were evaluated. Survival curves were calculated with the Kaplan-Meier method, and differences were evaluated with log-rank test. Cox proportional hazards model was used in the univariate and multivariate survival analyses. TP expression showed a positive correlation with advances in histologic differentiation (P =.025), lymph node metastasis (P =.083), lymphatic invasion (P =.049), venous invasion (P =.042), and cancer stage (P =.002). The patients' survival rates after surgery were higher (P =.0041) in those with negative TP than in those with positive TP. The overall estimated hazard ratio for death in patients with TP expression was 6.24 according to univariate analysis (P =.013). Multivariate analysis showed that TP was a significant prognostic factor adjusted for other clinicopathologic variables. With a new highly sensitive monoclonal antibody to TP, the present results indicated that TP expression is associated with CRC progression and invasion and closely correlated with poor prognosis in postoperative CRC patients. Moreover, TP expression is an independent prognostic factor in CRC patients.


Canine distemper viral infection threatens the giant panda population in China.
We evaluated exposure to canine distemper virus (CDV) in eight wild giant pandas (Ailuropoda melanoleuca) and 125 unvaccinated domestic dogs living in and around Foping National Nature Reserve (FNNR), China. Seventy-two percent of unvaccinated domestic dogs (mixed breed) had neutralizing antibodies for CDV due to exposure to the disease. The eight wild giant pandas were naïve to CDV and carried no positive antibody titer. RT-PCR assays for hemagglutinin (H) gene confirmed the presence of CDV in 31 clinically ill dogs from several areas near FNNR. Genomic sequence analysis showed that the 21 canine CDV were highly homologous to each other and belonged to the Asian-1 genotype. They showed high homology with the GP01 strain sequenced from a fatally infected giant panda, suggesting cross-species infection. Observational and GPS tracking data revealed home range overlap in pandas and dogs around FNNR. This study shows that CDV is endemic in domestic dogs near FNNR and that cross-species CDV infection threatens the wild giant panda population.


Neuropsychiatric changes following penetrating head injury in children.
Penetrating head injuries demand the prompt attention of a neurosurgeon. While most neurosurgical centers are experienced in the acute management of these injuries, less is known about the long-term neuropsychiatric sequelae of penetrating head trauma. In adults, direct injury to the frontal lobe classically has been associated with mental status changes. However, there is less published data in children. We report the case of a 12-year-old boy who suffered a penetrating head injury to the frontal lobes secondary to a self-inflicted gunshot wound, and experienced subsequent resolution of pre-existing bipolar disorder and new onset of attention deficit hyperactivity disorder. Children with penetrating head injury require close multidisciplinary follow-up in order to monitor, and accordingly implement management strategies, for associated sequelae, including behavioral and neuropsychiatric changes.


Host-specific evasion of the alternative complement pathway by schistosomes correlates with the presence of a phospholipase C-sensitive surface molecule resembling human decay accelerating factor.
Schistosoma mansoni parasites recovered from the blood stream were found to be nonactivators of the alternative complement pathway (ACP) when exposed to sera of homologous but not heterologous host species. Schistosomes could be converted into activators of the homologous ACP by treatment with phospholipase C. Antibodies to either human or guinea pig decay accelerating factor (DAF), a 70-kDa glycosylphosphatidylinositol anchored membrane glycoprotein which controls ACP activation on the mammalian cell plasma membrane, bound to the surface of immature schistosomes and immunoprecipitated a molecule of similar molecular mass from detergent extracts of surface iodinated parasites. Phospholipase C treatment drastically reduced the reactivity of the worms with the anti-DAF antibodies. These data suggest that schistosomes evade the ACP by inserting functional host DAF into their surfaces, possibly through adsorption of the molecule's lipophilic diacyglycerol membrane anchor moiety into the outer lipid bilayer of the parasite.


