Histoculture drug response assay for gefitinib in non-small-cell lung cancer.
There are many predictive factors for gefitinib sensitivity, including epidermal growth factor receptor (EGFR) gene mutation, EGFR copy number, and k-ras mutation. To investigate all of them is too expensive. We evaluated the chemosensitivity for gefitinib in non-small-cell lung cancer (NSCLC) using a histoculture drug response assay (HDRA). Surgically resected fresh tumor specimens from 22 patients with NSCLC were used. There were 13 male and 9 female patients, ranging in age from 49 to 84 (average 70) years old. Sixteen patients (73%) were smokers. Sixteen adenocarcinomas, four squamous cell carcinomas, and two other histological types were included. Small pieces of viable cancer tissue were placed on the collagen gel and then cultured for 7 days in the presence of gefitinib. The HDRA was successful in all specimens. A dose-response relation was observed between inhibition rates and gefitinib concentration (p = 0.016). The inhibition rate at 20 microg/ml (IR(20)) in adenocarcinoma without smoking (39.2% +/- 35.1%, n = 6) was higher than that with smoking (2.2% +/- 5.0%, n = 10, P = 0.001) and that of nonadenocarcinoma (16.9% +/- 23.6%, n = 6, P = 0.09). Gene mutation analysis was performed in two of three adenocarcinomas without smoking, which showed especially high IR(20) values, and sensitizing mutations were observed in these specimens. A cutoff inhibition rate of approximately 40%-50% appeared to be suitable for a concentration of 20 microg/ml. HDRA appears to be applicable for evaluating sensitivity to gefitinib in NSCLC. It provides a convenient method for predicting the response to gefitinib in patients with NSCLC whose fresh tumor specimens are available.


Crystallization of medium-length 1-alcohols in mesoporous silicon: an x-ray diffraction study.
The linear 1-alcohols n-C(16)H(33)OH, n-C(17)H(35)OH, n-C(19)H(39)OH have been imbibed and solidified in lined up, tubular mesopores of silicon with 10 and 15 nm mean diameters, respectively. X-ray diffraction measurements reveal a set of six discrete orientation states ("domains") characterized by a perpendicular alignment of the molecules with respect to the long axis of the pores and by a fourfold symmetry about this direction, which coincides with the crystalline symmetry of the Si host. A Bragg peak series characteristic of the formation of bilayers indicates a lamellar structure of the spatially confined alcohol crystals in 15 nm pores. By contrast, no layering reflections could be detected for 10 nm pores. The growth mechanism responsible for the peculiar orientation states is attributed to a nanoscale version of the Bridgman technique of single-crystal growth, where the dominant growth direction is aligned parallel to the long pore axes. Our observations are analogous to the growth phenomenology encountered for medium length n -alkanes confined in mesoporous silicon [A. Henschel, T. Hofmann, P. Huber, and K. Knorr, Phys. Rev. E 75, 021607 (2007)] and may further elucidate why porous silicon matrices act as an effective nucleation-inducing material for protein solution crystallization.


Group additivity calculations of the thermodynamic properties of unfolded proteins in aqueous solution: a critical comparison of peptide-based and HKF models.
A recent paper in this journal [Amend and Helgeson, Biophys. Chem. 84 (2000) 105] presented a new group additivity model to calculate various thermodynamic properties of unfolded proteins in aqueous solution. The parameters given for the revised Helgeson-Kirkham-Flowers (HKF) equations of state for all the constituent groups of unfolded proteins can be used, in principle, to calculate the partial molar heat capacity, C(o)p.2, and volume, V2(0), at infinite dilution of any polypeptide. Calculations of the values of C(o)p.2 and V2(0) for several polypeptides have been carried out to test the predictive utility of the HKF group additivity model. The results obtained are in very poor agreement with experimental data, and also with results calculated using a peptide-based group additivity model. A critical assessment of these two additivity models is presented.


Histologic features of surgically removed fallopian tubes.
The fallopian tube is a common specimen in a pathology laboratory. It may be examined either alone as a salpingectomy or tubal ligation specimen, or as part of a more complex specimen from a hysterectomy and/or oophorectomy operation. Although the common histologic findings in the fallopian tube have been described previously, to our knowledge no study has documented the frequency of histologic changes in fallopian tubes removed for all reasons or associations with clinical history. Hematoxylin-eosin-stained slides from 287 fallopian tube specimens were reviewed without knowledge of the clinical history. Three categories and associated subcategories of histologic findings were identified (listed in descending order of frequency): stromal and architectural alterations (fibrosis, intramuscular edema, cellular luminal contents, inclusion cysts, Walthard nests, pigmentosis tubae, Wolffian duct remnants, decidualized stroma, endosalpingiosis, and metastatic carcinoma), epithelial characteristics (cytologic atypia, vacuolization, metaplasia, and tufting), and inflammatory changes (intramuscular mast cells, plasma cells, neutrophils, and lymphoid follicles). Histologic findings were correlated with clinical history, surgery type, and age. Intramuscular edema was identified in 12.5% of specimens, most frequently in postpartum women. Plical fibrosis (35.5% of specimens), epithelial atypia (7.3%), epithelial vacuolization (6.6%), and epithelial tufting/stratification (3.5%) correlated with increased patient age. Inflammatory cells were relatively common; 69% of specimens contained intramuscular mast cells, 19.9% had stromal plasma cells, 10.5% had neutrophils, and 2.1% had lymphoid follicles. This study provides data that may be valuable for surgical pathologists involved in identifying and characterizing common histologic changes in surgically removed fallopian tubes.


Massive acroosteolysis in adult T-cell leukemia/lymphoma.
Adult T-cell leukemia/lymphoma is a relatively uncommon disease, most often found in Japan, the Caribbean, the southeastern United States, and South America. To date there have been few reports of its skeletal manifestations. A case is reported in a 44-year-old man in which a short history of swelling of the hands and feet and painful motion in the fingers was followed by the rapid development of severe acroosteolysis.


Metabolism of ethylbenzene in the rat during long-term intermittent inhalation exposure.
After exposure of rats to atmospheres of 50, 300 or 600 p.p.m. ethylbenzene six hours/day, five days/week, for a max. of 16 weeks, the concn. of ethylbenzene in perirenal fat and the urinary excretion of 1-phenylethanol, omega-hydroxyacetophenone, mandelic, phenylglyoxylic, hippuric and phenaceturic acids were measured at the second, fifth and ninth weeks. Excretion of metabolites into urine increased in a dose-related manner, but less than linearly. The level of exposure, but not the duration of exposure, markedly affected the pattern of the metabolites in the urine. The concn. of ethylbenzene in perirenal fat was low at 50 p.p.m., high at 300 p.p.m. and higher still at 600 p.p.m., but not in proportion to the increased dose.


[Infection following surgery of the gastrointestinal tract in newborn infants].
In a retrospective study we examined the postoperative course of 642 children who had been operated on during the newborn period. 247 of them had been operated on for disorders of the gastrointestinal tract. 27.5% of these developed septicaemia: We showed that the frequency of sepsis could be reduced by perioperative antibiotic cover in all diseases with the exception of necrotising enterocolitis where antibiotic treatment was performed. Septicaemic courses were most frequent in premature infants and in those with necrotising enterocolitis. These results will be examined further in a subsequent prospective study.


Frequency analysis of functional Ig C epsilon gene expression in the presence and absence of interleukin 4 in lipopolysaccharide-reactive murine B cells from high and low IgE responder strains.
Nonresponder SJL mice produce low levels of antigen-specific IgE after immunization, compared to responder strains. Young athymic BALB/c nude mice are unable to produce antigen-specific or total IgE in their serum. These mice also have very numbers of background IgE-secreting cells in their lymphoid organs. High-responder BALB/c mice do have substantial numbers of background IgE-secreting cells while low-responder AKR mice show intermediate numbers. Similar differences were found when analyzing lipopolysaccharide (LPS)-reactive B cells in cell suspensions of spleen and bone marrow in limiting dilution cultures. Limiting dilution analysis of T cell-depleted splenic B cell cultures revealed that the defective IgE production in SJL mice is not due to an intrinsic B cell defect. This defect can be substantially overcome by addition of exogenous interleukin 4 (IL4) to these cultures. Furthermore, it was shown in limiting dilution cultures that SJL thymocyte feeder cells were able to suppress IgE production by LPS-activated high-responder BALB/c B cells. The addition of IL4 or neutralizing antibodies against IL4 or interferon-gamma to these cultures helped to overcome this suppressive effect to a large extent. We conclude that different IgE responder types are caused, at least in part, by a defective IL4 production or by a defect in the TH2 system that is functionally detectable at the level of thymocytes.


Lymphoscintigraphy and gamma probe-guided surgery in papillary thyroid carcinoma: the sentinel lymph node concept in thyroid carcinoma
The authors report the use of lymphoscintigraphy and gamma probe-guided resection of the sentinel lymph node in a 65-year-old woman with clinically and cytologically indicated metastasizing papillary thyroid carcinoma. The results of the preoperative lymphoscintigraphy corresponded well with FDG PET and histologic findings, which gives promise of its validity in thyroid carcinoma. With experience in ultrasound-guided fine-needle aspiration biopsy, this method can be performed without any serious side effects for the patient. The validity of the sentinel lymph node concept in thyroid carcinoma and a possible improvement of nodal staging and local recurrence rate must still be proved.


Information transfer and communication in surgery: a systematic review.
We conducted a systematic review of published literature to gain a better understanding of interprofessional information transfer and communication (ITC) in hospital setting in the field of surgical and anesthetic care. Communication breakdowns are a common cause of surgical errors and adverse events. Medline, Embase, PsycINFO, Cochrane Database of Systematic Reviews, and hand search of articles bibliography. Of the 4027 citations identified through the initial electronic search and screened for possible inclusion, 110 articles were retained following title and abstract reviews. Of these, 38 were accepted for this review. Data were extracted from the studies about objectives, clinical domain, methodology including study design, sample population, tools for assessing communication, results, and limitations. Information transfer failures are common in surgical care and are distributed across the continuum of care. They not only lead to errors in care provision but also lead to patient harm. Most of the articles have focused on ITC process in different phases especially in operating room. None of the studies have looked at whole of the surgical care process. No standard tool has been developed to capture the ITC process in different teams and to evaluate the effect of various communication interventions. Uses of standardized communication through checklist, proformas, and technology innovations have improved the ITC process, with an effect on clinical and patient outcomes. ITC deficits adversely affect patient care. There is a need for standard measures to evaluate this process. Effective and standardized communication among healthcare professionals during the perioperative process facilitates surgical safety.


