[Comparison of two methods of local anaesthesia for laparotomy in cattle].
To compare the feasibility and efficacy of two methods of local anaesthesia with procaine 2% for flank laparotomy in cattle. MATERIAL UND METHODS: A total of 100 cattle undergoing laparotomy were divided into two groups of 50: one group underwent a modified infiltration anaesthesia (MIA) technique consisting of an incisional line block combined with an inverted L-block, and the other group underwent proximal paravertebral anaesthesia (PPVA). Indications for laparotomy were displaced abomasum, caecal disorders, rumenotomy and exploratory laparotomy. The two methods were compared with regard to the reaction of the cows to the application of anaesthesia, the degree of difficulty and the amount of time and anaesthetic agent required. The reactions of the cattle to incision of the various layers of the abdominal wall, abdominal exploration and surgical closure of the abdomen were assessed. Both techniques required a mean of 8 minutes to complete but the MIA method was considered more difficult than the PPVA (p=0.13). The PPVA required significantly (p<0.001) less procaine than the MIA (144 vs. 195ml). Comparison of the two techniques with respect to different types of pain reactions (no reaction, non-specific reaction, specific reaction) during cutting of the different layers of the abdominal wall revealed that PPVA provided significantly (p=0.01) better analgesia than the MIA. After PPVA, pain reactions to incision of the external oblique abdominal muscle were more severe, but reactions to abdominal exploration and to suturing the two oblique abdominal muscles were significantly (p<0.05) milder than after MIA. Neither technique resulted in consistent and complete elimination of pain reactions in every patient, but overall PPVA had better results than the MIA. The analgesic effect of both techniques could be improved by repeated administration of procaine and mild tranquillization (Xylazine; 0.01mg/kg i.v.) before laparotomy. For PPVA, a combination of procaine and epinephrine should be used. It would be advantageous to have anaesthetic agents, e.g. lidocaine, that are more potent than procaine 2% for local analgesia in cattle.


Multiple forms of messenger ribonucleic acid encoding glycodelin in male genital tract.
Glycodelin-A is a human endometrium-derived glycoprotein with contraceptive and immunosuppressive activities. Recently, we found that seminal plasma contains immunoreactive glycodelin (GdS) that is differentially glycosylated and has no contraceptive activity. We now report localization and variant forms of GdS in the male genital tract. Northern blot and reverse transcription-PCR analyses showed that GdS mRNA is expressed in the seminal vesicles and ampulla of the vas deferens. Immunohistochemical staining localized GdS to the epithelial cells and lumen of glands in the seminal vesicles and ampullary part of the vas deferens. The same tissues and cells contained glycodelin mRNA as localized by in situ hybridization. Whereas the major reverse transcription-PCR products were identical to the glycodelin-A cDNA from decidual expression library, there were also several splicing variants of GdS mRNA. Seminal plasma also contained smaller immunoreactive forms of the GdS protein. Some of them were posttranslational cleavage products of GdS, because incubation of 125I-labeled GdS in seminal plasma resulted in smaller molecular weight cleavage products. Based on these results, we concluded that multiple forms of glycodelin mRNA are expressed in the male genital tract, including those lacking the coding sequences for the glycosylation sites, and that seminal plasma has proteolytic activity that cleaves GdS.


Fingerprinting Biogenic Aldehydes through Pattern Recognition Analyses of Excitation-Emission Matrices.
Biogenic carbonyls, especially aldehydes, have previously demonstrated their potential to serve as early diagnostic biomarkers for disease and injury that have not been fully realized owing, in part, to the lack of a rapid and simple point-of-care method for aldehyde identification. The ability to determine which carbonyl compound is elevated and not just the total aldehydic load may provide more disease- or injury-specific diagnostic information. Toward this end, a novel fluorophore is presented that is able to form a complex with biogenic carbonyls under catalyst-free conditions so as to give a fluorescent fingerprint of the resulting hydrazone. The successful identification of bound carbonyls was accomplished with a newly described algorithm that applied principal curvature analysis of excitation-emission matrices to reduce surface features to ellipse representations, followed by a pattern-matching routine. With this algorithm, carbonyls were identified over a range of concentrations, and mixture components were successfully parsed. Overall, the results presented lay the groundwork for novel implementations of chemometrics to low-cost, rapid, and simple-to-implement point-of-care diagnostics.


Modeling the growth of the Goettingen minipig.
The Goettingen minipig developed at the University of Goettingen, Germany, is a special breed for medical research. As a laboratory animal it has to be as small and light as possible to facilitate handling during experiments. For achieving the breeding goal of small body size in the future, the growth pattern of the minipig was studied. This study deals with the analysis of minipig BW by modeling growth with linear and nonlinear functions and comparing the growth of the minipigs with that of normal, fattening pigs. Data were provided by Ellegaard Goettingen minipigs, Denmark, where 2 subpopulations of the Goettingen basis population are housed. In total 189,725 BW recordings of 33,704 animals collected from birth (d 0) to 700 d of age were analyzed. Seven nonlinear growth functions and 4 polynomial functions were applied. The growth models were compared by using the Akaike's information criterion (AIC). Regarding the whole growth curve, linear polynomials of third and fourth order of fit had the smallest AIC values, indicating the best fit for the minipig BW data. Among the nonlinear functions, the logistic model had the greatest AIC value. A comparison with fattening pigs showed that the minipigs have a nearly linear BW development in the time period from birth to 160 d. Fattening pigs have very low weight gains in their first 7 wk in relation to a specific end weight. After 7 wk, fattening pigs have increased growth, resulting in a growth curve that is more sigmoid than the growth curve of the minipig. Based on these results, further studies can be conducted to analyze the growth with random regression models and to estimate variance components for optimizing the strategies in minipig breeding.


Isosteviol attenuates streptozotocin-mediated diabetic nephropathy in rats by upregulating and stimulating adenosine monophosphate-activated protein kinase.
Diabetic nephropathy (DN) is the major microvascular complication of type 1 diabetes mellitus (T1DM). Impairment in adenosine monophosphate-activated protein kinase (AMPK) activity was shown to mediate the pro-oxidant and inflammatory mechanisms underlying DN. Isosteviol (ISV), isolated from Stevia rebaudiana, has antioxidant and anti-inflammatory properties and alleviates non-alcoholic fatty liver disease and lethal septic shock by activating AMPK. The effect of ISV on DN is unknown. This study examined if ISV alleviates DN in T1DM in adult male rats by activating AMPK. Diabetes was induced in rats by a single intraperitoneal (i.p.) injection of streptozotocin (STZ) (65 mg/kg). Five groups of rats (n=8 each) were designed and included: control, ISV (20 mg/kg orally), STZ (diabetic), STZ + ISV (20 mg/kg orally), STZ + ISV + CC (compound C/an AMPK inhibitor) (0.2 mg/kg, i.p). Fasting glucose and insulin levels, assessment of kidney function tests, lipid profile analysis, measurements of markers of oxidative stress and inflammation, PCR and Western blotting analysis, and histological studies of the kidneys were conducted. With no effect on fasting glucose or insulin levels (p>0.05), ISV reduced serum levels of cholesterol, triglycerides (TGs), and low-density lipoprotein cholesterol (LDL-c) (p<0.01). ISV also increased urinary creatinine excretion, reduced urinary albumin levels, and alleviated tubular and glomerular damage of STZ-diabetic kidneys. ISV also lowered the renal levels of malondialdehyde (MDA) (p<0.01), tumor necrosis factor-alpha (TNF-α) (p<0.01), interleukin-6 (IL-6) (p<0.01), and mRNA and nuclear protein levels of nuclear factor kappaB (NF-κB) in both the control and diabetic rats. Concomitantly, ISV increased the phosphorylation of AMPK (p<0.05), levels of superoxide dismutase (SOD) (p<0.01), catalase (CAT) (p<0.01), total glutathione (GSH) (p<0.01), and mRNA and nuclear protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2) (p<0.01) in the kidneys of the control and diabetic rats. Co-administration of CC prevented all renal protective effects of ISV and reversed all these effects. In conclusion, AMPK-induced inhibition of NF-κB and activation of Nrf2 entails the nephroprotective effect of ISV in STZ-diabetic rats.


[The diagnosis and therapeutic approach in acute necrotic-hemorrhagic pancreatitis].
The work contains the clinical and therapeutic analysis of a group of 72 patients with acute necrotic-haemorrhagic pancreatitis (ANHP), admitted in the period 1979-1989 to the Ist Surgical Clinic of the Municipal Clinical Hospital of Bucharest. The etiology of ANHP, its clinical forms of manifestation, the peculiarities of shock and its dynamic course are shown and discussed. Stress is laid on the criteria of severity, on the course and on the complications occurred. The therapeutic results are commented in detail and the mortality is studied in a complex way, by analysing both the terminal clinical manifestations and the results of anatomicopathological examinations.


Isomers of HSCO: IR absorption spectra of t-HSCO in solid Ar.
Irradiation of an Ar matrix sample containing H2S and CO (or OCS) with an ArF excimer laser at 193 nm yields trans-HSCO (denoted t-HSCO). New lines at 1823.3, 931.6, and 553.3 cm(-1) appear after photolysis and their intensity enhances after annealing; secondary photolysis at 248 nm diminishes these lines and produces OCS and CO. These lines are assigned to C-O stretching, HSC-bending, and C-S stretching modes of t-HSCO, respectively, based on results of 13C-isotopic experiments and theoretical calculations. Theoretical calculations using density-functional theories (B3LYP and PW91PW91) predict four stable isomers of HSCO: t-HSCO, c-HSCO, HC(O)S, and c-HOCS, listed in increasing order of energy. According to calculations with B3LYP/aug-cc-pVTZ, t-HSCO is planar, with bond lengths of 1.34 A (H-S), 1.81 A (S-C), and 1.17 A (C-O), and angles angle HSC congruent with 93.4 degrees and angle SCO congruent with 128.3 degrees; it is more stable than c-HSCO and HC(O)S by approximately 9 kJ mol(-1) and more stable than c-HOCS by approximately 65 kJ mol(-1). Calculated vibrational wave numbers, IR intensities, and 13C-isotopic shifts for t-HSCO fit satisfactorily with experimental results. This new spectral identification of t-HSCO provides information for future investigations of its roles in atmospheric chemistry.


