Organizational culture affecting quality of care: guideline adherence in perioperative antibiotic use.
The objective of this work was to elucidate aspects of organizational culture associated with hospital performance in perioperative antibiotic prophylaxis using quantitative data in a multicenter and multidimensional study. Cross-sectional retrospective study using a survey data and administrative data. Eighty-three acute hospitals in Japan. A total of 4856 respondents in the organizational culture study, and 23 172 patients for the quality indicator analysis. Multilevel models of various cultural dimensions were used to analyze the association between hospital organizational culture and guideline adherence. The dependent variable was adherence or non-adherence to Japanese and CDC guidelines at the patient level and main independent variable was hospital groups categorized according to organizational culture score. Other control variables included hospital characteristics such as ownership, bed capacity, region and urbanization level of location. The multilevel analysis showed that hospitals with a high score in organizational culture were more likely to adhere to the Japanese and CDC guidelines when compared with lower scoring hospitals. In particular, the hospital group with high scores in the 'collaboration' and 'professional growth' dimensions had three times the odds for Japanese guideline adherence in comparison with low-scoring hospitals. Our study revealed that various aspects of organizational culture were associated with adherence to guidelines for perioperative antibiotic use. Hospital managers aiming to improve quality of care may benefit from improving hospital organizational culture.


Histamine prevents functional and morphological alterations of submandibular glands induced by ionising radiation.
Xerostomia is a common, disturbing side-effect among patients treated with radiotherapy for head-and-neck cancer. The aim of the present work was to investigate whether histamine could prevent salivary gland dysfunction and histological alterations exerted by ionising radiation. Forty-eight rats were divided into four groups. Histamine and histamine-5 Gy groups received a daily subcutaneous histamine injection (0.1 mg/kg) starting 24 h before irradiation. Histamine-5 Gy and untreated-5 Gy groups were irradiated with a single dose of whole-body Cesium-137 irradiation. Control and untreated-5 Gy groups were given daily saline injections. Three days post irradiation metacholine-induced salivary secretion was measured or animals were sacrificed and submandibular gland (SMG) removed, stained and histological characteristics were evaluated. Proliferation and apoptosis markers were studied by immunohistochemistry. Radiation decreased salivary secretion by 40% in comparison to untreated rats, which was associated with loss of SMG mass, alteration of epithelial architecture, partial loss of secretor granular material, diminished proliferation and a remarkable apoptotic response. In contrast, histamine completely reversed the reduced salivation induced by radiation, conserved glandular mass with normal appearance and preserved the structural organisation of secretor granules. Radiation-induced toxicity is prevented by histamine essentially by suppressing apoptosis of ductal and acinar cells, reducing the number of apoptotic cells per field (19.0 ± 3.8 vs. 106.0 ± 12.0 in untreated animals, P < 0.001), and also by preventing the radiation-induced decrease in cell proliferation. Histamine prevents morphological and functional radiation-induced damage on SMG, representing a potential radioprotector for treatment of patients undergoing radiotherapy for head and neck malignancies.


Impact of trisomy 8 on expression of genes located on chromosome 8 in different AML subgroups.
Trisomy 8 is the most frequently observed trisomy in acute myeloid leukemia (AML) occurring as a sole karyotype abnormality or in addition to other chromosome aberrations. It was the aim of this study to analyze the impact of trisomy 8 on the expression of genes located on chromosome 8 in distinct AML subgroups characterized by different chromosome abnormalities in addition to trisomy 8. Gene expression analyses were performed on a total of 567 AML cases comprising the following subgroups: +8 sole, +8 within a complex aberrant karyotype, +8 in addition to t(15;17), inv(16), t(8;21), 11q23/MLL, or other abnormalities, AML with normal karyotype and the before mentioned subgroups without trisomy 8. A significant higher mean expression of genes located on chromosome 8 was observed in subgroups with +8 in comparison to their respective control groups. A varying number of significantly higher expressed genes was identified in all comparisons. No gene was significantly overexpressed in all comparisons, and no distinct gene expression pattern was identified allowing the identification of cases with trisomy 8. In conclusion, the gain of chromosome 8 leads to a higher expression of genes located on chromosome 8. However, no consistent pattern of genes was identified, which shows a higher expression in all AML subtypes with trisomy 8. These data suggest that trisomy 8 rather provides a platform for a higher expression of chromosome 8 genes which are individually up-regulated by the respective primary genetic abnormalities. Therefore, trisomy 8 in AML determines no specific disease characteristic but is a disease modulating secondary event.


Intracellular distribution of actin in cells of the organ of Corti: a structural basis for cell shape and motility.
Immunofluorescence staining and phalloidin labeling have provided localization of actin in the sensory and supporting cells of the inner ear at the light microscopic level. However, with electron microscopy, neither actin nor actin filaments have been found in the outer hair cell body. This paper describes various techniques utilized to preserve and identify cytoplasmic actin at the ultrastructural level. Post-embedding staining of Lowicryl K4M sections, pre-embedding staining of permeabilized cells of the organ of Corti, pre-embedding staining of vibratome sections, and pre-embedding staining of permeabilized dissociated cells documented the presence of actin, but each of these techniques was best suited to localize actin in specific parts of the cell. Cytoplasmic actin was labeled when isolated cells were lightly fixed and membranes were permeabilized with detergent--conditions under which the cell ultrastructure was compromised. Under conditions of optimal fixation, cytoplasmic filaments embedded in the dense granular matrix of the hair cell cytoplasm were observed.


Shrapnel management.
With the increased incidence of terrorism worldwide, it is important for surgeons to understand the role of shrapnel injury in mass casualty events. Several diagnostic modalities are available, including plain radiography, computed tomography, ultrasound, angiography, and computerized surgical navigation based on real-time acquisition of fluoroscopic data. Shrapnel management techniques are selected based on the following chronologic phases: acute, subacute, and late.


Effect of structured interviews on evaluation time in pediatric community mental health settings.
The purpose of this study was to determine whether a structured interview administered by a master's-level clinician and reported to physicians before an initial evaluation would reduce physicians' evaluation time without compromising diagnostic accuracy or clinical outcomes in a pediatric sample. A sample of 225 children and adolescents who were seen in public-sector community facilities was randomly assigned either to receive a structured interview (the Schedule for Affective Disorders and Schizophrenia for School-aged Children-Present and Lifetime Versions) by a trained interviewer before the initial physician visit or to receive assessment as usual. Clinical outcome data were collected prospectively, with follow-up at four months. Physicians' evaluation time was reduced by approximately half among physicians who were given preliminary diagnostic information. Physicians' diagnoses were strongly related to the results of the structured interview. Physicians' having access to previously obtained diagnostic information was associated with better psychosocial functioning at follow-up in terms of peer relations and spare-time activities compared with assessment as usual. Adding a trained diagnostic interviewer to the clinical team could reduce physicians' initial diagnostic evaluation time and improve diagnostic reliability and psychosocial outcomes.


Extensible multiplex real-time PCR for rapid bacterial identification with carbon nanotube composite microparticles.
The early diagnosis of pathogenic bacteria is significant for bacterial identification and antibiotic resistance. Implementing rapid, sensitive, and specific detection, molecular diagnosis has been considered complementary to the conventional bacterial culture. Composite microparticles of a primer-immobilized network (cPIN) are developed for multiplex detection of pathogenic bacteria with real-time polymerase chain reaction (qPCR). A pair of specific primers are incorporated and stably conserved in a cPIN particle. One primer is crosslinked to the polymer network, and the other is bound to carbon nanotubes (CNTs) in the particle. At the initiation of qPCR, the latter primer is released from the CNTs and participates in the amplification. The amplification efficiency of this cPIN qPCR is estimated at more than 90% with suppressed non-specific signals from complex samples. In multiplexing, four infective pathogens are successfully discriminated using this cPIN qPCR. Multiplex qPCR conforms with the corresponding singleplex assays, proving independent amplification in each particle. Four bacterial targets from clinical samples are differentially analyzed in 30min of a single qPCR trial with multiple cPIN particles.


Autoimmune Progesterone Dermatitis: A Systematic Review.
Autoimmune progesterone dermatitis (AIPD) is a cyclical, cutaneous reaction to endogenous progesterone that occurs throughout the menstrual cycle. The cutaneous manifestations of AIPD vary greatly from patient to patient, ranging anywhere from urticaria to erythema multiforme to anaphylaxis. As such, recognition, diagnosis, and management of this condition are difficult for clinicians. In the present article, we conducted a systematic review of 112 articles and 132 individual cases to summarize the clinical features and presentation of AIPD while also summarizing the successes and failures of different treatment plans. Despite the great variety in clinical presentations, it is clear from the data that ovulation-suppressing medical therapies and surgery have the greatest success in treating AIPD, whereas more commonly used therapies such as antihistamines and systemic corticosteroids frequently fail in providing any relief. Further research is necessary to determine the exact pathogenesis of AIPD and allow for more targeted treatment.


Envelope protein complexes of Mycobacterium avium subsp. paratuberculosis and their antigenicity.
Mycobacterium avium subsp. paratuberculosis (MAP) is the causative agent of Johne's disease, a chronic enteric disease of ruminant animals. In the present study, blue native PAGE electrophoresis and 2D SDS-PAGE were used to separate MAP envelope protein complexes, followed by mass spectrometry (MS) to identify individual proteins within the complexes. Identity of individual proteins within complexes was further confirmed by MS upon excision of spots from 2D SDS-PAGE gels. Among the seven putative membrane complexes observed, major membrane protein (MAP2121c), a key MAP antigen involved in invasion of epithelial cells, was found to form a complex with cysteine desulfurase (MAP2120c). Other complexes found included those involved in energy metabolism (succinate dehydrogenase complex) as well as a complex formed by Cfp29, a characterized T cell antigen of Mycobacterium tuberculosis. To determine antigenicity of proteins, Western blot was performed on replicate 2D SDS-PAGE gels with sera from noninfected control cows (n=9) and naturally infected cows in the subclinical (n=10) and clinical (n=13) stages of infection. Clinical animals recognized MAP2121c in greater proportion than subclinical and control cows, whereas cysteine desulfurase recognition was not differentiated by infection status. To further characterize antigenicity, recombinant proteins were expressed for 10 of the proteins identified and evaluated in an interferon-gamma (IFN-γ) release assay as well as immunoblots. This study reveals the presence of protein complexes in the cell envelope of MAP, suggesting protein interactions in the envelope of this pathogen. Furthermore the identification of antigenic proteins with potential as diagnostic targets was characterized.