A Reduction in Intracellular Reactive Oxygen Species Due to a Mutation in NCF4 Promotes Autoimmune Arthritis in Mice.
The mechanisms linking deficits in the phagocytic NADPH oxidase 2 (NOX2) complex to autoimmunity are so far incompletely understood. Deficiency in neutrophil cytosolic factor 1 (NCF1) inactivates the NOX2 complex, leading to a dramatic reduction of intra- and extracellular reactive oxygen species (ROS) and enhanced susceptibility to autoimmune disease. The contribution of intracellular NOX2 activity to autoimmune regulation is, however, unknown. Another component of the NOX2 complex, NCF4, directs the NOX2 complex to phagosomal membranes via binding to phosphatidylinositol 3-phosphate (PtdIns3P) and has been proposed to regulate intracellular ROS levels. To address the impact of NCF4 and selective changes in intracellular ROS production on autoimmune inflammation, we studied collagen-induced arthritis (CIA) and mannan-induced psoriatic arthritis-like disease (MIP) in mice lacking NCF4 and mice with a mutation in the PtdIns3P-binding site of NCF4. Targeted deletion of Ncf4 (Ncf4-/-) led to severe defects in overall ROS production due to concomitant reduction of NCF2 and NCF1. These mice displayed delayed neutrophil apoptosis and enhanced innate immune responses, and they developed aggravated CIA and MIP. Disruption of the PtdIns3P-binding site by targeted mutation (Ncf4*/*) resulted in selective defects in intracellular NOX2 activity, which entailed milder effects on innate immunity and MIP but clearly promoted susceptibility to CIA. Innovation and Conclusion: This is, to our knowledge, the first study addressing the development of autoimmunity in an organism with selectively compromised NOX2-dependent intracellular ROS levels. Our data reveal a specific role for NCF4-mediated intracellular ROS production in regulating autoimmunity and chronic inflammation. Antioxid. Redox Signal. 25, 983-996.


Caveolin-1-mediated post-transcriptional regulation of inducible nitric oxide synthase in human colon carcinoma cells.
Reactive oxygen species are now widely recognized as important players contributing both to cell homeostasis and the development of disease. In this respect nitric oxide (NO) is no exception. The discussion here will center on regulation of the inducible form of nitric oxide synthase (iNOS) for two reasons. First, only iNOS produces micromolar NO concentrations, amounts that are high by comparison with the picomolar to nanomolar concentrations resulting from Ca2(+)-controlled NO production by endothelial eNOS or neuronal nNOS. Second, iNOS is not constitutively expressed in cells and regulation of this isoenzyme, in contrast to endothelial eNOS or neuronal nNOS, is widely considered to occur at the transcriptional level only. In particular, we were interested in the possibility that caveolin-1, a protein that functions as a tumor suppressor in colon carcinoma cells (Bender et al., 2002; this issue), might regulate iNOS activity. Our results provide evidence for the existence of a post-transcriptional mechanism controlling iNOS protein levels that involves caveolin-1-dependent sequestration of iNOS within a detergent-insoluble compartment. Interestingly, despite the high degree of conservation of the caveolin-1 scaffolding domain binding motif within all NOS enzymes, the interaction detected between caveolin-1 and iNOS in vitro is crucially dependent on presence of a caveolin-1 sequence element immediately adjacent to the scaffolding domain. A model is presented summarizing the salient aspects of these results. These observations are important in the context of tumor biology, since down-regulation of caveolin-1 is predicted to promote uncontrolled iNOS activity, genotoxic damage and thereby facilitate tumor development in humans.


Subglottic stenosis in children: a conservative approach.
Subglottic stenosis may be either congenital or acquired and is one of the commonest causes of acute and chronic airways obstruction in neonates and infants. Most acquired stenoses result from perinatal intubation. The management of these lesions remains controversial, particularly regarding the timing of surgical intervention. At Alder Hey Children's Hospital a series of 33 patients with subglottic stenosis have been reviewed. A conservative approach, employing long-term tracheotomy as the mainstay of treatment, has achieved a success rate of 72.7%, and only 3 patients have so far needed corrective surgery (9%), of which 1 has been decannulated to date. One patient (3%) died of bronchopulmonary dysplasia. We believe that, where close follow-up is possible, a conservative approach is the method of choice.


Autacoid interactions in the regulation of blood flow in the human placenta.
1. Interactions between autacoids may play important roles in the regulation of blood flow in the foetal placenta. In order to investigate this aspect of placental haemodynamics, human normal-term placentae were perfused in vitro and the responses of the foetal vessels to various combinations of vasoactive agents were determined. 2. Vasoconstriction responses to 5-hydroxytryptamine (5-HT) were potentiated in the presence of endothelin-1 (ET-1), the thromboxane A2-mimetic U46619 and a nitric oxide synthase inhibitor, N-nitro-L-arginine (NOLA), but not in the presence of angiotensin II. 3. N-Nitro-L-arginine caused vasoconstriction of the perfused placenta and indomethacin attenuated this effect and blocked the potentiation of the 5-HT response by NOLA. 4. Indomethacin did not affect ET-1-induced pressure increases and infusion of U46619 had no effect on release of ET-like immunoreactivity into the foetal placental circulation. 5. The present study provides evidence of interactions between several autacoids in human perfused placentae in vitro. These interactions may play important roles in foetal placental haemodynamics in normal or pathological situations.


MiR-610 functions as a tumor suppressor in oral squamous cell carcinoma by directly targeting AGK.
MicroRNA-610 (miR-610) functions as a tumor suppressor in various types of cancers. However, whether miR-610 acted as a functional miRNA in oral squamous cell carcinoma (OSCC) is still largely unknown. The current study was designed to explore the expression pattern and function of miR-610 in OSCC and to investigate the possible molecular mechanisms. Quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) was performed to detect the expression of miR-610 in OSCC tissues and cells lines. The associations between miR-610 expression and clinicopathologic features and prognosis were analyzed. Proliferation, migration, and invasion capacities of OSCC cells were assessed after overexpressing miR-610. The regulation of acylglycerol kinase (AGK) by miR-610 was confirmed by Western blotting, Dual-Luciferase reporter assays and rescue experiments. We found that miR-610 expression was significantly down-regulated in both OSCC tissues and cell lines. Low miR-610 expression was associated with advanced T classification, TNM stage and poorer prognosis of OSCC patients. Functionally, the overexpression of miR-610 significantly suppressed OSCC cells proliferation, migration, invasion and EMT process. Mechanistically, AGK was confirmed to be the downstream target of miR-610 in OSCC cells. Furthermore, forced expression of AGK could rescue the inhibiting roles on cell proliferation and metastasis induced by miR-610 in OSCC cells. Our findings highlight the important role of miR-610 in regulating OSCC progression by targeting AGK, indicating that miR-610 may represent a novel potential therapeutic target and prognostic marker for OSCC.


A unit-based intervention aimed at improving patient adherence to pharmacological thromboprophylaxis.
Pharmacological thromboprophylaxis is necessary among many hospitalised patients to prevent venous thromboembolism (VTE). However, a significant number of clinician-ordered doses are not administered with many doses refused by patients. We aimed to assess the impact and sustainability of a multifaceted intervention to improve medication adherence to pharmacological thromboprophylaxis. The intervention included a standardised nursing response to patient refusal, daily assessment of VTE prophylaxis usage and regular feedback on refusal rates. We conducted a quasi-experimental study of patients admitted between January 2010 and November 2012 to one of six hospital intervention units (three medical and three oncology units) or five control units. The primary outcome was the proportion of VTE prophylaxis doses missed for any reason. A total of 20,208 admissions occurred at the six hospital units during the study period. In the pre-post analysis, the rate of missed and refused doses decreased significantly after the intervention (24.7% to 14.7% and 18.3% to 9.4%, respectively; p value <0.01 for both comparisons). In multiple regression models with interrupted time series analysis, the intervention was associated with an immediate and sustained decrease in missed (adjusted OR 0.64; 95% CI 0.55 to 0.74 and 0.98; 95%CI 0.97 to 0.99) and refused doses (adjusted OR per month 0.58; 95% CI 0.48 to 0.71 and 0.97; 95%CI 0.96 to 0.98). No immediate or sustained reduction in missed or refused doses was observed in the control units. Implementation of a multifaceted intervention resulted in an immediate and sustained decrease in the proportion of missed and refused doses of pharmacological thromboprophylaxis. Efforts aimed at increasing patient adherence are a promising approach to improve rates of VTE thromboprophylaxis administration.


Immunomodulatory effects of Alliums and Ipomoea batata extracts on lymphocytes and macrophages functions in White Leghorn chickens: in vitro study.
We previously described that supplementary garlic, onion and purple sweet potato (PSP) enhance humoral immune response in White Leghorn chickens. In the present in vitro study, we investigated the effects of garlic (GE), onion (OE) and PSP (PSPE) extracts on proliferation, interleukin (IL)-2 and interferon (INF)-γ gene expression of stimulated lymphocytes. The effects on microbicidal activity, reactive oxygen species (ROS) and nitric oxide (NO) productions of stimulated peritoneal macrophages were studied as well. The results showed that GE augmented Concanavalin A (ConA)-induced splenocytes (4, 8 and 16µg/mL) and thymocytes (2, 4 and 8µg/mL) proliferations, and gene expression of IL-2 (8 and 16µg/mL) and INF-γ (16µg/mL). None of the examined extracts had mitogenic effect nor stimulated bursacytes response to phorbol 12-myristate 13-acetate (PMA). Macrophages exhibited superior microbicidal activity and ROS production with GE at 4 and 8µg/mL and with OE at 25.6µg/mL. None of the extracts showed stimulatory effects on NO production. The extracts showed concentration-dependent inhibitory effects on all measured parameters at higher concentrations. Taken together, it is likely that garlic has direct stimulatory effects on immune cell functions, whereas the in vitro inhibitory effects of onion and PSP were likely attributed to high flavonoid contents.


Mastocytosis and atopy: a study of 33 patients with urticaria pigmentosa.
Thirty-three patients with histologically verified urticaria pigmentosa were studied for coexisting atopic disease by means of history, skin prick testing with five common inhalants and serological investigation for total IgE and specific IgE antibodies to five common inhalants. The prevalence of atopy in urticaria pigmentosa was similar to that observed in the normal Swiss population, both on the basis of history (7/33 = 21%) and of positive skin prick tests to common inhalants (12/33 = 36%). However, total serum IgE levels were significantly lower (geometric mean value 16.8 kU/l) than in a control group of 52 Swiss blood donors of comparable age and sex distribution (geometric mean value 43.0 kU/l, t = 2.93, P less than 0.005). Specific IgE antibodies to common inhalants were also observed less frequently in urticaria pigmentosa patients than in controls, although this difference was not statistically significant. Low total and specific IgE values in patients with urticaria pigmentosa may be explained by increased absorption of circulating IgE to abundant tissue mast cells.