Olodaterol for the treatment of chronic obstructive pulmonary disease: a narrative review.
Inhaled bronchodilators are the key-stone of chronic obstructive pulmonary disease (COPD) management. Olodaterol 5 µg, a long-acting β2-adrenoceptor agonist (LABA) is one such bronchodilator indicated as a once-daily maintenance therapy. Areas covered: This article reviews the several trials that have assessed olodaterol as a COPD therapy. It covers safety and tolerability data and provides the reader with an expert opinion on its use as a treatment for COPD. Expert opinion: Olodaterol improves lung function for 24 h and reduces rescue medication use. It may also improve dyspnea, exercise tolerance, and health-related quality of life. It is well tolerated with an acceptable cardiovascular and respiratory adverse event profile. There is some evidence that olodaterol, as well as other LABAs, can reduce exacerbation frequency, but not FEV1 decline and death. LABAs alone are indicated in group A/B COPD subjects. Olodaterol and indacaterol are administered once-daily and may offer an adherence advantage over other LABAs with more frequent dosing schedules. Co-administration of an olodaterol/tiotropium fixed dose combination in a single inhaler device is recommended as step-up in group A/B COPD subjects not sufficiently treated by olodaterol alone or as initial therapy in those with severe exertional dyspnea.


Threshold distribution of equal states for quantitative amplitude fluctuations.
Objective. The distribution of equal states (DES) quantifies amplitude fluctuations in biomedical signals. However, under certain conditions, such as a high resolution of data collection or special signal processing techniques, equal states may be very rare, whereupon the DES fails to measure the amplitude fluctuations.Approach. To address this problem, we develop a novel threshold DES (tDES) that measures the distribution of differential states within a threshold. To evaluate the proposed tDES, we first analyze five sets of synthetic signals generated in different frequency bands. We then analyze sleep electroencephalography (EEG) datasets taken from the public PhysioNet.Main results. Synthetic signals and detrend-filtered sleep EEGs have no neighboring equal values; however, tDES can effectively measure the amplitude fluctuations within these data. The tDES of EEG data increases significantly as the sleep stage increases, even with datasets covering very short periods, indicating decreased amplitude fluctuations in sleep EEGs. Generally speaking, the presence of more low-frequency components in a physiological series reflects smaller amplitude fluctuations and larger DES.Significance. The tDES provides a reliable computing method for quantifying amplitude fluctuations, exhibiting the characteristics of conceptual simplicity and computational robustness. Our findings broaden the application of quantitative amplitude fluctuations and contribute to the classification of sleep stages based on EEG data.


"You've gotta know the community": minority women make recommendations about community-focused health research.
To determine what ethnic and racial minority women recommend as the best approaches to participatory health research in their communities. To achieve this goal, this study focused on HIV prevention research. In 2003, Seven African American and seven Latina women (ages 33 to 52), all members of an HIV Prevention Collaborative Board, participated in individual interviews, lasting about 90 minutes each. Participants discussed their involvement in participatory research, and made recommendations as to how health researchers might better engage their communities. Data were coded independently by two coders following standard procedure for content analysis. Women's voices and expertise can help guide health-related research. This study shows that: (1) participatory HIV prevention research should be founded on trust and commitment, leading to social support; (2) research partners ought to come from diverse backgrounds and be knowledgeable about the community and willing to work on common objectives; and (3) collaborative partnerships ought to portray an image of strength and cohesion, and a clear articulation of the mission around a research project. To develop meaningful health research, researchers need to establish long-term ongoing relationships with community collaborators, including minority women from diverse backgrounds. Researchers ought to take a holistic approach working with communities, and ought to consider their research interests vis-a-vis the community's needs.


[Evaluation of multi-disciplinary treatment combined with intra-arterial chemotherapy for carcinoma of the meso-pharynx].
Forty-seven cases of carcinoma of the mesopharynx , treated from 1973 to 1981 at Gunma Cancer Center, were evaluated. The following results were obtained, According to histopathologic diagnosis, 37 were well-differentiated squamous cell carcinoma and other cases were poorly differentiated squamous cell carcinoma. Classification of the site of the disease showed the most frequent site was lateral wall type (31 cases, 65.9 per cent) followed by anterior wall (9 cases), superior wall (5 cases), and posterior wall types (2 cases). According to TN classification, there were 1 case in T1, 14 cases in T2, 24 cases in T3, and 7 cases in T4, N distribution revealed 27 cases N0, 20 cases N1, N2 and N3. The most common treatment was intraarterial chemotherapy using 5-FU combined with external irradiation (15 cases, 31.9 per cent), external irradiation alone (14 cases, 29.7 per cent), external irradiation with Radium (8 cases, 17.0 per cent), and combined with cryosurgery 5 cases, 10.6 per cent). The five-year cumulative survival rate was 35.3 per cent. The lesion of mesopharyngeal carcinoma takes various forms, so the treatment policy cannot be a standard one. Thus multi-disciplinary treatment should be applied for this disease.


The association between job strain and coronary heart disease: a meta-analysis of prospective cohort studies.
Studies about work stress and the risk of coronary heart disease (CHD) have yielded inconsistent results. This meta-analysis aimed to investigate the association between job strain and the risk of CHD. We searched PubMed and Embase databases for studies reporting data on job strain and the risk of CHD. Studies were included if they reported multiple-adjusted relative risk (RR) with 95% confidence interval (CI) with respect to CHD from job strain. Fourteen prospective cohort studies comprising 232,767 participants were included. The risk of CHD was increased in high-strain (RR 1.26; 95% CI 1.12-1.41) and passive jobs (RR 1.14; 95% CI 1.02-1.29) but not in active jobs (RR 1.09; 95% CI 0.97-1.22), when compared with low-strain group. The increased risk of CHD in high-strain and passive jobs was mainly driven by studies with a follow-up duration of ≥ 10 years. Neither the low-control (RR 1.06; 95% CI 0.93-1.19) nor high-demand (RR 1.13; 95% CI 0.97-1.32) dimension was independently associated with the risk of CHD. Individuals with high-strain and passive jobs were more likely to experience a CHD event. Intervention programs incorporating individual and organizational levels are crucial for reducing job strain and the risk of CHD.


Treatment with zoledronic acid subsequent to odanacatib prevents bone loss in postmenopausal women with osteoporosis.
Treatment with zoledronic acid 5 mg maintained bone turnover markers in the premenopausal range, increased lumbar spine bone mineral density, and maintained hip bone mineral density in women previously treated with odanacatib 50 mg weekly. The development of odanacatib (ODN), a cathepsin K inhibitor, for treatment of osteoporosis was discontinued due to an increased risk of cardiovascular events. As the treatment is considered reversible, participants from the LOFT trial in Aarhus, Denmark, were offered treatment with zoledronic acid (ZOL). Sixty-seven postmenopausal women were treated with ZOL 5 mg and followed for 12 months. Of these, 39 had received ODN for 7 years and 28 had received placebo for 5 years and ODN for 2 years. Bone turnover markers (BTM) were measured 3, 6, and 12 months after ZOL, and DXA of spine and hip were performed at time of ZOL treatment and after 12 months. Within the entire study population, BMD at the lumbar spine increased by 2.8 ± 0.9% (mean ± SEM) (p < 0.01) from baseline to month 12. There was no significant change in BMD at the total hip (p = 0.17) or femoral neck (p = 0.39). There was no difference in the changes in BMD from baseline to 12 months between the two groups at any site (p ≥ 0.20 for all). CTX increased by 107 ± 9% (p < 0.001), PINP by 102 ± 16% (p < 0.001), osteocalcin by 32 ± 6% (p = 0.001) and BSAP by 79 ± 37% (p = 0.001) between 3 and 12 months after ZOL. At month 12, BTM were still within the premenopausal reference range. S-25-hydroxyvitamin D increased (p = 0.059), while PTH (p = 0.007) and eGFR (p = 0.014) decreased during the year following ZOL administration. Treatment with ZOL 5 mg maintained BTMs in the premenopausal range and prevented bone loss in women previously treated with ODN.


Predictors of outcome in schizophrenia.
Several factors have been reported to be associated with poor outcome in psychosis. A prospective study was conducted to identify and subsequently assess the relative prognostic value of factors that might assist in the earlier identification of patients likely to have a poor outcome. The results confirmed that certain factors, including male gender, family history of schizophrenia, structural brain abnormalities, absence of adverse life events, and tardive dyskinesia, were indeed associated with poor outcome.


Costs of colorectal cancer in different states of the disease.
This cross-sectional study estimates the resource use and costs among prevalent colorectal cancer (CRC) patients in different states of the disease. Altogether 508 Finnish CRC patients (aged 26-96; colon cancer 56%; female 47%) answered a questionnaire enquiring about informal care, work capacity, and demographic factors. Furthermore, data on direct medical resource use and productivity costs were obtained from registries. Patients were divided into five mutually exclusive groups based on the disease state and the time from diagnosis: primary treatments (the first six months after the diagnosis), rehabilitation, remission, metastatic disease, and palliative care. The costs were calculated for a six-month period. Multivariate modeling was performed to find the cost drivers. The costs were highest during the primary treatment state and the advanced disease states. The total costs for the cross-sectional six-month period were €22 200 in the primary treatment state, €2106 in the rehabilitation state, €2812 in the remission state, €20 540 in the metastatic state, and €21 146 in the palliative state. Most of the costs were direct medical costs. The informal care cost was highest per patient in the palliative care state, amounting to 33% of the total costs. The productivity costs varied between disease states, constituting 19-40% of the total costs, and were highest in the primary treatment state. The first six months after the diagnosis of CRC are resource intensive, but compared with the metastatic disease state, which lasts on average for 2-3 years, the costs are rather modest. Informal care constitutes a remarkable share of the total costs, especially in the palliative state. These results form a basis for the evaluation of the cost effectiveness of new treatments when allocating resources in CRC treatment.


[Necrotizing angiitis with or without asthma. Clinical, biological and etiological differences. Role of hepatitis B virus].
Sixty-five cases of necrotizing angiitis, including 20 with asthma (group A) and 45 without asthma (group B) were studied retrospectively. All patients were investigated for markers of hepatitis B, at least the HBs antigen. Skin lesions and arthralgias were more common in group B patients. Eosinophilia during angiitis was almost constant in group A and was observed in only 6% of group B patients. Renal involvement, hepatic lesions and arterial hypertension seemed to be more frequent in group B but the difference was not significant. The HBs antigen was present in 1/20 patients of group A and in 17/45 patients of group B (p less than 0.01). The anti-HBs antibody was found with equal frequency in both groups. The clinical and biological differences observed between these two groups of patients strongly suggest that necrotizing vasculitis with and without asthma are two separate nosological entities and in particular, that they have different causes.