Medicine and the Making of a City: Spaces of Pharmacy and Scholarly Medicine in Seventeenth-Century Stockholm.
This essay takes seventeenth-century Stockholm as its point of departure in discussing the many spaces to which early modern medicine belonged, in particular the court, the cityscape, the site of the pharmacy, and the city's Collegium Medicum. It shows how scholarly medicine and pharmacy arose along with the city itself. They were a part of the city and of its many interlaced local, European, and global flows and relationships. Thus the essay offers new perspectives on medicine as part of, and a driving force behind, Stockholm's transition from a medieval town to the capital of an early modern state, as well as the city's integration into the early modern system of global trade. It also shows how a switch of perspective may relocate pharmacy to the center of the seventeenth-century medical world. By focusing on the city, rather than on specific professional groups, the essay seeks to problematize the alleged special importance of physicians for early modern medicine and the view that physicians held a superior status in relation to other medical practitioners, as well as to artisans/craftsmen.


Polymorphisms in the human X-linked pyruvate dehydrogenase E1 alpha gene.
Pyruvate dehydrogenase E1 alpha deficiency is an X-chromosome-linked disorder, often with fatal consequences. We have searched for genetically useful polymorphisms in or near this gene. No restriction fragment length polymorphisms were detected using a battery of 36 different restriction enzymes and probing with a full-length cDNA fragment, or two single-copy genomic fragments located within intron 8, and 15 kb 3' of the coding region, respectively. The chemical cleavage method was then applied to the detection of base changes in or near the gene. One polymorphism was found in exon 8 of the coding region. However, no base changes were detected in intron 3 or in the part of intron 8 covered by fragment gB2. Three blocks of microsatellite DNA containing variable numbers of CA-repeats were isolated from the 5' end of the gene and characterized. Length polymorphisms in these microsatellite DNAs were analysed using the polymerase chain reaction. Although the three loci are tightly linked, the polymorphisms appear not to be in disequilibrium, making them useful markers in linkage studies of the pyruvate dehydrogenase E1 alpha gene. Of 31 females analysed 12(39%) were heterozygous for at least one length polymorphism of the three (CA)n alleles.


Preparation and Identification of a Monoclonal Antibody Against Cystatin C.
Cystatin C (Cys C) has been shown to be an excellent marker of renal function, especially when evaluating the early stages of acute kidney injury. It is less affected by age, gender, muscle mass, and ethnicity. The detection of Cys C is important and has broad application prospects. Therefore, we have developed a panel of monoclonal antibodies against Cys C that can be used to establish an enzyme-linked immunosorbent assay (ELISA) kit and paired for further use in other methods of detecting Cys C. This study describes the preparation, application, and characterization of monoclonal antibodies used in ELISA. The antibodies were developed by PEG fusion of the SP2/0 cells with splenic B cells from Cys C immunized BALB/c mice. Antibody-producing cells were identified by ELISA and Western blot analysis. By way of cloning and screening, four hybridoma cell lines were established. Simultaneously large-scale monoclonal antibodies produced in mice ascites were prepared. The results showed that the cell clone 8D12 could be used in immunohistochemical staining. With the ELISA additivity test, we got a preliminarily finding that the monoclonal antibodies were not on the same epitope. The antibody matching test showed that 5D7 and 7A8 successfully paired with 8D12, and the optimal reaction conditions were initially identified.


Co-induction of hepatic IGF-I and progranulin mRNA by growth hormone in tilapia, Oreochromis mossambiccus.
Like IGF-I, progranulin (pgrn) is a growth factor involved in tumorigenesis and wound healing. We report here the identification and characterization of pgrn cDNA in tilapia and the regulation of its expression by growth hormone (GH). The tilapia pgrn cDNA was cloned by RT-PCR amplification, using gene specific oligonucleotides as amplification primers. The cDNA contains an open reading frame encoding a peptide of 206 amino acid residues (aa) that contains a presumptive signal peptide (23 aa) and two repeat units of granulin (grn, 51 and 52 aa, respectively) franked by a GAP of 49 aa and the carboxyl terminus with 31 aa. The two predicted grn peptides are arranged in tandem repeats interrupted by a GAP peptide. RT-PCR analysis revealed that high levels of prgn mRNA were present in several tissues such as spleen, gastric cecum, intestine, fat tissue, gill, kidney, eye and pancreas, and lower levels in liver, muscle, heart, brain, skin and stomach. Administration of a single dose (500 ng/g body weight) of recombinant seabream growth hormone (rbGH) by intraperitoneal (ip) injection into one-month-old tilapia resulted in an obvious increase of IGF-I and pgrn mRNA (2.7-fold and 2.5-fold, respectively) in the liver at three hours post-GH treatment. The peptide levels of pgrn in the liver of GH-treated fish also were substantially induced over controls at 12h post-GH treatment as detected by western immuno-blot analysis. The co-induction of IGF-I and pgrn following GH treatment may suggest the involvement of pgrn in GH regulated growth in tilapia.


Application of different types of free foot flaps in hand surgery.
From 1987, nine types of free vascularized flaps or combined flaps from the foot were used to treat 26 cases of hand injury with tissue loss. They were: (1) combined flap of 4 toe dorsums, big toe pulp, first toe web, and dorsalis pedis flap with long extensor tendons of the toes, (2) composite skin flap with the second metatarsophalangeal joint, (3) wrap-around flap from the great toe, (4) first toe web flap, (5) toe pulp flap with only an artery and a nerve, (6) wrap-around flap of the great toe with a dorsalis pedis flap, (7) second toe with dorsalis pedis flap, (8) dorsalis pedis flap, and (9) first toe web flap with second metatarsal bone. All flaps survived. All the patients have used their reconstructed hand. Of the final motor functions of the reconstructed hands, 68.8% are excellent, 27.3% are good, 3.9% are fair. Of the final cosmetic results of the reconstructed hands, 76.9% are excellent, 15.3% are good, 7.8% are acceptable. Of the patients, 64.9% are satisfied with the final results of the donor sites, 31.2% feel it is acceptable, and 3.9% feel it is unsatisfactory. The selection, indication, merits and demerits of vascularized foot flaps and attentive points in the operations are discussed in this paper.


Impact of sarcopenia in borderline resectable and locally advanced pancreatic cancer patients receiving stereotactic body radiation therapy.
Total psoas area (TPA), a marker of sarcopenia, has been used as an independent predictor of clinical outcomes in gastrointestinal (GI) cancers as a proxy for frailty and nutritional status. Our study aimed to evaluate whether TPA, in contrast to traditional measurements of nutrition like body mass index (BMI) and body surface area (BSA), was predictive of outcomes in borderline resectable pancreatic cancer (BRPC) and locally advanced pancreatic cancer (LAPC) patients receiving stereotactic body radiation therapy (SBRT). Retrospective analysis of an institutional review board approved database of 222 BRPC and LAPC treated with SBRT from 2009-2016 yielded 183 patients that met our selection criteria of pre-SBRT computed tomography (CT) imaging with an identifiable L4 vertebra. Once the L4 vertebral level was identified, the bilateral psoas muscles were manually contoured. This area was normalized by patient height, with units described in mm2/m2. Receiver operating characteristic (ROC) curves were generated for TPA, BMI, and BSA to elicit clinically relevant cutoffs. Regression and Kaplan-Meier analyses were used to correlate toxicity with survival functions. Low TPA (OR =1.903, P=0.036) was predictive of acute toxicities, and only TPA was predictive of Grade 3 or higher acute toxicities (OR =10.24, P=0.007). Both findings were independent of tumor resectability. Pain (P=0.003), fatigue (P=0.040), and nausea (P=0.039) were significantly associated with low TPA. No association was identified between any measurement of nutritional status and the development of late toxicities, overall survival, local progression or local recurrence. However, BRPC patients survived longer (median =21.98 months) than their LAPC (median =16.2 months) counterparts (P=0.002), independent of nutritional status. TPA measurement is readily available and more specific than BMI or BSA as a predictor of acute radiotoxic complications following SBRT in BRPC/LAPC patients. A TPA of <500 mm2/m2 is a clinically relevant cutoff that can direct physicians to address expected complications of pain, fatigue, and nausea. However, tumor resectability remains as the only predictor of overall survival in this cohort.


Teicoplanin pharmacokinetics in critically ill patients on continuous veno-venous hemofiltration.
Pharmacokinetics of teicoplanin (TP) was assessed in critically ill patients on continuous veno-venous hemofiltration (CVVH), in eleven patients, after the first dose and in another four after repeated administration. The TP peak concentration amounted to 55.44 +/- 15.90 microg/ml and 81.28 +/- 28.55 microg/ml (mean +/- SD), the trough concentration 6.4 +/- 1.7 microg/ml and 21.3 +/- 5.0 microg/ml, the half-life 15.7 +/- 5.7 and 35.1 +/- 12.3 h, the apparent volume of distribution 0.84 +/- 0.22 and 0.48 +/- 0.09 l/kg and the TP clearance 39 +/- 12 and 11 +/- 4 ml/h/kg after the first dose and after repeated administration, respectively. The mean sieving coefficient of TP was 0.15. After a 1,200 mg loading dose, daily maintenance doses of 600 - 1,800 mg were required for achieving trough levels of 15 - 25 microg/ml. Therapeutic drug monitoring is indispensable during CVVH because of a considerable variability of TP pharmacokinetics.


Vietnam's Evolving Healthcare System: Notable Successes and Significant Challenges.
From regional and rural grassroots to a nationwide level, Vietnam has established a four-tiered hierarchical healthcare system, comprising national, provincial, district, and commune healthcare centers. Over the last three decades, alongside increasing provision of universal health insurance coverage and cutting healthcare expenditure, the country has demonstrated its dedication to preventative medicine and health promotion. Recent investment in research, development, and production has led to "homegrown" vaccines for SARS-CoV-2 now undergoing clinical trial. Nevertheless, despite substantial progress in improving health outcomes for the entire population, the healthcare sector experiences significant challenges. The current public system is paper-based, requires digitalization, and lacks information technology support. In common with many other countries, there is a vast disparity in the distribution of healthcare professionals between cities and rural areas, as well as between private and public sectors. Consequently, public healthcare in remote locations is particularly underserved. Moreover, ongoing underfunding caused by high out-of-pocket expenses for the average salary, as well as stigmatization of sensitive health issues by a largely conservative populace, demand a well-articulated and culturally sensitive approach. As the level of smartphone ownership and internet coverage are both comparatively high for Southeast Asia, the introduction of telemedicine, mobile health applications, and other digital health solutions may be both practicable and beneficial. Importantly, in order to develop healthcare facilities and reduce patient direct payments, the key issue of funding must be addressed. In order to overcome disease-related stigma, a locally tailored program of community education, awareness, and engagement is required. In summary, in several ways, Vietnam provides a role model for developing healthcare systems in low- and middle-income countries. There are undoubted hurdles to overcome, but the country continues to construct a healthcare system that is accessible and affordable for the majority.