Imaging and sensing of cadmium in cells.
Cadmium is one of the highly toxic transition metals for human beings and is known as a human carcinogen. Once humans are exposed to Cd(2+) on a chronic basis, Cd(2+) primarily accumulates in the liver and kidney where it forms complexes with small peptides and proteins via sulfhydryl groups. Complexed Cd(2+) or the ionic Cd(2+) is then taken up by target cells and tissues and exerts the toxicity. However, the question of how non-essential Cd(2+) crosses the cell membranes remains unanswered. Furthermore, the molecular mechanism of Cd(2+)-induced physiological signaling disruption in cells is still not fully elucidated. Investigations of Cd(2+) uptake kinetics, distributions, and concentrations in cells require chemical tools for its detection. Because of the easy use and high spatiotemporal resolution, optical imaging using fluorescence microscopy is a well-suited method for monitoring Cd(2+) in biological samples. This chapter summarizes design principles of small molecule fluorescent sensors for Cd(2+) detection in aqueous solution and their photophysical and metal-binding properties. Also the applications of probes for fluorescence imaging of Cd(2+) in a variety of cell types are demonstrated.


The utility of repeat enzyme immunoassay testing for the diagnosis of Clostridium difficile infection: a systematic review of the literature.
Over the last 20 years, the prevalence of healthcare-associated Clostridium difficile (C. diff) disease has increased. While multiple tests are available for the diagnosis of C. diff infection, enzyme immunoassay (EIA) testing for toxin is the most used. Repeat EIA testing, although of limited utility, is common in medical practice. To assess the utility of repeat EIA testing to diagnose C. diff infections. Systematic literature review. Eligible studies performed >1 EIA test for C. diff toxin and were published in English. Electronic searches of MEDLINE and EMBASE were performed and bibliographies of review articles and conference abstracts were hand searched. Of 805 citations identified, 32 were reviewed in detail and nine were included in the final review. All studies except one were retrospective chart reviews. Seven studies had data on number of participants (32,526), and the overall reporting of test setting and patient characteristics was poor. The prevalence of C. diff infection ranged from 9.1% to 18.5%. The yield of the first EIA test ranged from 8.4% to 16.6%, dropping to 1.5-4.7% with a second test. The utility of repeat testing was evident in outbreak settings, where the yield of repeat testing was 5%. Repeat C. diff testing for hospitalized patients has low clinical utility and may be considered in outbreak settings or when the pre-test probability of disease is high. Future studies should aim to identify patients with a likelihood of disease and determine the utility of repeat testing compared with empiric treatment.


Primary meningeal osteosarcoma of the brain during childhood. Case report.
Primary meningeal osteosarcomas are rare tumors, with only 19 reported cases in the literature; only 4 of these, including the present case, are in pediatric patients. In this report, the authors present the case of an 8-year-old boy with a history of generalized tonic-clonic seizures who was found to harbor a meningeal osteosarcoma within the sylvian fissure. Initial working diagnoses included meningioma and glioma. After tumor enlargement and progressive symptoms, the patient underwent a large frontotemporal craniotomy and complete resection of the lesion, which recurred 6 and 12 months after the initial surgery and was surgically treated after each recurrence. The rarity of primary meningeal osteosarcomas can make their diagnosis difficult, and histopathological evaluation is mandatory for diagnosis. Because of their fast progression, they must be treated aggressively by means of surgery, chemotherapy, and radiotherapy.


A review of cervical cancer screening intervention research: implications for public health programs and future research.
In this paper we review the published literature with respect to cervical cancer screening intervention research. Mass media campaigns appear to work best in promoting cervical cancer screening when multiple media are used, when they promote specific screening programs that eliminate or reduce access barriers, or when they are used in combination with other strategies. Many positive examples of using outreach staff to promote cervical cancer screening, as well as using mobile examination rooms in the community, were found. Substantial evidence that letters mailed to patient populations are efficacious was found, especially in promoting interval screening; however, bulk mailings to nonpatient populations have generally not been successful. Both physician and patient prompts have shown promise as well as opportunistic screenings in both the outpatient and the inpatient settings. In addition, several strategies for reducing loss to follow-up among women with abnormal test results were identified, including telephone follow-up, educational mailouts, audiovisual programs, clinic-based educational presentations and workshops, transportation incentives, and economic vouchers. Of special note is the success of other countries in establishing centralized recall systems to promote interval screening for cervical cancer. Ultimately, such systems could replace the need for opportunistic screening in underserved populations and perhaps many community outreach efforts. It is argued that health departments represent a logical starting point for developing a network of recall systems in the United States for underserved women.


Cardiac function and hematocrit level.
Patients on dialysis have an age-adjusted death rate 3.5 times that of the general population. The most common cause of death in patients on dialysis is cardiovascular disease. We prospectively followed a cohort of 433 patients in three centers for a mean of 41 months. Mean hemoglobin level at the beginning of dialysis was 8.39 (+/- 1.7) g/dL, and the mean hemoglobin level during follow-up was 8.84 (+/- 1.5) g/dL. Using Cox's regression model, we found that anemia predicted mortality independently of age, diabetes mellitus, cardiac failure, hypoalbuminemia, serum creatinine, mean arterial pressure, or echocardiographic heart disease. The independent relative risk (RR) of mortality was 1.18 per 1.0 g/dL decrease in hemoglobin level. Anemia also independently predicted the de novo occurrence of congestive heart failure when the same covariates were controlled for (RR, 1.49 per 1.0 g/dL decrease). Anemia was also independently predictive of heart failure at the start of dialysis (RR, 1.14 per 1.0 g/dL decrease) and heart failure recurrence (RR, 1.25 per 1.0 g/dL decrease). Left ventricular hypertrophy is present in 75% of patients on dialysis at the start of therapy for end-stage renal disease. It independently predicts mortality. Our prospective cohort study identified increasing age, hypertension, and anemia as risk factors for its development. One controlled study and several uncontrolled studies demonstrated improvement (but not complete regression) of elevated left ventricular mass in patients on dialysis treated with recombinant human erythropoietin (epoetin).


Usefulness of serial assessment of natriuretic peptides in the emergency department for patients with acute decompensated heart failure.
The value of natriuretic peptides, both B-type natriuretic peptide (BNP) and N-terminal prohormone brain natriuretic peptide (NTproBNP), for determining diagnosis, severity, and prognosis of emergency department (ED) patients with acute decompensated heart failure (ADHF) has been well documented. Emerging data support the hypothesis that repeated natriuretic peptide determinations in the acute phase of ADHF may assist in confirming the diagnosis, monitoring drug therapy, and evaluating the adequacy of patient stabilization. Data from the authors' group demonstrate that in patients admitted to the ED for acute dyspnea, serial NTproBNP measurement at admission and 4, 12, and 24 hours later was useful in confirming the diagnosis of ADHF compared with patients with chronic obstructive pulmonary disease. Moreover, in the same patients receiving intensive intravenous diuretic therapy, there was a progressive reduction of NTproBNP blood levels from hospitalization to discharge (P<.001), accompanied by clinical improvement and stabilization of heart failure. More recently, the authors also demonstrated that in ADHF patients improving with diuretics, a progressive reduction in BNP levels was observed, starting 24 hours after ED admission and continuing until discharge. Comparing BNP and NTproBNP, there was a significant correlation between NTproBNP and BNP levels but not between NTproBNP's and BNP's percent variation compared with baseline. In ADHF, serial ED measurements of BNP are useful for monitoring the effects of treatment. A reduction in BNP from admission to discharge is indicative of clinical improvement.


Anatomical evidence for interaction of ACTH1-39 immunostained fibers and hypothalamic paraventricular neurons that project to the dorsal vagal complex.
Anatomical evidence is presented for an interaction of ACTH1-39 immunostained fibers and a specific population of hypothalamic paraventricular (PVN) neurons; these neurons project to the dorsal vagal complex (DVC) of brainstem medulla. Bilateral injection of 10% HRP-WGA into DVC is incorporated into nerve terminals and transported retrogradely to cell bodies in the parvocellular subdivision of PVN, as revealed by standard HRP-WGA histochemistry or antibody to wheatgerm agglutinin followed by immunocytochemical techniques. Labeled cells are localized predominantly in the ventral portion of the caudal medial parvocellular subdivision and ventrolaterally in the posterior subnucleus of PVN. Few labeled cells are seen in the anterior parvocellular PVN, rostrally in the medial parvocellular component and in the dorsal cap. HRP-WGA cells are rarely observed in the magnocellular divisions of PVN. Dual-staining immunocytochemical-retrograde tracing techniques in the same tissue section demonstrate ACTH1-39 fibers in intimate anatomical proximity to parvocellular PVN neurons that project to DVC. It is suggested that this interaction may partially account for the known cardiovascular effects of opiocortins and supports the role of the paraventricular nucleus in hypothalamic integration and modulation of cardiovascular control.


Ganser syndrome after solitary confinement in prison: a short review and a case report.
A short review of the Ganser syndrome is given. The condition is a rare, probably dissociative, disorder with transient Vorbeireden as the central symptom. The case of a middle-aged man developing a transient Ganser syndrome after long-term solitary confinement in a remand prison is presented. Systematic investigation of 268 remand prisoners confirms the rarity of the syndrome, as only the case subject had this disorder.


[Diagnostic value of the cortico-medullary contrast on dynamic CT and MRI in chronic renal parenchymal diseases].
Correlation between cortico-medullary contrast (CMC) and dynamic CT or MRI for chronic renal parenchymal diseases was evaluated compared with serum creatinine level (Cr). Forty two kidneys of 23 patients were chronic glomerulonephritis (12), chronic pyelonephritis (12), chronic renal failure (4), and other diseases (14). Thirty two kidneys with low Cr (under 1.6) were demonstrated the good CMC by dynamic CT and T1-weighted image (IR) of 0.5 T. Six with middle of Cr (between 1.6 and 3.0) were showed a decrease in CMC and four with high Cr (over 3.0) had no CMC. CMC correlated with Cr.


The vestibular aqueduct in patients with Meniere's disease. A temporal bone histopathological investigation.
Meniere's disease (idiopathic endolymphatic hydrops) was studied in human temporal bone histology sections. Measurements were made of the area, length, width, angle, position, and external aperture of the vestibular aqueduct in 27 temporal bones of individuals with this disease. These measurements were compared with measurements of the same parameters in 88 normal temporal bones. It was found that small vestibular aqueducts were more often observed in the temporal bones of patients with Meniere's disease than in temporal bones from individuals without this disorder. The difference in size of the vestibular aqueduct in bones with hydrops and normal bones was statistically significant.