[Changes of CYP2E1 activity in diabetic rat model].
Diabetic rat model was induced by alloxan. To evaluate CYP2E1 activity indirectly, the activities of aniline dehydroxylase and other drug metabolic enzymes were measured. The pharmacokinetic profile of chlorzoxazone(CZX), a drug probe for CYP2E1, was obtained after a single oral dose of 50 mg.kg-1. The results indicated that diabetes increased aniline dehydroxylase activity by 53%. The Cmax and AUC of chlorzoxazone in diabetic rats were reduced 37% and 34%, respectively. The Tpeak of 6-hydroxychlorzoxazone in diabetic rats was shortened apparently. The hydroxylation index described by the AUC ratio of 6-hydroxychlorzoxazone to chlorzoxazone or the ratio of concentration of 6-hydroxychlorzoxazone to chlorzoxazone, which indicated the ability of hydroxylation, was increased in diabetes. In conclusion, diabetes can induce CYP2E1 activity, suggesting that diabetic patients should be cautious when taking some therapeutic drugs which metabolized by CYP2E1.


The effects of bradykinin on the contractile activity of the isolated rat ovary.
Studies of ovarian contractility were carried out on 43 rat ovaries maintained in vitro. Eighteen ovaries showed spontaneous motility. In 65 of 155 tests (42%), synthetic bradykinin (3.75-25.0 ng/ml saline) produced sustained increases in ovarian tone, or stimulated phasic contractions. Failure to respond was related to the stage of the oestrous cycle. Sensitivity was highest around ovulation (00.00-04.00 h oestrus), when there were 25 responses in 26 tests, and the linear relationship between the response and the logarithm of the concentration suggested a threshold of 2.9 ng/ml saline. Sensitivity fell later in oestrus, and reached its lowest point in metoestrus (1 response in 20 tests). Since the plasma kinin system is activated before ovulation, and the threshold to bradykinin was within reported plasma kinin levels, it seems possible that plasma kinins are involved in contractile processes associated with ovulation.


Gastric erosions: radiological and endoscopic aspects.
Varioliform gastric erosion is a common lesion which can be reliably diagnosed radiologically. The diagnosis was established in 27 (1.7%) of 1,600 detailed radiological examinations made in 1975. There was a good correlation with gastroscopic findings.


REG I expression predicts long-term survival among locally advanced thoracic squamous cell esophageal cancer patients treated with neoadjuvant chemoradiotherapy followed by esophagectomy.
The prognosis for patients with locally advanced thoracic esophageal cancer is extremely unfavorable. We have been administering neoadjuvant chemoradiotherapy (CRT) followed by esophagectomy to these patients and studying whether REG I expression in untreated endoscopic biopsy specimens is predictive of patient responsiveness to CRT and/or survival after treatment. Between 1992 and 2003, 47 patients with T4 (direct invasion of adjacent organs) thoracic esophageal cancers were administered neoadjuvant CRT followed by esophagectomy. REG I expression was assessed in untreated endoscopic biopsy specimens and correlated with clinical and histological responses and survival in 37 patients who had also undergone curative surgery. Among the 37 cases that received CRT followed by surgery, the therapeutic response rate for neoadjuvant CRT was 68%, and a complete histological response in resected specimens from the primary lesion was achieved in 8 (22%) patients. These clinical and histological responses to neoadjuvant CRT did not significantly correlate with survival, however. By contrast, 9 patients were judged REG-positive based on analysis of their untreated endoscopic biopsy specimens, and their cumulative survival rate was significantly higher than that of the 28 REG-negative patients (P = 0.0073). Univariate analysis showed REG I expression to be a prognostic factor (P = 0.0386) that increased the risk of death 8.4-fold. Evaluation of REG I expression in untreated endoscopic biopsy specimens may provide a basis for new treatments of locally advanced thoracic squamous cell esophageal cancers.


