[Histopathologic study on cyclocryotherapy of human and monkey eyes].
To evaluate the lesion and repair process of the ciliary body and adjacent tissues in glaucomatous human eyes and normal monkey eyes with cyclocryotherapy. We used light and electron microscopy to observe the ciliary body and adjacent tissues in five glaucomatous human eyes and five normal monkey eyes which were given cyclocryotherapy. Five absolute glaucomatous eyes were given cyclocryotherapy from one and a half to 3 years before the enucleation. One eye had no coagulated spots on the ciliary process, but five eyes had coagulated spots on the pars plana. The pigment epithelial cells were atrophic or had disappeared, but non-pigment epithelial cells had proliferated by one or two layers. At the lesion of monkey pars plicata cyclocryotherapy up to three months, melanophage phagocytosed pigment epithelium and melanocytes accumulated, although the proliferation of non-pigment epithelial cells was seen. At the lesion of monkey pars plana cyclocryotherapy melanophage accumulation was also marked, although non-pigment epithelial proliferation was greater than in pars plicata cyclocryotherapy. As cyclocryotherapy is a blind therapy, it is uncertain and difficult to destroy the ciliary process precisely. The repair process continued up to three months after monkey cyclocryotherapy, but it took up to one year and 6 months after human cyclocryotherapy.


Establishment of an arbitrary PCR for rapid identification of Tn917 insertion sites in Staphylococcus epidermidis: characterization of biofilm-negative and nonmucoid mutants.
Transposon mutagenesis with the Enterococcus faecalis transposon Tn917 is a genetic approach frequently used to identify genes related with specific phenotypes in gram-positive bacteria. We established an arbitrary PCR for the rapid and easy identification of Tn917 insertion sites in Staphylococcus epidermidis with six independent, well-characterized biofilm-negative Tn917 transposon mutants, which were clustered in the icaADBC gene locus or harbor Tn917 in the regulatory gene rsbU. For all six of these mutants, short chromosomal DNA fragments flanking both transposon ends could be amplified. All fragments were sufficient to correctly identify the Tn917 insertion sites in the published S. epidermidis genomes. By using this technique, the Tn917 insertion sites of three not-yet-characterized biofilm-negative or nonmucoid mutants were identified. In the biofilm-negative and nonmucoid mutant M12, Tn917 is inserted into a gene homologous to the regulatory gene purR of Bacillus subtilis and Staphylococcus aureus. The Tn917 insertions of the nonmucoid but biofilm-positive mutants M16 and M20 are located in genes homologous to components of the phosphoenolpyruvate-sugar phosphotransferase system (PTS) of B. subtilis, S. aureus, and Staphylococcus carnosus, indicating an influence of the PTS on the mucoid phenotype in S. epidermidis.


Color processing in macaque striate cortex: electrophysiological properties.
We have shown in the accompanying paper that optical imaging of macaque striate cortex reveals patches that are preferentially activated by equiluminant chromatic gratings compared with luminance gratings. These imaged color patches are highly correlated, although not always in one-to-one correspondence, with the cytochrome-oxidase (CO) blobs. In the present study, we have investigated the electrophysiological properties of neurons in the imaged color patches and the CO blobs. Our results indicate that individual blobs tend to contain cells of only one type of color opponency: either red/green or blue/yellow. Individual imaged color patches, however, can bridge blobs of similar opponency or differing opponency. When imaged color patches contain two blobs of differing opponency, the cells in the bridge region exhibit mixed color properties that are not opponent along the two cardinal color axes (either red/green or blue/yellow). Two blobs within a single imaged color patch receive input from the same eye or from different eyes. In the latter case, the bridge region between blobs contains binocular cells that are color selective. Because the cells recorded in imaged color patches were more color selective and unoriented than cells outside of color patches, color properties appear to be organized in a clustered and segregated fashion in primate V1.


Tanshinone IIA ameliorates diabetic cardiomyopathy by inhibiting Grp78 and CHOP expression in STZ-induced diabetes rats.
Diabetic cardiomyopathy (DCM), one of the common diabetic complications, causes a high rate of mortality in patients with diabetes. Tanshinone IIA (TSIIA), one of the components of Salvia miltiorrhiza (Danshen), has anti-oxidative stress activity and is widely used to treat diabetes-associated diseases. However, its efficacy on DCM remains unclear. The present study aimed to investigate the potential therapeutic function of TSIIA on DCM in an experimental diabetic rat model. Streptozotocin (STZ)-induced diabetic rats were intraperitoneally injected with TSIIA for 6 weeks. The present results indicated that blood glucose concentration was slightly reduced in the low-dose TSIIA treatment group. TSIIA injection was also noted to improve cardiac function, and restore loss of mitochondrial cristae, swollen mitochondrial matrix and disorganized myofibrils in myocardial cells, which are thought to be characteristics of apoptosis. Furthermore, TSIIA injection could increase the activity of superoxide dismutase in STZ-induced diabetic rats, and suppress the endoplasmic reticulum (ER) stress signaling pathway via reducing the expression of glucose-regulated protein 78 and C/EBP homologous protein. These results provide evidence that TSIIA may ameliorate DCM in diabetic rats, possibly via suppressing oxidative stress and ER stress activation.


Onychocosmeceuticals.
The nail is the largest skin appendage. In addition to its important physiological and sensory functions, it is also of great esthetic importance. Complaints of brittle or soft nails are frequent, particularly among women. Innumerable preparations claiming to improve the nail quality are being sold; however, most have no proven beneficial effect. Also, surgery cannot enhance nail quality but improve shape and size abnormalities.


[Distribution and drug resistance of pathogens in infected organ donors from donation after the citizen death].
Objective: To investigate the distribution and drug resistance of pathogens in infected organ donors from donation after the citizen death (DCD). Methods: Clinical data of 217 DCD donors from January 2013 to June 2017 were retrospectively analyzed.The phlegm, urine, blood and drainage fluid from all of the donors were routinely cultured.The infection rate of the donors, the composition ratio of pathogens and the distribution of specimen sources were observed and the drug resistance was analyzed. Results: Of all the 217 donors, 128 were infected and the infection rate was 59%.A total of 218 pathogens were isolated from these infected donors, including 55.5% (121/218) of gram-negative pathogens, 33.5% (73/218) of gram-positive pathogens followed by 11.0% (24/218) of fungi.The pathogenic specimens were mainly derived from sputum samples (72.5%), followed by urine (15.6%). The mainly two gram-negative pathogens were Klebsiella pneumonia and Acinetobacter baumannii.Klebsiella pneumonia exhibited varying degree of resistance to commonly used antibiotics, whereas susceptible to imipenem and meropenem.Acine-tobacterbaumannii was highly resistant to most of the antibiotics, and the drug resistance rate of imipenem and meropenem was over 60%, displaying a tendency of multi-drug resistance.Staphylococcus aureus, as the mainly gram-positive pathogen, was generally resistant to penicillin and clindamycin, but still sensitive to tovancomycin, teicoplanin and linezolid. Conclusions: DCD donors have a high infection rate, and respiratory infection is most common. Gram-negative pathogens are the primary pathogens causing infection in DCD donors.Klebsiella pneumonia maintain susceptible to imipenem and meropenem, while Acinetobacter baumannii reveals a tendency of multi-drug resistance.Gram-positive pathogens are still sensitive to vancomycin, teicoplanin and linezolid.


High-resolution profiles of gene expression and DNA methylation highlight mitochondrial modifications during early embryonic development.
Well-organized mitochondrial functions and dynamics are critical for early embryonic development and are operated via a large number of mitochondria-related genes (MtGs) encoded by both the nuclear and the mitochondrial genome. However, the mechanisms underlying mitochondrial modifications during the critical window between blastocyst implantation and postimplantation organogenesis are poorly understood. Herein, we performed high-resolution dynamic profiling of MtGs to acquire a more detailed understanding of mitochondrial modifications during early development. Our data suggest that the resumption of mitochondrial mass growth is not only facilitated by increased mitochondrial biogenesis and mitochondrial DNA (mtDNA) replication, but also by the appropriate balance between mitochondrial fission and fusion. In addition, increased levels of reactive oxygen species (ROS) resulting from enhanced mitochondrial functions may be the critical inducer for activating the glutathione (GSH)-based stress response system in early embryos. The appropriate balance between the mitochondrial stress response and apoptosis appears to be significant for cell differentiation and early organogenesis. Furthermore, we found that most MtGs undergo de novo promoter methylation, which may have functional consequences on mitochondrial functions and dynamics during early development. We also report that mtDNA methylation can be observed as early as soon after implantation. DNMT1, the predominant enzyme for maintaining DNA methylation, localized to the mitochondria and bound to mtDNA by the implantation stage. Our study provides a new insight into the involvement of mitochondria in early mammalian embryogenesis. We also propose that the epigenetic modifications during early development are significant for modulating mitochondrial functions and dynamics.


Hoffa's Fat Pad-associated Solitary Neurofibroma as the Cause of Anterior Knee Pain: A Case Report.
Infrapatellar peripheral neural tumors, particularly neurofibromas, are rather rare entities reported in the literature. They are slow-growing lesions that usually do not exhibit clinical manifestations other than interspecific swelling or pain; hence, their diagnosis can be quite challenging. Therefore, scrutiny should include not only traditional clinical assessment and imaging but also more specific molecular biology techniques, such as immunohistochemistry. We present the clinical, imaging, histological, and immunohistochemical features of a unique case of solitary neurofibromain a 33-year-old female presenting chronic anterior knee pain. The tumor was completely removed through a surgical approach. Although cases of a solitary neurofibroma originating within Hoffa's fat pad are extremely rare; the entity should be considered in the differential diagnosis when symptomatology is not alleviated with appropriate treatments.


[Usefulness and limitations in ultrasonography for diagnosing neck lymph node metastases in patients with hypopharyngeal squamous cell carcinoma: comparison with pathological findings following neck dissection].
We evaluated the usefulness and limitations in ultrasonography (US) for diagnosing neck lymph node metastases in patients with hypopharyngeal cancer by comparing the results of preoperative US examinations with postoperative pathological findings following neck dissection. Seventy-five previously untreated patients with hypopharyngeal squamous cell carcinoma underwent a curative procedure that included neck dissection. Preoperatively, all patients were examined by palpation, computed tomography (CT), and US. Postoperatively, all dissected neck lymph nodes were submitted for pathological examination. Results of pre-and postoperative examinations were then compared. US accuracy for each lymph node was 93.9%, while sensitivity was 78.0%, since hypopharyngeal cancer metastasizes early and easily to the neck lymph nodes, and it is difficult to detect small, pathologically positive nodes. Nine of 75 cases showed latent neck recurrence, and two of these were underestimated by US. The major cause for neck recurrence was considered to be the high rate of metastases in such cases, rather than a reduced dissection field. It is not rare to find very small, pathologically positive lymph nodes that US cannot detect in hypopharyngeal cancer. Efforts must therefore be expanded to improve the accuracy of US diagnosis. Care must also be taken when selecting cases for no or limited neck dissection.