Effects of a genetically modified potato on a non-target aphid are outweighed by cultivar differences.
Insect-plant interactions may be unintentionally affected when introducing genetically modified (GM) crops into an agro-ecosystem. Our aim was to test the non-target effects of a late blight-resistant GM potato on Myzus persicae in greenhouse and climate room experiments and understand how position and number of R gene insertions can affect non-targets in GM events. We also aimed to compare results to baseline differences among three conventional potato varieties varying in resistance to late blight. Aphid development and survival were affected by some GM events in the first generation, though effects disappeared in the second generation. Effects were not dependent on the presence of a marker gene or the insertion of a second resistance gene. Positional effects of gene insertion influenced aphid performance on certain GM events. However, aphid fitness varied considerably more between conventional potato varieties than between Désirée and the GM events. Comparing different GM events to the non-transformed variety is relevant, since unintended effects of insertion can occur. Our protocols can be recommended for in planta risk assessments with aphids. Ecological perspective is gained by selecting several measured endpoints and by comparing the results with a baseline of conventional cultivars.


Identification of metastasis-related genes in a mouse model using a library of randomized ribozymes.
Libraries of randomized ribozymes have considerable potential as tools for the identification of functional genes critically involved in a biological phenotype of interest in vitro. We have used a ribozyme library in an in vivo mouse model to identify genes related to metastasis. We injected weakly metastatic melanoma cells that had been treated with the library intravenously into mice. We then isolated ribozymes that accelerated metastasis from pulmonary tumors that had developed from metastasizing cells. As candidates for metastasis-related genes that were targets of the isolated ribozymes, we identified five unknown and three known genes: stromal interaction molecule 1 (STIM1), polymerase gamma2 accessory subunit (Polg2), and cytochrome P450, family 2, subfamily d, polypeptide 22 (Cyp2d22). Repression of four of these by small interfering RNAs indeed resulted in the accelerated mobility of cells in in vitro scratch-wound assay. The further characterization of these candidate genes would provide clues to the complex mechanism(s) of metastasis.


The longest acenes.
For a long time, the largest known member of the acene series was hexacene, consisting of six linearly fused benzene rings. The next higher member, heptacene, is so highly reactive that either stabilization using substituents is required or matrix isolation techniques need to be employed for the detection of the parent hydrocarbon. This Record Review summarizes recent research that culminated in the synthesis of substituted and parent nonacene.


QUANTITATIVE ASSESSMENT OF SOME PREVENTIVE HEALTH SERVICES PROVIDED FOR ADOLESCENT INDIVIDUALS IN DUBAI.
The United Arab Emirate (UAE) of Dubai, faces significant adolescent health problems. In 2009, evidence based clinical guidelines were developed for primary health care professionals in Dubai to help reduce adolescent health problems. This research study explores adolescents' self-reports about health education services received between 2008 and 2010. The sample consisted of 730 public high school students in grades 10 through 12 between the ages of 15 and 19. 357 (48.9%) of the sample were males and 373 (51.1%) were female. The major language spoken in the home was Arabic (77.4%). All students completed a 27-item survey in Arabic that was adapted from the Young Adult Health Care Survey (YAHCS). The YAHCS is a 56-item research instrument traditionally administered in English and Spanish. The sample reported they had received little or no health education from their health care providers. 94.2% reported receiving no information about using a helmet for bicycle and motorbike safety; 88.2% reported receiving no information about drug use; and 81.9% reported that they received no information about smoking. The instrument also explored the health education material students received within the last 12 months. 65.5% of the sample reported seeing and/or hearing safety tips; 84.9% reported hearing and/or seeing health information about healthy diet, physical activity and exercise; and 79.2% reported seeing and/or hearing information about the risks of smoking and substance abuse.


Versican/PG-M is essential for ventricular septal formation subsequent to cardiac atrioventricular cushion development.
Versican (Vcan)/proteoglycan (PG)-M is a large chondroitin sulfate proteoglycan which forms a proteoglycan/hyaluronan (HA) aggregate in the extracellular matrix (ECM). We tried to generate the Vcan knockout mice by a conventional method, which resulted in mutant mice Vcan(Δ3/Δ3) whose Vcan lacks the A subdomain of the G1 domain. The Vcan knockout embryos died during the early development stage due to heart defects, but some Vcan(Δ3/Δ3) embryos survived through to the neonatal period. The hearts in Vcan(Δ3/Δ3) newborn mice showed normal cardiac looping, but had ventricular septal defects. Their atrioventricular canal (AVC) cushion was much smaller than those of wild-type (WT) embryos, and the extracellular space for cardiac jelly was narrow. The Vcan deposition in the Vcan(Δ3/Δ3) AVC cushion had decreased, whereas the HA deposition was maintained and condensed. In the tip of ventricular septa, both Vcan and HA had decreased. The cell proliferation based on the number of Ki67-positive cells had remarkably increased in both the AVC cushion and ventricular septa, compared with that of WT embryos. Vcan(Δ3/Δ3) seemed to have endocardial and mesenchymal mixed characteristics. When the ex vivo explant culture of these regions was performed on the collagen gel, hardly any migration to make sufficient space for the ECM construction was apparent. Our results suggest that the proteoglycan aggregates are necessary in both the AVC cushion and ventricular septa to fuse interventricular septa, and the Vcan A subdomain plays an essential role for the interventricular septal formation by constituting the proteoglycan aggregates.


Self-assembling nanocomplexes from insulin and water-soluble branched polyesters, poly[(vinyl-3-(diethylamino)- propylcarbamate-co-(vinyl acetate)-co-(vinyl alcohol)]-graft- poly(L-lactic acid): a novel carrier for transmucosal delivery of peptides.
The design of carriers for protein delivery that provide protection against enzymatic degradation and facilitate protein transport across epithelial surfaces, thus avoiding parenteral administration, remains a challenge. Self-assembling nanoscale protein/polymer complexes might present a promising approach. We synthesized water-soluble, amphiphilic polyesters, poly[(vinyl-3-(diethylamino)-propylcarbamate-co-(vinyl acetate)-co-(vinyl alcohol)]-graft-poly(L-lactic acid), containing a positively charged backbone, and studied the spontaneous formation of nanocomplexes (NC) with insulin. NC were characterized using dynamic light scattering, zeta-potential measurements, and atomic force microscopy (AFM). Insulin loading was determined with HPLC, and the binding constants were obtained by isothermal titration calorimetry (ITC). The NC formation was followed using nephelometric and light scattering techniques. Water-soluble, positively charged, branched polyesters with amphiphilic properties were obtained in a three-step polymer-analogous reaction. The degree of amine substitution, DS, in the PVAL backbone was varied between 0.04 and 0.5, and grafting this backbone with L-lactide increased the molecular weight from 18 kDa to 81 kDa. The polymer composition was optimized to facilitate NC formation with insulin resulting in a DS of 0.09 and a poly(L-lactide) side chain substitution of 0.5 with an average chain length of two lactic acids. Depending on polymer composition, stable NC of 200-500 nm diameter were formed with insulin, and the binding constants ranged from 4.7 x 10(5) to 9.5 x 10(6) M(-1). Positively charged surface charges ranging from +5 to +35mV and an insulin loading up to 98% of 33 IU/mL were obtained. The NC visualized by AFM revealed spheroidal particles with an entangled internal structure. It was demonstrated that this class of multifunctional polymers is capable of self-assembly with a peptidic substrate. The resulting nanosized complexes offer the potential for mucosal insulin/protein delivery and merit further investigations under in vivo conditions.


Assessment of the potential efficacy of blind perineural injection techniques for blockade of the saphenous, obturator, and lateral cutaneous femoral nerves in dog cadavers.
OBJECTIVE To evaluate the potential efficacy of blind perineural injection techniques to provide nerve blockade of the saphenous, obturator, and lateral cutaneous femoral nerves by assessing the distribution along those nerves of 3 volumes of an injected staining solution in dog cadavers. ANIMALS 18 canine cadavers. PROCEDURES The anatomic characteristics of the target nerves were evaluated by dissection in 3 cadavers. The saphenous nerve was located by the use of superficial anatomic landmarks and a loss-of-resistance test. The obturator and lateral cutaneous femoral nerves were located by the use of superficial anatomic landmarks. Following perineural administration of 3 volumes (0.1, 0.2, and 0.3 mL/kg) of staining solution near the target nerves in 15 cadavers, the distribution of the staining solution along the nerves was evaluated. Staining that extended ≥ 2 cm along the target nerves was considered to be compatible with an effective clinical nerve block. RESULTS In all cadavers, nerves were appropriately stained by the blind techniques used here. The staining distribution along the nerves was considered to be optimal after perineural injection of 0.2 mL of staining solution/kg in the obturator and lateral cutaneous femoral nerves and 0.3 mL of staining solution/kg in the saphenous nerve. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that the evaluated blind perineural injection techniques may be an inexpensive, safe, and clinically effective method to block the saphenous, obturator, and lateral cutaneous femoral nerves in dogs.


Prospective study of 210 consecutive cases of endocapsular phacoemulsification using the AMO SI-30NB 3-piece foldable lens.
To assess the acceptability of clinical outcome achieved with use of the SI-30NB lens, as well as the incidence of any lens related complications. This prospective study evaluated 210 consecutive eyes undergoing endocapsular phacoemulsification cataract surgery (EPECS), with implantation of the AMO SI-30NB foldable three-piece lens, commencing with the first patient in our practice receiving this implant. There was 99% follow-up for at least three months, with a mean of nine months, and a range of three to 14 months. Incisions were a maximum of 3.2 mm in size, and this allowed minimisation of astigmatism, and maximisation of early visual rehabilitation. The final visual acuity results were excellent, with 95% of cases achieving corrected vision of 6/12 or better. All cases without pre-existing ocular pathology achieved corrected vision of 6/6, apart from a single case which achieved 6/9, but the patient died before follow-up. The lens-related complication rate was less than 1% (two patients). No decentration of any other implant occurred, and no patient complained of edge glare. There were no cases of iris chafing or pigment dispersion. Only three patients (1.4%) required Yag posterior capsulotomy in the first 14 months of the study. Central bag-bag fixation was achieved in 206 of the 210 cases in the study (98%). The results achieved using the SI-30NB lens with a small incision phaco procedure were excellent. Lens-related complications occurred in only two cases and very few cases have had problems with posterior capsular opacification.