The immunologic role of the gastrointestinal tract.
During the past few decades, researchers have shed new light on the role of nutritional support in the immunocompromised critically ill patient. "Nutritional pharmacology" has become the catch phrase of the 1990s due to the impact of selected nutrients on host immune defenses. When feasible, enteral nutrition is preferred to parenteral nutrition to preserve the integrity of the gut mucosal barrier, especially when administered jejunally in the early stages of hypermetabolism. Glutamine and fiber provide necessary fuels for the gastrointestinal tract, whereas arginine and omega-3 fatty acids exert beneficial effects on certain cells of the immune system. Daly et al demonstrated that "enteral nutrition with supplemental arginine, RNA nucleotides and omega-3 fatty acids (Impact, Sandoz Nutrition, Minneapolis, MN) compared with a standard enteral diet, significantly improved immune, metabolic and clinical outcomes (22% mean reduction in length of stay) in UGI cancer patients undergoing surgery." Although more research is needed in the area of nutritional pharmacology, newly available nutrient-specific enteral products (Table 1) provide promise for altering the clinical outcome of immunocompromised patients.


The Interdisciplinary Rehabilitation Care Team and the Role of Physical Therapy in Survivor Exercise.
Rehabilitation professionals offer expertise in functional assessment, treatment of impairments and functional limitations, and disability prevention. To optimize recovery, and often prior to participating in community-based exercise programming, survivors may need rehabilitation services from a range of healthcare professionals, including physiatrists, nurses, nutritionists, psychologists, and speech, occupational, and physical therapists. Survivors with physical impairments and functional limitations may benefit from interdisciplinary rehabilitation and physical therapy, including tailored therapeutic exercise interventions. A literature review was conducted using the key words cancer survivor, cancer rehabilitation, impairment, fatigue, lymphedema, chemotherapy-induced peripheral neuropathy, and exercise. MEDLINE®, EMBASE, Cochrane Database of Systematic Reviews, and CINAHL® databases were searched. Nurses play a critical role in identifying survivors whose function or fitness is compromised to the point where participation in community-based exercise programming would be inappropriate or unsafe. The interdisciplinary rehabilitation care team can help facilitate the survivor's transition to community-based exercise programming.


4-Nitrobenzoate inhibits coenzyme Q biosynthesis in mammalian cell cultures.
Coenzyme Q (Q) is an electron transporter in the respiratory chain and a lipid-soluble antioxidant that decreases in humans with age. Here we show that 4-nitrobenzoate inhibited 4-hydroxybenzoate:polyprenyl transferase (Coq2) in a competitive manner and dose-dependently decreased Q in mammalian cells without accumulation of Q intermediates. As 4-nitrobenzoate neither interfered with mitochondrial respiration nor induced oxidative stress, it should prove a valuable tool for studies on both Q deficiency and Q supplementation.


ZFAS1 knockdown inhibits viability and enhances cisplatin cytotoxicity by up-regulating miR-432-5p in glioma cells.
Long non-coding RNA (lncRNA) zinc finger antisense 1 (ZFAS1) is a novel vital oncogenic lncRNA that is dysregulated in various types of cancers, including glioma. According to TargetScan prediction, miR-432-5p is a target of ZFAS1. Herein, we aimed to determine whether there was a correlation between ZFAS1 and miR-432-5p and to explore their roles in glioma. The expression levels of ZFAS1 and microRNA (miR)-432-5p in clinical tissues and cell lines were measured using RT-qPCR. Cell viability was detected using MTT assay. Cell apoptosis was examined using flow cytometry. The association between ZFAS1 and miR-432-5p was confirmed using luciferase reporter and RNA pull-down assays. Zinc finger antisense 1 expression was up-regulated, while miR-432-5p expression was down-regulated in both glioma tissues and cells. Knockdown of ZFAS1 and miR-432-5p overexpression inhibited cell viability and enhanced the chemosensitivity of glioma cells to cisplatin. MiR-432-5p was a direct target of ZFAS1 in glioma cells. Inhibition of miR-432-5p blocked the effects of ZFAS1 knockdown on cell viability and cisplatin sensitivity. Knockdown of ZFAS1 inhibited the viability and enhanced cisplatin sensitivity via targeting miR-432-5p in glioma cells.


Israeli Arab Muslim women's willingness to be screened for intimate partner violence: A survey.
In the present study, we explored whether the research model based on the Theory of Reasoned Action predicts Israeli Arab Muslim women's willingness to be screened for intimate partner violence at healthcare facilities. Three hundred women completed a questionnaire. Most women (68.4%) expressed willingness to be screened, however, only 16% of them had been screened over the past year. Women's beliefs about screening for intimate partner violence and the support of significant others were found to predict this willingness. The study may constitute an initial foundation for determining national policy with the aim of detecting and eradicating the phenomenon among this unique population.


Endoscopic creation and repair of fetal cleft lip.
In utero repair of several life-threatening malformations in the human fetus is now a clinical reality, yet fetal surgery still poses significant risks to both the mother and the unborn child. Preterm labor is a major problem and is directly related to the large hysterotomy required for fetal exposure. Endoscopic surgical manipulation of the fetus, through small uterine "ports," solves this problem and may eventually permit fetal intervention for non-life-threatening malformations. In this pilot study we demonstrated the feasibility of performing endoscopic surgery on the fetus in situ. A lip incision was created and repaired using endoscopic microsurgical techniques in midgestation fetal lambs. This represents the first application of this technique for in utero fetal intervention.


[Substantiation of patients' length stay in hospital after acute myocardial infarct].
To study and validate the duration of optimal hospital stay for postmyocardial infarction patients and to specify indications for their discharge. The trial enrolled 187 patients with large- and small-focal acute myocardial infarction. The patients were divided into two groups by different speed of activization and hospital stay. There were no significant differences between the groups with different duration of hospital stay by working ability and invalidism. Temporary disability in patients who have undergone standard rehabilitation was longer than in patients on the shorter-program rehabilitation. Performance of exercise tests on day 14 distinguished patients with a favourable long-term prognosis who were candidates for shorter rehabilitation program. The program of quicker rehabilitation (a two-times decrease in the hospital stay) can be applied to patients with uncomplicated myocardial infarction without damage to their health.


A first-principles model for prediction of product dose uniformity based on drug substance particle size distribution.
The unit dose uniformity (UDU) of low-dose drug products can be affected by active pharmaceutical ingredient (API) particle size. UDU relative standard deviation increases as the fraction of large API particles increases and/or as the unit dose decreases. Control of API particle size has traditionally been based on the empirical relationship of d(90) and/or d(50) statistics to drug product uniformity. Several articles have been written that have identified a theoretical relationship between these particle size statistics, dose, and the probability of meeting US Pharmacopeial UDU testing criteria (Huang CY, Ku S. 2010. Int J Pharm 383:70-80; Rohrs B, Amidon G, Meury R, Secreast P, King H, Skoug C. 2006. J Pharm Sci 95(5):1049-1059; Huang CY, Ku S. 2010. J Pharm Sci 99:4351-4362; Yalkowsky SH, Bolton S. 1990. Pharm Res 7(9):962-966). However, these theoretical relationships assume a fixed shape for the API particle size distribution (PSD, i.e., lognormal) and do not account for changes in the distribution shape. A more rigorous method for predicting the effect of a given PSD on UDU is to evaluate the contribution of individual particle size bins on UDU variability. The latter approach is taken in this work, and the derivation reveals that the individual contribution of particles size bins can be expressed completely in terms of a single-particle-size statistic, D[6,3]. D[6,3] is therefore a valid predictor of UDU, regardless of the shape of the PSD (e.g., multimodal) and can form the basis of a particle size control strategy for low-dose drug products.


Testosterone, Sex Hormone-Binding Globulin and Nonalcoholic Fatty Liver Disease: a Systematic Review and Meta-Analysis.
Endogenous sex hormones are associated with the risk of diabetes and metabolic syndrome. Recent studies suggested the role of these hormones in nonalcoholic fatty liver disease (NAFLD). We conducted a systematic review and meta-analysis of observational studies investigating the association between sex hormones and NAFLD. A comprehensive search of the databases of the MEDLINE and EMBASE was performed from inception through April 2016. The inclusion criterion was the observational studies that assessed the association of serum total testosterone (TT) and sex-hormone binding globulin (SHBG) and NAFLD. We calculated pooled effect estimates of TT and SHBG with 95% confidence intervals (CI) comparing between subjects with and without NAFLD by using random-effects model. Sixteen trials comprising 13,721 men and 5,840 women met the inclusion criteria. TT levels were lower in men with NAFLD (MD = -2.78 nmol/l, 95%CI -3.40 to -2.15, I2 = 99%) than in those without. Men with higher TT levels had lower odds of NAFLD whereas higher TT levels increased the odds of NAFLD in women. In both sexes, SHBG levels were lower in patients with NAFLD than controls and this inverse association was stronger in women than men and higher SHBG levels were associated with reduced odds of NAFLD. Our meta-analysis demonstrated a sex-dependent association between TT and NAFLD. Lower TT levels are associated with men with NAFLD and inversely associated with women with NAFLD, whereas higher SHBG levels are associated with lower NAFLD odds in both men and women.


[Preventive effects of multi-glycoside of Tripterygium wilfordii on glomerular lesions in experimental diabetic nephropathy].
To observe the preventive effects of multi-glycoside of Tripterygium wilfordii (GTW) on glomerular lesions in experimental diabetic nephropathy (DN). The DN model of rats was established with streptozotocin (STZ) and intervened with GTW. In the same time, normal, benazepril, and vehicle control groups were set up. After 8 weeks of oral treatment with GTW (50 mg x kg(-1) BW), benazepril (6 mg x kg(-1) BW), and vehicle (physiological saline), the changes of body weight, urine albumin (UA1b), blood glucose (BG), serum creatinine (Scr), blood urea nitrogen (BUN) and glomerular morphology were examined. In addition, the level of protein expression of alpha-smooth muscle actin (alpha-SMA) and collagen type I in glomeruli was determined by immunofluorescence. Both GTW and benazepril reduced UA1b. GTW ameliorated glomerular injury, such as mesangial cell proliferation, alpha-SMA and collagen type I over-expression, in DN model. Compared with benazepril, beneficial effects of GTW on glomerulusclerosis were more significant (total cell number: GTW group 54.44 +/- 2.41, benazepril group microg/67.83 +/- 4.41, P < 0.05; alpha-SMA score: GTW group 1.98 +/- 0.52, benazepril group 2.27 +/- 0.46, P < 0.05; collagen type I score: GTW group 2.11 +/- 0.37, benazepril group 2.88 +/- 0.58, P < 0.05). Preventive effects of GTW on glomerular lesion in DN model are related to decreasing UA1b and ameliorating glomerulusclerosis.