Recent advances in understanding the antineoplastic mechanisms of farnesyltransferase inhibitors.
Farnesyltransferase (FTase) inhibitors (FTI) have broad antineoplastic actions targeting both cancer cells and mesenchymal cells involved in tumor angiogenesis. The small GTPases H-Ras, Rheb, and RhoB and the centromere proteins CENP-E and CENP-F are relevant targets of farnesylation inhibition; however, their relative importance in the antineoplastic effect of FTIs may vary in different cell types at different stages of the cell cycle and at different stages in oncogenesis. Three recent studies argue that Ras-independent and perhaps even FTase-independent properties are important to the antineoplastic action of this class of drugs. In mice, genetic ablation of FTase does not abolish the oncogenic activity of Ras, limiting the original conception of FTIs as an effective means to target Ras in cancer cells. FTase may not be the sole molecular target of these agents, and one study has suggested that FTIs act by targeting geranylgeranyl transferase II. Lastly, we have obtained evidence that induction of reactive oxygen species and reactive oxygen species-mediated DNA damage by FTIs may be critical for their antineoplastic action as a class. Together, these findings may alter thinking about how to apply FTIs in the clinic.


[Reduction of intussusception by air enema in children--experience over a 13-year period].
Intussusception is a relatively common pediatric emergency. The accepted treatment is closed reduction using barium or air enema and surgery when it has failed. We present our 13-year experience using air enema for treatment of intussusception, emphasizing the reduction with repeated delayed air enema. Between February 1990 and December 2002, air enema procedures were performed in pediatric patients in cases with suspected intussusception. Prior to the procedure, all patients were sedated with meperidine hydrochloride (0.5 mg/kg) or morphine (0.1 mg/kg). Before 1993, surgery was performed after the first ineffective attempt of air enema reduction. Since 1993, in the case of failure of the first attempt, two additional trials of air reduction were performed at an interval of 45-60 minutes prior to surgery. A total of 225 air enema procedures were performed in 201 children (129 males, aged 10.4 +/- 9.1 months, range 8-63 months) with suspicion of intussusception. The diagnosis was confirmed in 148 (66%) out of the 225 procedures performed. A successful reduction of intussusception (by one attempt or more) was achieved in 125 (86%) out of the 148 procedures with proved intussusception. Twenty-one (14%) patients were operated on after the failure of closed reduction. Spontaneous reduction was demonstrated under fluoroscopy in two (0.8%) studies. No complications of the air enema were noted. During 1990-1993, a single reduction attempt of the intussusception by air enema was performed. Successful reduction during this period was achieved in 19 (70%) out of 27 patients and 8 (30%) children were operated on. During the period 1993-2002, we used repeated delayed attempts to obtain reduction of intussusception among 174 patients. The success rate was 89% (108 out of 121 patients) and only 13 (11%) children were operated on. Air enema is an efficient and safe diagnostic and therapeutic tool for intussusception in the pediatric population.


Complementary therapies: what is the evidence for their use?
Complementary therapies are being increasingly used by patients and health-care professionals, but often with little awareness of the evidence for their use. The Internet offers a valuable and easy-to-use resource for assessing a growing amount of published information. Nurses need to be aware of a treatment's effectiveness and warn patients of potential risks or unprofessional claims.


Electroporation-mediated gene therapy.
Non-viral gene transfer is markedly enhanced by the application of in vivo electroporation. Electroporation is a safe and efficient system to introduce genes to a wide variety of tissues, including skeletal muscle, tumors, kidney, liver and skin. Electroporation has been demonstrated to be effective in numerous disease models. This review focuses on the principles of electroporation and the target tissues employed for gene therapy. Based on the accumulation of positive results, the first clinical study for the treatment of malignant melanoma is now underway, and preclinical studies have suggested that electroporation is useful as a gene therapy protocol.


Polyurethane Microgel Based Microtissue: Interface-Guided Assembly and Spreading.
Colloidal gels are three-dimensional networks of microgel particles and can be utilized to design microtissues where the differential adhesive interactions between the particles and cells, guided by their surface energetics, are engineered to spatially assemble the cellular and colloidal components into three-dimensional microtissues. In this work we utilized a colloidal interaction approach to design cell-polyurethane (PU) microgel bimodal microtissues using endothelial cells (ECs) as a normal cell model and a nonmalignant breast cancer cell line (MCF-7) as a cancer cell model. PU microgels were developed from a library of segmental polyurethanes with poly(ethylene glycol) soft segment and aliphatic diisocyanate/l-tyrosine based chain extender as hard segment to modulate the interactions between PU colloidal particles and cells. The surface energies of the microgel particles and cells were estimated using Zisman's critical surface tension and van Oss-Good-Chaudhury theory (vOGCT) from liquid contact angle analysis. Binary interaction potentials between colloidal PU particles and cells and the ternary interaction between colloidal PU particle, cell, and collagen I/Matrigel were calculated to explain the formation of microtissues and their spreading in extraneous biomatrix respectively by using classical and extended DLVO theory (XDLVO). Furthermore, rheological analysis and in silico simulations were used to analyze the assembly and spreading of the PU microgel based microtissues. In vitro experiments showed that ECs and MCF-7 displayed more differentiated (EC spreading/MCF-7 lumen formation) character when mixed with microgel particles that were stable in aqueous medium and more undifferentiated character (EC nonspreading/MCF-7 spreading) when mixed with microgel particles unstable in aqueous medium.


Hepatic lesions and bacterial changes in mice during infection of Fusobacterium necrophorum.
Liver abscesses were induced in male albino mice within 1 week after intraperitoneal inoculation of viable Fusobacterium necrophorum LA19 culture. Fusobacteremia was transitory and reached a peak 2 h after inoculation then sharply declined until its disappearance 24 h post inoculation. By contrast, the number of fusobacteria in the liver increased rapidly during the first 4 h post inoculation and continued to do so less rapidly until the last sampling time (48 h post inoculation). There were small or large areas of necrosis, usually surrounded by inflammatory cells, small focal accumulations of lymphocytes, plasma cells, and macrophages in areas of parenchyma with no degenerations, generalized proliferation of Kupffer cells, and a few accumulations of fibrin and leukocytes on the surface. Ultrathin sections of infected liver tissues reveled both intact and partially degraded F. necrophorum cells enclosed in phagocytic and digestive vacuoles of mononuclear cells, The results indicate that macrophages play a key role in the pathogenesis of liver abscesses.


Aurora B kinase is a potent and selective target in MYCN-driven neuroblastoma.
Despite advances in multimodal treatment, neuroblastoma (NB) is often fatal for children with high-risk disease and many survivors need to cope with long-term side effects from high-dose chemotherapy and radiation. To identify new therapeutic targets, we performed an siRNA screen of the druggable genome combined with a small molecule screen of 465 compounds targeting 39 different mechanisms of actions in four NB cell lines. We identified 58 genes as targets, including AURKB, in at least one cell line. In the drug screen, aurora kinase inhibitors (nine molecules) and in particular the AURKB-selective compound, barasertib, were the most discriminatory with regard to sensitivity for MYCN-amplified cell lines. In an expanded panel of ten NB cell lines, those with MYCN-amplification and wild-type TP53 were the most sensitive to low nanomolar concentrations of barasertib. Inhibition of the AURKB kinase activity resulted in decreased phosphorylation of the known target, histone H3, and upregulation of TP53 in MYCN-amplified, TP53 wild-type cells. However, both wild-type and TP53 mutant MYCN-amplified cell lines arrested in G2/M phase upon AURKB inhibition. Additionally, barasertib induced endoreduplication and apoptosis. Treatment of MYCN-amplified/TP53 wild-type neuroblastoma xenografts resulted in profound growth inhibition and tumor regression. Therefore, aurora B kinase inhibition is highly effective in aggressive neuroblastoma and warrants further investigation in clinical trials.


In vitro comparison of working length determination using three different electronic apex locators.
The aim of this study was to compare the accuracy of the apex-locating functions of DentaPort ZX, Raypex 5 and Endo Master electronic apex locators (EALs) in vitro. Thirty extracted human single-rooted teeth with mature apices were used for the study. The real working length (RWL) was established by subtracting 0.5 mm from the actual root canal length. All teeth were mounted in an alginate model that was especially developed to test the EALs and the teeth were then measured with each EAL. The results were compared with the corresponding RWL, which was subtracted from the electronically determined distance. Data were analyzed using a paired-samples t-test, a Chi-square test and a repeated measure analysis of variance evaluation at the 0.05 level of significance. Statistical analysis showed that no significant difference was found among all EALs (P > 0.05). The accuracy of the EALs was evaluated and all of the devices showed an acceptable determination of electronic working length between the ranges of ±0.5 mm.


Gallic Acid: Review of the Methods of Determination and Quantification.
Gallic acid (3,4,5 trihydroxybenzoic acid) is a secondary metabolite present in most plants. This metabolite is known to exhibit a range of bioactivities including antioxidant, antimicrobial, anti-inflammatory, and anticancer. There are various methods to analyze gallic acid including spectrometry, chromatography, and capillary electrophoresis, among others. They have been developed to identify and quantify this active ingredient in most biological matrices. The aim of this article is to review the available information on analytical methods for gallic acid, as well as presenting the advantages and limitations of each technique.


A noninvasive tumor oxygenation imaging strategy using magnetic resonance imaging of endogenous blood and tissue water.
To present a novel imaging strategy for noninvasive measurement of tumor oxygenation using MR imaging of endogenous blood and tissue water. The proposed approach for oxygen partial pressure (pO2) estimation is based on intravoxel incoherent motion diffusion MRI and the dependence of the blood R2 relaxation rate on the inter-echo spacing measured using a multiple spin-echo Carr-Purcell-Meiboom-Gill sequence and weak-field diffusion model. The accuracy of the approach was validated by comparison with (19)F MRI oximetry. The results in eight rats at 4.7 T showed that tumors have longer T1 (1980 ± 186 ms) and T2 (59 ± 9 ms) relaxation times, heterogeneous blood volume fraction (0.23 ± 0.1), oxygen saturation level (Y) (0.53 ± 0.12), and pO2 (36 ± 15 mmHg) distributions compared with normal muscle (T1 1480 ± 86 ms, T2 29 ± 2 ms, blood volume fraction 0.22 ± 0.03, Y 0.49 ± 0.06, and pO2 39 ± 5 mmHg). pO2 estimates based on the novel (1)H approach were essentially identical with (19)F observations. The study indicates that noninvasive measurement of tumor pO2 using (1)H MRI derived multiparametric maps is feasible and could become a valuable tool to evaluate tumor hypoxia.