Hyperinvasiveness of Listeria monocytogenes sequence type 1 is independent of lineage I-specific genes encoding internalin-like proteins.
Listeriosis is a severe disease caused by the opportunistic bacterial pathogen Listeria monocytogenes (L. monocytogenes). Previous studies indicate that of the four phylogenetical lineages known, lineage I strains are significantly more prevalent in clinical infections than in the environment. Among lineage 1, sequence type (ST1) belongs to the most frequent genotypes in clinical infections and behaves hyperinvasive in experimental in vitro infections compared to lineage II strains suggesting that yet uncharacterized virulence genes contribute to high virulence of certain lineage I strains. This study investigated the effect of four specific lineage I genes encoding surface proteins with internalin-like structures on cellular infection. CNS derived cell lines (fetal bovine brain cells, human microglia cells) and non-CNS derived cell lines (bovine macrophage cells, human adenocarcinoma cells) that represent the various target cells of L. monocytogenes were infected with the parental ST1 strain and deletion mutants of the four genes. Despite their association with lineage I, deletion of the four genes investigated did not dampen the hyperinvasiveness of the ST1 strain. Similarly, these genes did not contribute to the intracellular survival and intercellular spread of L. monocytogenes ST1, indicating that these genes may have other functions, either during the infection process or outside the host.


Organ Doses From Diagnostic Medical Radiography-Trends Over Eight Decades (1930 to 2010).
This study provides a retrospective assessment of doses to 13 organs for the most common radiographic examinations conducted between the 1930s and 2010, taking into account typical technical parameters used for radiography during those years. This study is intended to be a resource on changes in medical diagnostic radiation exposure over time with a specific purpose of supporting retrospective epidemiological studies of radiation health risks. The authors derived organ doses to the brain, esophagus, thyroid, red bone marrow, lungs, breast, heart, stomach, liver, colon, urinary bladder, ovaries, and testes based on 14 common radiographic procedures and compared, when possible, with doses reported in the literature. These dose estimates were based on radiographic exposure parameters described in textbooks widely used by radiologic technologists in training from 1939 to 2010. The derived estimated doses presented here are believed to be representative of typical organs for an average-size adult who might be considered to be similar to the reference person. There were large variations in organ doses noted among the different types of radiographic examinations. Doses were highest in organs within the area imaged and next highest in organs in close proximity to the area imaged. Estimated organ doses have declined substantially [overall 22-fold (±38)] over time as a consequence of changes in technology, imaging protocols and protective measures. For some examinations, only slight differences were observed in doses for the decades of the 1960s, 1970s, and 1980s due to minor changes in technical parameters. Substantial dose reductions were observed in the 1990s and 2000s.


Long non-coding RNA LINC00958 and microRNA miR-627-5p provide candidate diagnostic biomarker and participate tumor progression in laryngeal squamous cell carcinoma: a retrospective study.
Laryngeal squamous cell carcinoma (LSCC) is known for its high morbidity and mortality. Long non-coding RNAs and miRNA have been found to play important roles in cancer progression. However, the roles of LINC00958 and miR-627-5p in LSCC and their mechanisms remain unclear. Therefore, it is important to explore its role in LSCC. The results of this study show that the expression of LINC00958 was significantly increased (p<0.001), but the expression of miR-627-5p was significantly decreased in LSCC serum specimens and cell lines (p<0.001). Silencing LINC00958 or overexpression of miR-627-5p could inhibit the proliferation (p<0.05) and migration (p<0.01) of LSCC cells. According to the results of dual luciferase reporter assay, it was known that LINC00958 could target miR-627-5p (p<0.01). ROC experiment results showed that LINC00958 was used to distinguish LSCC patients from healthy controls, OSCC patients from healthy controls and LSCC patients from OSCC patients, and the areas under the curve (AUC) were 0.970, 0.809 and 0.811, respectively. Meanwhile, we found that serum miR-627-5p could also be used to distinguish LSCC patients from healthy controls, oral squamous cell carcinoma (OSCC) patients from healthy controls, and LSCC patients from OSCC patients, with the AUC of 0.975, 0.870, and 0.800, respectively. Pearson analysis showed that the expression level of LNIC00958 was negatively correlated with the expression level of miR-627-5p (r= -0.725, p<0.001). Overall, The results of this study show that LINC00958 and miR-627-5p may be used as new diagnostic markers for LSCC. In addition, LINC00958/miR-627-5p axis opens a new way for the diagnosis and treatment of LSCC.