A randomized, double-blind comparison of sulbactam/ampicillin and clindamycin for the treatment of aerobic and aerobic-anaerobic infections.
In a randomized, prospective, double-blind trial, sulbactam/ampicillin was compared with clindamycin in terms of efficacy and safety for the treatment of bacterial infections. Both sulbactam/ampicillin and clindamycin were given with gentamicin when this course was indicated by clinical or laboratory findings. In five patients the site of infection was pleuropulmonary; in 14, bone; in 11, skin and soft tissue; and in one, intraabdominal. The commonest anaerobes isolated were anaerobic cocci and Bacteroides species; the commonest aerobic and facultative bacteria were Enterobacteriaceae, Pseudomonas aeruginosa, and various gram-positive cocci. All of six assessable patients given sulbactam/ampicillin alone had satisfactory clinical responses, as did seven of nine patients given sulbactam/ampicillin plus gentamicin, all of six patients given clindamycin alone, and six of nine patients given clindamycin plus gentamicin. Pathogens were totally or partially eradicated in four of five, eight of nine, four of five, and three of nine assessable patients given these same regimens. Adverse reactions and laboratory abnormalities were relatively uncommon. Overall, sulbactam/ampicillin was as effective as clindamycin in the treatment of aerobic or mixed aerobic-anaerobic infections; however, the concomitant use of gentamicin was frequently required with both regimens.


Pepsi® or Coke®? Influence of acid on dasatinib absorption.
Dasatinib is a second generation ABL kinase inhibitor used in the management of chronic myeloid leukemia or Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL). Dasatinib's bioavailability is highly dependent on gastric pH. When proton-pump inhibitors (PPIs) are co-administered with dasatinib, absorption is significantly reduced. Cola intake at the time of drug administration has been demonstrated to lead to relevant increases in the bioavailability for other acid labile drugs during PPI treatment. This manuscript reviews the relevant literature supporting a strategy of temporarily lowering the gastric pH with a carbonated beverage at the time of drug administration. The use of cola provides an easy to implement way to significantly improve dasatinib bioavailability, especially during concomitant use of a PPI.


Human small bowel as model for poisoning with organophosphorus compounds.
In previous experiments, human and rat small bowel samples have been successfully used to study the spasmolytic effect of (potential) therapeutics in carbamate-constricted bowel specimens. Additionally, transferability from rat to human data was shown in the previous study. In the present study, the effects of atropine, scopolamine, MB327, HI-6 as well as obidoxime were examined in organophosphorus-poisoned human small bowel specimens. All substances were tested with at least seven concentrations in samples previously exposed to the nerve agent sarin. Furthermore, the cholinesterase reactivation potential of all substances was investigated. The test substances displayed a spasmolytic effect allowing the calculation of dose-response curves and EC50s. The parasympatholytic compound scopolamine had the strongest relaxing effect (EC50 = 0.05 μM) followed by atropine (EC50 = 0.07 μM). HI-6 and obidoxime were capable to reactivate the sarin-inhibited cholinesterase activity in small bowel samples. Both substances restored AChE activity in a dose-dependent way, with HI-6 being more potent (HI-6 EC50 = 3.8 μM vs obidoxime EC50 = 197.8 μM). Summarizing, our isolated human small bowel setup is a suitable tool to investigate the smooth muscle relaxing effect of (candidate) therapeutics for organophosphorus compound poisoning i.e. sarin exposure in a complex 3D tissue model.


Body temperature daily rhythm adaptations in African savanna elephants (Loxodonta africana).
The savanna elephant is the largest extant mammal and often inhabits hot and arid environments. Due to their large size, it might be expected that elephants have particular physiological adaptations, such as adjustments to the rhythms of their core body temperature (T(b)) to deal with environmental challenges. This study describes for the first time the T(b) daily rhythms in savanna elephants. Our results showed that elephants had lower mean T(b) values (36.2 +/- 0.49 degrees C) than smaller ungulates inhabiting similar environments but did not have larger or smaller amplitudes of T(b) variation (0.40 +/- 0.12 degrees C), as would be predicted by their exposure to large fluctuations in ambient temperature or their large size. No difference was found between the daily T(b) rhythms measured under different conditions of water stress. Peak T(b)'s occurred late in the evening (22:10) which is generally later than in other large mammals ranging in similar environmental conditions.


Metacognitive Octonion-Valued Neural Networks as They Relate to Time Series Analysis.
In this paper, a metacognitive octonion-valued neural network (Mc-OVNN) learning algorithm and its application to diverse time series prediction are presented. The Mc-OVNN is comprised of two components: the octonion-valued neural network that represents the cognitive component and the metacognitive component that serves to self-regulate the learning algorithm. At each epoch, the metacognitive component decides if, how, and when learning occurs. The algorithm deletes unneeded samples and only stores those that will be used. This decision is determined by the octonion magnitude and the seven phases. To evaluate the Mc-OVNN algorithm's performance, it is applied to five real-world forecasting problems: the power consumption of a home in Honolulu, HI, USA, Box and Jenkins J series, Euro to Algerian Dinar (DZ) real-time conversion rates, the Mackey-Glass equation, and Europe Brent oil price prediction in a time series. When comparing the Mc-OVNN to other relevant techniques, Mc-OVNN displays its capability for efficient time series prediction. The real-time evaluation of the proposed algorithm is presented using the power consumption of a home in Boumerdès, Algeria, as a case study.


PROX1 is a specific and dynamic marker of sacral neural crest cells in the chicken intestine.
The enteric nervous system (ENS) is a complex network constituted of neurons and glial cells that ensures the intrinsic innervation of the gastrointestinal tract. ENS cells originate from vagal and sacral neural crest cells that are initially located at the border of the neural tube. In birds, sacral neural crest cells (sNCCs) first give rise to an extramural ganglionated structure (the so-called Nerve of Remak [NoR]) and to the pelvic plexus. Later, sNCCs enter the colon mesenchyme to colonize and contribute to the intrinsic innervation of the caudal part of the gut. However, no specific sNCC marker has been described. Here, we report the expression pattern of prospero-related homeobox 1 (PROX1) in the developing chick colon. PROX1 is a homeobox domain transcription factor that plays a role in cell type specification in various tissues. Using in situ hybridization and immunofluorescence techniques, we showed that PROX1 is expressed in sNCCs localized in the NoR and in the pelvic plexus. Then, using real-time quantitative PCR we found that PROX1 displays a strong and highly dynamic expression pattern during NoR development. Moreover, we demonstrated using in vivo cell tracing, that sNCCs are the source of the PROX1-positive cells within the NoR. Our results indicate that PROX1 is the first marker that specifically identifies sNCCs. This might help to better identify the role of the different neural crest cell populations in distal gut innervation, and consequently to improve the diagnosis of diseases linked to incomplete ENS formation, such as Hirschsprung's disease.


Neuronavigation-guided Endoscopic Endonasal Excision of Schwannoma-like Chordoma of Meckel's Cave: A Case Report.
Chordomas are locally aggressive malignant tumors due to their recurrence potential and originate from embryonic notochord remnants. Chordomas can originate anywhere on the axial skeleton. They are extradural and spread by bone destruction. Chordomas are locally aggressive tumors that invade the dura mater, and may also present with secondary intradural growth. The Meckel's cave location of chordomas has been very rarely reported in the literature. Chordomas located in Meckel's cave can be radiologically confused with trigeminal schwannomas. Herein, we report a case of Meckel's cave chordoma that was successfully excised through neuronavigation-guided endoscopic endonasal excision, a technique commonly used in skull base surgeries.


Characterization and maturation of alveolar macrophages procured from BCG-induced pulmonary granulomas.
Pulmonary macrophages from BCG-induced granulomas were separated according to their densities into six fractions by the use of discontinuous gradients of Percoll. A comparative study of distribution profiles of lavaged rabbit alveolar cells obtained 16 or 28 days after vaccination revealed that 16 days after vaccination there were small numbers of low-density cells (fractions 1 and 2) and large numbers of high-density cells (fractions 4 and 5). In contrast, 28 days after vaccination there was a marked increase in the numbers of macrophages in fractions 1 and 2 and relatively small numbers of high-density cells in fractions 4 and 5. Macrophages of fractions 1 and 2 (densities of 1.030-1.050) were large and mature in appearance and expressed low levels of acid phosphatase and beta-glucuronidase. Although macrophages in fraction 1 commonly showed signs of degeneration, they were the most active in terms of reducing nitroblue tetrazolium (NBT). Macrophages of fractions 3 and 4 (densities of 1.050-1.068) were smaller, appeared intact and fully mature, showed no signs of degeneration, and expressed the highest levels of the above enzymes, although their ability to reduce NBT was less than that in cells from fractions 1 and 2. The cells of fractions 5 and 6 (densities of 1.068-1.074) were small, expressed low levels of the above enzymes, and their ability to reduce NBT was minimal. These results indicate that density may be a reliable correlate of the maturity of macrophages harvested from BCG-induced granulomas.


The effects of glibenclamide, a blocker of K+ ATP-sensitive potassium channels, on diaphragmatic fatigue during endotoxaemia in pigs.
An in vivo porcine model of endotoxaemia was used to study the effects of glibenclamide, a K+ ATP-sensitive potassium channel blocker. Escherichia coli lipopolysaccharides (LPS, 70 micrograms/kg, i.v., as a bolus) were infused into anaesthetized, mechanically ventilated, indomethacin-treated pigs. After 120 min of endotoxaemia, glibenclamide was administered (10 mg/kg, i.v., over 5 min) to half the pigs. The strength at different frequencies of stimulation (10, 20, 30, 50 Hz, 20 V,) 1 s) and the endurance capacity (10 Hz, 20 V, 30 s) of the diaphragm were evaluated after 120 min of endotoxaemia and 5, 10, 20 and 30 min after drug infusion. Glibenclamide transiently increased the blood pressure without changing the decreased cardiac output and at the same time further impaired the diaphragmatic activity. The reduced ability of the diaphragm to generate force in response to different electrical stimulations was shown by a significant reduction in strength. The endurance index decreased 5 min after glibenclamide infusion, returning to the pre-glibenclamide values by 150 min. These results indicate that glibenclamide modifies the activity of vascular smooth muscle and of the diaphragm.


Acute myocardial infarction in a 28 year man with familial hypercholesterolemia.
Familial hypercholesterolemia is a single gene disorder. It has autosomal dominant pattern of inheritance. We report a 28-year-old man who presented with acute myocardial infarction. He had xanthomas and an elevated serum low density lipoprotein cholesterol (LDL-C). His only sibling, 32-year-old brother have similar cutaneous lesions and lipid profile. His mother and maternal uncle died at a young age due to myocardial infarction. This report is to emphasize the need to clinically recognize xanthomas and its familial inheritance with elevated LDL-C, premature atherosclerosis. Early diagnosis and early initiation of treatment will save the affected individual and the other family members.