Surface-induced phase transitions in ultrathin films of block copolymers.
We study theoretically the lamellar-disorder-lamellar phase transitions of AB diblock and tetrablock copolymers confined in symmetric slitlike pores where the planar surface discriminatingly adsorbs A segments but repels B segments, mimicking the hydrophobic/hydrophilic effects that have been recently utilized for the fabrication of environmentally responsive "smart" materials. The effects of film thickness, polymer volume fraction, and backbone structure on the surface morphology have been investigated using a polymer density-functional theory. The surface-induced phase transition is manifested itself in a discontinuous switch of microdomains or a jump in the surface density dictated by the competition of surface adsorption and self-aggregation of the block copolymers. The surface-induced first-order phase transition is starkly different from the thickness-induced symmetric-asymmetric or horizontal-vertical transitions in thin films of copolymer melts reported earlier.


Treating azotemia-induced anemia with erythropoietin improves diabetic eye disease.
Coincidental with the pandemic growth of diabetes as the prime cause of end-stage renal disease (ESRD), blindness attributable to diabetic retinopathy has become a major concern for all those involved in the care of diabetic ESRD patients. Vision loss is linked to progression of proliferative retinopathy and macular edema. Extracted from a study of azotemic anemic pre-ESRD patients treated with erythropoietin, a cohort of five diabetic subjects was reassessed in terms of stability of renal function, changes in blood rheology, and course of diabetic eye disease. All subjects reported subjective improvement in well-being, including enhanced effort tolerance following an increase in hematocrit from a baseline level of to 29.6 +/- 2.0% to a level of 39.5 +/- 2.4% after one year of treatment with erythropoietin (P = <0.0005). Neither hypertension nor deterioration of renal function was noted in any subject. Three patients with macular edema evinced substantive improvement-based stable vision and documented resolution noted in flourescein angiography. Erythropoietin treatment of anemic azotemic diabetic patients is well tolerated. In a small observational retrospective study of three patients with macular edema, retention of vision and resolution of exudates was noted.


Matching preparatory intervention to coping style: The effects on children's distress in the dental setting.
Investigate the effects of matching preparatory interventions to patient's coping styles. Participants were 61 children, with a restricted age range of 6 through 9 years old (mean age was 7.9 years), who underwent dental restoration. Participants were randomly assigned to an information intervention, a relaxation intervention, or a control condition. Play and parent-report of sensitization/repression were indices of coping style. The first hypothesis, that play would relate to sensitization/repression, was tested using Pearson correlations. The second hypothesis, that interventions that were congruent with patients' coping styles would be more effective than incongruent interventions, was tested using MANCOVAs. No relation was found between play and coping style. The "congruency hypothesis" was supported for self-reported distress immediately following the intervention. On behavioral distress variables, the interaction between sensitization/repression and condition was contrary to the congruency hypothesis. Implications for future research and clinical intervention with pediatric populations were discussed.


Elevated Serum Lysophosphatidylcholine in Patients with Systemic Lupus Erythematosus Impairs Phagocytosis of Necrotic Cells In Vitro.
Impaired clearance of dying and dead cells by professional and amateur phagocytes plays a crucial role in the etiology of systemic lupus erythematosus (SLE). While dying, cells expose and release a plethora of eat-me and find-me signals to ensure their timely removal before entering the dangerous stage of secondary necrosis. A well-described chemoattractant for macrophages is dying cell-derived lysophosphatidylcholine (LPC). However, its implications for and/or its association with SLE disease, so far, have not been examined. In the present study, we analyzed the LPC serum concentrations of patients with SLE and rheumatoid arthritis (RA). Subsequently, we examined if and to which extent the measured serum concentrations of LPC and an LPC-rich environment can impact the phagocytosis of necrotic cells. Sera from patients with SLE, RA, and normal healthy donors (NHD) were characterized for several parameters, including LPC concentrations. Phagocytosis of dead cells by human macrophages in the presence of SLE and NHD sera was quantified. Additionally, the impact of exogenously added, purified LPC on phagocytosis was analyzed. Patients with SLE had significantly increased LPC serum levels, and high serum LPC of SLE patients correlated significantly with impaired phagocytosis of dead cells in the presence of heat-inactivated serum. Phagocytosis in the presence of sera from NHD showed no correlation to LPC levels, but exogenous addition of purified LPC in the range as measured in SLE patients' sera led to a concentration-dependent decrease. Our data show that high levels of LPC as observed in the sera of SLE patients have a negative impact on the clearance of dead cells by macrophages. Chemoattraction requires a concentration gradient. The higher the LPC concentration surrounding a dying or dead cell, the smaller the achievable gradient upon LPC release will be. Thus, it is feasible to assume that elevated LPC levels can interfere with the build-up of a local LPC gradient during cell death, and hence might play a role in the establishment and/or perpetuation of SLE disease.


Five-year survival following chemotherapy of non-small cell lung cancer.
Five-year survival of patients with inoperable non-small cell lung carcinoma is rare. We report a patient with inoperable large cell lung carcinoma who is apparently cured after receiving a course of combination chemotherapy. As the primary treatment of inoperable non-small cell carcinoma, we recommend combination chemotherapy over radiation therapy because: Chemotherapy gives a response rate of 30-40%; Quality of survival following chemotherapy appears better than following radiation therapy; Chemotherapy following radiation therapy appears to be ineffective.


Successful intra-abdominal resection of a 24 kg ovarian granulosa cell tumor in a Warmblood mare.
Granulosa cell tumors (GCTs) are the most common ovarian tumors in mares. The classical presentation of a GCT is a unilaterally enlarged ovary appearing as a multicystic honeycomb mass. In rare cases, GCTs cause hemoperitoneum as a result of the rapid growth of the tumor. The clinical diagnosis of GCT is usually based on history, rectal examination, ultrasonographic examination, and serum hormone analysis, and surgical removal of the affected ovary is the treatment of choice. The different surgical approaches are based on the dimension of the GCT. A 7-year-old mare was referred to the department for horses due to suspicion of a large colon impaction. The mare presented with clinical signs of colic, fever, and signs of hypovolemic shock. Rectal and ultrasonographic examination showed hemoperitoneum and a honey-comb mass within the abdomen, and a GCT as the cause of an acute hemoperitoneum was diagnosed based on the serum level of anti-Müllerian hormone. After stabilization of the mare, the GCT was removed through a ventral midline incision. Because of the enormous dimensions of the GCT, intra-abdominal partial resection of the tumor using a tenotomy knife was necessary to exteriorize the ovarian pedicle. At 3 months follow-up, the mare was ridden for her intended use. This report provides an approach to an uncommon case of a very large and heavy GCT.


Dihydroartemisinin and gefitinib synergistically inhibit NSCLC cell growth and promote apoptosis via the Akt/mTOR/STAT3 pathway.
Non‑small cell lung cancer (NSCLC) is among the leading causes of cancer‑associated mortality worldwide. In clinical practice, therapeutic strategies based on drug combinations are often used for the treatment of various types of cancer. The present study aimed to investigate the effects of the combination of dihydroartemisinin (DHA) and gefitinib on NSCLC. Cell Counting kit 8 assay was used to evaluate cell viability. Transwell assays were performed to investigate cellular migration and invasion, and cellular apoptosis was evaluated using the terminal deoxynucleotidyl transferase dUTP nick‑end labeling assay. Flow cytometry was used to investigate cell cycle distribution and the expression levels of target proteins were determined using western blot analysis. The results of the present study demonstrated that DHA (5, 10, 20, 50 and 100 µM) reduced cancer cell viability in a dose‑dependent manner in the NCI‑H1975 human NSCLC cell line and significantly enhanced gefitinib‑induced apoptosis. Furthermore, DHA and gefitinib co‑administration induced cell cycle arrest in G2/M phase, which was associated with a marked decline in the protein expression levels of G2/M regulatory proteins, including cyclin B1 and cyclin‑dependent kinase 1. The addition of DHA appeared to potentiate the inhibitory actions of gefitinib on the migratory and invasive capabilities of NCI‑H1975 cells. DHA and gefitinib co‑administration also downregulated the expression levels of phosphorylated (p)‑Akt, p‑mechanistic target of rapamycin, p‑signal transducer and activator of transcription 3 and B‑cell lymphoma 2 (Bcl‑2), and upregulated the expression of Bcl‑2‑associated X protein. In conclusion, the present results suggested that the combination of DHA and gefitinib may have potential as a novel and more effective therapeutic strategy for the treatment of patients with NSCLC.


The EXACT description of biomedical protocols.
Many published manuscripts contain experiment protocols which are poorly described or deficient in information. This means that the published results are very hard or impossible to repeat. This problem is being made worse by the increasing complexity of high-throughput/automated methods. There is therefore a growing need to represent experiment protocols in an efficient and unambiguous way. We have developed the Experiment ACTions (EXACT) ontology as the basis of a method of representing biological laboratory protocols. We provide example protocols that have been formalized using EXACT, and demonstrate the advantages and opportunities created by using this formalization. We argue that the use of EXACT will result in the publication of protocols with increased clarity and usefulness to the scientific community. The ontology, examples and code can be downloaded from http://www.aber.ac.uk/compsci/Research/bio/dss/EXACT/.


Comparison of clinical characteristics in episodic and chronic obsessive-compulsive disorder.
Our objective in this study was to compare the demographics and clinical characteristics of patients with episodic and chronic obsessive-compulsive disorder (OCD). We recruited 128 outpatients with a primary diagnosis of OCD according to DSM-IV diagnostic criteria. The episodic (n=24) and chronic (n=104) OCD patient groups were compared with respect to demographic variables and scores from various psychiatric rating scales. The severity of compulsions was found to be significantly lower in the episodic OCD group than in the chronic OCD group. When the frequency of Axis I disorders was assessed in the two groups, bipolar disorder was found to have a significantly higher prevalence rate in the episodic OCD group than that in the chronic OCD group. The results of our study point to the possibility of an association between a subgroup of OCD with an episodic course and bipolar disorder. The evidence of such a relationship, which needs to be confirmed in a larger sample, might expand the scope of the clinical assessment and therapy of this subgroup of OCD.