Extreme value theory as a framework for understanding mutation frequency distribution in cancer genomes.
Currently, the population dynamics of preclonal cancer cells before clonal expansion of tumors has not been sufficiently addressed thus far. By focusing on preclonal cancer cell population as a Darwinian evolutionary system, we formulated and analyzed the observed mutation frequency among tumors (MFaT) as a proxy for the hypothesized sequence read frequency and beneficial fitness effect of a cancer driver mutation. Analogous to intestinal crypts, we assumed that sample donor patients are separate culture tanks where proliferating cells follow certain population dynamics described by extreme value theory (EVT). To validate this, we analyzed three large-scale cancer genome datasets, each harboring > 10000 tumor samples and in total involving > 177898 observed mutation sites. We clarified the necessary premises for the application of EVT in the strong selection and weak mutation (SSWM) regime in relation to cancer genome sequences at scale. We also confirmed that the stochastic distribution of MFaT is likely of the Fréchet type, which challenges the well-known Gumbel hypothesis of beneficial fitness effects. Based on statistical data analysis, we demonstrated the potential of EVT as a population genetics framework to understand and explain the stochastic behavior of driver-mutation frequency in cancer genomes as well as its applicability in real cancer genome sequence data.


Is it worthwhile to screen patients with type 2 diabetes mellitus for subclinical Cushing's syndrome?
Variable prevalence of subclinical Cushing's syndrome (SCS) has been reported in patients with type 2 diabetes mellitus (T2DM), making the need for screening in this population uncertain. It is unknown if this variability is solely due to study-related methodological differences or a reflection of true differences in ethnic predisposition. The objective of this study is to explore the prevalence of SCS in Asian Indian patients with T2DM. In this prospective single center study conducted in a tertiary care referral center, 993 T2DM outpatients without any discriminatory clinical features (easy bruising, facial plethora, proximal muscle weakness, and/or striae) of hypercortisolism underwent an overnight 1 mg dexamethasone suppression test (ODST). ODST serum cortisol ≥1.8 μg/dl was considered positive, and those with positive results were subjected to 48 h, 2 mg/day low dose DST (LDDST). A stepwise evaluation for endogenous hypercortisolism was planned for patients with LDDST serum cortisol ≥1.8 μg/dl. Patients with positive ODST and negative LDDST were followed up clinically and re-evaluated a year later for the development of clinically evident Cushing's syndrome (CS). In this largest single center study reported to date, we found 37 out of 993 (3.72%) patients had ODST serum cortisol ≥1.8 μg/dl. None of them had LDDST cortisol ≥1.8 μg/dl, nor did they develop clinically evident CS over a follow-up period of 1 year. Specificity of ODST for screening of CS was 96.3% in our cohort. None of the T2DM outpatients in our cohort had SCS, hence cautioning against routine biochemical screening for SCS in this cohort. We suggest screening be based on clinical suspicion only.


The importance of the derivative in sex-hormone cycles: a reason why behavioural measures in sex-hormone studies are so mercurial.
To study the dynamic changes in cognition across the human menstrual cycle, twenty, healthy, naturally-cycling women undertook a lateralized spatial figural comparison task on twelve occasions at approximately 3-4 day intervals. Each session was conducted in laboratory conditions with response times, accuracy rates, eye movements, salivary estrogen and progesterone concentrations and Profile of Mood states questionnaire data collected on each occasion. The first two sessions of twelve for the response variables were discarded to avoid early effects of learning thereby providing 10 sessions spread across each participant's complete menstrual cycle. Salivary progesterone data for each participant was utilized to normalize each participant's data to a standard 28 day cycle. Data was analysed categorically by comparing peak progesterone (luteal phase) to low progesterone (follicular phase) to emulate two-session repeated measures typical studies. Neither a significant difference in reaction times or accuracy rates was found. Moreover no significant effect of lateral presentation was observed upon reaction times or accuracy rates although inter and intra individual variance was sizeable. We demonstrate that hormone concentrations alone cannot be used to predict the response times or accuracy rates. In contrast, we constructed a standard linear model using salivary estrogen, salivary progesterone and their respective derivative values and found these inputs to be very accurate for predicting variance observed in the reaction times for all stimuli and accuracy rates for right visual field stimuli but not left visual field stimuli. The identification of sex-hormone derivatives as predictors of cognitive behaviours is of importance. The finding suggests that there is a fundamental difference between the up-surge and decline of hormonal concentrations where previous studies typically assume all points near the peak of a hormonal surge are the same. How contradictory findings in sex-hormone research may have come about are discussed.