Attachment of Bacteroides gingivalis to collagenous substrata.
The ability of Bacteroides gingivalis 381 to attach to hydroxyapatite (HA) beads, treated with either human type I or type IV collagen, or to particles of bovine bone collagen was studied. All preparations were blocked with human albumin prior to being incubated with 3H-thymidine-labeled B. gingivalis 381 cells. The presence of collagen on HA surfaces (C-HA) significantly promoted attachment of the organism. HA treated with Type IV collagen bound B. gingivalis cells more effectively than did HA treated with type I collagen. Attachment of two additional strains of B. gingivalis to HA was also promoted by collagen. Binding to type I or type IV C-HA occurred rapidly, and equilibrium was attained within 45 min. B. gingivalis 381 cells also bound to particles of bovine bone collagen, and this appeared to be biphasic. Heating the bacteria abolished their ability to bind to C-HA. Attachment of B. gingivalis 381 cells to HA treated with type I collagen was strongly inhibited by the presence of soluble type I or type IV collagen, or gelatin, but not by the presence of human albumin, salivary proline-rich protein 1, or saliva. Human serum, fibronectin, fibrinogen, certain protease inhibitors, and some peptides were also inhibitory. 3H-fibronectin bound to bovine bone collagen particles and blocked the attachment of 14C-B. gingivalis cells. Mild trypsin treatment of the fibronectin-collagen complex restored its ability to promote 14C-B. gingivalis attachment concomitant with the loss of 3H-fibronectin. We suggest that elevated levels of proteases in the gingival sulcus, such as are associated with poor oral hygiene and gingivitis, might remove fibronectin and expose collagen molecules in the basement membrane, thereby promoting the attachment of B. gingivalis cells and facilitating their invasion into gingival tissues.


Subacute sclerosing panencephalitis: a case with fulminant course after ACTH.
We report a 24-month-old male who developed rapidly progressive subacute sclerosing panencephalitis 17 months after measles infection. This patient had a history of measles infection at the age of 7 months and manifested acute encephalitis 1 month later. Developmental delay observed after encephalitis began to improve after a few months. His control electroencephalogram was normal at the age of 14 months. He was admitted to the hospital with flexor spasms and sudden head drops at the age of 24 months. His electroencephalogram revealed slow waves in the posterior regions of the brain. Vigabatrin was begun; his seizures increased with vigabatrin, and adrenocorticotropic hormone was added to the therapy. After five doses of adrenocorticotropic hormone, his clinical findings deteriorated rapidly. His second electroencephalogram revealed periodic discharges synchronized with myoclonias. He was diagnosed as having subacute sclerosing panencephalitis on the basis of clinical and laboratory findings. He lapsed into a vegetative state within a week and died at the age of 25 months. We report this rapidly progressive case to emphasize the importance of recognition of subacute sclerosing panencephalitis before applying steroids in children with myoclonic seizures.


Spurious hypophosphatemia associated with multiple myeloma.
To report on the phenomenon of spurious hypophosphatemia associated with multiple myeloma. A case report is presented, and the pertinent published literature is reviewed. The mechanisms by which multiple myeloma can cause both true and false hypophosphatemia are discussed, as are methods by which the important distinction between these conditions can be made. At the time of surgical treatment of a hip fracture, an 80-year-old man with a history of multiple myeloma was found to have hypophosphatemia. Despite intravenous administration of large amounts of phosphate, the low phosphate values persisted. Only when a blood sample was submitted to another laboratory that used a different technique for determining phosphate was a normal phosphate level reported. In patients with multiple myeloma, the myeloma protein can cause biochemical interference with certain phosphate assays, which could lead to false results. This phenomenon should be considered in such patients in order to avoid inappropriate and potentially dangerous phosphate replacement therapy.


Acuity systems dialogue and patient classification system essentials.
Obtaining resources for quality patient care is a major responsibility of nurse leaders and requires accurate information in the political world of budgeting. Patient classification systems (PCS) assist nurse managers in controlling cost and improving patient care while appropriately using financial resources. This paper communicates acuity systems development, background, flaws, and components while discussing a few tools currently available. It also disseminates the development of a new acuity tool, the Patient Classification System. The PCS tool, developed in a small rural hospital, uses 5 broad concepts: (1) medications, (2) complicated procedures, (3) education, (4) psychosocial issues, and (5) complicated intravenous medications. These concepts embrace a 4-tiered scale that differentiates significant patient characteristics and assists in staffing measures for equality in patient staffing and improving quality of care and performance. Data obtained through use of the PCS can be used by nurse leaders to effectively and objectively lobby for appropriate patient care resources. Two questionnaires distributed to registered nurses on a medical-surgical unit evaluated the nurses' opinion of the 5 concepts and the importance for establishing patient acuity for in-patient care. Interrater reliability among nurses was 87% with the author's acuity tool.


Lyme disease of the brainstem.
Lyme disease is a multisystem infectious disease caused by the tick-borne spirochete, Borrelia burgdorferi. Central nervous system (CNS) involvement typically causes local inflammation, most commonly meningitis, but rarely parenchymal brain involvement. We describe a patient who presented with clinical findings suggesting a brainstem process. Magnetic resonance imaging (MRI) and positron emission tomography (PET) suggested a brainstem neoplasm. Prior to biopsy, laboratory evaluation led to the diagnosis of Lyme disease. Clinical and imaging abnormalities improved markedly following antimicrobial therapy. We describe Lyme disease involvement of the cerebellar peduncles with hypermetabolism on PET. Although MRI is the primary imaging modality for most suspected CNS pathology, the practical applications of PET continue to expand.


Kinetoplast DNA, mitochondrial DNA with a difference.
Kinetoplast DNA occurs in flagellated protozoa belonging to the order Kinetoplastida. Kinetoplast DNA contains tens of maxicircles and thousands of minicircles which are catenated into a single network in each cell. Maxicircles contain genetic information analogous to that in other mitochondrial DNAs. Maxicircles encode mitochondrial ribosomal RNAs and hybridize with mitochondrial gene sequences from other organisms. Minicircles evolve rapidly, may not be transcribed, and vary greatly in total complexity among genera. The functions of minicircles and the network structure are unknown.


Presence of two different active nirS nitrite reductase genes in a denitrifying Thauera sp. from a high-nitrate-removal-rate reactor.
The nirS nitrite reductase genes were studied in two strains (strains 27 and 28) isolated from two denitrifying reactors and characterized as Thauera according to their 16S rRNA gene sequences. Strain 28 contains a single nirS sequence, which is related to the nirS of Thauera mechernichensis, and strain 27 contains two nirS sequences; one is similar to the nirS sequence from Thauera mechernichensis (gene 2), but the second one (gene 8) is from a separate clade with nirS from Pseudomonas stutzeri, Azoarcus species, Alcaligenes faecalis, and other Thauera species. Both genes were expressed, but gene 8 was constitutively expressed while gene 2 was positively regulated by nitrate.


A hybrid-strategy-improved butterfly optimization algorithm applied to the node coverage problem of wireless sensor networks.
To increase the node coverage of wireless sensor networks (WSN) more effectively, in this paper, we propose a hybrid-strategy-improved butterfly optimization algorithm (H-BOA). First, we introduce Kent chaotic map to initialize the population to ensure a more uniform search space. Second, a new inertial weight modified from the Sigmoid function is introduced to balance the global and local search capacities. Third, we comprehensively use elite-fusion and elite-oriented local mutation strategies to raise the population diversity. Then, we introduce a perturbation based on the standard normal distribution to reduce the possibility of the algorithm falling into premature. Finally, the simulated annealing process is introduced to evaluate the solution's quality and improve the algorithm's ability, which is helpful to jump out of the local optimal value. Through numerous experiments of the international benchmark functions, the results show the performance of H-BOA has been significantly raised. We apply it to the WSN nodes coverage problem. The results show that H-BOA improves the WSN maximum coverage and it is far more than other optimization algorithms.


4-D facial expression recognition by learning geometric deformations.
In this paper, we present an automatic approach for facial expression recognition from 3-D video sequences. In the proposed solution, the 3-D faces are represented by collections of radial curves and a Riemannian shape analysis is applied to effectively quantify the deformations induced by the facial expressions in a given subsequence of 3-D frames. This is obtained from the dense scalar field, which denotes the shooting directions of the geodesic paths constructed between pairs of corresponding radial curves of two faces. As the resulting dense scalar fields show a high dimensionality, Linear Discriminant Analysis (LDA) transformation is applied to the dense feature space. Two methods are then used for classification: 1) 3-D motion extraction with temporal Hidden Markov model (HMM) and 2) mean deformation capturing with random forest. While a dynamic HMM on the features is trained in the first approach, the second one computes mean deformations under a window and applies multiclass random forest. Both of the proposed classification schemes on the scalar fields showed comparable results and outperformed earlier studies on facial expression recognition from 3-D video sequences.


LONG-DISTANCE GENE FLOW IN THE SEDENTARY BUTTERFLY, EUPHILOTES ENOPTES (LEPIDOPTERA: LYCAENIDAE).
The relationship between gene flow and geographic proximity has been assessed for many insect species, but dispersal distances are poorly known for most of these. Thus, we are able to assess the concordance between vagility and gene flow for only a few species. In this study, I documented variation at six allozyme loci among Washington and Oregon populations of the sedentary, patchily distributed, lycaenid butterfly, Euphilotes enoptes (Boisduval) to assess whether the relationship between gene flow and geographic distance is consistent with the dispersal biology of this species. Both a phenogram based on genetic distances between populations and a regression analysis of gene flow estimates on geographic distances showed a pattern consistent with genetic isolation by distance. Many estimates of gene flow among pairs of populations separated by more than 100 km exceeded the equivalent of 10 individuals exchanged per generation, a value much greater than would be predicted from the limited dispersal ability of this species. However, based on the allozyme data, genetic neighborhood size was estimated to be approximately 39 individuals, a value that is consistent with poor vagility. The results of this study speak to the power of stepping-stone gene flow among populations and are compared to the results of other studies that have examined the relationship between dispersal and gene flow in sedentary insects.