[Value of acetic acid smear test for cervical cancer screening].
At present, the incidence of cervical cancer is still high in less developed areas of China; one of the reasons is that cytology in screening for cervical cancer is not feasible in these areas. The aim of this study was to analyze the sensitivity and specificity of acetic acid smear test as a cervical cancer screening test, and evaluate the value of this method for cervical cancer screening. Acetic acid smear test was performed on 1997 previously unscreened women aged 35-45 years in Xiangyuan County, Shanxi Province. All women had cervical cytology, testing for high-risk types of human papillomavirus DNA, colposcopy, an endocervical curettage and at least five cervical biopsies. Biopsies were done at the lesions, or one biopsy at 2, 4, 8, 10 o'clock at the squamocolumnar junction in each normal quadrant. According to histological diagnosis, 43 women had CIN II, 31 had CIN III, and 12 had invasive carcinoma. In two women only the endocervix was positive. Smear test yielded normal results in 1445 women (72.4%), low-grade squamous intraepithelial lesions (LSILs, CIN I) in 525 (26.3%), high-grade squamous intraepithelial lesions (HSILs, CIN II- III) in 21 (1.1%), and cancer in 6 (0.3%). With abnormal visual inspection defined as LSILs or worse, the sensitivity of acetic acid smear test for HSILs or worse was 70.9% (61 of 86), the specificity was 74.3% (1420 of 1911). The sensitivity was 64.9% for smaller lesions (37 of 57), and 88.9% for larger lesions (24 of 27) (P=0.03). The sensitivity of colposcopy for high-grade SILs or worse was 81.4% (70 of 86), the specificity was 76.5% (1462 of 1911). This study showed the high specificity and sensitivity of acetic acid smear test as a primary screening test for cervical cancer. Acetic acid smear test and colposcopy have similar specificity profiles for CIN II or more severe lesions. Acetic acid smear test as a primary screening test will be possible and effective with the benefits of low-cost and simple test in low-resource settings.


Effect of barium tetraborate on the separation of tryptic digests of proteins by zone electrophoresis in uncoated capillaries.
A simple, fast, efficient and reproducible method for peptide separations in CZE is reported. It consists in running tryptic digests of peptides in an uncoated capillary, in a BGE composed of tetraborate as a buffering ion, in which the typical sodium counterion is substituted with barium. Efficient absorption of this divalent cation to ionized silanols and barium silicate precipitation seem to be able to shield effectively the silica surface from separands. This is demonstrated by the fact that, when tBa(2+) ions are present in solution (from pH 8.5 up to pH 11.0), the electroendoosmotic flow is reversed; such reversal being progressively higher at higher pH values, by up to a four-fold. Separations become progressively better at higher pH values, whereas at pH 11 in sodium tetraborate they are dramatically worsened. It is further hypothesized that the barium silicate layer further protects the silica surface against dissolution and corrosion which is quite substantial at pH 11.


Hyperhomocysteinemic mice show cognitive impairment without features of Alzheimer's disease phenotype.
Hyperhomocysteinemia (HHcy) is associated with cognitive impairment and Alzheimer's disease. Whether this association is mechanistic remains unclear. Here, we used a mouse model to test the hypothesis that HHcy increases levels of amyloid-β (Aβ) transporters in microvessels that form the blood-brain barrier, elevates Aβ content (Aβ40 and Aβ42) in the brain, and impairs cognitive performance. Mice with HHcy and age-matched, non-HHcy controls (Ctrl) were studied in two age groups: adult (6.2 ± 0.4 months of age) and old (19 ± 2.0 months of age). Levels of Aβ transporters, RAGE, LRP1, and Pgp, were not different between HHcy and Ctrl mice. Though there was an increase in overall brain Aβ levels with age, there were no differences between HHcy and Ctrl groups in cortex, hippocampus, or midbrain/diencephalon. Despite the lack of difference in Aβ, old mice with HHcy showed significant cognitive impairment on Morris water maze tests compared with Ctrl mice. We conclude that HHcy leads to cognitive impairment without many of the changes currently thought to be relevant to promoting the AD phenotype.


Comparing intralesional triamcinolone and verapamil-triamcinolone injections in keloids: A single-blinded randomised clinical trial.
In this clinical trial, we investigated the efficacy of two treatment methods for keloids resulting from surgical incisions: intralesional triamcinolone injections alone versus in combination with verapamil. Patients were divided into two groups: one received triamcinolone alone (Group T) and the other received a triamcinolone-verapamil blend (Group VT). Regular treatments were conducted until the keloids were nearly flat or for a maximum of eight sessions. Both groups showed significant improvements, but Group VT saw quicker resolution of skin redness and needed fewer sessions. Though the Vancouver Scar Scale (VSS) scores were generally similar across both groups, Group VT exhibited greater improvements, leading to lower final scores. The VT group also attained normal scar flexibility faster than the T group. These findings suggest that the combination of verapamil and triamcinolone provides a more effective treatment for keloids, thereby highlighting the potential of verapamil in scar reduction.


Reasons why women have induced abortions: a synthesis of findings from 14 countries.
Many reasons inform women's reproductive decision-making. This paper aims to present the reasons women give for obtaining induced abortions in 14 countries. We examined nationally representative data from 14 countries collected in official statistics, population-based surveys, and facility-based surveys of abortion patients. In each country, we calculated the percentage distribution of women who have abortions by main reason given for the abortion. We examined these reasons across countries and within countries by women's sociodemographic characteristics (age, marital status, educational attainment, and residence). Where data are available, we also studied the multiple reasons women give for having an abortion. In most countries, the most frequently cited reasons for having an abortion were socioeconomic concerns or limiting childbearing. With some exceptions, little variation existed in the reasons given by women's sociodemographic characteristics. Data from three countries where multiple reasons could be reported in the survey showed that women often have more than one reason for having an abortion. This study shows that women have abortions for a variety of reasons, and provides a broad picture of the circumstances that inform women's decisions to have abortions. Future research should examine in greater depth the personal, social, economic, and health factors that inform a woman's decision to have an abortion as these reasons may shed light on the potential consequences that unintended births can have on women's lives.


Differentiation of metastatic follicular thyroid cancer from hepatocellular carcinoma using Hep Par 1.
Hepatocellular carcinoma usually arises in a cirrhotic liver. Multiple hepatic nodules in a non-cirrhotic liver are more likely to be metastatic. The primary focus commonly arises from the gastrointestinal tract, breast or lung, but in the absence of these a primary liver pathology must be considered. The case is reported of a middle-aged woman presenting with multiple nodules on computed tomography with no clinically apparent primary for whom results of initial diagnostic investigations were potentially misleading.


Oxygen Isotopic Composition of Some Right-and Left-Coiled Foraminifera.
Right-and left-coiled foraminiferal species were collected from living and fossil faunas from different habitats. A difference in the oxygen isotopic composition of right-and left-coiled specimens was observed. Deposition of calcium carbonate by right-and left-coiled Foraminifera takes place, at least in the species measured, during non-coincident periods of the year.


Performance evaluation of algae assisted microbial fuel cell under outdoor conditions.
This study reports for the first time an operation of an outdoor algae assisted Microbial Fuel Cell (MFC). The MFC (10 L) comprised of low-cost materials like rock phosphate blended clayware & low-density polyethylene bags as anodic & cathodic chamber respectively. Algae biomass after lipid extraction at 2 g/l served as electron donor at the anode. Chlorella vulgaris at cathode provided oxygen as electron acceptor and served as lipid source. The MFCs performed well in all aspects namely energy recovery, algae productivity, and cost of operation. The 5% RP-MFCs gave 0.307 kg/m3d algal productivity, 0.09 kg/m3d lipid productivity, and 11.5318 kWh/m3 of net energy recovery (NER). Rock phosphate served as a slow and constant source of phosphorus supporting algae growth. Proteobacteria (45.14%) were the dominant phyla while Alicyliphilus (5.46%) and Dechloromonas (4.74%) were the dominant genera at the anode. The estimated cost of the system was $11.225 only.


Activation of an endogenous suicide response after perturbation of rRNA synthesis leads to neurodegeneration in mice.
Transcription of rRNA genes is essential for maintaining nucleolar integrity, a hallmark for the healthy state and proliferation rate of a cell. Inhibition of rRNA synthesis leads to disintegration of the nucleolus, elevated levels of p53, and induction of cell suicide, identifying the nucleolus as a critical stress sensor. Whether deregulation of rRNA synthesis is causally involved in neurodegeneration by promoting cell death and/or by inhibiting cellular growth has however not been addressed. The transcription factor TIF-IA plays a central role in mammalian rRNA synthesis, regulating the transcriptional activity of RNA polymerase I. To investigate the consequences of nucleolar perturbation in the nervous system, we have chosen to specifically ablate the gene encoding the transcription factor TIF-IA in two different contexts: neural progenitors and hippocampal neurons. Here, we show that ablation of TIF-IA leads to impaired nucleolar activity and results in increased levels of the proapoptotic transcription factor p53 in both neural progenitors and hippocampal neurons but induces rapid apoptosis only in neural progenitors. Nondividing cells of the adult hippocampus are more refractory to loss of rRNA transcription and face a protracted degeneration. Our study provides an unexploited strategy to initiate neurodegeneration based on perturbation of nucleolar function and underscores a novel perspective to study the cellular and molecular changes involved in the neurodegenerative processes.