Hospital Outcomes in Uninsured Patients With Disease and Disorders of Nervous System: A National Cohort Study During a Decade in the United States.
Objectives Health insurance is associated with better outcomes in the admitted patient population, even after adjusting for other factors such as race and socioeconomic status. However, the literature is limited on the relationship between insurance status and hospital outcomes in patients hospitalized with the disease of nervous system. Methods This cross-sectional study used the Nationwide Inpatient Sample (NIS) database to achieve the results. All Major Diagnostic Category (MDC) codes from patients discharged for disease and disorders of nervous system between the years 2005 to 2014 were queried and analyzed for the impact of lack of insurance on patient outcome. Results Among 4,737,999 discharges, 5.6% had no insurance. The hospital mortality rate among uninsured and insured patients was 4.1% and 3.7%, respectively (P<0.001). In the multivariate analysis, hospital mortality of uninsured patients was higher in the elderly (aOR: 4.74[CI:4.52-4.97], P<0.001), those with comorbidities (aOR: 2.23[CI:2.18-2.27], P<0.001), Asians (aOR: 1.16[CI:1.12-1.20]. P<0.001), in rural areas (aOR: 1.44[ 95%CI:1.41-1.48], P<0.001) and those in the lowest household income quartile (aOR: 1.03[CI:1.01-1.05], P<0.001). The average length of stay (LOS) was shorter for the uninsured (4.79±8.26 vs 4.96±7.55 days, P<0.001). Conclusions The findings suggest that lack of health insurance is correlated with hospital mortality in patients hospitalized with disease and disorders of nervous system, with an increased disparity in vulnerable populations.


MSeg-Net: A Melanoma Mole Segmentation Network Using CornerNet and Fuzzy K-Means Clustering.
Melanoma is a dangerous form of skin cancer that results in the demise of patients at the developed stage. Researchers have attempted to develop automated systems for the timely recognition of this deadly disease. However, reliable and precise identification of melanoma moles is a tedious and complex activity as there exist huge differences in the mass, structure, and color of the skin lesions. Additionally, the incidence of noise, blurring, and chrominance changes in the suspected images further enhance the complexity of the detection procedure. In the proposed work, we try to overcome the limitations of the existing work by presenting a deep learning (DL) model. Descriptively, after accomplishing the preprocessing task, we have utilized an object detection approach named CornerNet model to detect melanoma lesions. Then the localized moles are passed as input to the fuzzy K-means (FLM) clustering approach to perform the segmentation task. To assess the segmentation power of the proposed approach, two standard databases named ISIC-2017 and ISIC-2018 are employed. Extensive experimentation has been conducted to demonstrate the robustness of the proposed approach through both numeric and pictorial results. The proposed approach is capable of detecting and segmenting the moles of arbitrary shapes and orientations. Furthermore, the presented work can tackle the presence of noise, blurring, and brightness variations as well. We have attained the segmentation accuracy values of 99.32% and 99.63% over the ISIC-2017 and ISIC-2018 databases correspondingly which clearly depicts the effectiveness of our model for the melanoma mole segmentation.