A prospective observational study of needle-handling practices at a University Veterinary Teaching Hospital.
To determine the period prevalence of needlestick injury (NSI) at the Massey University Veterinary Teaching Hospital (VTH) and to identify handling and disposal practices that may contribute to the risk of NSI. Observations of personnel were conducted in the equine (EVH) and companion animal (CAH) clinics of the VTH during scheduled clinical activities over 9- and 10-day periods, respectively. The number and type of NSI incidents, needle uncapping, capping and disposal events were recorded for veterinarians, nurses and other personnel (visitors and students). The number of needle-related practices, as a proportion of observations, were compared between CAH and EVH, and veterinarians, nurses and others using χ(2) tests. Needlestick injury was not observed during 190 and 163 needle handling and disposal observations in the CAH and EVH, respectively. Uncapping of needles by mouth was observed and was practised more by veterinarians (15/119; 13%) than nurses (2/42; 5%) and others (6/193; 3%) (p=0.001). Two-handed needle recapping after use was observed 265/354 times, and the one handed scooping technique was rarely observed (8/352). In the case of needle disposal, EVH workers used a container that was not purpose built for disposal more than CAH staff (p=0.02), or placed them in a pocket more frequently (p=0.003). Needle disposal containers were available on adjacent bench tops for 65/190 (34%) CAH observations, but no EVH observations. For 51/163 (31%) EVH observations the needle disposal containers were located on the ground, whereas none were observed there in the CAH. No approved sharps containers were observed in the immediate EVH and CAH work areas for 47/163 (28.8%) and 1/191 (0.5%) needle-handling activities, respectively. Unsafe needle-handling practices must be reduced by policies and training programmes to encourage safe needle-related practices, and ensuring that approved sharps containers are available in close proximity to where needles are used.


Mucormycosis in a transplant recipient.
Mucormycosis classically occurs in patients who have uncontrolled diabetes who develop rhinocerebral disease. A fatal case of rhinocerebral infection caused by Rhizopus arrhizus in a 53-year-old man who had received a renal homograft three years previously is reported. Only five similar cases have been documented, all since 1970. Although direct smears of the purulent nasal exudate revealed the presence of numerous Gram-negative bacilli, later identified as Haemophilus influenzae, the diagnosis of mucormycosis was made by demonstrating the typical broad, nonseptate branched hyphae in the necrotic tissue obtained by surgical debridement of the paranasal sinuses. Culture of this material revealed growth of mold-like fungus which, upon direct microscopic examination, showed sporangiophores bearing spherical sporangia arising directly from a cluster of root-like structures of rhizoids. Despite the immediate institution of therapy with amphotericin B postoperatively, the patient died 48 hours later. Subsequently, the Rhizopus isolated was shown to be resistant to both amphotericin B and 5-fluorocytosine. The present case and two others stress the importance of an aggressive diagnostic approach to patients suspected of having mucormycosis, because the usual microbiologic technics are frequently, inexplicably, unsuccessful, and possibly even misleading in this disease.


Influence of ScaI and natriuretic peptide (NP) clearance receptor polymorphisms of the NP System on NP concentration in chronic heart failure.
Genetic variants related to the natriuretic peptide (NP) system [ScaI mutated allele (A1) of the atrial NP (ANP) gene and the C variant of the natriuretic peptide clearance receptor (NPRC) gene] have been identified as independent risk factors for cardiovascular morbidity and mortality. Despite the importance of NPs in heart failure (HF), the role of these polymorphisms in HF has not been evaluated. We screened 124 HF patients [mean (SD), age 66 (12) years, 100 men, ejection fraction 32% (10%), New York Heart Association (NYHA) class I-II 65, III-IV 59] for NP concentrations [ANP, brain NP (BNP) and amino-terminal pro-BNP (NT-proBNP)] and for the ScaI and NPRC variants. ScaI polymorphism had no effect on NP concentration in the NYHA I-II subgroup. Conversely, in severe HF, A1 carriers had higher ANP (P < or =0.05), BNP (P <0.01), and NT-proBNP (P <0.01) than A2A2 patients. After multivariate adjustment, A1 presence remained an independent predictor for increased NP. Regarding NPRC polymorphism in mild HF, higher ANP (P <0.05) and BNP (P <0.05) were observed in CC than A allele carriers. After multivariate adjustment, however, this association did not remain significant. In severe HF, the NPRC polymorphism had no effect on NP. The ScaI polymorphism of the ANP gene might be an important additive genetic factor influencing neurohormonal activation and disease progression in severe HF. The NPRC polymorphism is not an independent determinant of NP concentration in HF.


Long term outcomes data for the Burns Registry of Australia and New Zealand: Is it feasible?
Incorporating routine and standardised collection of long term outcomes following burn into burn registries would improve the capacity to quantify burn burden and evaluate care. To evaluate methods for collecting the long term functional and quality of life outcomes of burns patients and establish the feasibility of implementing these outcomes into a multi-centre burns registry. Five Burns Registry of Australia and New Zealand (BRANZ) centres participated in this prospective, longitudinal study. Patients admitted to the centres between November 2009 and November 2010 were followed-up at 1, 6, 12 and 24-months after injury using measures of burn specific health, health status, fatigue, itch and return to work. Participants in the study were compared to BRANZ registered patients at the centres over the study timeframe to identify participation bias, predictors of successful follow-up were established using a Generalised Estimating Equation model, and the completion rates by mode of administration were assessed. 463 patients participated in the study, representing 24% of all BRANZ admissions in the same timeframe. Compared to all BRANZ patients in the same timeframe, the median %TBSA and hospital length of stay was greater in the study participants. The follow-up rates were 63% at 1-month, 47% at 6-months; 40% at 12-months, and 21% at 24-months after injury, and there was marked variation in follow-up rates between the centres. Increasing age, greater %TBSA and opt-in centres were associated with greater follow-up. Centres which predominantly used one mode of administration experienced better follow-up rates. The low participation rates, high loss to follow-up and responder bias observed indicate that greater consideration needs to be given to alternative models for follow-up, including tailoring the follow-up protocol to burn severity or type.


Polycythemia vera is not initiated by JAK2V617F mutation.
The somatic JAK2(V617F) mutation is seen in most polycythemia vera (PV) patients; however, it is not clear if JAK2(V617F) is the PV-initiating mutation. In order to examine this issue, we developed a novel real-time quantitative allele-specific PCR, in which allelic discrimination is enhanced by the synergistic effect of a mismatch in the -1 position, and a locked nucleic acid (LNA) nucleoside at the -2 position. Determination of allelic frequencies was reproducible (SD = 1.5%) and sensitive--0.1% mutant allele detected in 40 ng of DNA. The JAK2(V617F) frequency in clonal granulocytes from 3 PV females was less than 50% (27.5 +/- 11) and in 7 females greater than 50% (75 +/- 10.5). We also found that wild-type JAK2 BFU-E colonies from PV patients can grow without erythropoietin. The identification of the primary genetic lesion resulting in PV is essential for the development of novel therapeutic strategies. Our studies correlating the frequency of JAK2(V617F) mutant allele and clonality, as well as the presence of homozygous wild-type JAK2 erythropoietin-independent erythroid colonies, provide compelling evidence that the JAK2(V617F) is not the PV-initiating mutation. This supports a model wherein the JAK2(V617F) mutation arises as a secondary genetic event. Furthermore, our results indicate that an undefined molecular lesion, preceding JAK2(V617F), is responsible for clonal hematopoiesis in PV. We conclude that development of therapeutic strategies that target the JAK2(V617F) clonal cells may not be sufficient for eradication of PV.


Active ingredients of Inula helenium L. exhibits similar anti-cancer effects as isoalantolactone in pancreatic cancer cells.
Isoalantolactone is one of the major active ingredients from Inula helenium L. However, it is low cost-effective to isolate isoalantolactone from Inula helenium L. In this study, we optimized the extraction strategy and obtained a mixture of active ingredients with exact proportion (termed as F35), which were alloalantolactone, alantolactone and isoalantolactone at the ratio of 1/5/4 respectively. The anti-tumor activity of F35 was compared with isoalantolactone on pancreatic cancer cells. As a result, F35 showed nearly the same anti-proliferation activity as isoalantolactone in two cell lines. Both F35 and isoalantolactone could induce mitochondrion-related apoptosis at the concentration of 6 μg/ml. In addition, F35 inhibited colony-formation and migration of PANC-1 and SW1990 cells. To conclude, F35 exhibited similar anti-proliferation and anti-migration effect as isoalantolactone on two pancreatic cancer cell lines, suggesting that alantolactone or alloalantolactone might have comparable anti-tumor effect as isoalantolactone.


The comparative efficacy of diamphenethide and rafoxanide against fasciola gigantica in sheep.
Efficacy of diamphenethide ("Coriban", Burroughs Wellcome) and rafoxanide ("Ranide", Merck Sharpe & Dohme, Ltd.) was evaluated in lambs against 8-week old experimentally induced Fasciola gigantica infection. Results were assessed by the reduction in worm counts at post-mortem examination 8 weeks after treatment. Diamphenethide at a dosage rate of 100 mg/kg body weight was found 99.4 per cent effective. Rafoxanide at a dosage rate of 10 mg/kg body weight showed 98.78 per cent efficacy. Six weeks following treatment, infected animals treated with either drug exhibited significantly greater weight gain than the non-treated infected animals.


Total or Subtotal Colectomy with Primary Anastomosis for Occlusive Left Colon Cancer: A Safe, Acceptable and Applicable Procedure.
Occlusive left colon cancer is a major emergency setting in colon cancer with high morbidity and mortality rates. Different surgical treatment exist since there is no clear guidelines for the best treatment. We have conducted this retrospective study in order to evaluate the safety, morbidity, and bowel movement status of the operated patients. One-hundred and one left occlusive colon cancer patients were operated of total or subtotal colon resection with primary anastomosis from March 2000 till March 2017 in Hotel Dieu de France hospital. We analyzed the sex ratio, age, caecum condition, tumor localization, number of synchronous adenoma and adenocarcinoma, Dukes stage, major complications and the number of stools per day at 3 and 12 months after surgery. Mean hospital stay was 7.8 days. Thirteen complications were observed in 11 (10.9%) patients, in which one (1%) patient had splenectomy for severe hemorrhage. Six synchronous adenocarcinoma and 40 adenoma with dysplasia were diagnosed on pathology specimens proximal to occlusion site. Caecum laceration was found in 33 (32.6%) of cases. No patient had anastomotic leak. After 12 months of surgery, the average bowel movement was 2 stools per day. Our study showed that treating occlusive left colon cancer with total or subtotal colectomy with primary anastomosis is a safe procedure, with a good bowel movement status and presents the advantage to resect an important number of synchronous tumors and adenomas proximal to the occlusion site.