Association between 24-hour ambulatory blood pressure and erythrocyte n-3 polyunsaturated fatty acids in Korean subjects with hypertension.
N-3 polyunsaturated fatty acids (PUFAs) are known to have antihypertensive properties, but the association between 24-hour ambulatory blood pressure and the tissue content of n-3 PUFA remains controversial. The purpose of the present study was to investigate the hypothesis that the level of erythrocyte n-3 PUFA is inversely related with 24-hour ambulatory blood pressure after adjustment for relevant confounders. Fifty-one male and 49 female Korean patients were included in this study. Twenty-seven of the patients were defined as having hypertension. There were significant differences in age, body mass index, sex, marital status, and family history of hyperlipidemia between hypertensive and nonhypertensive subjects, and these factors were therefore considered to be confounding factors. Multivariate-adjusted regression analysis showed that erythrocyte fatty acids were not significantly associated with the risk of hypertension after adjusting for confounders. However, Pearson correlation analysis showed that 24-hour ambulatory systolic blood pressure (SBP) was significantly and negatively correlated with n-3 PUFA (r = -0.228, P = .027) and eicosapentaenoic acid (r = -0.270, P = .008), but not with docosahexaenoic acid (r = -0.156, P = .131). Multivariate-adjusted regression analysis also showed that intake of protein, vitamin B(2), vitamin E, and cholesterol increased the risk of hypertension after adjusting for confounders. In addition, Pearson correlation analysis showed that fat and cholesterol consumption was positively correlated with SBP, but carbohydrate intake was negatively correlated with SBP. In conclusion, erythrocyte n-3 PUFA did not reduce the risk of hypertension but were negatively correlated with 24-hour ambulatory SBP in the Korean population.


Combining chemotherapy with biological response modifiers in treatment of cancer.
Combinations of chemotherapeutic agents with various biological response modifiers ("biomodulators") in the treatment of cancer are now being tested. Since most (though not all) chemotherapy is immunosuppressive, the schedules by which the chemotherapeutic agents and the biomodulators are combined are of critical importance. This review summarizes the effects of chemotherapy on immunity and suggests the most logical ways in which these categories of drugs might be combined with biomodulators. Specific examples are also provided of combination therapies that have proved useful or that are of significant potential utility. An understanding of the types of action and the mechanisms of action of specific chemotherapeutic agents and specific biomodulators may help to achieve additive effects (possibly synergism) with these combinations. At the very least, that understanding will avoid the hazard of one modality's negating the effects of the other.


Regional optic nerve damage in experimental mouse glaucoma.
To assess the relationship between regional variation of axon loss and optic nerve head anatomy in laser-induced experimental glaucoma in the mouse. Experimental glaucoma was induced unilaterally in eight NIH Swiss black mice. Intraocular pressure (IOP) was measured for 12 weeks, and the mice were killed. The eyes were enucleated, and both optic nerves were dissected and processed conventionally for electron microscopy. Low- and high-magnification images of the optic nerve cross sections 300 microm posterior to the globe were collected systematically and masked before analysis. For each nerve, cross-sectional area was measured in low-magnification micrographs. Axon number and density were determined in the high-magnification micrographs. Loss of axonal density was compared between the superior and inferior and nasal and temporal areas of the optic nerve cross section. Additional cross-section micrographs were collected at 10- or 20-microm intervals throughout the optic nerve head. In the treated (glaucoma) eyes, mean IOP was 44% higher than that in the control eyes. The optic nerve cross-sectional area, mean axonal density, and total axonal number were significantly less than those in the control eyes (P < 0.01 for each). Axon loss in the superior optic nerve was greater than in the inferior optic nerve in each glaucomatous eye (P = 0.012). The ratio of axonal density in the superior and inferior optic nerve (superior-to-inferior [S/I] ratio) in all treated eyes was <1.0 and significantly lower than that in the control eyes (P = 0.012). The central retinal vessels occupied approximately 20% of the central optic nerve head cross-sectional area, gradually shifted position ventrally as they progressed toward the scleral foramen (the mouse does not have a lamina cribrosa), and exited the inferior retrobulbar optic nerve adjacent to the posterior of the globe. Ocular hypertension in the mouse eye sufficient to cause optic nerve damage induces preferential loss of superior optic nerve axons. Optic nerve axon loss appeared less among the axons that were near the major optic nerve blood vessels at the scleral foramen. Topographic differences in optic nerve axon loss should be considered when evaluating optic nerve damage in experimental laser-induced glaucoma in the mouse.


Characterization of lung function impairment in adults with bronchiectasis.
Characteristics of lung function impairment in bronchiectasis is not fully understood. To determine the factors associated with lung function impairment and to compare changes in spirometry during bronchiectasis exacerbation and convalescence (1 week following 14-day antibiotic therapy). We recruited 142 patients with steady-state bronchiectasis, of whom 44 with acute exacerbations in the follow-up were included in subgroup analyses. Baseline measurements consisted of chest high-resolution computed tomography (HRCT), sputum volume, purulence and bacteriology, spirometry and diffusing capacity. Spirometry, but not diffusing capacity, was examined during acute exacerbations and convalescence. In the final multivariate models, having bronchiectasis symptoms for 10 years or greater (OR = 4.75, 95%CI: 1.46-15.43, P = 0.01), sputum culture positive for Pseudomonas aeruginosa (OR = 4.93, 95%CI: 1.52-15.94, P<0.01) and HRCT total score being 12 or greater (OR = 7.77, 95%CI: 3.21-18.79, P<0.01) were the major variables associated with FEV1 being 50%pred or less; and the only variable associated with reduced DLCO was 4 or more bronchiectatic lobes (OR = 5.91, 95%CI: 2.20-17.23, P<0.01). Overall differences in FVC and FEV1 during exacerbations and convalescence were significant (P<0.05), whereas changes in other spirometric parameters were less notable. This applied even when stratified by the magnitude of FEV1 and DLCO reduction at baseline. Significant lung function impairment should raise alert of chest HRCT abnormality and sputum culture positive for Pseudomonas aeruginosa, in patients with predominantly mild to moderate steady-state bronchiectasis. Acute exacerbations elicited reductions in FVC and FEV1. Changes of other spirometric parameters were less significant during exacerbations. ClinicalTrials.gov NCT01761214.


Scaffolding proteins in highly purified rat olfactory cilia membranes.
Odour-mediated signal transduction is a complex process that occurs in the cilia of olfactory sensory neurons. To gain insight in to the molecular organization of the odour transduction machinery, we developed a procedure to purify olfactory cilia membranes by differential centrifugation of rat olfactory epithelium extracts. We tested whether known scaffolding proteins that might participate in the assembly of the complex chemotransduction apparatus are present in the purified membrane fraction. Utilizing immunoblotting and immunohistochemistry, we show that the multidomain scaffolding proteins ProSAP/Shanks and calcium/calmodulin-dependent serine protein kinase CASK are present in the olfactory cilia. Ion channels involved in chemotransduction could be reconstituted into planar lipid bilayers for electrophysiological recordings. Our procedure should allow the identification of further chemotransduction-related proteins.


Abstinence and initiation of treatment following inpatient detoxification.
This prospective cohort study compared in-patients who remained abstinent and initiated aftercare treatment following detoxification with those who did not. Of 110 patients enrolled, 58% (46/79) were totally abstinent and 72% (67/93) initiated treatment during the first 30 days following hospital discharge. Patients who relapsed after hospital discharge were more likely than those who remained abstinent to have a primary drug-use disorder (p = 0.05), prior mental health treatment (p = .007), or previous incarceration (p = 0.035). Those who initiated aftercare treatment were less likely to have had prior mental health treatment than those who did not (p = .046).


Effects of the anticholinergic drug prifinium bromide on urinary bladder contractions in rat in vivo and in guinea-pig in vitro.
The parenteral and enteral effects of prifinium bromide (CAS 4630-95-9; in the following referred to as prifinium), a quaternary ammonium anticholinergic drug, were investigated on contractions of the rat urinary bladder by cystometry and compared with those of atropine, oxybutynin and terodiline. Additionally, in vitro experiments were carried out with the isolated guinea-pig detrusor muscle to clarify the mechanisms of action of these effects. In intravenous doses, all the drugs reduced the amplitude of the contractions in the cystometric studies. The inhibition was dose-dependent, but was not entirely even at the respective largest doses. According to the 40% inhibitory doses, prifinium was as active as atropine, and 10 and 100 times more active than oxybutynin and terodiline, respectively. The potency ratios of the drugs in their in vivo effects were in good agreement with those of their in vitro anticholinergic effects, which were determined with carbachol-induced contractions in the isolated guinea-pig detrusor muscle. On the other hand, in the in vitro studies, prifinium and atropine had little or no effect on contractions induced by electrical stimulation, KCl and BaCl2, whereas oxybutynin and terodiline antagonized all of the stimuli to a similar extent. These findings indicate that the anticholinergic activity of prifinium may be only one factor in the mechanisms of its in vivo inhibition of the rat bladder contractions. Finally, intraduodenal doses of prifinium also inhibited the contractions of the rat bladder, and the effects of the drug by this route were almost the same as those of oxybutynin and terodiline.


Rheology of hyaluronic acid and dynamic facial rejuvenation: Topographical specificities.
Sound knowledge of the rheology of hyaluronic acids is fundamental for facial rejuvenation procedures. Hyaluronic acid implants are subjected to complex mechanical forces within the facial tissues that vary depending on the anatomical region. Analysis of these forces is important to establish the rheological specifications of hyaluronic acid implants in each specific zone. This approach will optimize the correction of age-related loss of volume, since the filler will be chosen as a function of the mechanics of the anatomical zone, with the objective to respect facial dynamics.


A finite element analysis of ceramic restorations in endodontically treated premolars.
To investigate the level and distribution of stresses in endodontically treated maxillary premolar teeth restored using various cavity designs of bonded all-ceramic restorations. The hypothesis tested was that the various all-ceramic approaches, including incorporating a pulp chamber extension in the restoration, had no influence on the stresses in the restored tooth unit. Finite element packages Patran and Abaqus were used for the stress analysis. The cavity designs investigated include: (1) inlay (I); (2) inlay with palatal cusp coverage (IPC); (3) onlay (O); (4) inlay with pulp chamber extension (IPE); (5) inlay with palatal cusp coverage and pulp chamber extension (IPCPE); and (6) onlay with pulp chamber extension (OPE). In each case, tensile stresses were found to be concentrated subjacent to the occlusal fossa. Peak tensile stress and peak shear stress values along the tooth/restoration interface for IPC, O IPCPE and OPE cavity designs were found to be associated with the axiogingival line angle. Overall, the order of the various forms of restoration investigated in terms of the maximum principal stress (from greatest to lowest) was as follows: IPE > IPCPE > OPE > I > IPC > O.