[Oral effectiveness of the calcium-antagonist Ro 11-1781 (Tiapamil) in supraventricular and ventricular extrasystoles (author's transl)].
The effectiveness of the calcium-antagonist Ro 11-1781 (Tiapamil) was investigated in 23 patients with extrasystoles of different origin using continuous ECG recordings. Two 24-hour ECG recordings were registered without antiarrhythmic medication, one of these as a placebo period, and 3 during oral application of 3 x 200 mg/day Ro 11-1781, if the state of the health of the patients allowed it. No positive effects of Ro 11-1781 in supraventricular and ventricular extrasystoles were demonstrable, supported by 8 premature terminations of the study. The missing antiarrhythmic effectiveness of Ro 11-1781 corresponds to Verapamil in oral application.


Nutritional properties of green gram germinated in mineral fortified soak water: I. Effect of dehulling on total and bioaccessible nutrients and bioactive components.
The study aimed at investigating the effect of germinating green gram (Vigna radiata, GG) in mineral fortified soak water on total and bioaccessible nutrients and bioactive components in whole and dehulled GG. Whole GG was soaked in water fortified with iron (100 or 200 mg/100 ml) or zinc (50 or 100 mg/100 ml), germinated and a portion was dehulled. Whole and dehulled grains were analyzed for selected total and in vitro digestible/bioaccessible constituents. GG germinated in water served as controls. GG germinated in mineral fortified soak water had high iron and zinc content in whole and dehulled grains. Protein and calcium content did not differ significantly. In vitro digestible starch and protein was higher in dehulled grains. A remarkable increase in bioaccessible iron and zinc was seen in grains germinated in mineral fortified water, the increase was more at lower level of fortification of levels for both minerals. Both total and bioaccessible bioactive components, total phenols, tannins and flavonoids were significantly lesser in grains germinated in fortified water. Germinating pulses in fortified water can be used as a pre-processing technology for fortification of minerals.


First Dorsal Metacarpal Artery-pedicled Second Metacarpal Vascularized Bone Graft for Nonunion after Thumb Carpometacarpal Arthrodesis.
Arthrodesis is a reliable surgical procedure for treating thumb carpometacarpal osteoarthritis. However, the most frequent and problematic complication of arthrodesis is nonunion. Although postarthrodesis-related nonunion is a common complication, the indications and results of revision procedures for this pathological condition have not been well documented. A 59-year-old man underwent arthrodesis for thumb carpometacarpal osteoarthritis, which resulted in painful nonunion 7 months after the surgery. We performed revision surgery for this pathological condition, using first dorsal metacarpal artery-pedicled second metacarpal vascularized bone graft. This method resulted in successful bone union and pain relief. First dorsal metacarpal artery-pedicled second metacarpal vascularized bone grafting could be an alternative method for nonunion, which is a common complication after thumb carpometacarpal arthrodesis.


Double-blind, placebo-controlled trial comparing long-term suppressive with short-term oral acyclovir therapy for management of recurrent genital herpes.
A total of 156 patients with frequently recurring genital herpes were enrolled in a randomized, double-blind, one-year trial comparing long-term suppressive and intermittent oral acyclovir therapy with placebo in the management of recurrent genital herpes. Subjects received either suppressive treatment with acyclovir, 400 mg twice daily for one year, and 200 mg five times per day for five days, for short-term treatment of recurrences; intermittent treatment with placebo, twice daily for one year, and oral acyclovir, 200 mg five times per day for five days, for short-term treatment of recurrences; or treatment with placebo, twice daily for one year, and five times per day for five days for short-term treatment of recurrences. Median time to first recurrence was 250 days for the suppressive group, 28 days for the intermittent group, and 23 days for the placebo group (p = 0.001). The median number of days per month with active disease was 0.32 for the suppressive group, 4.18 for the intermittent group, and 4.72 for the placebo group (p less than 0.001), with a median recurrence rate per 30-day treatment period of 0.08 recurrences/patient in the suppressive group, 0.70 in the intermittent group, and 0.74 in the placebo group (p less than 0.001). Median duration of recurrence was 5.0 days in the suppressive group compared with 6.0 days in the combined intermittent acyclovir plus placebo group (p = 0.001), and was reduced from 7.0 to 6.0 days when intermittent acyclovir treatment was compared with placebo treatment (p = 0.05). Daily administration of oral acyclovir for one year is superior to intermittent or placebo treatment in the management of patients with frequently recurring genital herpes.