Effect of fatty acids on the β-oxidation system and thioesterase of Lactococcus lactis subspecies lactis.
The influence of fatty acids on the β-oxidation system and thioesterase of Lactococcus lactis was investigated in this study. The results showed that fatty acids (C8:0-C16:0) significantly inhibited the growth of Lactococcus lactis, and laurate (C12:0) had the highest bactericidal effects. We detected the maximum activity of β-oxidation at different incubation times (8, 12, and 18h) to be 6.460, 7.751, and 8.203, respectively, and the maximum activity of thioesterase at different incubation times (8, 12, and 18h) to be 19.498, 27.180, and 12.800, respectively. Fatty acids were seen to induce the β-oxidation system and activity of thioesterase; decanoic acid (C10:0) and palmitic acid (C16:0) were also seen to induce the β-oxidation system of Lactococcus lactis, but the induced ability was significantly different. Octanoic acid (C8:0) and palmitic acid (C16:0) were seen to induce thioesterase activity in Lactococcus lactis. When 1mM palmitic acid (C16:0) was added to M17 broth, the activity of thioesterase increased 5-fold after 2min; however, adding octanoic acid (C8:0) changed the activity little. Evidence showed that the ability to induce the β-oxidation system and thioesterase activity was related to the fatty acids' chain lengths.


Intradiskal extravasation with low-volume cement filling in percutaneous vertebroplasty.
Adjacent fracture formation after percutaneous vertebroplasty has been reported in literature. The purpose of this study was to determine whether intervertebral disk extravasation is related to adjacent fracture formation in low-volume cement-filling vertebroplasty. A retrospective analysis of 308 patients having vertebroplasty was undertaken. Anteroposterior and lateral procedural fluoroscopy radiographs were analyzed for mild, moderate, or severe disk extravasation. Symptomatic refracture location relative to the presence or absence of extravasation was analyzed on follow-up fluoroscopy radiographs. Of the 308 patients in the study, 81 patients had disk extravasation at a total of 85 vertebral levels; 40 levels had mild extravasation, 38 levels had moderate extravasation, and 7 had severe extravasation. Of the 40 levels with mild extravasation, 6 new adjacent fractures occurred next to the disk leakage. Of the 38 with moderate extravasation, 6 new adjacent fractures occurred. Of the 7 levels of severe extravasation, only one new adjacent fracture occurred. Hence, a total of 13 adjacent fractures occurred next to disk extravasation; 13 nonadjacent fractures also occurred in the patients with disk extravasation. In the patients without disk extravasation, 28 adjacent and 24 nonadjacent subsequent fractures occurred. The average available cement volumes injected into vertebral bodies causing disk leakage ranged from 4.78 to 5.60 mL. With low-volume cement-filling percutaneous vertebroplasty, we cannot conclude (level of significance alpha = .05) that for patients who have a new fracture there is significance between the location of the fracture and the occurrence of disk extravasation.


Organic cation transporter 3: Keeping the brake on extracellular serotonin in serotonin-transporter-deficient mice.
Mood disorders cause much suffering and are the single greatest cause of lost productivity worldwide. Although multiple medications, along with behavioral therapies, have proven effective for some individuals, millions of people lack an effective therapeutic option. A common serotonin (5-HT) transporter (5-HTT/SERT, SLC6A4) polymorphism is believed to confer lower 5-HTT expression in vivo and elevates risk for multiple mood disorders including anxiety, alcoholism, and major depression. Importantly, this variant is also associated with reduced responsiveness to selective 5-HT reuptake inhibitor antidepressants. We hypothesized that a reduced antidepressant response in individuals with a constitutive reduction in 5-HTT expression could arise because of the compensatory expression of other genes that inactivate 5-HT in the brain. A functionally upregulated alternate transporter for 5-HT may prevent extracellular 5-HT from rising to levels sufficiently high enough to trigger the adaptive neurochemical events necessary for therapeutic benefit. Here we demonstrate that expression of the organic cation transporter type 3 (OCT3, SLC22A3), which also transports 5-HT, is upregulated in the brains of mice with constitutively reduced 5-HTT expression. Moreover, the OCT blocker decynium-22 diminishes 5-HT clearance and exerts antidepressant-like effects in these mice but not in WT animals. OCT3 may be an important transporter mediating serotonergic signaling when 5-HTT expression or function is compromised.


Stress analysis in edentulous mandibular bone supporting implant-retained 1-piece or multiple superstructures.
The aim of this study was to investigate the stress distribution in mandibular bone supporting a single or separate multiple implant-retained superstructures. Three-dimensional finite element models consisting of the mandibular bone, 8 implants, and 1 or more superstructures were created. Vertical and oblique loads were directed onto the occlusal areas of the superstructures to simulate the maximum intercuspal contacts and working contacts, such as the canine-protected and group function occlusion. The unseparated 1-piece superstructure generated the lowest maximum equivalent stresses in the peri-implant bone, followed by the 2-piece superstructure separated at the midline. For the 3-piece superstructure, which was separated between the canine and the premolar, the maximum stress was lower when the canine on the working side was loaded than when the posterior teeth were loaded. Separating the 1-piece superstructure into 2- to 4-piece superstructures increased the mechanical stress around supporting implants. Canine load on the working side is distributed well in 1-piece and 3-piece superstructures. Based on the results of this finite element model study, canine protected occlusion is recommended for 1-piece and 3-piece superstructures. The unseparated superstructure was more effective in relieving stress concentration in the edentulous mandibular bone than the separated superstructures.


How long should young infants less than two months of age with moderate-mortality-risk signs of possible serious bacterial infection be hospitalised for? Study protocol for a randomised controlled trial from low- and middle-income countries.
Hospitalisation and a seven-day injectable antibiotics course are recommended by the World Health Organization (WHO) to treat suspected clinical neonatal sepsis / possible serious bacterial infection (PSBI). Some infants presenting with PSBI signs associated with a moderate risk of mortality may only need a two-day hospitalisation followed by outpatient care treatment with oral antibiotics to complete seven days of antibiotics. A multi-centre, individually randomised, open-label trial will be conducted in seven sites in six countries: Bangladesh, Ethiopia, India (two sites), Nigeria, Pakistan and Tanzania. A common protocol will be used with the same study design, including the participants, intervention, comparison, outcomes, quality control, and analysis procedures. 0-59 days old infants presenting with moderate-mortality risk signs (low body temperature (<35.5°C), movement only when stimulated, stopped feeding well) or two or more signs of clinical severe infection (CSI) will be assessed and pre-enrolled. After 48 hours of hospital stay, clinically stable infants with a negative C-reactive protein test will be randomised either to hospital discharge on oral amoxicillin (intervention) or continued hospitalisation (control) arm. The intervention arm will receive oral amoxicillin for five days, whereas the control arm will receive injection gentamicin plus injection ampicillin for five more days plus supportive therapy if needed. We plan to enrol 5250 eligible young infants, 2625 infants in each of the two study arms. An experienced, well-trained independent outcome assessor will visit all enrolled cases on days 4, 8 and 15 after the initiation of treatment to assess the study outcomes in both intervention and control arms. The primary outcome of poor clinical outcome defined as death between randomisation and day 15 of initiation of treatment, deterioration during the 7-day treatment period, or persistence of the presenting sign of CSI at the end of the 7-day treatment period will be compared to assess if an early discharge and outpatient treatment leads to superior or at least non-inferior clinical outcome than continued inpatient treatment. The harmonisation of activities, including methods and processes, will be carried out diligently. Central training will be conducted by the WHO coordinating team, a central data coordination centre to collate all data, standardisation exercises for all clinical signs and internal and external monitoring. All the selected sites have extensive research experience. Through regular online and physical meetings, data-based monitoring, and physical site visits by WHO monitors, quality assurance and harmonisation will be ensured. This trial has been approved by the WHO and local site institutional ethics committees. If the results show that young infants with moderate-mortality risk PSBI signs can be safely and effectively treated on an outpatient basis after a shorter hospital stay, it will reduce the burden on the hospitals, potentially reduce nosocomial hospital infections and increase access to treatment for families with poor access to health facilities. It may also reduce the health system costs (human and materials) and allow the overburdened hospitals to pay more attention to critically ill young infants. In addition, this evidence will contribute to making a case for reviewing the WHO PSBI guideline. International Standard Randomised Controlled Trial Number, ISRCTN16872570.


Immunoelectron microscopic demonstration of antigenic sites on lymphoid cells using a human monoclonal antibody (Ha6D3).
The reactivity of a human monoclonal antibody directed against human B and T lymphocytes was tested for the first time at the ultrastructural level. The antigenic sites detected by this antibody were localized on the surface membrane of lymphocytes and, to a lesser extent, in the cytoplasm on membranes of the endoplasmic reticulum and perinuclear envelop of some centroblasts and immunoblasts. Ultrastructural demonstration of target antigen detected by human monoclonal antibodies may be important prior to therapeutic application of these antibodies.


Integrating novel primary- and secondary-prevention strategies: the next challenge for cervical cancer control.
The advent of prophylactic vaccines against human papillomavirus (HPV) infection, the cause of cervical cancer, and of new molecular methods to screen for this disease have become key developments in cancer control in the last 5 years. Although Pap cytology has had a significant history as a key method for cervical cancer screening, not all countries have benefited from this technology or have been able to implement the necessary public health steps to manage and treat the precancerous lesions that are detected by the Pap test. Testing of cervical exfoliated cells for DNA of oncogenic HPV types has been proven to be more accurate than Pap cytology. The latter test's high specificity makes it an ideal technique to triage women who are found to be HPV positive via a primary screen. HPV testing followed by Pap testing only for HPV-positive women is a promising strategy for screening women in the post-vaccination era.