Growth of β-Ga2O3 and GaN nanowires on GaN for photoelectrochemical hydrogen generation.
Enhanced photoelectrochemical (PEC) performances of Ga(2)O(3) and GaN nanowires (NWs) grown in situ from GaN were demonstrated. The PEC conversion efficiencies of Ga(2)O(3) and GaN NWs have been shown to be 0.906% and 1.09% respectively, in contrast to their 0.581% GaN thin film counterpart under similar experimental conditions. A low crystallinity buffer layer between the grown NWs and the substrate was found to be detrimental to the PEC performance, but the layer can be avoided at suitable growth conditions. A band bending at the surface of the GaN NWs generates an electric field that drives the photogenerated electrons and holes away from each other, preventing recombination, and was found to be responsible for the enhanced PEC performance. The enhanced PEC efficiency of the Ga(2)O(3) NWs is aided by the optical absorption through a defect band centered 3.3 eV above the valence band of Ga(2)O(3). These findings are believed to have opened up possibilities for enabling visible absorption, either by tailoring ion doping into wide bandgap Ga(2)O(3) NWs, or by incorporation of indium to form InGaN NWs.


[Demons-Meigs' syndrome. Report of a case with ovarian tumor of the granulosa].
We report an original and atypical case of Meigs' syndrome with bilateral pleural blood effusion and without ascites in a woman with a rare ovarian tumour involving the stratum granulosum. Excision of the tumour rapidly resulted in the pleural effusion drying up.


Radiographic outcomes of transcrestal and lateral sinus floor elevation: One-year results of a bi-center, parallel-arm randomized trial.
To comparatively evaluate the radiographic outcomes of transcrestal and lateral sinus floor elevation (tSFE and lSFE, respectively) when applied concomitantly with implant placement. Patients with at least 1 edentulous site with residual bone height (RBH) of 3-6 mm were enrolled in a bi-center, parallel-arm, randomized trial. Both tSFE and lSFE were associated with a bovine-derived xenograft, and implants were inserted concomitantly. In lSFE group, the antrostomy was covered with a resorbable collagen membrane. Marginal bone loss and the maturation of the grafted area were evaluated on periapical radiographs at 6 and 12 months. Twelve-month CT/CBCT was used to assess the effect of grafting procedures circumferentially around the implant. A per-protocol analysis was performed. The per-protocol study population consisted of 26 patients in the tSFE group and 28 patients in the lSFE group. At 12 months, the median proportion of the implant surface in contact with the peri-implant radiopaque area was 100% in both groups, with no significant inter-group difference. Suboptimal bone-to-implant contact was observed in 13% and 3.6% of tSFE and lSFE cases, respectively. In both groups, marginal bone loss was minimal (≤1 mm) and infrequent, and the radiographic aspect was suggestive of an advanced stage of maturation. At sites with RBH of 3-6 mm where implants are placed concomitantly with sinus floor elevation, tSFE and lSFE are both highly predictable in obtaining an implant surface completely embedded in a radiopaque area at 12 months post-surgery. (ClinicalTrials.gov ID: NCT02415946).


Elucidating differences in metal absorption efficiencies between terrestrial soft-bodied and aquatic species.
It is unknown whether metal absorption efficiencies in terrestrial soft-bodied species can be predicted with the same metal properties as for aquatic species. Here, we developed models for metal absorption efficiency from the dissolved phase for terrestrial worms and several aquatic species, based on 23 metal physicochemical properties. For the worms, the absorption efficiency was successfully related to 7 properties, and is best predicted with the ionic potential. Different properties (8 in total) were found to be statistically significant in regressions predicting metal absorption in aquatic species, with the covalent index being the best predictor. It is hypothesized that metal absorption by soft-bodied species in soil systems is influenced by the rate of metal supply to the membrane, while in aquatic systems accumulation is solely determined by metal affinity to membrane bound transport proteins. Our results imply that developing predictive terrestrial bioaccumulation and toxicity models for metals must consider metal interactions with soil solids. This may include desorption of a cation bound to soil solids through ion exchange, or metal release from soil surfaces involving breaking of metal-oxygen bonds.


Met-enkephalin-Arg6-Gly7-Leu8 exists together with Met-enkephalin-Arg6-Phe7, Met-enkephalin and Leu-enkephalin in human stomach.
Studies on the nucleotide sequence of cloned DNA complementary to mRNA for preproenkephalin A from adrenal medulla and human pheochromocytoma have revealed that this precursor contains 4 copies of methionine-enkephalin(Met-Enk) and one copy each of leu-enkephalin (Leu-Enk), methionine-enkephalin-Arg6-Gly7-Leu8(Met-Enk-Arg6-Gly7-Leu8) and methionine-enkephalin-Arg6-Phe7(Met-Enk-Arg6-Phe7). We have demonstrated the existence of Met-Enk-Arg6-Gly7-Leu8 together with Met-Enk, Leu-Enk and Met-Enk-Arg6-Phe7 in human gastric antrum, using high performance liquid chromatography(HPLC) coupled with radioimmunoassays for these opioid peptides. The ratio of molar concentrations of these peptides in human gastric antrum is almost equal to the ratio of these peptides contained in preproenkephalin A. Furthermore, gel filtration studies on Sephadex G-50 showed that most of immunoreactivities of these peptides were eluted at the elution position of each synthetic peptide without any detectable immunoreactivities at high molecular weight positions. In addition, most of immunoreactivities of these four opioid peptides were detected in the muscular layer of the gastric antrum. These results indicate the presence of Met-Enk-Arg6-Gly7-Leu8 together with Met-Enk, Leu-Enk, and Met-Enk-Arg6-Phe7 in human gastric antrum and further suggest that these opioid peptides are derived from the same precursor as preproenkephalin A in the adrenal medulla and the processing of preproenkephalin A is almost completed in the human stomach.


Peptide alpha-amidation activity in human plasma: relationship to gastrin processing.
C-terminal amidation is an essential processing step towards bioactivation of many peptides including gastrin. This reaction is catalysed by peptidylglycine alpha-amidating mono-oxygenase (PAM, EC 1.14.17.3) which converts the glycine extended precursors on their carboxyl termini to the des-glycine amidated peptide products. In the case of gastrin, most of the amidation is thought to occur in the antrum. However substantial quantities of glycine extended gastrin and PAM are present in plasma. It is unclear whether circulating PAM reflects the secretory activity of the gastrin secreting cell or whether PAM is involved in the postsecretory processing of gastrin. The aim of the present study was to relate the circulating amidation activity to the plasma concentrations of glycine extended and amidated gastrins. Plasma PAM, gastrin-amide and gastrin-gly were measured in subjects with different gastrin secretory status: healthy subjects basally and following a meal, members of families with multiple endocrine neoplasia type 1 (MEN-1) with normal and high plasma gastrin, and patients with hypergastrinaemic atrophic gastritis. Patients with MEN-1 and hypergastrinaemia tended to have a higher plasma PAM activity than MEN-1 subjects with normal circulating G-NH2 indicating a cosecretion of hormone and PAM. However in contradistinction to patients with medullary thyroid carcinoma, PAM activity does not appear to be a useful tumour marker of gastrinoma. Hypergastrinaemia from a non-tumour source (hypergastrinaemic non-atrophic gastritis) was associated with a lower plasma PAM activity than in normal subjects and may reflect the secretion of a greater proportion of already amidated gastrin. In general, there was no relationship between plasma PAM activity and the ratio of amidated to non-amidated gastrin suggesting that circulating PAM was not involved in the amidation of gastrin. Feeding increased circulating gastrin but had no effect on plasma PAM activity. The results support the view that gastrin is amidated at the site of its synthesis and that hypergastrinaemia is associated with elevated plasma amidating enzyme activity only when the gastrin originates from tumour sources.


Concanavalin X-phenyl beta-D-glucopyranoside interactions. A molecular graphics-QSAR analysis.
Poretz and Goldstein showed that X-phenyl beta-D-glucopyranosides prevent the agglutination of concanavalin A with polysaccharides and derived inhibition constants for the process. Using their data the binding of 25 glucosides to concanavalin is now shown to be correlated with the molar refractivity of the substituents on the phenyl ring. This is interpreted to mean that it is the bulk of the substituents and not their hydrophobicity which prevents the union of concanavalin and the polysaccharide. These results are similar to those found for other haptens preventing antibody-antigen interaction.


Effectiveness of galactose-based intravenous contrast medium on color Doppler sonography of deeply located hepatocellular carcinoma.
The purpose of this study is to examine the effectiveness of intravenously injectable sonographic contrast medium for color Doppler sonographic diagnosis of deeply located hepatocellular carcinoma. Subjects were 7 hepatocellular carcinomas, an adenomatous hyperplasia and a hemangioma located more than 7 cm below the abdominal surface. Levovist, a galactose-based sonographic contrast medium was injected through median cubital vein as a phase-two clinical study, and the pre- and post-enhanced color Doppler sonographic findings of these lesions were compared. The incidence of the positive findings for hepatocellular carcinoma increased from 29% (2/7) to 86% (6/7) of hepatocellular carcinoma after contrast enhancement. Positive findings were 0% in other cases even after enhancement. Levovist brought a certain improvement in the visualization of the tumor vessel by color Doppler sonography without any noteworthy side effects. Contrast enhancement was useful for the diagnosis of liver lesions suspected to be hepatocellular carcinoma by ordinary sonography, but could not be confirmed by color Doppler sonography.


Treatment of prolapsed conjunctiva.
Prolapse of conjunctiva from the superior cul-de-sac, an infrequent complication of levator resection surgery, has been observed by us to have occurred following craniofacial reconstruction for craniostenosis. Three cases of conjunctival prolapse are presented: two that followed maximal external levator resections, and one that occurred after a supraorbital rim advancement and a subsequent cerebrospinal fluid leak. The causes of conjunctival prolapse and its appropriate treatment are reviewed.


Comparison of microscopy, real-time PCR and a rapid immunoassay for the detection of Giardia lamblia in human stool specimens.
Giardia lamblia is one of the most common intestinal parasites worldwide, with microscopy being the diagnostic reference standard for use with human stools. However, microscopy is time-consuming, labour-intensive and lacks sensitivity when single stools are examined. In the present study, microscopy, real-time PCR and a rapid immunoassay were compared for the detection of G. lamblia in human stools. All three methods were highly sensitive, with values of 99%, 100% and 98%, respectively. Specificity and positive and negative predictive values were >or=97%, except when using real-time PCR, for which the specificity and positive predictive value were 92% and 93%, respectively. The lower specificity of real-time PCR was associated mostly with failure to detect specimens regarded as true positives for G. lamblia DNA, although cross-contamination was suspected in a minority of cases because of the large amount of G. lamblia DNA present in most positive specimens. It was concluded that microscopy should remain the primary diagnostic tool for identifying G. lamblia in human stools, mainly because of its ability to simultaneously detect other gastrointestinal parasites. However, the simple and rapid immunoassay is a valuable tool to decrease turn-around time. Real-time PCR provides additional sensitivity, although there is a risk of cross-contamination. Based on this observation, and the need for other real-time assays to be developed to detect other intestinal parasites, real-time PCR is currently useful only as an additional test supplementary to microscopy.