Comparative costs of laparoscopically assisted vaginal hysterectomy.
To audit the performance of laparoscopically assisted vaginal hysterectomy (LAVH) in a gynaecological practice with regard to cost and clinical outcome when compared to the surgical alternatives available. LAVH was performed on 50 women and both monetary and time cost parameters analysed and compared with those of 30 women undergoing either abdominal hysterectomy, vaginal hysterectomy or endometrial resection. The cost of LAVH was approximately twice that of abdominal hysterectomy and almost three times that of vaginal hysterectomy. The theatre time was longer for LAVH than for the above and in a similar ratio. Patient recovery was superior with LAVH when compared with abdominal hysterectomy but not when compared with standard vaginal hysterectomy. LAVH has a role in providing patients with the option of avoiding abdominal hysterectomy, although the role will differ depending upon the differing criteria used by surgeons for selecting patients for standard vaginal hysterectomy.


Measuring femoral and rotational alignment: EOS system versus computed tomography.
Computed tomography (CT) is currently the reference standard for measuring femoral and tibial rotational alignment. The EOS System is a new biplanar low-dose radiographic device that allows 3-dimensional lower-limb modelling with automated measurements of femoral and tibial rotational alignment (torsion). Femoral and tibial torsion measurements provided by the EOS System are equivalent to those obtained using CT. In a retrospective analysis of 43 lower limbs in 30 patients, three senior radiologists measured femoral and tibial torsion on both CT and EOS images. Agreement between CT and EOS values was assessed by computing Pearson's correlation coefficient and interobserver reproducibility by computing the intraclass correlation coefficient (ICC). Femoral torsion was 13.4° by EOS vs. 13.7° by CT (P=0.5) and tibial torsion was 30.8° by EOS vs. 30.3° by CT (P=0.4). Strong associations were found between EOS and CT values for both femoral torsion (P=0.93) and tibial torsion (P=0.89). With EOS, the ICC was 0.93 for femoral torsion and 0.86 for tibial torsion; corresponding values with CT were 0.90 and 0.92. The EOS system is a valid alternative to CT for lower-limb torsion measurement. EOS imaging allows a comprehensive evaluation in all three planes while substantially decreasing patient radiation exposure. Level III, case-control.


Highly Stable HfO2 Memristors through van der Waals Electrode Lamination and Delamination.
Memristors have attracted considerable attention in the past decade, holding great promise for future neuromorphic computing. However, the intrinsic poor stability and large device variability remain key limitations for practical application. Here, we report a simple method to directly visualize the origin of poor stability. By mechanically removing the top electrodes of memristors operated at different states (such as SET or RESET), the memristive layer could be exposed and directly characterized through conductive atomic force microscopy, providing two-dimensional area information within memristors. Based on this technique, we observed the existence of multiple conducting filaments during the formation process and built up a physical model between filament numbers and the cycle-to-cycle variation. Furthermore, by improving the interface quality through the van der Waals top electrode, we could reduce the filament number down to a single filament during all switching cycles, leading to much controlled switching behavior and reliable device operation.


[Determination of ten aminoglycoside residues in milk and dairy products using high performance liquid chromatography-tandem mass spectrometry].
A high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/ MS) analytical method was developed for the simultaneous determination of ten aminoglycoside residues (streptomycin, dihydrostrepmycin, neomycin, kanamycin, tobramycin, gentamycin, apramycin, hygromycin B, paromomycin, and amkacin) in milk and dairy products. The sample was extracted with 5% trichloroacetic acid aqueous solution, then the extract was purified by a hydrophilic-lipophilic balance (HLB) cartridge. The ten aminoglycoside residues were separated by ion-pair reversed phase high performance liquid chromatography. Heptafluorobutyric acid was used as ion pair agent due to its volatility. Then the analytes were detected by electrospray ionization tandem mass spectrometry. The pretreatment condition of the sample, the HPLC condition and the MS operation parameters were optimized. The results showed that the linearities of the ten aminoglycoside residues in 20-1000 microg/L had the correlation coefficient between 0.9946-0.9997. The recoveries ranged from 71.2% and 101.7% with the relative standard deviations of 3.4%-13.8%. The proposed method was successfully applied to the determination of the mass concentrations of the analytes in related samples, which provides a simple, and convenient method for the quality control of milk and dairy products. Furthermore, this method is effective for the safety monitoring of aminoglycoside residues in milk and dairy products.


Kappa agonist-induced diuresis: evidence for stereoselectivity, strain differences, independence of hydration variables and a result of decreased plasma vasopressin levels.
Marked diuresis has previously been reported after administration of kappa opioid agonists. The present study shows that this effect is stereospecific; MR-2034 markedly increased urinary output over the dose range 0.08 to 1.25 mg/kg, whereas the opposite isomer, MR-2035, was markedly less potent. Bremazocine increased urinary output in Long-Evans hooded and Sprague-Dawley albino rats as well as lean and fatty Zucker rats. In the lean Zucker and the albino rats, bremazocine produced an inverted U-shaped diuretic dose-effect curve, an effect characteristic of kappa agonists with mu agonist activity. This pattern was not seen with the fatty Zucker rats or the Long-Evans hooded rats. The full kappa agonists bremazocine, ethylketazocine and U-50,488 increased urinary output under three different conditions of hydration: water loaded, normal hydration and water deprived. In contrast, the partial kappa agonists reliably only increase urinary output under the normal hydration condition. The diuretic effects of full and partial kappa agonists correlated with plasma vasopressin levels in water-deprived rats. The full kappa agonists (ethylketazocine, U-50,488, tifluadom and MR-2034) suppressed plasma vasopressin levels below the threshold of detectability of the radioimmunoassay, whereas the partial kappa agonists (nalorphine and butorphanol) suppressed vasopressin levels compared with control values but did not have the efficacy of the full kappa agonists. All these results support the hypothesis that kappa agonists produce their diuretic effect by suppression of plasma vasopressin levels.


Assessment of a modified household food weighing method in a study of bone health in China.
A 'modified' household dietary method to estimate individual intakes from total household intakes was evaluated in comparison to the individual food weighing method, i.e. direct weighing of foods consumed by individuals. Foods consumed by the household were weighed and recorded over a 3 day period and were proportionally allocated to a specific person in the household by using energy conversion factors based on age, gender and physical activity. The individual dietary intakes were standardized by body weight (ratio of individual body weight to reference body weight from Chinese Recommended Daily Allowances (Acta Nutr. Sin. 12, 1-9), and were compared with the estimates from the individual food weighing method for both accuracy and associations with bone density. The subjects were randomly selected from five rural countries in China, characterized by different dietary patterns. A total of 712 women aged 35-75 years participated in the dietary and bone measurements. Nutrient intakes estimated by the modified household method (adjusting for body weight were very similar to those obtained by the individual method (r = 0.53-0.78, P < 0.001), except for sodium which had the largest deviation from the individual methods (r = 0.23, P < 0.001). Calcium intakes were 405 +/- 271 and 409 +/- 323 mg/day, respectively, as estimated by the individual and modified household methods. A very similar degree of correlation with radial bone density also was obtained for both calcium estimates. The results indicate that the modified household method is appropriate for assessing food intakes of individuals in large nutritional studies.


Implementing advance directives in the primary care setting.
Despite the potential benefits of advance directives, few patients complete them. This study examined whether barriers to advance decision making can be overcome via a combined educational and administrative intervention targeted at physicians. The subjects consisted of all the internists (n = 6) at a primary care physician home care (HC) service and all the internists (n = 4) at a primary care nursing home (NH) service. Physicians were given a 5-week course on the law relating to advance directives. Administrative consent was obtained to permit physicians to spend additional time with patients to discuss advance directives. Physicians were asked to discuss advance directives with newly enrolled patients and to assist interested patients to complete directives. During the first 2 months of the trial, physicians did not approach any patients. Therefore, the study design was changed to include all active patients, and physicians received additional training that involved observing and leading discussions with their own patients. Physicians approached 74 of 356 competent HC patients, of whom 48 (65%) completed directives. All 42 competent NH patients were approached, and 38 (90%) completed directives. Most patients who completed a directive chose relatives as proxies. Most directed that life-sustaining treatment be withheld in the event they were permanently unconscious (HC, 81%; NH, 92%). Other common choices were to decline long-term mechanical ventilation (HC, 58%; NH, 79%), long-term artificial nutrition (HC, 44%; NH, 79%), and cardiopulmonary resuscitation (HC, 27%; NH, 66%). Physicians can overcome initial reluctance to integrate advance decision making into primary care provided to elderly patients. Teaching physicians about the law is not sufficient to change behavior; physicians also need practical experience discussing directives with patients. Our high patient response suggests that a physician-directed intervention is sufficient to achieve high rates of completing directives without additional, concomitant patient-directed intervention.


Bone histology and calcium metabolism in patients with nephrotic syndrome and normal or reduced renal function.
Bone histology and its relationship with calcium metabolism was evaluated in adult patients with nephrotic syndrome: 29 had normal renal function (GFR 103 +/- 4 ml/min/1.73 m2) (group 1) and 20 had renal insufficiency (GFR 31 +/- 4 ml/min/1.73 m2) (group 2). In group 1, serum PTH, 1.25-HCC and 24.25-HCC levels were normal, while 25-HCC values were reduced. Bone histology was normal in 76% of the patients, while 17% had isolated osteomalacia and 7% an associated bone resorption. Group 2 showed a higher incidence of bone resorption when compared with a matched group of patients with renal failure and no proteinuria (40% vs. 13%) and a comparable frequency of isolated mineralization defect (25% vs. 34%). PTH levels were definitely increased and serum total calcium and all the vitamin D metabolites were reduced. A significant correlation between the apparent duration of the disease and the severity of osteodystrophy was found only in group 2. In conclusion, no constant derangement of calcium metabolism and bone histology is evident in patients with nephrotic syndrome and normal renal function, while patients with persistent proteinuria are at high risk of osteodystrophy even in the early phases of renal failure.