Role of interstitial inflammation in the pathogenesis of polycystic kidney disease.
Interstitial infiltrates, consisting of macrophages and other inflammatory cells, have been consistently reported in human and animal models of polycystic kidney diseases (PKD). However, the mechanisms underlying this inflammation are not well defined. Evidence suggests that interstitial inflammation in PKD is driven by pro-inflammatory chemoattractants such as monocyte chemoattractant protein-1 (MCP-1), and cytokines such as tumour necrosis factor (TNF)-α. Putative upregulated inflammatory pathways include JAK-STAT and nuclear factor (NF)-κB signalling. In addition, the genetic mutations of PKD may further complicate the relationship between inflammation and cystic disease, by increasing the susceptibility to inflammatory injury, and facilitating interactions between the genetically determined cystoproteins and biological mediators of inflammation. Moreover, the roles of interstitial inflammation in promoting cyst growth and progression to kidney failure in PKD are not clearly understood. Although anti-inflammatory therapies have attenuated cystogenesis in animal models, inflammatory cells may also have reparative actions. Thus, in developing therapies for PKD, it is prudent to consider the potential negative outcomes of ablating inflammation, and whether it is more viable to target certain inflammatory pathways over others.


Evaluating the role of dithiolane rich fraction of Ferula asafoetida (apiaceae) for its antiproliferative and apoptotic properties: in vitro studies.
Asafoetida resin has been reported for various biological activities but its use has been widely restricted owing to its pungent smell and pool water solubility. In vitro study of the anticancer potential of microwave-extracted essential oil (EO) of Ferula asafoetida. The phytochemical investigation and in vitro cytotoxicity assessment was carried out in two human liver cancer cell lines. The expression of NFKB1, TGFB1, TNF, CASP3 was analyzed by reverse transcription polymerase chain reaction. Ferula asafoetida EO contains high concentrations of dithiolane, which possess antiproliferative activity in human liver carcinoma cell lines (HepG2 and SK-Hep1) in a dose-dependent manner. The bioactive compounds in F. asafoetida are capable of induction of apoptosis and altered NF-kB and TGF-β signalling with increase in caspase-3 and TNF-α expression. Further elucidation of bioactive molecules and underlying mechanisms could lead to potential intervention in liver cancer in animal models. The safety and efficacy as well as the mode of EO action in animal models would be highly crucial.


Quantum calculations of the photoelectron spectra of the OH-·NH3 anion: implications for OH + NH3→ H2O + NH2 reaction dynamics.
We present the results of quantum dynamics calculations for analyzing the experimentally measured photoelectron spectra of the OH-·NH3 anion complex. Detachment of an excess electron of OH-·NH3 initially produces a molecular arrangement, which is close to the transition-state structure of the neutral OH + NH3→ H2O + NH2 hydrogen abstraction reaction due to the Franck-Condon principle, and thus finally leads to the OH + NH3 or H2O + NH2 asymptotic channel. We used both the path integral method and the reduced-dimensionality quantum wave packet method to simulate the photoelectron spectra of the OH-·NH3 anion. The calculated spectra were found to be in qualitative agreement with the experimental spectra. It was found that the photodetached complex mainly dissociates into the OH + NH3 channel; however, we found that the hydrogen exchange process also contributes to the photodetachment spectra.


Massive pancreatic serous effusions.
The condition of massive pancreatic serous effusion is being increasingly recognized as a specific complication of pancreatitis. It occurs as a result of leakage of pancreatic juice into the pleural or peritoneal cavity after disruption of the duct system. Five such cases are described. The difficulties in making the diagnosis are mainly due to the absence of symptoms of pancreatitis, and most patients present because of the effects of the effusion. Once suspected, the diagnosis is confirmed by the demonstration of a grossly elevated amylase level in the fluid. A rational surgical approach is usually successful, and depends on the demonstration of a leak from a pseudocyst or disruption of the pancreatic duct system.


Comparison of embryonated chicken eggs with MDCK cell culture for the isolation of swine influenza virus.
Embryonated chicken eggs (ECE) and the Madin-Darby canine kidney (MDCK) cell line were compared for isolation of swine influenza virus (SIV) from nasal swabs and tissue samples. Samples originated from 30 pigs experimentally inoculated with 2 x 106 to 2 x 10(7) embryo infectious dose 50% (EID50)/mL of swine influenza strain A/Swine/Indiana/1726/88 (H1N1). The results were analyzed with McNemar's chi-squared test for symmetry. The results indicated that more samples were SIV-positive with ECE than with tissue culture (P < 0.001), suggesting that ECE remains the system of choice for isolation of SIV. It is recommend that routine use of both SIV isolation systems will increase the sensitivity of detection of virus shedding by considering the differences in growth and tropism of diverse SIV strains.


[Pulmonary Chondroma; Report of a Case].
A 66-year-old man was pointed out a nodular shadow in the right lower lobe by chest computed tomography (CT) 4 years ago. Since the size of the shadow has been increasing for 4 years, he hospitalized for surgery. Partial resection of the right lower lobe was performed. Histopathologically, the tumor was composed of cartilage tissue without epithelial components, and was diagnosed as a chondroma. Postoperative course was uneventful and there has been no recurrence at 1 years and 8 months after surgery.


Clinical activity of androgen deprivation therapy in patients with metastatic/relapsed androgen receptor-positive salivary gland cancers.
Androgen deprivation therapy has some clinical activity in selected salivary gland cancer histotypes, with androgen receptor expression. We retrospectively analyzed patients with androgen receptor-expressing recurrent/metastatic salivary gland cancer, treated with androgen deprivation therapy. Protein expression of androgen receptor and ErbB family members was investigated. Progression-free survival (PFS) and overall survival (OS) were the main endpoints. Seventeen patients were identified. No significant toxicities were reported. Overall response rate was 64.7%; 3-year PFS and 5-year OS were 11.8% and 19.3%, respectively. Androgen receptor overexpression may be sustained by gain of chromosome X (58%) and TP53 mutation (44%). No association between response to androgen deprivation therapy and epidermal growth factor receptor (EGFR), human epidermal growth factor receptor (HER)2, HER3 expression, PIK3CA mutations, or phosphatase and tensin homolog (PTEN) deletion was identified. We confirm the activity of androgen deprivation therapy in androgen receptor-expressing recurrent/metastatic salivary gland cancers. The hypothesis that an androgen receptor increased gene copy number may represent a possible mechanism of primary resistance should be further investigated.


Isokinetic peak torque ratios and shoulder injury history in adolescent female volleyball athletes.
Few researchers have examined shoulder strength in adolescent volleyball athletes despite increasing levels of participation in this age group. To compare medial and lateral isokinetic peak torque of the rotator cuff among skill levels and between athletes with and without a history of shoulder injury. Cross-sectional design. The Human Performance Lab and Athletic Training Lab. Thirty-eight female adolescent club volleyball athletes from 10 to 15 years of age (mean = 13.02 +/- 1.60 years). We measured concentric and eccentric peak torque of the medial and lateral rotators of the shoulder and calculated resultant cocking and spiking ratios based on peak torque values. Athletes at higher skill levels had higher peak torque measurements in concentric and eccentric medial and lateral rotation compared with the athletes at lower skill levels. No differences in peak torque existed between participants with or without an injury history 6 months before the study. Strength ratios did not differ across skill levels, but previously injured participants produced lower eccentric medial rotation to concentric lateral rotation ratios compared with participants without a history of injury (P = .02). At the highest skill level, previously injured participants produced lower eccentric lateral rotation to concentric medial rotation ratios compared with participants without an injury history (P = .04). Differences in medial and lateral shoulder rotator strength ratios appear to be related more to injury prevalence than to absolute strength. Shoulder dysfunction related to strength ratio deficits also may exist in adolescent female volleyball athletes. Preventive shoulder strengthening programs focused on improving eccentric strength and correcting imbalances between medial and lateral rotators may be warranted for all female adolescent volleyball athletes.


Unification of Perdew-Zunger self-interaction correction, DFT+U, and Rung 3.5 density functionals.
This Communication presents a unified derivation of three different approximations used in density functional theory (DFT): the Perdew-Zunger self-interaction correction (PZSIC), the Hubbard correction DFT+U, and the Rung 3.5 density functionals. All three approximations can be derived by introducing electron self-interaction into the Kohn-Sham (KS) reference system of noninteracting electrons. The derivation uses the Adiabatic Projection formalism: one projects the electron-electron interaction operator onto certain states, introduces the projected operator into the reference system, and defines a density functional for the remainder. Projecting onto individual localized KS orbitals recovers our previous derivation of the PZSIC [B. G. Janesko, J. Phys. Chem. Lett. 13, 5698-5702 (2022)]. Projecting onto localized atom-centered orbitals recovers a variant of DFT+U. Projecting onto localized states at each point in space recovers Rung 3.5 approaches. New results include an "atomic state PZSIC" that does not require localizing the KS orbitals, a demonstration that typical Hubbard U parameters reproduce a scaled-down PZSIC, and a Rung 3.5 variant of DFT+U that does not require choosing atom-dependent states.


Ultrasonic assessment of the postmenopausal uterus.
To assess the role of different forms of ultrasound in the evaluation of peri- and postmenopausal uterus. B-mode ultrasound, colour and pulsed Doppler sonography, three-dimensional ultrasound and three-dimensional power Doppler sonography are non-invasive tools used repeatedly for assessing morphology and vascularity of the uterus and uterine lesions in peri- and postmenopausal patients. The application of transvaginal colour Doppler to the peri- and postmenopausal patients for the screening for endometrial and myometrial malignancy may be a viable option if combined with ovarian screening in the same scan. In this way the capital costs would be shared and oncological preventive medicine for postmenopausal women could be initiated. Three-dimensional and power Doppler ultrasound offers improved visualisation of uterine lesions, displays an entire volume, offers accurate volume estimation and enables retrospective review of stored data. Interactive rotation of power Doppler rendered images provides improved visualisation of the uterine vasculature. Further technological development of the ultrasound imaging techniques could result in reduction of both the potential risks and economic cost of the invasive diagnostic procedures in postmenopausal patients such as dilatation and curettage operations. Same techniques can be used for early detection of endometrial malignancy in asymptomatic postmenopausal women as well as for prediction of the depth of myometrial invasion.


[Actinomyces pneumonicus var. altamicus var. nov., a producer of new altamycin antibiotics].
Actinomycete LIA-0788 was isolated from a soil sample. By its morphological and cultural features the actinomycete was close to Actinomyces pneumonicus and differed from it in the antibiotic properties. This provided classification of actinomycete LIA-0788 as Act. pneumonicus var. altamicus var nov. The culture produced altamycins A and B, new antibiotics. Their physico-chemical characteristics is presented.