[The effect of crisis intervention by the visiting nurse with cancer patients].
This study was undertaken at Yonsei University Medical Center to identify the crisis responses and nursing problems of patients who had been diagnosed with cancer, and changing patterns of grieving over time periods, and to analyse the effectiveness of follow up care through home visiting nursing. This study was carried out in three stages. The 1st study data were collected from a total of 205 patients who had been diagnosed with cancer from Sept. 1 to Dec. 31, 1987 using a cross-sectional method. The 2nd study data were collected three times from 30 patients with cancer at 4 weeks intervals from March 1 to June 31, 1988 using a longitudinal method. The 3rd study data were collected from two different groups from March 1 to June 31, 1988. One was an experimental group who was visited by nurses and the other one was a control group not visited by nurses. The subjects of the 3rd study consisted of 60 patients with cancer and a Quasi-experimental research design was used. The results were as follows: 1. The patients did not experience one stage at a time among the five stages of grieving, denial, anger, bargaining, depression and acceptance, as identified by Kübler Ross. They experienced a combination of stages, especially of the bargaining and the depression stages. This stages did not change with the passing of time. 2. The patients expressed more physical and socioeconomical problems than emotional problems. And they used more problem coping methods than emotional coping methods. 3. Follow up care through home visiting nursing positively influenced the patient's quality of life, especially their physical well-being and symptom control. The patients responded positively to the home visiting nursing, stating that it was helpful to them. It was concluded that the development of a home visiting nursing program is needed for the effective home care of patients with cancer.


Medical nebulizer performance: effects of cascade impactor temperature.
During operation of a jet nebulizer, the temperature of the nebulizer outlet could decrease by more than 10 degrees C, depending on the nebulizer type and operating conditions, such as driving flow rate and fill volume. The droplet size distribution generated from the nebulizer can be measured by a cascade impactor. However, when the cascade impactor is operated at ambient room temperature, the droplets could evaporate because of the temperature difference between the nebulizer outlet and the body of the impactor. An 8-stage cascade impactor was used to measure the particle size distribution from 4 different types of jet nebulizer (LC Plus, Side-Stream, VixOne, and Micromist) in 2 temperature conditions: ambient (22 degrees C) and low (10 degrees C). Two different formulations, albuterol (aqueous solution) and budesonide (suspension), were used. There was a significantly larger (p < 0.05) mass median aerodynamic diameter and smaller respirable fraction for each nebulizer with the impactor at low temperature than with the impactor at ambient temperature. The mass median aerodynamic diameter of the nebulizers with the impactor operating at low temperature appeared 15-130% larger than with the impactor operating at ambient temperature, for both formulations. The respirable fraction also changed from 10% when the impactor was operated at low temperature to 65% when the impactor was operated at ambient temperature. The results provide important information for the use of a cascade impactor to measure the particle-size distribution of nebulizer aerosols.


Determinants of Condom Use among Selected Migrant Commercial Farm Workers in South Africa.
Previous studies have shown that HIV prevalence rates are relatively high while condom use is low in migrant communities in South Africa. Using data from the Integrated Biological and Behavioural Surveillance Survey implemented by the International Organisation for Migration in 2010 among farm workers, this study seeks to investigate factors associated with condom use among migrant men and women in selected commercial farms in two provinces of South Africa. The study analysed 943 sexually active non-South Africans working in selected farms. Data analysis was undertaken at univariate, bivariate and multivariate levels using logistic regression producing odds ratios to examine the associations at 5% level of significance. The results showed that access to free condoms, financial stability and staying away from spouse increased the odds of condom use among migrant farm workers in Limpopo and Mpumalanga. Amongst men being financially stable and having access to free condoms significantly increased the odds of using condoms. Amongst women being married reduced the odds of using condoms while access to free condoms and living away from spouse significantly increased condom use. Determinants of condom use vary between male and female migrants. HIV prevention policies and programmes targeting migrant farm workers should be gender sensitive.