Ameliorative Effect of Gallic Acid in Doxorubicin-Induced Hepatotoxicity in Wistar Rats Through Antioxidant Defense System.
Hepatotoxicity has been found to be one of the main side effects associated with doxorubicin (Dox) administration in cancer therapy. The aim of the present study was to examine the ameliorative effect of gallic acid (GA) in Dox-induced hepatotoxicity. Sixty male Wistar rats of 10 rats per group were used in this study and were randomly divided into 6 experimental groups (A-F). Rats in Group A served as the control group and received distilled water orally for 7 days; Group B was given Dox at 15 mg/kg body weight intraperitoneally (IP) on Day 8. Group C was given GA at 60 mg/kg body weight orally for 7 days + Dox at 15 mg/kg IP on Day 8. Group D was given GA at 120 mg/kg body weight orally for 7 days + Dox at 15 mg/kg IP on day 8. Rats in Groups E and F were administered GA alone at 60 and 120 mg/kg body weight orally for 7 days, respectively. Dox administration led to a significant reduction in hepatic reduced glutathione and nonprotein thiol (NPT) together with significant increase in hepatic malondialdehyde, hydrogen peroxide generation, superoxide dismutase, and catalase activity; hepatic glutathione peroxidase and glutathione-S-transferase activity were significantly inhibited in Dox-treated rats. The serum alanine aminotransferase (ALT), alkaline phosphatase, and total bilirubin concentrations were significantly elevated following Dox administration. Pretreatment with GA ameliorated Dox-induced hepatotoxicity and oxidative stress. The results suggest that GA may offer protection against hepatic damage in Dox cancer chemotherapy.


[Observation of the effects of warming-up and role-playing in psychodrama in terms of mood rating].
The purpose is to make an appropriate list of terms that describe person's moment-to-moment changes in moods during psychodrama sessions. Seventy nurse students participated in a series of psychodrama sessions, consisting of a session of warming-up and two sessions of role playing. They rated their moods at the beginning of the sessions and after each session, on a five-point scale for each of the 55 terms, which were supposed to cover all kinds of moods during psychodrama sessions. After analyzing variations (using factor analyses) of subjects' ratings, three factors were found to be sufficient for describing their moods, and the terms in the list were eventually reduced to sixteen. Changes of moods analyzed through the ratings of sixteen scales were related significantly with subjects' performances of warming-up and role playing.


Axoplasmic transport in the crayfish nerve cord. The role of fibrillar constituents of neurons.
(a) Axoplasmic transport of tritium-labeled proteins in crayfish nerve cord was confirmed at a slow rate of 1 mm/day. A second proteinaceous component which moves at a rate of 10 mm/day was also detected. Radioautography and biochemical analysis indicate that proteins migrating at these velocities have a perikaryal origin and move caudad within axons as sharply defined peaks. (b) Evidence is presented for the blockage of the slow and the fast movement of proteins by intraganglionic injection of the anti-mitotic agent vinblastine sulfate (0.1 mM). (c) Electron microscope observations of vinblastine-treated ganglia revealed a reduction in the number of axonal microtubules and the formation of intracellular aggregates presumably composed of microtubular protein. (d) These findings would be compatible with the involvement of microtubules in both slow and fast axoplasmic transport. However, the block induced by vinblastine was detected in regions of the cord (up to 10 mm away from the injection site) where the number and morphology of microtubules appeared unaltered. In addition, axons showing effects of vinblastine occasionally contained mitochondria with remarkably dense and thickened membranes. (e) In association with the surfaces of axonal microtubules are lateral filamentous elements (40-80 A in diameter) which also showed vinblastine-induced alterations. Our observations indicate that such filiform structures, associated with microtubules, may be a necessary component in the transport mechanism(s).


Cloning, nucleotide sequence, and regulatory analysis of the Nitrosomonas europaea dnaK gene.
The dnaK gene of an ammonia-oxidizing bacterium, Nitrosomonas europaea, was cloned and sequenced. It was found that the dnaK gene product was highly homologous to previously analyzed dnaK gene products from other organisms at the amino acid level. Two partial open reading frames located upstream and downstream of the dnaK gene were also found and identified as grpE and dnaJ genes, respectively, by the predicted amino acid homology of their gene products to other bacterial GrpE and DnaJ proteins. Transcription of the dnaK gene was strongly induced by a heat shock from 30 to 37 degrees C. An analysis of the expression of the dnaK gene fused to the lacZ translational reporter gene also showed eightfold increase in beta-galactosidase activity after the heat shock induction. Heat-inducible transcription start sites of the dnaK gene, revealed by primer extension analysis, were located 16 and 17 nucleotides upstream from the translational start codon of the dnaK gene, and the predicted promoter sequence showed a homology to the consensus sequence of sigma 32-dependent heat shock promoters of gram-negative bacteria. The upstream region of the dnaK gene did not contain the inverted repeat structure that was involved in the regulation of the heat shock gene of several gram-negative and gram-positive bacteria. Therefore, we conclude that the heat shock regulatory mechanism of the N. europaea dnaK gene may be similar to the sigma 32-dependent mechanism observed in other gram-negative bacteria.


The backstroke swimming start: state of the art.
As sprint swimming events can be decided by margins as small as .01 s, thus, an effective start is essential. This study reviews and discusses the 'state of the art' literature regarding backstroke start biomechanics from 23 documents. These included two swimming specific publications, eight peer-reviewed journal articles, three from the Biomechanics and Medicine in Swimming Congress series, eight from the International Society of Biomechanics in Sports Conference Proceedings, one from a Biomechanics Congress and one academic (PhD) thesis. The studies had diverse aims, including swimmers' proficiency levels and data collection settings. There was no single consensus for defining phase descriptions; and kinematics, kinetics and EMG approaches were implemented in laboratory settings. However, researchers face great challenges in improving methods of quantifying valid, reliable and accurate data between laboratory and competition conditions. For example, starting time was defined from the starting signal to distances as disparate as ∼5 m to 22.86 m in several studies. Due to recent rule changes, some of the research outcomes now refer to obsolete backstroke start techniques, and only a few studies considered the actual international rules. This literature review indicated that further research is required, in both laboratory and competition settings focusing on the combined influences of the current rules and block configuration on backstroke starting performances.


Shell thickness-controlled synthesis of Au@Ag core-shell nanorods structure for contaminants sensing by SERS.
The accessibility of contaminants detection methods is urgently required for environmental and food safety control. In this report, we developed the Au@Ag core-shell nanorod structures for contaminants sensing by surface-enhanced Raman spectroscopy (SERS). The silver shell thickness and the corresponding plasmon wavelength of Au@Ag core-shell nanorods were tuned by changing the coating time and the silver precursor amount. Moreover, these structures exhibit ultra-sensitive detection ability for Nile blue A dye and Fenobucarb pesticide sensing by SERS. Interestingly, the highest Raman enhancement factor is obtained for the Au@Ag core-shell sample with a minimal silver shell thickness leaded by the optimal enhancement of the electromagnetic field of bimetallic structures. Hence, our report demonstrates that the combination of unique features of two plasmonic metals into core-shell structures promises potential applicability in SERS-based analysis.


Investigation of in vivo antioxidant property of Abelmoschus esculentus (L) moench. fruit seed and peel powders in streptozotocin-induced diabetic rats.
Abelmoschus esculentus (L.) Moench. fruit is a commonly consumed vegetable in many countries due to its rich medicinal value. However, till date, in vivo antioxidant property of A. esculentus has not been scientifically documented in animal models. The present investigation was aimed to evaluate the in vivo antioxidant property of A. esculentus (L.) Moench. peel and seed powder (AEPP and AESP) in streptozotocin (STZ)-induced diabetic rats. In rats, acute toxicity assessment of AEPP and AESP at 2 g/kg did not show any toxicity. Diabetes was induced by STZ (60 mg/kg, i.p.) injection and diabetic rats received AEPP (100 and 200 mg/kg) as well as AESP (100 and 200 mg/ kg) orally up to 28 days. At the end of the 28 day, diabetic rats were killed and liver, kidney and pancreas were collected to determine superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), and lipid peroxidation level. In diabetic rats, significant (P < 0.001) reduction of liver, kidney and pancreas SOD, CAT, GPx, GSH levels and increase in thiobarbituric acid reactive substances (TBARS) were observed as compared to normal control rats. Administration of both doses of AEPP and AESP significantly (P < 0.001 and P < 0.01) increased liver, kidney and pancreas SOD, CAT, GPx, GSH levels and decreased TBARS (P < 0.001) levels in diabetic rats compared to diabetic control rats. Our findings confirmed that A. esculentus peel and seed powder has significant in vivo antioxidant property in diabetic rats.


'Deadwells', Urban growth and the threat to public health: an interwar perspective.
The paper reviews the range of threats to public health arising from large-scale housing development in those areas beyond the reach of mains drainage. Citing the limited number of legal precedents available, the paper traces the response made by the City of Norwich, when the purity of its water supplies was found to be threatened in the late 1920s by the cesspools being constructed on the estates near, or just beyond, the city limits. Insights are gained into the administrative and technical devices available to local and central government, as they sought to pioneer improvements in the standards of sanitation and, thereby, the degree to which water supplied could be given protection.


Standard of care and controversies in the adjuvant endocrine treatment of hormone-responsive early breast cancer.
Hormone-responsive early breast cancer is a highly curable disease. In premenopausal women, tamoxifen (TAM) is still the standard treatment. Nowadays, up to 10 years of TAM can be safely administered, especially in women who remain premenopausal. Patients who are considered to be perimenopausal should be initially treated like premenopausal patients. Depending on their serum hormone levels, these patients can be safely switched to an aromatase inhibitor (AI) therapy once the estradiol (E2) and follicle-stimulating hormone (FSH) levels prove the established postmenopausal status. In postmenopausal women, several sequences of endocrine treatment are available. The AI therapy can be induced upfront or sequentially by switching from Tam to AI and vice versa. Extended endocrine therapy, by adding up to 5 years of letrozole after 5 years of TAM, has also been proven to be beneficial in certain patient subgroups. Genotyping of cytochromes such as CYP2D6 did not have any added value in identifying patients who are at higher risk of recurrence. Nevertheless, in all patients the side effects need to be given high consideration. New strategies developed to overcome endocrine resistance are tested in clinical studies. New co-administered drugs such as specific inhibitors of mammalian target of rapamycin (mTOR), Src, or phosphatidylinositol 3-kinase (PI3K) do improve endocrine responsiveness in metastatic disease and will eventually be introduced in the treatment of early breast cancer.