RURS' elbow guard: an innovative treatment of the thumb-sucking habit in a child with Hurler's syndrome.
Thumb sucking is the process of sucking on the thumb for oral pleasure. Thumb and finger sucking habits, or nonnutritive sucking, are considered to be the most prevalent of oral habits. Some parents are concerned by thumb sucking and may even try to restrain the infant or child. In most cases, this is not necessary. Most children stop thumb sucking on their own. When older children continue to suck their thumbs, it could mean they are bored, anxious, or have emotional problems such as depression. This article presents a case report of a child with Hurler's syndrome along with thumb sucking/biting habit. Hurler's syndrome, also known as mucopolysaccharidosis I, is a rare condition inherited as an autosomal-recessive trait. It represents the classical prototype of mucopolysaccharide disorder. A unique appliance to prevent thumb sucking/biting was developed and termed as "RURS' elbow guard," which was successfully used to break thumb sucking of the child with Hurler syndrome. The present report also describes the steps in fabrication of this new habit-breaking appliance, which is also designed to protect the finger from the effects of the sucking habit.


Chemical Cutting of Perovskite Nanowires into Single-Photon Emissive Low-Aspect-Ratio CsPbX3 (X=Cl, Br, I) Nanorods.
Post-synthetic shape-transformation processes provide access to colloidal nanocrystal morphologies that are unattainable by direct synthetic routes. Herein, we report our finding about the ligand-induced fragmentation of CsPbBr3 perovskite nanowires (NWs) into low aspect-ratio CsPbX3 (X=Cl, Br and I) nanorods (NRs) during halide ion exchange reaction with PbX2 -ligand solution. The shape transformation of NWs-to-NRs resulted in an increase of photoluminescence efficiency owing to a decrease of nonradiative decay rates. Importantly, we found that the perovskite NRs exhibit single photon emission as revealed by photon antibunching measurements, while it is not detected in parent NWs. This work not only reports on the quantum light emission of low aspect ratio perovskite NRs, but also expands our current understanding of shape-dependent optical properties of perovskite nanocrystals.


Bioequivalence and pharmacokinetic evaluation of two tablet formulations of carvedilol 25-mg: a single-dose, randomized-sequence, open-label, two-way crossover study in healthy Chinese male volunteers.
Carvedilol is a nonselective-blocking agent and is used in the treatment of hypertension and angina pectoris. The aim of this study was to evaluate bioequivalence of two 25-mg tablet formulations of carvedilol following single oral dose in adult male volunteers. This was a randomized, single-dose, open-label, crossover bioequivalence study. Plasma samples were collected before dosing and at 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12 and 24 h after dosing. Plasma concentrations of Carvedilol were determined by using a validated LC-MS/MS method. Statistical analysis of the pharmacokinetic parameters Cmax, AUC0-24, and AUC0-∞ was conducted to determine bioequivalence. 23 healthy male Chinese volunteers were enrolled in the study. The mean (SD) Cmax, AUC0-24, and AUC0-∞ values after administration of the test and reference formulations, respectively, were as follows: 73.71 (34.04) vs. 78.93 (43.64) ng/mL, 285.1 (147.0) vs. 296.9 (176.1) ng/mL · h, and 296.5 (161.4) vs. 303.4 (177.9) ng/mL · h. The 90% CIs of the ratios (test vs. reference) for the ln-transformed Cmax, AUC0-24, and AUC0 - ∞ were 85.3% to 114.3%, 90.4% to 107.6%, and 90.9% to 108.4%, respectively, meeting the criteria of SFDA, FDA and EMEA for bioequivalence. The relative bioavailability of the test formulation to reference formulation was 100.1%. Both formulations were generally well tolerated and no serious AEs were reported in the study. The 90% CIs for the ratios of mean Cmax, AUC0-24, and AUC0-∞ met the regulatory criteria for bioequivalence.


Cystic management in a 10-year old child.
Cysts are among the most common lesions found in the oral cavity. These may be developmental in origin or secondary to chronic infections. Untreated, cysts may expand causing local tissue destruction and deformities. Basically, two treatment methods are employed. Enucleation and/or Marsupialization. The following case involves a child treated at the College of Dentistry, University of the Philippines, for a large cystic lesion involving the permanent cuspid and the deciduous dentition. The lesion was accidentally discovered on a panoramic radiograph. The child underwent extraction of deciduous teeth and marsupialization, which later helped in the eruption of the malposed permanent teeth.


Auxiliary Partial Orthotopic Living Liver Transplant for Wilson Disease.
Wilson disease is a genetic disease involving copper metabolism disturbances that result in copper accumulations, especially in the liver and brain. Wilson disease can be treated with pharmacologic agents, such as chelators that induce urinary excretion of copper or zinc salts that inhibit copper absorption in the digestive tract. Liver transplant is the only treatment option for Wilson disease when liver failure has occurred. In some patients, that is, in those with Child-Pugh A score, neurologic disease can be seen without hepatic failure. Our recommendation is for these patients to have auxiliary partial orthotopic liver transplant. Here, we present a 36-year-old male patient with neurologic disease associated with Wilson disease who had successful related living-donor auxiliary partial orthotopic liver transplant using a left lobe. The patient, as a result of neurologic symptoms that included tremor walking and speaking problems and low serum ceruloplasmin level of 7 mg/dL, was diagnosed with Wilson disease, and a liver biopsy was performed. Chronic necroinflammatory disease activity was 4/18, and the patient received chelation treatment. His hepatic functions were normal. The donor was the patient's 57-year-old father whose liver function tests were also normal. The graft-to-recipient weight ratio was 1% using a left lobe graft. After transplant, serum ceruloplasmin levels on day 15 and month 1 were 14 and 19 mg/dL. At month 1, liver function tests were normal. Doppler ultrasonography showed normal vascular flow of the native liver and the graft. The patient's neurologic symptoms were progressively reduced. Progressive neurologic deterioration with no hepatic insufficiency is considered a suitable indication for auxiliary partial orthotopic liver transplant; this procedure is suggested before the neurologic and liver failure symptoms of Wilson disease occur.


Prediction of paclitaxel resistance in breast cancer: is CYP1B1*3 a new factor of influence?
This article focuses on the recent findings by Marsh and colleagues, and also discusses recent findings with regards to breast cancer. Taxanes are amongst the most active agents in the treatment of breast cancer. However, many tumors are intrinsically resistant. Therefore, it would be an enormous progress, if factors could be identified that reliably differentiate between taxane-sensitive and -resistant patients. Marsh and colleagues analyzed the CYP1B1*3 (Val432Leu) polymorphism in patients with high-risk stage III and IV breast cancer, who received dose-intense paclitaxel in combination with doxorubicin and cyclophosphamide. They report for the first time that patients with two leucine alleles in codon 432 of CYP1B1 experience a longer progression-free survival compared with patients with the Val/Leu or Val/Val genotypes. If confirmed in independent cohorts CYP1B1*3 may prove to be an important factor that helps to differentiate between paclitaxel-sensitive and resistant breast cancer patients. However, the mechanism behind the association between CYP1B1*3 and prognosis of paclitaxel-treated patients remains unclear. Several studies provide strong evidence that CYP1B1 does not influence tumor progression independently from paclitaxel chemotherapy, and that CYP1B1 itself does not alter paclitaxel resistance. In addition, CYP1B1 mRNA expression does not correlate with paclitaxel sensitivity of primary tumor cells. Although still speculative, a possible explanation is an association between CYP1B1*3 with still unknown factors that, on their part, influence paclitaxel sensitivity. In the future, studies with SNP chips and studies on the transcriptome, proteome and metabolome level should be performed in order to identify signatures differentiating between paclitaxel-sensitive and -resistant patients.


Widespread effects of alcohol on white matter microstructure.
Evidence suggests that chronic misuse of alcohol may preferentially affect the integrity of frontal white matter (WM) tracts, which can impact executive functions important to achieve and maintain abstinence. Global and regional WM microstructure was assessed using diffusion magnetic resonance measures of fractional anisotropy (FA) for 31 abstinent alcoholics (ALC) with an average of 25 years of abuse and approximately 5 years of sobriety and 20 nonalcoholic control (NC) participants. Data processing was conducted with FreeSurfer and FSL processing streams. Voxelwise processing of the FA data was carried out using tract-based spatial statistics. Clusters of significance were created to provide a quantitative summary of highly significant regions within the voxelwise analysis. Widespread, bilateral reductions in FA were observed in ALC as compared to NC participants in multiple frontal, temporal, parietal, and cerebellar WM tracts. FA in the left inferior frontal gyrus was associated with drinking severity. This study found widespread reductions in WM integrity in a group of ALC compared to NC participants, with most pronounced effects in frontal and superior tracts. Decreased FA throughout the frontostriatal circuits that mediate inhibitory control may result in impulsive behavior and inability to maintain sobriety.


WATER FROM DIFFERENT SOURCES USED FOR THE IRRIGATION OF VEGETABLES TO BE MARKETED: RESEARCH ON Cryptosporidium spp., Giardia spp., AND COLIFORMS IN PARANA, BRAZIL.
The aim of this work was to compare, from a parasitological ( Cryptosporidium spp. and Giardia duodenalis), bacteriological (total and thermotolerants coliforms) and physicochemical perspective, water sources used for drinking and irrigation of vegetables intended to be sold for human consumption. From January 2010 to May 2011, samples of different water sources from vegetable producing properties were collected; 100 liters for parasitological analysis, 200 mL for bacteriological analysis, and five liters for physicochemical analysis. Water samples were filtered under vacuum with a kit containing a cellulose acetate membrane filter, 1.2 µm (Millipore(r), Barueri, SP, Brazil). The material retained on the membrane was mechanically extracted and analyzed by direct immunofluorescence (Merifluor(r)kit). From 20 rural properties investigated, 10 had artesian wells (40 samples), 10 had common wells (40 samples), and one had a mine (four samples), the latter contaminated by Cryptosporidium spp. In samples from artesian wells, 90 to 130 meters depth, 42.5% were positive for total coliforms and 5.0% were identified to have abnormal coloration. From the samples of common wells, 14 to 37 meters depth, 87.5% were contaminated with total coliforms, 82.5% were positive for thermotolerant coliforms, and 12.5% had color abnormalities. We did not detect the presence of Giardia spp. or Cryptosporidium spp. in artesian and common wells. The use of artesian or common wells is an important step in the control of the spreading of zoonoses, particularly Cryptosporidium spp. and Giardia spp., as well as artesian wells for coliform control in local production of vegetables to be marketed.