Tet1 Overexpression and Decreased DNA Hydroxymethylation Protect Neurons Against Cell Death After Injury by Increasing Expression of Genes Involved in Cell Survival.
Spinal cord and neuron injury result in loss of muscle function, sensation, or autonomic function in the body. Tet1 produces 5-hydroxymethylcytosin. The conversion was proposed as the initial step of deoxyribonucleic acid demethylation in mammals. However, effects of Tet1 expression and hydroxymethylation status on neuron injury remain unclear. Therefore the current study was designed to explore effects of Tet1 expression and hydroxymethylation status on cell survival and gene expression after neuron injury. Mouse models of spinal cord injury and cell model of neuron injury were created. Animals were sacrificed, and injured spinal cord tissue was harvested. Neuron-like cells were cultured after scratch injury. Hydroxymethylated deoxyribonucleic acid concentration was detected, and Tet1 expression was examined by qPCR. Neuron-like cells were divided into 3 groups: control, injury, and azacytidine + injury (before injury, cells were pretreated with azacytidine) groups. Culture supernatant was collected, and lactate dehydrogenase concentration was detected. Meanwhile, injured neuron-like cells were divided into 3 groups: negative control, Tet1 overexpression, and Tet1 interference. Relative expression of Tet1, BDNF, NTF3, A20, FLIP, HSP70, HSP90, HSP27, and Bcl2 in neuron-like cells was detected by qPCR. In addition, neuron-like cells were divided into 7 groups. Tet1 expression and deoxyribonucleic acid hydroxymethylation increased initially and decreased thereafter after neuron injury in both animal and cell models. Percentages of dead cells increased significantly in neuron-like cells after injury. The percentages of dead cells markedly decreased in injured neuron-like cells that were pretreated with azacytidine. The percentages of dead cells increased markedly in the Tet1 interference group and decreased significantly in the Tet1 overexpression group. Expression of Tet1, BDNF, A20, FLIP, HSP70, HSP90, and Bcl2 decreased significantly after injury. Azacytidine pretreatment in injured neuron-like cells markedly increased expression of Tet1, BDNF, NTF3, A20, FLIP, HSP70, HSP90, HSP27, and Bcl2. Moreover, Tet1 interference significantly decreased the expression of Tet1, BDNF, A20, FLIP, HSP70, and HSP90 in neuron-like cells, whereas Tet1 overexpression markedly increased the expression of Tet1, BDNF, NTF3, A20, FLIP, HSP70, HSP90, HSP27, and Bcl2. BDNF interference significantly increased percentages of dead cells after injury. BDNF interference also markedly decreased the protection of azacytidine and Tet1 overexpression against cell death. Tet1 overexpression and demethylation caused by azacytidine protect neurons against cell death after injury by increasing expression of genes involved in cell survival.


Functional reconstitution of U6 snRNA in nematode cis- and trans-splicing: U6 can serve as both a branch acceptor and a 5' exon.
Maturation of nuclear pre-mRNAs in nematodes requires both cis- and trans-splicing. Both processing pathways involve analogous two-step phosphotransfer reactions and both are dependent upon the integrity of U6 snRNA. We have developed a functional reconstitution assay to assess the U6 snRNA sequence requirements for cis- and trans-splicing. Branch formation between the splicing substrates and U6 snRNA was observed. The frequency of this event was greatly enhanced when a highly conserved sequence in U6 snRNA was altered by mutation. In cis- and trans-splicing reactions reconstituted with this mutant U6 snRNA the liberated exon of U6 proceeded through the second step of splicing using the appropriate splice acceptor sites. These results demonstrate covalent interactions between a U snRNA required for splicing and a splicing substrate, and they provide evidence for an unexpected degree of catalytic flexibility within the spliceosome.


[Acute intervention for ST-elevation myocardial infarction].
Rapid revascularization of every presenting patient is the goal of modern therapy of ST-elevation myocardial infarction (STEMI). With respect to the current situation at least one half of all these patients will be treated medically using thrombolysis, prehospital or in hospital. Invasive diagnosis and revascularization (percutaneous intervention [PCI], coronary artery to bypass graft [CABG]) should be done promptly. Primary PCI performed in a timely manner by experienced interventional cardiologists in specialized centers is the best option in the management of patients with STEMI. Transfer PCI is an effective method of treatment for patients initially admitted to a hospital without PCI facilities and should be completed within 90 minutes of transfer time. Rescue-PCI following unsuccessful thrombolysis (< 50 % ST-resolution 90 minutes post thrombolysis) improves prognosis by restoring coronary flow. If planned immediate PCI after thrombolytic therapy is not indicated, PCI immediately after high dosage of glycoprotein IIb/IIIa-Inhibitors in combination with a high dose of clopidogrel may give good results.


Biochemical composition and antioxidant activity affected by spraying potassium sulfate in black grape (Vitis vinifera L. cv. Rasha).
The physiological and metabolic processes involved with grapevine growth and production are influenced by key macro- and micronutrients. Potassium is an essential plant nutrient that affects growth and fruit quality. In this study, the impact of foliar spraying of potassium sulfate (K2 SO4 ) on qualitative characteristics of grape berries was evaluated in the cultivar 'Rasha', a commonly cultivated cultivar in Kurdistan province of Iran. Leaves of the fully grown vines were sprayed with each of the 1.5 and 3 g L-1 K2 SO4 solutions once (1 month after petal senescence) and twice (15 days after first spraying). The control plants were sprayed with distilled water. Various biochemical contents and enzyme activities on the ripe berries were analyzed. Significant increases in anthocyanin, total protein content, and antioxidant enzyme activities were observed in the berries treated twice with 3 g L-1 K2 SO4 . Concentrations of total carbohydrate, phenol, and antioxidant activity in berries sprayed with K2 SO4 were higher than in the controls. We observed a strong correlation between antioxidant activity and different phenolic compounds. These findings suggest that K2 SO4 treatment influences biosynthesis of phenolic compounds and antioxidant enzymes. Thus, treatment by K2 SO4 could improve nutritional and qualitative attributes of grape. © 2018 Society of Chemical Industry.


Synthesis and reactivity of a Ru(I) dimer devoid of pi-acid ligands.
Zinc reduction of [(Cym)RuCl(2)](2) gives [(Cym)RuCl](2), (Cym = 1,4-Me(i)PrC(6)H(4)), whose reactivity is evaluated. This Ru(I) dimer with two bridging chlorides shows no reactivity towards H(2), N(2), N(2)O or methyl triflate, but does add HCl to form (Cym)(2)Ru(2)HCl(3). Attempts to form a monomeric monovalent ruthenium complex with dppm, Ph(2)PCH(2)PPh(2), gives disproportionation to (Cym)RuCl(2)(eta(1)-dppm) and (Cym)Ru(eta(2)-dppm). With terpyridyl, the analogous disproportionation behavior is observed, to form Ru(terpy)(2)(2+) and a zero valent product, which decomposed before it could be isolated. The molecular orbitals, from a DFT calculation, of [(Cym)RuCl](2) show the LUMO to be in a sterically crowded region of the molecule, and thus helps to account for the reactivity targeted for small and more nucleophilic reagents, while the HOMO is accessible to reaction with HCl.


Intracranial extension of inverted papilloma: An unusual and potentially fatal complication.
The purpose of this article is to define the outcome of intracranial extension of inverted papilloma and outline a rationale for management of this rare clinical presentation. A review of patients with intracranial extension of inverted papilloma reported in the literature (18 patients), or treated in our institution (3 patients ) was performed. The data of these 21 patients were consolidated with regard to clinical presentation, treatment, and outcome. Nine patients, including 1 of our cases, had coexisting squamous cell carcinoma and therefore were excluded from the analysis. Twelve patients with "pure" inverted papilloma formed the basis of this study. The majority of patients (83%) with intracranial inverted papilloma had recurrent disease. Patients with extradural disease had a survival rate of 86% with an average follow-up of 4.4 years. Eighty-six percent of these survivors were treated with craniofacial resection. In contrast, 75% of patients with intradural inverted papilloma were dead of disease with an average follow-up of 9.3 months regardless of the treatment modality. Intracranial extension of inverted papilloma is mostly associated with recurrent disease. Intracranial extradural inverted papilloma can be effectively controlled with craniofacial resection. Intracranial intradural involvement of inverted papilloma has a poor prognosis regardless of treatment. Aggressive treatment of intranasal inverted papilloma may be the most important factor in preventing intracranial presentation.


Efficient thermal- and photocatalysts made of Au nanoparticles on MgAl-layered double hydroxides for energy and environmental applications.
Composites of the noble metal Au supported on MgAl-LDHs were prepared by a simple impregnation-reduction method to be used as thermal- and photocatalysts for the photocatalytic degradation of ciprofloxacin and thermocatalytic decomposition of formic acid to produce hydrogen. A collection of techniques, including X-ray diffraction (XRD), transmission electron microscopy (TEM) and X-ray photoelectron spectroscopy (XPS) were employed to determine the structure and morphology properties of the as-prepared Au/MgAl-LDHs. The presence of surface Au(0) in Au/MgAl-LDHs was confirmed by TEM and XPS analyses. For the first time, we compared the effect of the surfactant PVP on the catalyst and found that the Au/MgAl-LDH composite with Au particle size of 2-8 nm had better catalytic activity than the (PVP@Au)/MgAl-LDH composite with Au particle size in the range of 1-5 nm. The sizes of Au NPs in the two catalysts were similar but had different effects on the catalytic performance. This indicated that the addition of PVP had an inhibitory effect on the catalytic activity of the catalyst. To evaluate the photostability of Au/MgAl-LDHs, recycle experiments for the photocatalytic degradation of ciprofloxacin were performed, and it was found that Au/MgAl-LDHs had good stability. Finally, we also applied Au/MgAl-LDHs in environmental catalysis and energy catalysis; we hope that they will be useful in practical applications.