Dyadic Behavior Analysis in Depression Severity Assessment Interviews.
Previous literature suggests that depression impacts vocal timing of both participants and clinical interviewers but is mixed with respect to acoustic features. To investigate further, 57 middle-aged adults (men and women) with Major Depression Disorder and their clinical interviewers (all women) were studied. Participants were interviewed for depression severity on up to four occasions over a 21 week period using the Hamilton Rating Scale for Depression (HRSD), which is a criterion measure for depression severity in clinical trials. Acoustic features were extracted for both participants and interviewers using COVAREP Toolbox. Missing data occurred due to missed appointments, technical problems, or insufficient vocal samples. Data from 36 participants and their interviewers met criteria and were included for analysis to compare between high and low depression severity. Acoustic features for participants varied between men and women as expected, and failed to vary with depression severity for participants. For interviewers, acoustic characteristics strongly varied with severity of the interviewee's depression. Accommodation - the tendency of interactants to adapt their communicative behavior to each other - between interviewers and interviewees was inversely related to depression severity. These findings suggest that interviewers modify their acoustic features in response to depression severity, and depression severity strongly impacts interpersonal accommodation.


Impact of a 21-Gene Recurrence Score Test on the Choice of Adjuvant Chemotherapy for Hormone Receptor-positive Early-stage Breast Cancer: A Prospective Study.
Studies have recommended a 21-gene recurrence score (RS) to optimize adjuvant treatment for patients with early-stage breast cancer (EBC) with hormone receptor-positive (HR+) and human epidermal growth factor receptor-2 negative (HER2-) tumors. This study aimed to prospectively evaluate the impact of this RS in Chinese patients with breast cancer. We prospectively collected 227 patients with EBC with estrogen receptor-positive (ER+) and HER2- tumors. We used one-way analysis of variance to compare the distribution of different risk groups based on a 21-gene RS assay. A Kruskal-Wallis test and either a chi-square or Fisher's exact test were used as appropriate to compare continuous and categorical variables, respectively. Of the 227 eligible women enrolled, 61.2%, 30%, and 8.8% of patients were in the low (≤17), intermediate (18-30) and high (≥31) RS groups, respectively. Of the patients with a low RS, 74.8% were overestimated into the intermediate-risk group by St. Gallen risk. The overall impact of the 21-gene RS was reduced use of chemotherapy (78/227, 34.4%). In addition, Ki67 expression was positively associated with the 21-gene RS (R=0.68). Among patients with ER+/HER2- EBC, the 21-gene RS was an effective method for making a chemotherapy decision. Ki67 was associated with 21-gene RS.


[Bilrubinemia after administration of nicotinic acid (author's transl)].
Nicotinic acid concentrations in the serum over 80 mug/100 ml induce at the start of high dosage nicotinic acid therapy an acute rise in bilirubin to 1-3mg/100 ml serum. Even after postprandial administration there are clearly raised bilirubin concentrations in the serum. After treatment for 1 week with 0.5 g nicotinic acid daily by mouth the bilirubin increase is no longer detectable. The increased bilirubin concentrations in the serum are apparently the result of a transient inhibition of glucuronyl-transferase and is not a symptom of an acute liver disorder. When starting high dosage nicotinic acid therapy, therefore, disorders of the bilirubin metabolism and liver function must be excluded by differential diagnosis in doubtful cases. Further investigations are necessary to see whether the high concentrations of nicotinic acid in the serum cause competition with other drugs for the bilirubin-specific glucuronyl-transferase.


Coxsackie virus in Southern California; isolation of a strain from stools of a patient.
Thirty-three stool specimens from 29 patients were examined for Coxsackie virus by the inoculation of suckling mice. Such a virus, designated "California I," was obtained from two stool specimens collected on successive days from a patient with so-called nonparalytic poliomyelitis. Neutralizing antibodies for the California I strain of Coxsackie virus could not be demonstrated in serum obtained from the patient early in the illness, but were present in convalescent serum.Serum from the patient's daughter, who previously had had a similar illness, neutralized the strain of virus isolated from the father. In pathologic examination of the skeletal muscles of mice infected with the California I virus, lesions typical of those produced by Coxsackie virus, group A, were noted. California I strain of the virus was not neutralized by immune serum prepared from several other strains of Coxsackie virus.


Fabrication of alumina-based metal nanocomposites by pressureless sintering and their mechanical properties.
The processing conditions to prepare nano-sized Cu and Mo dispersed Al2O3 (Al2O3/Cu and Al2O3/Mo) composites by pressureless sintering were explored. The composite powders of Al2O3/Cu and Al2O3/Mo were obtained by the hydrogen reduction of Al2O3/CuO and Al2O3/MoO3 powder mixtures and consolidated by pressureless sintering using infrared heating furnace with a heating rate of 200 degrees C/min. SEM and TEM analyses for the composite showed that the nano-sized metal particles were well distributed and situated on the grain boundaries of the Al2O3 matrix. The nanocomposites, sintered at 1300 to 1500 degrees C for 4 min, showed the relative density of above 90%. Maximum hardness of 16.1 GPa was obtained in Al2O3/Cu nanocomposites with sintering additive of 1 wt% MgO. The sintered nanocomposites exhibited the enhanced fracture toughness of above 4.5 MPa x m(1/2), compared with monolithic Al2O3. The mechanical properties were discussed in terms of observed microstructural characteristics.


MR imaging of in vivo recruitment of iron oxide-labeled macrophages in experimentally induced soft-tissue infection in mice.
To evaluate the feasibility of magnetic resonance (MR) imaging in depicting in vivo recruitment of iron oxide-labeled macrophages in experimentally induced soft-tissue infection. The study was performed according to the guidelines of the U.S. National Institutes of Health and recommendations of the committee on animal research. The protocol was approved by the local institutional review committee on animal care. Experimental soft-tissue infection in 12 mice was induced by inoculation with a 5 x 10(7) colony-forming units of Staphylococcus aureus into the left calf. Peritoneal macrophages were harvested from thioglycollate-treated mice, cultured, and labeled with iron oxide in vitro. The iron oxide-labeled macrophage (macrophage group, n = 6) or iron oxide solution (control group, n = 6) was administered through the tail vein. The left calf of the mice was imaged on days 2 and 3 with a 4.7-T MR unit. Changes in relative signal intensity (SI) and pattern of contrast material enhancement (macrophage distribution) were analyzed and compared with histopathologic findings. Statistical analysis was performed with the Wilcoxon matched-pairs signed rank test. On MR images obtained 24 hours after administration of macrophage labeled with iron oxide, a band-shaped lower SI zone was noted in the abscess wall, which corresponded to the distribution of the iron oxide-labeled macrophages at histopathologic examination. The relative SI of the abscess wall significantly decreased after injection of iron oxide-labeled macrophages (median, 0.42) compared with that before injection (median, 1.23) (P = .031). In the control group, the SI change after administration of iron oxide solution was not significant (P = .688). Homing of intravenously administered iron oxide-labeled macrophages can be monitored with MR imaging and may provide a tool to investigate interactions between macrophages and the invading pathogens.


[Fundamental and clinical studies on cefpiramide in the field of obstetrics and gynecology].
Fundamental and clinical studies were performed on cefpiramide (CPM), a new cephem antibiotic, with following results. Following a single intravenous administration of 1.0 g dose of CPM, the average serum level of CPM was 129.5 micrograms/ml after 1 hour and the half-life in beta-phase was about 5.0 hours. The transfer of CPM to the internal genital organs was found to be good. the transfer of CPM to retroperitoneal fluid was moderate. In clinical trial, CPM was given to 9 patients with obstetrical and gynecological infection. Efficacy was excellent in 1 case and good in 6 cases (effectiveness rate: 77.8%). No side effects were observed. In laboratory findings, a mild elevation of S-GOT was noted in 1 case.


Application of domestic microwave for urgent histopathology reporting: an evaluation.
Rapid diagnosis of histopathological material is becoming increasingly desirable. In neuropathology, crush smear preparation and frozen section diagnosis of tissues removed during operative procedures, have remained as essential tools for rapid diagnosis. Microwave technology has been introduced into the field of tissue processing and staining in past decade. Now-a-days even automated microwave assisted rapid tissue processors are available. In our study we have analysed the use of a domestic microwave (cost approximately Rs.5000) for urgent histoprocessing (30 minutes). This could be useful in small laboratories or the ones which are in the phase of establishing the department as the procedure is much more economical than obtaining a frozen section (which requires a cryostat worth 3-6 lakhs) and the interpretation of the section obtained does not require any extra experience as these resemble the routinely processed tissue sections. The advantages and limitations of the procedure have been discussed.


Determination of Carrier Polarity in Fowler-Nordheim Tunneling and Evidence of Fermi Level Pinning at the Hexagonal Boron Nitride/Metal Interface.
Hexagonal boron nitride (h-BN) is an important insulating substrate for two-dimensional (2D) heterostructure devices and possesses high dielectric strength comparable to SiO2. Here, we report two clear differences in their physical properties. The first one is the occurrence of Fermi level pinning at the metal/h-BN interface, unlike that at the metal/SiO2 interface. The second one is that the carrier of Fowler-Nordheim (F-N) tunneling through h-BN is a hole, which is opposite to an electron in the case of SiO2. These unique characteristics are verified by I- V measurements in the graphene/h-BN/metal heterostructure device with the aid of a numerical simulation, where the barrier height of graphene can be modulated by a back gate voltage owing to its low density of states. Furthermore, from a systematic investigation using a variety of metals, it is confirmed that the hole F-N tunneling current is a general characteristic because the Fermi levels of metals are pinned in the small energy range around ∼3.5 eV from the top of the conduction band of h-BN, with a pinning factor of 0.30. The accurate energy band alignment at the h-BN/metal interface provides practical knowledge for 2D heterostructure devices.


How large must a dose-optimization trial be?
Recently promulgated Draft Guidance from the US Food and Drug Administration Oncology Center of Excellence (OCE) recommends randomized, parallel dose-response trials for "dose optimization," but with vaguely stated aims that engage none of the statistical principles which typically attend randomization. Here, I advance a criterion for reasonable precision of such trials, and examine its implications for minimum enrollment, within a utility-based framework that acknowledges interindividual heterogeneity simultaneously in pharmacokinetics/pharmacodynamics and in the subjective evaluation of efficacy-toxicity trade-offs. Even when designed and conducted under ideal circumstances, reasonably sized trials of the kind advocated by OCE may need to enroll many hundreds of participants.