Genomic analysis of the smallest giant virus--Feldmannia sp. virus 158.
Genomic analysis of Feldmannia sp. virus 158, the second phaeovirus to be sequenced in its entirety, provides further evidence that large double-stranded DNA viruses share similar evolutionary pressures as cellular organisms. Reductive evolution is clearly evident within the phaeoviruses which occurred via several routes: the loss of genes from an ancestral virus core genome most likely through genetic drift; and as a result of relatively large recombination events that caused wholesale loss of genes. The entire genome is 154,641 bp in length and has 150 predicted coding sequences of which 87% have amino acid sequence similarities to other algal virus coding sequences within the family Phycodnaviridae. Significant similarities were found, for thirty eight coding sequences (25%), to genes in gene databanks that are known to be involved in processes that include DNA replication, DNA methylation, signal transduction, viral integration and transposition, and protein-protein interactions. Unsurprisingly, the greatest similarity was observed between the two known viruses that infect Feldmannia, indicating the taxonomic linkage of these two viruses with their hosts. Moreover, comparative analysis of phycodnaviral genomic sequences revealed the smallest set of core genes (10 out of a possible 31) required to make a functional nucleocytoplasmic large dsDNA virus.


Squalene synthase: a critical enzyme in the cholesterol biosynthesis pathway.
High levels of plasma low-density lipoprotein cholesterol (LDL-C) are a significant risk factor for heart disease. Statins (3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors) have been extensively used to treat high-plasma LDL-C levels and are effective in preventing heart disease. However, statins can be associated with adverse side effects in some patients and do not work effectively in others. As an alternative to statins, the development of cholesterol-lowering agents that directly inhibit squalene synthase have shown promise. Clinical studies have shown that squalene synthase inhibitors are effective in lowering plasma levels of total cholesterol and LDL-C. Squalene synthase plays an important role in the cholesterol biosynthesis pathway as it is responsible for the flow of metabolites into either the sterol or the non-sterol branches of the pathway. In addition, variants of the squalene synthase gene appear to modulate plasma cholesterol levels in human populations and therefore may be linked to cardiovascular disease. In this review, we examine squalene synthase and the gene that codes for it (farnesyldiphosphate farnesyltransferase 1). In particular, we investigate their role in the regulation of cellular and plasma cholesterol levels, including data that suggest that squalene synthase may be involved in the etiology of hypercholesterolemia.


Mitochondrial myopathy, cardiomyopathy, and pontine signal changes in an adult patient with isolated complex II deficiency.
Mitochondrial disorders resulting from an isolated deficiency of complex II of the respiratory chain is rarely reported. The phenotypic spectrum associated with these disorders is heterogeneous and still expanding. This report describes a patient who presented with myopathy, dilated cardiomyopathy, and pontine signal changes on magnetic resonance imaging. Muscle biopsy showed total absence of succinate dehydrogenase on enzyme histochemistry, negative succinate dehydrogenase subunit A (SDHA) activity on immunohistochemistry, and ultrastructural evidence of mitochondrial aggregates of varying sizes confirming the diagnosis of complex II deficiency. A unique phenotype with complex II deficiency is reported.


Linkage analysis between manic-depressive illness and the region on chromosome 15q involved in Prader-Willi syndrome, including two GABAA receptor subtype genes.
Cooccurrence of Prader-Willi syndrome and psychosis has been reported in a few cases. Prader-Willi syndrome is most often associated with interstitial deletion or uniparental disomy of chromosome 15q11-q13. The cooccurrence of Prader-Willi syndrome and psychosis may thus be due to deletion of, or in the case of uniparental disomy, duplication of a gene involved in the etiology of psychosis, possibly manic-depressive illness localized in this region. The region contains two assumed candidate genes for manic-depressive illness, the alpha 5 and beta 3 subunits of the gamma-aminobutyric acid (GABA)A receptor. This study investigates linkage between manic-depressive illness and this region. Furthermore, an additional case with Prader-Willi syndrome and psychosis is briefly described. No evidence of linkage was found assuming dominant or recessive modes of inheritance. Linkage to the GABAA receptor subunits was excluded assuming a dominant mode of transmission for all models, and to the proximal part of the chromosome 15q11-q13 region for broader phenotypic models. Negative though largely inconclusive lod scores were obtained assuming a recessive mode of transmission; however close linkage to the beta 3 subtype of the GABAA receptor was excluded.


How does neuropathophysiology affect the signs and symptoms of spinal disease?
A complex relationship exists between back pain and the presence of spinal disease. Particularly in chronic situations, back pain and its behavioural and emotional consequences are as likely to reflect the influence of psychosocial factors as any underlying spinal pathology. Nevertheless, physical factors are clearly important and it is significant that whereas in normal discs only the outer third of the annulus fibrosus is innervated, a much more extensive innervation develops in the presence of degeneration. Inflammation, as evidenced by leukocyte infiltration and expression of inflammatory mediators, is associated with disc degeneration and serves to alter the neural responses resulting in local and referred pain. It is probable that similar inflammatory processes, as well as direct root compression, contribute to radicular symptoms following disc herniation. An appreciation of these mechanisms encourages the search for novel treatments and permits a more rational and effective use of existing strategies for relieving pain.


Identifying quantitative trait locus by genetic background interactions in association studies.
Association studies are designed to identify main effects of alleles across a potentially wide range of genetic backgrounds. To control for spurious associations, effects of the genetic background itself are often incorporated into the linear model, either in the form of subpopulation effects in the case of structure or in the form of genetic relationship matrices in the case of complex pedigrees. In this context epistatic interactions between loci can be captured as an interaction effect between the associated locus and the genetic background. In this study I developed genetic and statistical models to tie the locus by genetic background interaction idea back to more standard concepts of epistasis when genetic background is modeled using an additive relationship matrix. I also simulated epistatic interactions in four-generation randomly mating pedigrees and evaluated the ability of the statistical models to identify when a biallelic associated locus was epistatic to other loci. Under additive-by-additive epistasis, when interaction effects of the associated locus were quite large (explaining 20% of the phenotypic variance), epistasis was detected in 79% of pedigrees containing 320 individuals. The epistatic model also predicted the genotypic value of progeny better than a standard additive model in 78% of simulations. When interaction effects were smaller (although still fairly large, explaining 5% of the phenotypic variance), epistasis was detected in only 9% of pedigrees containing 320 individuals and the epistatic and additive models were equally effective at predicting the genotypic values of progeny. Epistasis was detected with the same power whether the overall epistatic effect was the result of a single pairwise interaction or the sum of nine pairwise interactions, each generating one ninth of the epistatic variance. The power to detect epistasis was highest (94%) at low QTL minor allele frequency, fell to a minimum (60%) at minor allele frequency of about 0.2, and then plateaued at about 80% as alleles reached intermediate frequencies. The power to detect epistasis declined when the linkage disequilibrium between the DNA marker and the functional polymorphism was not complete.


Complete genome sequence and phylogenetic analysis of hepatitis B virus (HBV) isolates from patients with chronic HBV infection in Korea.
Although there is a report of high rate of hepatitis B virus (HBV) infection in South Korea, only a few entire genome sequences of HBV isolates from Korea have been reported. To obtain the complete nucleotide sequence of the Korean HBV, viral DNA was extracted from sera of Korean patients with chronic HBV infection who have not been exposed to any antiviral treatment. Complete genomic sequences were determined on three Korean HBV isolates. The entire genomic length of Korean HBV isolates, designated as KUHB84, KUHB81, and KUHB95, was 3,215 base pairs. No deletions and insertions were observed. Core promoter mutations (T1762/A1764) were detected in two isolates, KUHB84 and KUHB95. Phylogenetic analysis based on the entire genomic sequences showed that the Korean HBV isolates were genotype C and related closely to the Japanese HBV.


Long-term outcome of clozapine use for psychosis in parkinsonian patients.
A retrospective analysis was carried out on 39 parkinsonian patients on clozapine treatment >/=24 months for psychosis. The cohort had a mean age of 76 years and an average clozapine dose of 47 mg/day over 60 months of clozapine use. Of 39 patients, 13 (33%) patients were eventually admitted to nursing homes, 6 (46%) of whom died over a period of 5 years. The overall 5-year mortality rate in this cohort was 44% (17/39). Of 39 patients, 33 (85%) had continued partial/good response and 5 (13%) had complete resolution of psychosis. None discontinued clozapine due to motor worsening. Among patients who responded early on, the long-term efficacy of clozapine for psychosis was sustained. The risk of nursing home placement and mortality among parkinsonian patients treated with clozapine for psychosis in this geriatric cohort was better than that reported previously. Our data are more consistent with recently published long-term outcome data suggesting an improvement in the prognosis of parkinsonian patients with psychosis with the use of atypical antipsychotic agents such as clozapine.


Graphic kinematics, visual virtual work and elastographics.
In this paper, recent progress in graphic statics is combined with Williot displacement diagrams to create a graphical description of both statics and kinematics for two- and three-dimensional pin-jointed trusses. We begin with reciprocal form and force diagrams. The force diagram is dissected into its component cells which are then translated relative to each other. This defines a displacement diagram which is topologically equivalent to the form diagram (the structure). The various contributions to the overall Virtual Work appear as parallelograms (for two-dimensional trusses) or parallelopipeds (for three-dimensional trusses) that separate the force and the displacement pieces. Structural mechanisms can be identified by translating the force cells such that their shared faces slide across each other without separating. Elastic solutions can be obtained by choosing parallelograms or parallelopipeds of the appropriate aspect ratio. Finally, a new type of 'elastographic' diagram-termed a deformed Maxwell-Williot diagram (two-dimensional) or a deformed Rankine-Williot diagram (three-dimensional)-is presented which combines the deflected structure with the forces carried by its members.


[Results of comprehensive data collection concerning urologic laparoscopy].
To evaluate the current status of laparoscopy, the "Working Group Laparoscopy" of the German Urological Association performed a questionnaire among urologists in Germany. Of 300 questionnaires 183 were returned and analyzed (61%): 54% of the departments already performed laparoscopy and another 50% are planning to introduce this technique. The major concerns are economical (70%), long learning curve (92%), investment (53%), and lack of scientific data (76%). Simple nephrectomy, cryptorchism, and varicoceles are treated by 66, 59, and 58 of the 96 departments laparoscopically (of 183 resp.). Laparoscopic surgery for radical prostatectomy and tumor nephrectomy is done by 32 and 34 of 96 departments. Only a minority of the centers performs more than 40 laparoscopies per year and indication. Compared to a survey conducted in 1995, the acceptance level of this technique has increased (100% vs 48%). Only a minority of the departments performs more than 40 laparoscopic interventions per year for one indication.