The Expression and Functional Roles of miRNAs in Embryonic and Lineage-Specific Stem Cells.
The discovery of small non-coding RNAs began an interesting era in cellular and molecular biology. To date, miRNAs are the best recognized non-coding RNAs for maintenance and differentiation of pluripotent stem cells including embryonic stem cells (ES), induced pluripotent stem cells (iPSC), and cancer stem cells. ES cells are defined by their ability to self-renew, teratoma formation, and to produce numerous types of differentiated cells. Dual capacity of ES cells for self-renewal and differentiation is controlled by specific interaction with the neighboring cells and intrinsic signaling pathways from the level of transcription to translation. The ES cells have been the suitable model for evaluating the function of non-coding RNAs and in specific miRNAs. So far, the general function of the miRNAs in ES cells has been assessed in mammalian and non-mammalian stem cells. Nowadays, the evolution of sequencing technology led to the discovery of numerous miRNAs in human and mouse ES cells that their expression levels significantly changes during proliferation and differentiation. Several miRNAs have been identified in ectoderm, mesoderm, and endoderm cells, as well. This review would focus on recent knowledge about the expression and functional roles of miRNAs in embryonic and lineage-specific stem cells. It also describes that miRNAs might have essential roles in orchestrating the Waddington's landscape structure during development.


Isolation of CF cell lines corrected at DeltaF508-CFTR locus by SFHR-mediated targeting.
Cystic fibrosis is the most common inherited disease in the Caucasian population. About 70% of all CF chromosomes carry the DeltaF508 mutation, a 3-bp deletion that results in the loss of a phenylalanine at amino acid 508 in the CF transmembrane conductance regulator (CFTR) protein. Direct modification of the DeltaF508 locus of endogenous CFTR was achieved by small fragment homologous replacement (SFHR). Transformed human airway epithelial cells (CFBE41o(-)), homozygous for DeltaF508 mutation, were transfected with small fragments (491-bp) of wild-type (WT) CFTR DNA comprising exon 10 and the flanking introns. The DNA fragments were in a liposome-DNA complex at a charge ratio of 6:1 (+:-), respectively). The population of transfected cells was subcloned by limiting dilution at approximately 1 cell/well in 96-well plates. Individual colonies were isolated and analyzed. The DNA from several colonies was characterized by radiolabeled, nonallele-specific and radiolabeled, allele-specific PCR amplification, as well as by genomic DNA fingerprinting. The CFTR-WT allele was detected in five of these colonies by allele-specific PCR amplification thus indicating that the cell lines carried both WT and DeltaF alleles. DNA fingerprint analysis confirmed that the colonies were isogenic and derived from the parental CFBE41o(-) cell line. Although, the WT allele was detected by allele-specific PCR, it was not detected initially when the same samples were analyzed by non allele-specific PCR. A sensitivity assay, mixing the genomic DNA of wild-type (16HBE14o(-)) and mutant (CFBE41o(-)) cell lines, indicated that the allele-specific PCR was at least 25-fold more sensitive than non allele-specific PCR. These results suggest that the colony is not yet clonal, but still contains a population of parental, CFBE41o(-) cells that have not been modified. Based on the mixing analysis, the proportion of corrected cells appears to be between 1 and 10% of the total population. Nonallele-specific reverse transcriptase PCR (RT-PCR) analysis of the CFTR mRNA indicated that two of the colonies expressed both WT and DeltaF508 CFTR mRNA, while one colony appeared to express only the WT mRNA. The mRNA results were confirmed by sequence analysis of 3' end primer extension products from the mRNA of CFTR exon 10 showing that the mRNA containing exon 10. Furthermore, a survey of primer extension products indicated no random insertion of the fragment in an expressed gene. This study demonstrates SFHR-mediated modification of the DeltaF508 allele in DeltaF508 homozygote human airway epithelial cells over multiple generations. The resultant cells express WT-CFTR mRNA and can be subcloned further to isolate isogenic clonal populations of cells.