[High dose rate brachytherapy: a potentially curative treatment for small invasive T1N0 endobronchial carcinoma and carcinoma in situ].
High dose rate brachytherapy (HDR-BT) is an option for treatment of small invasive endobronchial carcinoma and carcinoma in situ. This retrospective study describes the results of 33 consecutive patients treated with curative intent and followed up for more than one year. Between July 1994 and October 1999, 35 tumours were treated with HDR-BT alone using a standard protocol delivering 6 fractions of 5 Gy delivered across 1cm from the catheters over 3 to 6 weeks. In 31 patients, surgical treatment was ruled out because of histology (in situ carcinoma), history of pneumonectomy or significant co-morbidity. Two patients were treated for positive resection margins following pneumonectomy. All the tumours were Tis or T1 N0. The locations of tumours were: trachea - 2, main bronchus - 5, lobar - 20, and segmental - 8. Only one catheter was needed in 15 cases, 2 in 13 cases, 3 in 6 cases and 4 in 1 case. The median follow-up was 17 months (range, 5-53 months). The recurrence-free rate was 94.3% at 2 months and 86.2% at 6 months after the treatment. 15 patients (45.5%) developed local recurrence at a median time of 9 months. Three patients developed metastases. The 1-year and 2-year overall survival rate were 71.4% and 53.8% respectively and specific survival rates were 69.4% and 59%. One patient developed an acute pneumothorax, and late complications included 6 infections and 12 bronchial stenoses. There were no episodes of haemoptysis nor lethal complications. With strict selection criteria, HDR-BT can be a curative treatment for early invasive or in situ endobronchial carcinoma without serious toxicity. It is therefore a good alternative treatment with curative intent for inoperable patients.


No evidence for participation of non-adrenergic non-cholinergic subtances in brain death-related hemodynamic deterioration of the feline potential heart donor.
To onset of brain death (BD) is associated with a hyperdynamic cardiovascular response caused by the acute sympathetic release of catecholamines. This is followed by progressive hemodynamic deterioration which may preclude heart donation for transplantation. The mechanism of the hemodynamic collapse is not fully understood. Changes in plasma concentrations of non-adrenergic non-cholinergic (NANC) substances, neuropeptide-Y (NP-Y, a vasoconstrictor) and the vasodilators calcitonin gene-related peptide (CGRP) and substance P (SP), were studied in relation to BD-related hemodynamic alterations. Cats (6 BD and 6 controls (C)) were studied for 6 h. Heart rate (HR) and mean arterial pressure (MAP) were monitored. BD was induced at t = O min. At t = -5, 15, 60, 180 and 360 min, 5 ml arterial blood samples were taken. The plasma was collected and analyzed. The correlations between MAP and NANC levels were calculated. In the BD cats a maximal and significant increase in HR and MAP was observed at t = 2 min. HR returned to basal levels at t = 20 min and remained at that level. However, MAP deteriorated progressively to 53 +/- 8 mmHg (p 0.001 vs C) at/ = 360 min. NP-Y had increased from 59.7 +/- 2.5 to 110 +/- 20.2 pmol/l (p 0.05 vs C) at t = 15 min, had returned to basal value at t = 60 min and remained at that level. CGRP levels were lower and SP levels did not change vs C but both showed a trend towards higher levels at t = 360 min. The correlations between MAP and NP-Y, CGRP and SP appeared to be not significant. No evidence for participation of NANC substances could be demonstrated in brain death-related hemodynamic deterioration of the feline potential heart donor.


[Pilot-scale cultivation of Spirulina plantensis with digested piggery wastewater ].
The swine waste pretreated with coagulation sedimentation was used for the outdoor pilot-scale cultivation of Spirulina platensis isolated from digested piggery wastewater (DPW) in a raceway pond. The growth of S. platensis and removal of nitrogen/ phosphorus were studied, moreover, the conversion efficiency of total nitrogen (TN) or total phosphorus (TP) from DPW to S. platensis was calculated. On this basis, the existing problems and countermeasures during outdoor pilot-scale culture were analyzed and summarized combined with the laboratory research. We conducted 6 batches culture experiments, only 3 of which could reach the S. platensis harvest requirements (D560 >0. 8). Meanwhile, the 3 successful batches achieved removal of COD, ammonia nitrogen, TN, TP with corresponding 28. 6% -48. 5% , 0.4% -48. 5% , 41. 8% -48. 6% , 14. 3% -94. 5% , and the conversion efficiency of TN or TP from DPW to S. platensis reached 12. 1% -98. 5% , 21.2% -83.7% , respectively. High concentration of ammonia nitrogen and insect attack of remaining egg hatching in the pretreated swine waste were the main factors to cause the slow-growing of the 3 batches of S. platensis. Therefore, it is highly necessary for the removal of ammonia nitrogen with biological treatment technology and insect eggs with membrane to achieve a stable high productivity.


Physiopathologic atlas of thyroid scintigraphy.
Nuclear medicine is an excellent example of functional imaging. It has an established role in the evaluation and management of thyroid disorders. The physiologic and pathologic basis of radiotracer based thyroid imaging has been presented in this article. The same principles apply to the treatment of thyroid disorders using radioactive iodine.


Mutual interplay between ArcA and σE orchestrates envelope stress response in Shewanella oneidensis.
To survive and thrive in harsh and ever-changing environments, intricate mechanisms have evolved for bacterial cells to monitor perturbations impacting the integrity of their envelope and to mount an appropriate response to contain or repair the damage. In this study, we report in Shewanella oneidensis a previously undescribed mechanism for the envelope defect resulting from the loss of Arc, a two-component transcriptional regulatory system crucial for respiration. We uncovered σE , a master regulator establishing and maintaining the integrity of the cell envelope in γ-proteobacteria, as the determining factor for the cell envelope defect of the arcA mutant. When ArcA is depleted, σE activity is compromised by enhanced production of anti-σE protein RseA. Surprisingly, S. oneidensis σE is not essential for viability, but becomes so in the absence of ArcA. Furthermore, we demonstrated that there is an interplay between these two regulators as arcA expression is affected by availability of σE . Overall, our results underscore functional interplay of regulatory systems for envelope stress response: although each of the systems may respond to perturbation of particular components of the envelope, they are functionally intertwined, working together to form an interconnected safety net.


Synbiotics and the mucosal barrier in critically ill patients.
Outcome in severe and critical illnesses is strongly related to premorbid conditions: the strength of the mucosal barriers, the innate immune system, and the built-in resistance to disease. Early risk factors and determinants of poor outcome are factors such advanced age; impaired premorbid health status, especially diabetes and high body mass index (obesity); and immunosuppressive treatments. Combined supplementation of bioactive fibers and lactic acid bacteria (synbiotics) directly and indirectly influences several of these factors. Determinants for poor outcome are degree of oxidative stress, neutrophil activation, and infiltration of tissues, especially in the lungs. Attempts at early reduction of the exaggerated inflammatory storm and limitation of further impairment of the immune function are always given the highest priority. The supply of live lactic acid bacteria and plant fibers can dramatically reduce the hyperinflammation and also the infiltration by neutrophils of organs such as the lungs. New and efficient autopositioning and regurgitation-resistant feeding tubes provide instruments for the early supply of enteral nutrition with immune-boosting antioxidants and synbiotics. A meticulous choice of probiotic lactic acid bacteria is recommended because only a small minority of the lactic acid bacteria survive the harsh environment of the upper gastrointestinal tract, ferment strong semiresistant fibers such as inulin, and have the ability to control inflammation and eliminate unwanted pathogens, such as antibiotic-resistant microorganisms and Clostridium difficile.


Emergence of a thread-like pattern with charged phospholipids on an oil/water interface.
The spontaneous formation of a thread-like pattern with negatively charged lipids on an oil/water interface is reported. An analysis of the time-dependent change at the interface observed by fluorescence microscopy revealed that the thread-like pattern is generated through a two-step mechanism. First, inverted lipid micelles in the bulk-oil phase gradually diffuse onto the oil/water interface. Next, the micelles are adsorbed on the interface and self-assemble to form the thread-like pattern. The essential characteristics of this pattern formation are theoretically reproduced by a simple Monte Carlo simulation that takes into account the kinetics in the coalescence of charged micelles on a 2D interface.


Management options for the child with spastic cerebral palsy.
Knowledge of spasticity management for the child with cerebral palsy begins with understanding how cerebral palsy and spasticity are defined and related. The next step is learning what the treatment options are and how they can impact the child. There are many strategies for managing spasticity. This article focuses on pharmacologic and surgical approaches. Pharmacologic is further subdivided into medications taken by mouth, given through an injection (Botox) or delivered by a pump (baclofen). Surgery includes neurosurgical and orthopaedic procedures. Each treatment is reviewed using rationale, patient selection, delivery methodology, and management technique citing the advantages and disadvantages of each modality.


Some antiphospholipid antibodies bind to various serine proteases in hemostasis and tip the balance toward hypercoagulant states.
The body has an elaborate system that maintains blood circulation and rapidly stops bleeding when vessels are damaged. Abnormalities that disrupt this balance may lead to thrombosis. While beta(2)-glycoprotein I is generally accepted as the major antigen for antiphospholipid antibodies in the antiphospholipid syndrome, our accumulated studies show that some antiphospholipid antibodies bind homologous enzymatic domains of several serine proteases involved in hemostasis and fibrinolysis. Functionally, some of the protease-reactive antiphospholipid antibodies hinder anticoagulant regulation and resolution of clots, thus tip the balance toward thrombosis. Intriguingly, several serine protease-reactive antiphospholipid antibodies also react with beta(2)-glycoprotein I, and interactions between antiphospholipid antibodies and antigens are cross-inhibited, indicating that these antiphospholipid antibodies recognize conformational epitope(s) on beta(2)-glycoprotein I and target serine proteases. Viewed as a whole, these results extend previous reports that antiphospholipid antibodies bind to various hemostasis factors, and provide a new perspective about some antiphospholipid antibodies in terms of their binding specificities and related functional properties in promoting thrombosis.


Ghrelin and des-octanoyl ghrelin promote adipogenesis directly in vivo by a mechanism independent of the type 1a growth hormone secretagogue receptor.
Ghrelin promotes fat accumulation, despite potent stimulation of the lipolytic hormone, GH. The function of the major circulating isoform of ghrelin, des-octanoyl ghrelin, is unclear, because it does not activate the GH secretagogue receptor (GHS-R1a) and lacks the endocrine activities of ghrelin. We have now addressed these issues by infusing ghrelin, des-octanoyl ghrelin, or synthetic GHS-R1a agonists into three rat models with moderate, severe, or total GH deficiency. We show that in the context of significant GH secretion, the adipogenic effect of systemic ghrelin infusion is pattern dependent. However, this adipogenic action is not mediated by the pituitary hormones. Using a novel unilateral local infusion strategy, we demonstrate that ghrelin promotes bone marrow adipogenesis in vivo by a direct peripheral action. Surprisingly, this effect was also observed with des-octanoyl ghrelin, whereas a potent synthetic GHS-R1a agonist was ineffective. Thus, these adipogenic effects are mediated by a receptor other than GHS-R1a. This is the first in vivo demonstration of a direct adipogenic effect of des-octanoyl ghrelin, a major circulating form of ghrelin that lacks GH-releasing activity. We suggest that the ratio of ghrelin and des-octanoyl ghrelin production could help regulate the balance between adipogenesis and lipolysis in response to nutritional status.