Proposal of nursing care plan in people hospitalized with AIDS.
OBJECTIVE to elaborate and validate a proposal for a nursing care plan in people hospitalized with AIDS, in an infectious disease unit, using ICNP® version 2015. METHODS A cross-sectional study, followed by validation of content, performed with 20 nurses and 120 people, living with AIDS in an infectious disease unit of a hospital of infectious diseases in Northeast Brazil. The methodological trajectory was carried out in the following stages: elaboration of the diagnosis, nursing outcomes; Initial proposal of nursing interventions; Preparation of a care plan; And validation of the plan by field experts. RESULTS 42 diagnoses were elaborated and validated, 33 presented CVI > 0.80 (55.42%) among field experts. From this quantitative, 228 interventions were elaborated and 41 obtained a CVI > 0.80 (44.78%), considered validated. CONCLUSION The study allowed us to identify and validate nursing diagnoses, outcomes and interventions for the use in clinical practice, aiming to subsidize the process of care for people with AIDS.


Bedside spirometry in a tertiary care hospital: the cleveland clinic experience.
In contrast to outpatient, laboratory testing, which is performed by a small, dedicated group of pulmonary function technologists, inpatient, bedside spirometry at the Cleveland Clinic Hospital is performed less frequently and by a larger group of respiratory therapists with broader responsibilities. A 1998 audit of bedside spirometry tests at our hospital showed that American Thoracic Society acceptability and reproducibility criteria were infrequently met (15% of instances). To address that shortcoming, we initiated an improvement plan for bedside spirometry that included: (1) A didactic review of American Thoracic Society acceptability and reproducibility criteria that was videotaped and reviewed by all but one of the therapists performing spirometry; (2) limiting the number of operators to a "core group" to allow more tests per therapist; (3) producing printouts of the pulmonary function tests, which allows immediate review of volume-time and flow-volume curves; (4) central review of all tests by a pulmonary function technologist and feedback and constructive suggestions on test quality and reproducibility to operators. After initiating the program we performed a consecutive survey of all inpatient spirometry sessions performed from July 16, 1998, to March 2, 1999. During the survey period, 63.5% of the tests (n = 137) were deemed acceptable, exceeding the low baseline rate of 15% (p < 0.001). Values for forced expiratory volume in the first second were reproducible in 83.9% of sessions. Values for forced vital capacity were reproducible in 80.3% of sessions. A quality improvement program for bedside spirometry testing that emphasizes training and routine feedback on test quality can enhance the quality of inpatient spirometry testing.


Laser Treatment in Hirsutism: An Update.
Unwanted hair growth, which is a common aesthetic problem, has traditionally been treated using various techniques such as shaving, waxing, and epilation, but most of these provide only a temporary solution. Laser and light-based technology for hair removal has become one of the fastest growing procedures in modern cosmetic dermatology in the last decade. Clinical experience suggests that in the ideal subject with fair skin and dark hair, laser treatment can reduce hair growth significantly. This article reviews the various laser and light-based devices used for hair removal along with the various laser and patient parameters that affect the outcome of laser treatment for hair removal. Photoepilation, when properly used, offers clear advantages when compared with older, traditional techniques.


A comparison of the effects of commercially available hawthorn preparations on calcium transients of isolated cardiomyocytes.
We studied the potential cardiac effects of two alcohol extracts of commercially available hawthorn using rat cardiomyocytes and measuring calcium transients by real-time fluorescence spectrophotometry. One preparation was a blend of hawthorn flowers, leaves, and berries (extract #1), and the other (extract #2) was from a "berries-only" preparation. Fluorescent images and calcium transients were acquired concurrently. Addition of extract #1 resulted in the initiation of robust calcium transients and eventual calcium overload, while addition of extract #2 caused increased calcium sparking, initiation of calcium transients, and an increased beating rate but no calcium overload. To identify the mechanisms of increased calcium influx, adult rat cardiomyocytes were challenged with 10 microM ouabain, a Na(+),K(+)-ATPase inhibitor, and the calcium channel blocker nifedipine. The findings revealed that equal volumes of the two readily available hawthorn preparations demonstrated markedly different effects on isolated adult rat cardiomyocytes, suggesting important implications for patients who are using these preparations to supplement or even replace their prescribed cardiac medications as to which preparation(s) to use, and potential dire consequences, particularly in cardiac patients. Our study indicates that the mechanism of cardiac activity of hawthorn is via the Na(+),K(+)-ATPase and intracellular calcium concentrations are influenced.


Venovenous extracorporeal membrane oxygenation is effective against post-cardiotomy acute respiratory failure in adults.
Acute respiratory failure is a serious issue that occasionally occurs after weaning from cardiopulmonary bypass (CPB) after heart surgery. This condition can be refractory to mechanical ventilation and the mortality rate is high. Venovenous extracorporeal membrane oxygenation (VV-ECMO) is applied to treat acute lung failure after CPB at our institution. This report describes the use of VV-ECMO after cardiac surgery at a single institution. We analyzed the outcomes of 11 patients who developed severe acute respiratory failure requiring VV-ECMO after undergoing heart surgery with a cardiopulmonary bypass. Four (36.4%) patients died in hospital. One patient required conversion from VV- to venoarterial (VA-) ECMO because of circulatory instability. One patient each died of respiratory failure and heart failure and two died of ischemic colitis. Lung damage secondarily developed in these four patients to other disabled organs. Seven (63.6%) patients whose lungs were primarily disabled were weaned from VV-ECMO upon recovery from respiratory failure and were ambulatory at the time of discharge from hospital. The ratio of PaO2/FIO2 (P/F) at 24 h after starting VV-ECMO did not significantly differ between survivors and non-survivors (187.9 ± 57.7 vs. 135.5 ± 20.5, p = 0.10), but tended to be higher in survivors. Non-survivors were significantly older than survivors. Patients who develop severe acute respiratory failure after undergoing heart surgery using cardiopulmonary bypass derive a survival benefit from VV-ECMO.


Impact of the inner solute structure on the electrostatic mean-field and strong-coupling regimes of macromolecular interactions.
The structural diversity of the solute molecules involved in biomolecular processes necessitates the characterization of the forces between charged macromolecules beyond the point-ion description. From the field-theoretic partition function of an electrolyte confined between two anionic membranes, we derive a contact-value identity valid for general intramolecular solute structure and electrostatic coupling strength. In the electrostatic mean-field regime, the inner charge spread of the solute particles is shown to induce the twofold enhancement of the short-range Poisson-Boltzmann level membrane repulsion and a longer-range depletion attraction. Our contact theorem indicates that the twofold repulsion enhancement by solute size is equally present in the opposite strong-coupling regime of linear and spherical solute molecules. Upon the inclusion of the dielectric contrast between the electrolyte and the interacting membranes, the emerging polarization forces substantially amplify the solute specificity of the macromolecular interactions. Namely, the finite size of the dumbbell-like solute particles composed of similar terminal charges weakens the intermembrane repulsion. However, the extended structure of the solute molecules carrying opposite elementary charges such as ionized atoms and zwitterionic molecules enhances the membrane repulsion by several factors. We also show that these polarization forces can extend the range of the solute structure effects up to intermembrane distances exceeding the solute size by an order of magnitude. This radical alteration of the intermembrane interactions by the salt structure identifies the solute specificity as a key ingredient of the thermodynamic stability in colloidal systems.


Optical spatial solitons and modulation instabilities in transparent entangled polymer solutions.
Fully transparent nondilute polydiene solutions exhibit optical nonlinearities when irradiated by a low-power cw laser in the visible. The formation of optical spatial solitons is imaged through phase contrast microscopy. Both (2+1)D and (1+1)D modulational instabilities are evidenced as 2D and 1D arrays of linear filaments formed by beam defocusing or by using a cylindrical lens. The origin of the nonlinearity remains elusive.


Substance Use and Associated Health Conditions throughout the Lifespan.
A life stage perspective is necessary for development of age-appropriate strategies to address substance use disorders (SUDs) and related health conditions in order to produce better overall health and well-being. The current review evaluated the literature across three major life stages: adolescence, adulthood, and older adulthood. 1) Substance use is often initiated in adolescence, but it is during adulthood that prevalence rates for SUDs peak; and while substance involvement is less common among older adults, the risk for health complications associated with use increases. 2) Alcohol, tobacco, marijuana, and, increasingly, prescription medications, are the most commonly misused substances across age groups; however, the use pattern of these and other drugs and the salient impact vary depending on life stage. 3) In terms of health outcomes, all ages are at risk for overdose, accidental injury, and attempted suicide. Adolescents are more likely to be in vehicular accidents while older adults are at greater risk for damaging falls. Adulthood has the highest rates of associated medical conditions (e.g., cancer, sexually transmitted disease, heart disease) and mental health conditions (e.g., bipolar disorder, anxiety disorders, antisocial personality disorder). Prolonged heavy use of drugs and/or alcohol results in an array of serious health conditions. Addressing SUDs from a life stage perspective with assessment and treatment approaches incorporating co-occurring disorders are necessary to successfully impact overall health.


Hormonal regulation of lactate dehydrogenase-A through activation of protein kinase C pathways in MCF-7 breast cancer cells.
Lactate dehydrogenase A (LDH-A) is hormonally regulated in rodents, and increased expression of LDH-A is observed during mammary gland tumorigenesis. The mechanisms of hormonal regulation of LDH-A were investigated using a series of deletion and mutant constructs derived from the rat LDH-A gene promoter. Results of these studies show that constructs containing the -92 to -37 region of the LDH-A promoter are important for basal and E2-induced transactivation, and mutation of the consensus CRE motif within this region results in significant loss of basal activity and hormone-responsiveness. Gel mobility shift assays using nuclear extracts from MCF-7 cells show that both CREB and ATF-1 interact with the CRE. Studies with kinase inhibitors show that E2-induced activation of this CRE is dependent on protein kinase C, and these data indicate that LDH-A is induced through a non-genomic pathway of estrogen action.