[A case of Cushing's syndrome due to bilateral multiple adrenal adenomas].
We report a case of Cushing's syndrome due to bilateral adrenal adenomas. A 45-year-old woman was found to have Cushing's syndrome during the course of treatment for diabetes mellitus. The diagnosis of Cushing's syndrome was based on the absence of a diurnal rhythm in plasma cortisol and failure to suppress plasma cortisol by 1 or 4 mg of dexamethasone. The plasma level of adrenocorticotropic hormone (ACTH) was below the normal range, and plasma cortisol responded normally to rapid ACTH injection. Abdominal computed tomography revealed bilateral adrenal tumors. Bilateral uptake of radiocholesterol by the adrenal cortex was observed in adrenal scintigraphy. Bilateral adrenalectomy was performed. Microscopic examination and analysis of steroid contents by high performance liquid chromatography showed that the tumor was cortisol-producting adenoma.


Novel multilayer microcapsules based on soy protein isolate fibrils and high methoxyl pectin: Production, characterization and release modeling.
In this study, novel microcapsules were produced through the layer by layer adsorption of food-grade and plant-based polyelectrolytes, soy protein isolate (SPI) fibrils and high methoxyl pectin (HMP). The physical properties of the fibrils were investigated by TEM and AFM and the properties of the microcapsules such as size, uniformity, zeta potential, morphology, functional groups, modeling and the release kinetics of limonene were examined. The results revealed that SPI-fibrils had a thickness varying from 1 to 10nm and strand like structure. SEM images showed that the microcapsules were spherical and the thickness increased by the number of layers which led to the improvement of shell strength. The FTIR results confirmed that HMP and SPI-fibrils were adsorbed layer by layer as the walls of microcapsules and presence of limonene was stable into microcapsules. By increasing the number of layers of the shell from 2 to 6, the release rate of limonene decreased significantly. The index n in Rigter-Peppas model indicates that the release mechanism of limonene from multilayer microcapsules followed a non-Fick law. This method of microcapsule production is very simple and could be readily industrialized, especially for the manufacture of food products for vegetarians.


Rheumatoid Arthritis Masquerading as Fibromyalgia.
Symptoms of inflammatory arthritis such as rheumatoid arthritis (RA) can overlap with fibromyalgia syndrome (FMS). Moreover, FMS and RAcan coexist. Hence, the diagnosis of low intensity, antibody-negative RAmay present a challenge. Here, we present the case of a middle-aged woman thought to have FMS, osteoarthritis and osteoporosis for 4 years prior to being diagnosed as seronegative RAon musculoskeletal ultrasound (MSKUS). Targeted therapy with etanercept led to a complete clinical response and normalization of previously elevated C-reactive protein. We conclude that MSKUS is a sensitive tool for distinguishing low-intensity inflammatory arthritis from FMS with important clinical consequences.


[Clinical experiences with PACS: digital radiology].
We present our experience during the first 21 months of using hospital-wide network technology and digital archiving in connection with digital radiology in the Radiology Department at the SMZO/Danube hospital in Vienna. This means digital generation, archiving and distribution of radiographs as well as monitor reporting embedded in HIS and RIS. The clinical use of PACS demands full integration of all subsystems and modalities in a digital way, as was first realized at the Danube Hospital. With this approach, a reduction in radiation dose, improved communication and thus a reduction in the length of hospital stay and health care cost are attained.


The meaning of hope from the perspective of Chinese advanced cancer patients in Hong Kong.
This article reports a study to examine the meaning of hope from the perspective of Chinese advanced cancer patients in Hong Kong. Semi-structured interviews were conducted with a convenience sample of advanced cancer patients recruited from the palliative care unit of a local hospital. Data were saturated after 17 participants were interviewed. Qualitative content analysis was adopted to analyse the data. Hope as experienced by the participants was found to consist of five components: living a normal life, social support, actively letting go of control, reconciliation between life and death, and wellbeing of significant others. While hope is related to the wellbeing of patients with advanced cancer, successful palliative care partly depends on an awareness of the importance of hope in the end-of-life context and cultural sensitivity to the meanings behind it from the patients' own perspective.


Breastfeeding and lowering the risk of childhood obesity.
Breastfeeding might confer protection against obesity later in life, but the evidence is inconclusive. We tested the hypothesis that breastfeeding is associated with a reduced risk of obesity in a population-based sample of 32200 Scottish children studied at age 39-42 months in 1998 and 1999. Obesity was defined as body-mass index (BMI) at the 95th and 98th percentiles or higher. The prevalence of obesity was significantly lower in breastfed children, and the association persisted after adjustment for socioeconomic status, birthweight, and sex. The adjusted odds ratio for obesity (BMI > or = 98th percentile) was 0.70 (95% CI 0.61-0.80). Our results suggest that breastfeeding is associated with a reduction in childhood obesity risk.


A cross-sectional study of subjective complaints in patients with epilepsy who seem to be well-controlled with anti-epileptic drugs.
Side-effects of anti-epileptic drugs (AEDs) may be overlooked in patients with epilepsy in everyday clinical practice. The aim of this study was to assess the prevalence and severity of subjective complaints in patients who were considered to be well-controlled and to assess whether these complaints are related to medication, personality traits, or other determinants. We included patients with epilepsy who were considered to be well-controlled in a cross-sectional study in seven hospitals in the Netherlands. Their medication had not been changed for six months and an apparent reason to change the medication was lacking at the time of enrolment. Subjective complaints were assessed with a 46-item questionnaire. Using multivariable linear regression modeling, we assessed whether patient characteristics, epilepsy characteristics, medication, quality of life (Qolie-10), and personality traits (SCL-90) explained the presence and severity of complaints. Of 173 included patients, 67% reported moderate to severe subjective complaints on the questionnaire. Cognitive complaints were reported most frequently. Multivariate modeling showed that 61% of the variance in reported complaints could be explained by included determinants. The prevalence and severity of complaints was associated with AED polytherapy and higher scores on psycho neuroticism. Patients who were considered to be well-controlled proved to report an unexpectedly high number of subjective complaints. Both medication and aspects of personality contributed to the level of complaints. Our study illustrates that subjective side-effects are easily overlooked in everyday clinical practice, possibly because in practice a generally phrased question is used to detect side-effects.


Gastrointestinal pathology in rhesus monkeys with experimental SIV infection.
The updated results of current pathomorphological investigations in SIV-infected rhesus monkeys (Macaca mulatta) are summarized. After experimental infection with several SIVmac251 subtypes and various vaccination trails, 147 rhesus monkeys were morphologically examined until now. The pathology of the gastrointestinal tract in SIV-infected animals resembled those of human cases with HIV and AIDS. Alterations were considered to be primary SIV-induced (SIV enteropathy, giant cell disease) or secondary caused by opportunistic agents. Typical secondary gastrointestinal opportunistic infectious agents were parasites (Cryptosporidium sp., Trichuris sp., Trichomonas sp., Spironucleus sp.), viruses (cytomegalovirus, adenovirus) and bacteria (Mycobacterium simiae). Five animals developed malignant lymphomas involving the intestinal tract. The present observations revealed that SIV infection of rhesus monkeys provide an excellent model for studies on the pathogenesis of HIV in man.


The pathogenesis of respiratory syncytial virus disease in childhood.
Respiratory syncytial virus (RSV) is a leading cause of severe respiratory infection in infants and children. RSV is an RNA virus whose genome encodes 10 proteins. The G protein is responsible for viral attachment to cells whilst the F protein promotes syncytia formation. These proteins are also important in the immune response to RSV. Both the innate and adaptive arms of the cellular immune system are involved in the immunological response to RSV. The cytopathic effects of the virus explain many of the pathological findings in RSV disease. However, there is compelling evidence to suggest that the host cell immune response also has a prominent role in disease pathogenesis. Non-immunological factors may also be important.


Advanced trauma life support training for hospital staff.
Injury is responsible for an increasing global burden of death and disability. As a result, new models of trauma care have been developed. Many of these, though initially developed in high-income countries (HICs), are now being adopted in low and middle-income countries (LMICs). One such trauma care model is advanced trauma life support (ATLS) training in hospitals, which is being promoted in LMICs as a strategy for improving outcomes for victims of trauma. The impact of this health service intervention, however, has not been rigorously tested by means of a systematic review in either HIC or LMIC settings. To quantify the impact of ATLS training for hospital staff on injury mortality and morbidity in hospitals with and without such a training program. The search for studies was run on the 16th May 2014. We searched the Cochrane Injuries Group's Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), Ovid MEDLINE(R), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid OLDMEDLINE(R), Embase Classic+Embase (Ovid), ISI WOS (SCI-EXPANDED, SSCI, CPCI-S & CPSI-SSH), CINAHL Plus (EBSCO), PubMed and screened reference lists. Randomised controlled trials, controlled trials and controlled before-and-after studies comparing the impact of ATLS-trained hospital staff versus non-ATLS trained hospital staff on injury mortality and morbidity. Three authors applied the eligibility criteria to trial reports for inclusion, and extracted data. None of the studies identified by the search met the inclusion criteria for this review. There is no evidence from controlled trials that ATLS or similar programs impact the outcome for victims of injury, although there is some evidence that educational initiatives improve knowledge of hospital staff of available emergency interventions. Furthermore, there is no evidence that trauma management systems that incorporate ATLS training impact positively on outcome. Future research should concentrate on the evaluation of trauma systems incorporating ATLS, both within hospitals and at the health system level, by using more rigorous research designs.


Self-aggregated perfluoroalkylated hexa-peri-hexabenzocoronene fibers observed by cryo-SEM and fluorescence spectroscopy.
The self-assembled architectures in solution of a new HBC derivative bearing perfluoroalkylated side chains were investigated by optical excitation and emission spectroscopy and correlated to cryo-SEM, a new technique in organic chemistry.


A computational method to calculate the longitudinal wave evolution caused by interfaces between isotropic media.
This paper presents a computational method to calculate the reflected and transmitted ultrasonic fields at interfaces of complex geometry. The method is performed in two steps. As first step, the velocity potential impulse response from an arbitrary aperture is determined at the interface using the Rayleigh integral and considering the reflection and transmission coefficients. In a second step, the simulated fields are calculated by applying the Rayleigh-Sommerfeld integral to the whole, extended interface. In order to validate the method, some experimental cases as, for instance, plane and cylindrical concave surfaces between two media (water-acrylic) were tested. The experimental ultrasonic fields are in good agreement with those provided by the model. Furthermore, in the work, the compromise between the accuracy of the method and the computation time is studied.


Lung cancer in pregnancy: case reports and review of the literature.
Lung cancer diagnosed in pregnancy is rare. The number of reported cases has been escalating in recent years, probably reflecting the increasing number of women of reproductive age who smoke. This review presents three cases of lung cancer in pregnancy with different manifestations and outcomes, with a review of the literature. Physicians should have a low threshold using different diagnostic tools for investigating unusual symptoms during pregnancy without fear for fetal safety. Once diagnosed, lung cancer represents a major ethical and medical dilemma. The optimal management of lung cancer in pregnancy is not known, because of the rarity of the cases reported during pregnancy and insufficient follow-up data.