Irreversibility of nutritionally induced NIDDM in Psammomys obesus is related to beta-cell apoptosis.
Psammomys lapses into fully fledged diabetes when maintained on a high-energy diet. Progression to diabetes has been classified into stage A of normoglycemia and normoinsulinemia (<120 mg/ml and 100 mU/L, respectively); stage B of hyperinsulinemia (100-300 mU/L) with marked insulin resistance in the face of normoglycemia; stage C of pronounced hyperinsulinemia with hyperglycemia < or =500 mg/ml; stage D at 6-10 weeks after stage C, featuring further hyperglycemia and loss of insulin. Insulin resistance expressed in Psammomys at stages B and C was demonstrated by nonsuppression of the hepatic gluconeogenesis enzyme phosphoenolpyruvate carboxykinase by the endogenous hyperinsulinemia and by the reduced capacity of insulin to activate muscle and liver tyrosine kinase of the insulin receptor. Diabetes at stage C, but not at stage D, was fully reversed to stage A by restricting the food ration of animals by half (from 14 to 7 g/day) for 10-14 days. We examined islet beta cells of Psammomys in the four stages of progression to diabetes by staining for insulin as well as for apoptosis by the terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) and visualizing the biotin-labeled cleavage sites. Psammomys in stage A had insulin-laden beta cells. In stage B, a hypertrophy and partial insulin depletion of beta cells was evident with negative TUNEL staining. In stage C, beta cells were markedly depleted of insulin, and their number within the islets decreased, but the TUNEL staining was virtually negative. In stage D, beta cells were markedly diminished within the islets, almost void of insulin, showing distinct TUNEL staining of beta cells. These results indicate that prolonged exposure of islets to in vivo hyperglycemia with beta-cell overtaxation induces nuclear disintegration with irreversible damage to the insulin-secretion apparatus. This precludes the return to normalcy by restricting the food intake of Psammomys. The appearance of cells with TUNEL-positive staining may serve as a marker of impending irreversibility of nutritionally induced diabetes.


Malignant salivary gland tumors of the base of the tongue.
We present a 41-year retrospective study of patients with malignant salivary gland tumors of the base of the tongue treated at The University of Texas M. D. Anderson Hospital and Tumor Institute at Houston. This report characterized the patient group, documents their physical findings, analyzes survival, and draws some conclusions regarding clinical course and treatment options. When feasible, surgical resection is the preferred treatment, with planned postoperative radiotherapy when indicated by pathologic findings.


Functional Analysis of Two Odorant-Binding Proteins, MaltOBP9 and MaltOBP10, in Monochamus alternatus Hope.
Odorant-binding proteins (OBPs) are important for the perception of chemical signals by insects. Effective pest management strategies can be developed by understanding the host location mechanism and the physiological functions of OBPs in olfactory detection. In this study, we cloned two OBPs from Monochamus alternatus, where MaltOBP9 was highly expressed in multiple insect tissues and MaltOBP10 was highly expressed in the female antenna according to the results of qRT-PCR. The recombinant proteins were successfully purified in vitro. Immunocytochemistry indicated the high expression of MaltOBP9 and MaltOBP10 in the sensillum lymph of sensilla basiconica, sensilla trichodea, sensilla auricillica, and sensilla chaetica, thereby demonstrating their broad participation in semiochemical detection. Both proteins were localized in the inner cavity of mechanoreceptors and they exhibited broad binding abilities with volatiles from pine bark according to fluorescence competitive binding assays. Due to its broad binding ability and distribution, MaltOBP9 may be involved in various physiological processes as well as olfactory detection. MaltOBP10 appears to play a role in the fundamental olfactory recognition process of female adults according to its broad binding ability. These findings suggest that OBPs may have various physiological functions in insects, thereby providing novel insights into the olfactory receptive mechanism.


[Psychosocial climate in maternity hospitals from the perspective of parturients II. Predictors of womens satisfaction with perinatal care in the Czech Republic].
To identify the key determinants of parturients satisfaction with care provided in the Czech maternity hospitals and to draw up recommendation for good practice. Original study. Department of Psychology, Faculty of Philosophy, Charles University, Prague. Statistical analysis of data from the representative sample of Czech parturients (n = 1195) who gave birth from 2005 to 2012 in Czech maternity hospitals was conducted. Ordinal logistical regression (cumulative logit model) was used to identify predictors of womens satisfaction with intrapartum and postpartum care and their willingness to return and give birth in the same hospital as well as to recommend the hospital to others. The independent variables were the individual items of the KLI-P questionnaire measuring psychosocial climate in maternity hospitals and socio-demographic and anamnestic characteristics of parturients. Among the most important determinants of parturients satisfaction with care at delivery unit were well-timed provision of information concerning a treatment plan (OR = 2,79; p < 0,0001), privacy during the first stage of labour (OR = 2,81; p < 0,0001), kind and helpful attitude of physicians (OR = 2,67; p < 0,0001) and confidence in physicians (OR = 2,68; p = 0,0001). Among the most important determinants of satisfaction with care at after-birth unit were well-timed provision of information concerning a treatment plan (OR = 2,25; p < 0,0001), active breastfeeding support (OR = 2,19;p < 0,0001), availability of caregivers (OR = 2,16;p < 0,0001), multiparity (OR = 1,52; p = 0,0001), respect shownby staff employed in mother care (OR = 2,02; p = 0,0004) and kind and helpful attitude of staff employed in newborn care (OR = 1,86; p = 0,0005). When considering the future place of birth and recommendation of the hospital to others, women predominantly take into account the care provided at delivery unit. Intrapartal care evaluation was affected to a lesser degree by satisfaction with midwives as compared to satisfaction with physicians. Analyses of the most important predictors of satisfaction with perinatal care indicate the need for practice to focus on enhancing psychosocial competences (particularly communication skills) of health care providers, more active breastfeeding support and communication of consistent information (especially concerning newborn care) by caregivers at after-birth unit.


Benzo[a]pyrene-7,8-diol-9,10-epoxide suppresses the migration and invasion of human extravillous trophoblast HTR-8/SVneo cells by down-regulating MMP2 through inhibition of FAK/SRC/PI3K/AKT pathway.
Moderate invasion of trophoblasts into the endometrium is crucial for successful pregnancy. Benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE) is a carcinogenic metabolite of benzo[a]pyrene which causes various diseases. We investigated the effects of BPDE on migration and invasion of trophoblast HTR-8/SVneo cells. Migration and invasion of cells exposed to 0.25-1.0μM BPDE for 24h were significantly inhibited. Moreover, tube formation of human umbilical vein endothelial cell (HUVEC) was also significantly reduced after incubation with HTR-8/SVneo cells treated with 0.5-1.0μM BPDE. The protein and mRNA levels of FAK, SRC, PI3K, p-PI3K, AKT, p-AKT, endothelial nitric oxide synthase (eNOS) and its activity, and matrix metalloproteinase 2 (MMP2) significantly decreased with increasing BPDE concentration. The presence of SC79, activator of AKT, partially attenuates the inhibition effect of BPDE on migration and invasion, confirming the involvement of AKT pathway. Thus, BPDE suppresses migration and invasion of human trophoblast HTR-8/SVneo cells by inhibiting the expression of FAK, SRC and PI3K, consequently down-regulating PI3K/AKT signaling pathway. This study reveals the mechanism of Polycyclic aromatic hydrocarbons-inhibited migration and invasion of trophoblast, and enhanced our experimental understanding of the adverse effects of PAHs on embryo implantation in early pregnancy.


Noninvasive assessment of right ventricular diastolic function by electrical impedance tomography.
Electrical impedance tomography (EIT) offers the possibility to study blood volume changes within the right atrium during the cardiac cycle. The aim of this study was to determine the applicability of EIT in the assessment of right ventricular diastolic function in COPD. By means of region of interest analysis, impedance changes within the right atrium during the cardiac cycle were plotted as a function of time. As a diastolic index of the right ventricle, the right atrium emptying volume (RAEV), defined as the ratio between the volume change during the rapid filling phase relative to the total ventricular filling volume, was calculated. In a first study, the validity of the EIT method was assessed by comparison of the RAEV measured by EIT and MRI in a group of eight patients with severe COPD and seven control subjects. A second study was undertaken to assess the relation between RAEV and pulmonary artery pressure in a group of 27 patients measured by right-sided heart catheterization. The correlation coefficient between RAEV measured with MRI and EIT was 0.78. The difference between RAEV measured by MRI and EIT was 8.3 +/- 15.7% (mean +/- SD) for the control subjects and 3.5 +/- 10.9% for the COPD patients. RAEV values measured by EIT and MRI were larger in the control group (47.1 +/- 7.6%) compared with the patient group (38.1 +/- 10.4%). There was a clear nonlinear relationship between RAEV and the pulmonary artery pressure (y = 315 x-0.64, r = 0.83, p < 0.001). Our results indicate that RAEV measured by EIT is a useful noninvasive and inexpensive method for assessing right ventricular diastolic function in COPD patients.


A quartz crystal microbalance (QCM)-based easy setup device for real-time mass change detection under high-power RF plasma.
Sensing technologies serve a crucial role in monitoring and testing surface properties in biosensors, thin films, and many other industries. Plasma treatments are routinely used in most of these technologies to modify the surfaces of materials. However, due to the high radio frequency (RF) noise in plasma processes, real-time surface tracking is still rather difficult. In this study, we aim to construct an easy-to-set up mass change detection system capable of operating under RF plasma conditions. For this purpose, we have presented a novel technique that utilizes the quartz crystal microbalance sensor to detect mass changes in different plasma environments. The constructed device was then tested under 13.56 MHz, 100 W plasma atmosphere. The results showed that the resonance frequency of a crystal was successfully measured with 1.0 Hz resolution under the impact of plasma-induced high power of RF noise. Moreover, as a preliminary study, we used ethylenediamine (EDA) to track changes in resonance frequency under plasma conditions and observed noise-free signals in frequency-voltage curves. Furthermore, the system's sensitivity was found to be 3.8 ng/Hz, with a test molecule (EDA) deposition of about 380 ng in the RF plasma atmosphere. Overall, this study focused on creating a relatively new approach for detecting the real-time mass change in a strong RF environment, which we believe could be an improved and easy-to-set up technique for plasma-based processes such as surface coating, etching, and activation.