Oral health care education and its effect on caregivers' knowledge and attitudes: a randomised controlled trial.
The effect of an oral health care education programme (OHCE) upon nursing home caregivers was assessed in a randomised controlled trial. A self-administered questionnaire assessed oral health care knowledge and attitudes at baseline among 369 caregivers working in 22 nursing homes. Homes were randomly allocated to two groups. The intervention was a workplace OHCE. Caregivers assessed the value of the presentations. Questionnaires were re-administered 1 month (time 2) and 6 months (time 3) after the OHCE was delivered. The knowledge and attitude score means of the groups were compared. Open-ended questions solicited qualitative data. Questionnaire response rates at the three time points ranged from 76.3% to 85.4%. Two-thirds of caregivers employed at the time of the intervention attended the presentations. The OHCE was favourably assessed in 79% of responses. The intervention group significantly improved their scores over the control group at times 2 and 3 for knowledge (P<0.003) and attitude (P<0.001). Analysed across both arms at baseline, the main predictors for knowledge and attitude scores were age and dental attendance pattern. Qualitative responses showed an acceptance of caregivers' roles in oral health care and criticism of existing provision within homes. The OHCE was well received and resulted in improved oral health care knowledge and attitudes. When viewed with separately reported trial results of clients' oral health status, knowledge and attitude score improvements coincided with improved delivery of oral health care.


Endothelial dysfunction in the pathogenesis of pre-eclampsia in Ghanaian women.
Pre-eclampsia (PE) remains a disease of theories despite extensive research into its etiology. Alteration in the production of vascular endothelial growth factor (VEGF), a biomarker of endothelial dysfunction, is associated with pre-eclampsia although conflicting reports have been reported. The aim of the study was to determine and compare maternal serum levels of VEGF among pre-eclamptics, normotensive non pregnant and pregnant women. This was a cross-sectional study involving 100 women with pre-eclampsia, 102 women with normotensive pregnancy and 75 normotensives who were not pregnant. The study was carried out at Korle Bu Teaching Hospital (KBTH) from April to June in 2011. Basic socio-demographic and obstetric data were obtained by means of structured questionnaire. Following venesection, about 5mls of blood was sampled from the participants for the various tests. Enzyme Linked Immunosorbent Assay was used to determine the maternal serum levels of free VEGF. Data analysis was performed using SPSS version 20. Significant reduction in median serum levels of free VEGF was seen in both, normal pregnant [84.06 pg/ml (IQR: 78.90-99.67)] and pre-eclamptic women [4.71 pg/ml, (IQR: 3.41-7.93)] compared to the non-pregnant (395.85 pg/ml, IQR 234.93-625) with p < 0.001; the reduction was far greater in the pre-eclamptic group compared to that of normotensive pregnant group (p < 0.001). Early-onset pre-eclampsia had significantly more severe reduction in free VEGF levels (3.89, IQR: 2.60-5.67 pg/ml) compared to that of late onset PE (5.23, IQR: 3.78-16.97 pg/ml) with p<0.001 indicating a severer endothelial damage in former. Endothelial dysfunction contributes significantly to the pathogenesis of pre-eclampsia as demonstrated by profound decrease in maternal serum VEGF levels in PE compared to normotensive pregnancy and non-pregnancy state. The pathophysiology of early-onset pre-eclampsia may be partly explained by marked reduction in free serum VEGF levels with resultant severe endothelial dysfunction.


Binding geometry and photophysical properties of DNA-threading binuclear ruthenium complexes.
The DNA binding conformation and the photophysical properties of the semiflexible binuclear ruthenium complex [micro-bidppz(phen)4Ru2]4+ (2) were studied with optical spectroscopy and compared to the rigid, planar homologue in syn conformation [micro-dtpf(phen)4Ru2]4+ (3) and the parent "light-switch" complex [Ru(phen)2dppz]2+ (1). Comparison of calculated and observed absorption bands of the bridging ligand, bidppz, confirm earlier suggestions that 2 is significantly nonplanar, both free in solution and when intercalated into poly(dAdT)2, but the conclusion that the intercalated conformation is an anti rotamer is not substantiated by comparison of linear and circular dichroism spectra of 2 and 3. The behavior of the emission quantum yield as a function of temperature is similar for the two binuclear complexes 2 and 3 in different protic solvents, and a quantitative analysis suggests that, in solution, the solvent is more strongly hydrogen bonded to the excited state of 2 than to 1. However, the observation that for 2 the radiative rate constant increases to a value similar to 1 upon intercalation into DNA suggests that the difference between 1 and 2 in accepting hydrogen bonds is less pronounced when intercalated.


Enhancing generalizability of stroke clinical trial results: Illustrations from upper-limb motor recovery trials.
Broadening eligibility criteria has been a focus to increase the generalizability of trial findings. Using upper-limb motor trials conducted early post-stroke as the illustrative domain, we sought to (1) investigate whether the published aim and conclusion statements adequately reflect the generalizability of findings and (2) explore internal validity and feasibility as constraints to achieving generalizability. We systematically applied a conceptual model of a trial sampling process to published literature from systematic review and prospective cross-sectional data. The eligibility criteria reported and used to exclude patients were classified by consensus as related to safety, internal validity, feasibility, or a combination thereof. Categorical data were reported as counts/proportions, and continuous data were reported as median (interquartile range (IQR)). Thirty trials (n = 1638 participants) were included in the published literature and 1013 patients in the prospective data set. Thirty-seven percent of trials did not describe their target population in the aim and conclusion, and 80% did not report all trial screening data. Eligibility criteria related to internal validity were the most common type reported and applied to exclude patients across both data sets. In the prospective data set, 70% of patients were excluded for more than one reason. Key information to support the generalizability of trial findings was insufficiently reported in published upper-limb motor research conducted early post-stroke. Broadening eligibility criteria alone is unlikely to sufficiently improve trial inclusivity due to internal validity constraints. Trials could achieve inclusivity through targeting multiple sub-populations, that in combination, produce clinically relevant results that are applicable to a broader population.


Relation of the stages of change for exercise behaviors, self-efficacy, decisional-balance, and diet-related psycho-behavioral factors in young Japanese women.
A large proportion of young Japanese women is inactive. Exercise has important health benefits, however, abnormal weight/eating concerns and excessive dieting practices among physically active young women also have been reported in many cross-sectional studies. The purpose of this study was to examine the relationships between stages of change for exercise behaviors and exercise/dieting related psycho-behavioral factors using the Transtheoretical Model of behavior change as a theoretical framework. A cross-sectional study included 450 young Japanese women aged 18 to 21 (18.4+/-0.67 years). Subjects in precontemplation (n=111, 24.7%), contemplation (n=120, 26.7%), preparation (n=177, 39.3%), action (n=17, 3.8%), and maintenance (n=25, 5.6%) were compared on physique, body composition, current exercise practices, exercise self-efficacy, decisional balance (benefits and costs exercise), as well as dieting behaviors and weight/eating concerns. Stages of change for exercise behaviors were significantly related to exercise self-efficacy and perceived benefits as well as to dieting behaviors and weight/eating concerns. Subjects in the higher stages had higher self-efficacy, perceived benefits of exercise, and healthy dieting behaviors; however, some of them also had unhealthier dietary practices, higher phobia of obesity and obsession with eating than those in lower stages. These findings provide support for applying the transtheoretical model of exercise behavioral change to Japanese young women. Additionally, it is also important to pay attention to stage specific psycho-behavioral factors related to their dieting.


[Preliminary diagnostic evaluation of submucosal myoma using operative hysteroscopy].
The authors aim to underline the importance of preliminary diagnostic evaluation in the treatment of submucous leiomyoma using hysteroscopy. The study examined 18 patients monitored at the Institute of Obstetrics and Gynecology of "La Sapienza" University of Rome between January and December 1995 in whom it was possible to make a correct definition of the lesion to be treated (number, site, size, etc.) using 3 different diagnostic methods: hysteroscopy (HS), transvaginal scan (TSV) and transvaginal echohysterography (TVHS) The authors focused attention on three different parameters: leiomyoma size, extension (intracavity/intramural portion) and evaluation of the residual leiomyoma, which are essential for optimal endoscopic resection. HS enabled the number, size, site, origin, base, submucous portion and relations with tube operings to be evaluated, but did not allow the myometrial part of the lesion to be examined. Integration with TSV, even if this does not allow a precise definition of the extension, highlights the size, site, involvement of myometrial structure and relations with the perimetrium, thus allowing the possibility of evaluating the residual myometrium. Compared to the above methods, TVHS highlights the effective extension (namely the submucous/intramural portion) and localization of the neoformation.


Alphaherpesvirus glycoprotein M causes the relocalization of plasma membrane proteins.
Herpesvirus glycoprotein M (gM) is a multiple-spanning integral membrane protein found within the envelope of mature herpesviruses and is conserved throughout the Herpesviridae. gM is defined as a non-essential glycoprotein in alphaherpesviruses and has been proposed as playing a role in controlling final envelopment in a late secretory-pathway compartment such as the trans-Golgi network (TGN). Additionally, gM proteins have been shown to inhibit cell-cell fusion in transfection-based assays by an as yet unclear mechanism. Here, the effect of pseudorabies virus (PRV) gM and the herpes simplex virus type 1 (HSV-1) gM/UL49A complex on the fusion events caused by the HSV-1 glycoproteins gB, gD, gH and gL was investigated. Fusion of cells expressing HSV-1 gB, gD, gH and gL was efficiently inhibited by both PRV gM and HSV-1 gM/UL49A. Furthermore, expression of PRV gM or HSV-1 gM/UL49A, which are themselves localized to the TGN, caused both gD and gH/L to be relocalized from the plasma membrane to a juxtanuclear compartment, suggesting that fusion inhibition is caused by the removal of 'fusion' proteins from the cell surface. The ability of gM to cause the relocalization of plasma membrane proteins was not restricted to HSV-1 glycoproteins, as other viral and non-viral proteins were also affected. These data suggest that herpesvirus gM (gM/N) can alter the membrane trafficking itineraries of a broad range of proteins and this may have multiple functions.


Interplexiform cells of the goldfish retina.
Dopaminergic and glycinergic interplexiform cells (IPCs) in the goldfish retina were impregnated by using two new Golgi protocols. The two cell types have markedly different morphological characteristics: Dopaminergic IPCs have primary dendrites that descend into and stratify in the inner plexiform layer, where they give rise to processes that project to the outer plexiform layer. Conversely, glycinergic IPCs have primary dendrites that ascend to the outer plexiform layer and from this dendritic arbor, many processes then project into the inner plexiform layer. The apparent coverage of dopaminergic IPCs is almost four times that of glycinergic IPCs. Even so, the coverage of each glycinergic IPC in the outer plexiform layer allows it to provide an accurate copy of the S-space to the inner plexiform layer. Considering the known GABAergic and glycinergic synaptologies in the inner plexiform layer, the glycinergic IPC must form a major element in the retinal circuitry of the goldfish.