Interactions between the parasite's previous and current environment mediate the outcome of parasite infection.
The study of parasite virulence has generally focused on the conditions under which virulence is expected to increase or decrease over time and how the interactions between hosts and their environments may mediate the outcome of infection. Recently, parasite traits such as transmission, offspring production, and development have also been shown to be influenced by environmental variation. What is unclear is how variation in the parasite's environment may impact virulence. Recent theory demonstrates that plasticity can promote the evolution of decreased virulence; thus, understanding whether the parasite's environment can mediate virulence can improve predictions regarding the outcome of parasite infection. Here, an obligate mosquito parasite was reared in hosts fed high or low levels of food. Parasite oocysts (offspring) produced in these two host environments were subsequently fed to uninfected hosts. Parasites originating from well-fed hosts were found to be more virulent to these subsequent hosts compared to parasites originating from poorly fed hosts. Additionally, this effect was apparent only when current hosts were food deprived. These results demonstrate that parasite virulence was mediated by a cross-generational effect of the environment and that the overall outcome of infection was modified by variation in both the parasite's and host's environments.


New Dual P-Glycoprotein (P-gp) and Human Carbonic Anhydrase XII (hCA XII) Inhibitors as Multidrug Resistance (MDR) Reversers in Cancer Cells.
In a continuing search of dual P-gp and hCA XII inhibitors, we synthesized and studied new N,N-bis(alkanol)amine aryl diester derivatives characterized by the presence of a coumarin group. These hybrids contain both P-gp and hCA XII binding groups to synergistically overcome the P-gp-mediated multidrug resistance (MDR) in cancer cells expressing both P-gp and hCA XII. Indeed, hCA XII modulates the efflux activity of P-gp and the inhibition of hCA XII reduces the intracellular pH, thereby decreasing the ATPase activity of P-gp. All compounds showed inhibitory activities on P-gp and hCA XII proteins taken individually, and many of them displayed a synergistic effect in HT29/DOX and A549/DOX cells that overexpress both P-gp and hCA XII, being more potent than in K562/DOX cells overexpressing only P-gp. Compounds 5 and 14 were identified as promising chemosensitizer agents for selective inhibition in MDR cancer cells overexpressing both P-gp and hCA XII.


The association between local area immigrant fraction and prevalence of cardiovascular diseases in the United States: an observational study.
Local area immigrant fraction is strongly and positively correlated with local life expectancy in the United States. The aim of the study was to determine the relationship between local area immigrant fraction and local prevalence of coronary heart disease (CHD) and stroke. Cross-sectional study design, with ZIP code as the unit of observation. Demographic data was obtained from the American Community Survey, and linked to indicators of health access (e.g., insurance, annual check-ups, cholesterol screening), obesity, behavior (smoking, exercise), and cardiovascular outcomes data from the 2020 Population Level Analysis and Community Estimates. Multivariable regression and path analyses were used to assess both direct and indirect relationships among variables. CHD prevalence was lower in the second (3.9% relative difference, 95% CI: 3.1-4.5%), third (6.5%, 95% CI: 5.8-7.1%), and fourth (14.8%, 95% CI: 14.1-15.8%) quartiles of immigrant fraction compared to the lowest (p-trend <0.001). These effects remained robust in multivariable analysis following adjustment for indicators of access, obesity, and behavioral variables (p-trend <0.0001). For stroke, only the highest quartile demonstrated a significant difference in prevalence (2.1%, 95% CI: 1.2-3.0% with full adjustment). In CHD path analysis, ∼45% of the association of immigrant fraction was direct, and ∼55% was mediated through lower prevalence of deleterious behaviors (e.g., smoking). In stroke path analysis, the effect was entirely mediated through indirect effects. In the United States, ZIP codes with higher immigrant fractions have lower prevalence of cardiovascular diseases. These associations are partially mediated through differences in health behaviors at the community level. NIH (K08CA252635, P30AG0059304, K24HL150476), Stanford University, Rutgers University.


Does the time interval from the end of sperm processing to intrauterine insemination (lab-to-uterus time) affect treatment outcome?
Intra-uterine insemination is an essential component in the treatment of infertility. Success rates are dependent on clinical factors of the female partner, sperm quality, and preparation technique. The effect of the time interval between the end of sperm preparation in the lab, and its injection into the uterine cavity (lab-to-uterus time) is yet to be determined. To investigate the association between the lab-to-uterus time and the pregnancy rate. Partner and donor spermatozoa intra-uterine insemination cycles were included. Preparation for intra-uterine insemination of partners' fresh ejaculate or donor thawed spermatozoa was identical. The time interval from the completion of this stage to the actual intra-uterine injection was recorded. The lab-to-uterus intervals were divided into groups A (0-29 min), B (30-59 min), C (60-89 min), and D (90-180 min). Pregnancy was defined as two adequate consecutive doubling levels of hCG and the pregnancy rates were compared between the groups. A total of 267 female patients (138 partner spermatozoa, 129 donors) who had 470 intra-uterine insemination cycles (218 partner spermatozoa, 252 donors) were included. No significant differences in pregnancy rates per treatment cycle were found between the four lab-to-uterus interval groups: A (n = 96 cycles; 16.7%), B (n = 217; 19.4%), C (n = 121; 16.5%), and D (n = 36; 36.1%). No difference was found in the pregnancy rates between partner and donor spermatozoa. In the case of fresh partner spermatozoa, the pregnancy rates for groups were as follows: A (n = 40 cycles, 20%); B (n = 94; 14.9%), C (n = 70; 17.1%), and D (n = 14; 35.7%) (NS). In the case of thawed donor spermatozoa, the pregnancy rates (per cycle) for groups were as follows: A (n = 56; 14.3%), B (n = 123; 22.8%), C (n = 51; 15.7%), and D (n = 22; 36.4)% (NS). The intra-uterine insemination outcome was not affected by the lab-to-uterus time interval. Extended waiting up to 3 h for insemination did not have any detrimental effect on pregnancy rates, regardless if partner or donor spermatozoa was used.


[Exercise and physical activities for the prevention of osteoporotic fractures: a review of the evidence].
According that osteoporosis is the common condition in an aging society such as in Japan, much progress has been made in understanding the treatment and prevention of osteoporosis. Among potential risk factors, exercise and physical activities have been recognized as lifestyle factors that might influence the risk of osteoporosis and osteoporotic fractures. To assess the relationship between exercises including physical activities and the risk for low bone mass and osteoporosis-related fractures, a literature search over past 13 years was conducted. Accumulating evidence indicates that exercises decrease the risk for hip fractures among middle aged and older men and women. Exercises also help to maintain muscle strength, muscle volume, balance, and joint flexibility, which might prevent falls and fall-related fractures. One randomized controlled trial showed back-stretching exercise reduced the risk for vertebral fractures. The literature search also indicates that high-impact and/or weight-bearing exercise might increase the bone density in the elderly and the peak bone mass among young women, while there is no association between moderate or lower-impact exercise and bone mineral density. Future research should be required to evaluate the types and quantity of physical activity needed for the prevention of osteoporosis.


Identification of the capsular polysaccharides in Staphylococcus aureus clinical isolates by PCR and agglutination tests.
Staphylococcus aureus is a major cause of nosocomial and community-acquired infections. The predominance of two capsular polysaccharides, types 5 and 8, on the surface of clinical isolates led to the development of a conjugate vaccine (StaphVAX) based on capsular polysaccharides types 5 and 8 conjugated to a carrier protein. We have studied the capsular phenotypes and genotypes of 195 isolates representative of all clinical syndromes that encompassed both hospital and community-acquired infections. These isolates were mainly detected in France between January 2001 and December 2004. In this population, most of clinical isolates (87%) expressed either capsular polysaccharide type 5 (42%) or 8 (45%), whereas 13% were nontypeable by the serotyping method with antibodies specific to capsular polysaccharide type 5 or 8. These 26 nontypeable strains were further serotyped and were demonstrated to express the cell wall surface antigen 336, a polyribitol phosphate N-acetylglucosamine, which resembles cell wall teichoic acid. Among methicillin-resistant Staphylococcus aureus (MRSA) strains, we found a predominance of serotype 5 for 64% of strains, whereas MSSA isolates were predominantly capsular serotype 8 (60%). All S. aureus clinical isolates included in the present study have been investigated by PCR method, demonstrating that all isolates carried either the cap5 or the cap8 locus.


Conjunctival leiomyosarcoma: A case report and review of literature.
Leiomyosarcoma is a malignant mesenchymal tumor that is very uncommon in the conjunctiva. Nevertheless, we describe here the clinical manifestations, management, and prognosis of a rare case of leiomyosarcoma in this location. An 81-year-old male presented at a tertiary hospital with a rapidly growing mass. After performing biopsy, histopathological examination revealed the existence of a conjunctival leiomyosarcoma. On this diagnosis, a thorough metastatic screening was performed showing no enlarged lymph nodes or metastatic deposits anywhere in the body. To treat the condition, we performed an evisceration with clear margins and subsequent radiotherapy.


Analgesic use during pregnancy and risk of infant leukaemia: a Children's Oncology Group study.
Infant leukaemia is likely initiated in utero. We examined whether analgesic use during pregnancy was associated with risk by completing telephone interviews of the mothers of 441 infant leukaemia cases and 323 frequency-matched controls, using unconditional logistic regression. With the exception of a reduced risk for infant acute myeloid leukaemias with non-aspirin non-steroidal anti-inflammatory drugs (NSAID) use early in pregnancy (odds ratios=0.60; confidence intervals: 0.37-0.97), no statistically significant associations were observed for aspirin, non-aspirin NSAIDs, or acetaminophen use in early pregnancy or after knowledge of pregnancy. Overall, analgesic use during pregnancy was not significantly associated with the risk of infant leukaemia.


Experiential Self-Focus in Social Anxiety Disorder: Is it Beneficial?
Self-focused processing is a significant maintaining factor in cognitive models of social anxiety disorder (SAD), but it may also be analytic (detached, evaluative, maladaptive) or experiential (concrete, nonevaluative, adaptive). The current study aimed to investigate the effect of self-focus modes in a sample meeting criteria for SAD as previous studies have yielded mixed results. Individuals meeting criteria for SAD and nonanxious controls (N = 80, 77.5% female; mean age = 19.46) were randomly allocated to complete a task inducing analytic or experiential self-focused processing, followed by a social interaction task, including measurement of affective and cognitive variables. Controls demonstrated the expected benefits of experiential compared to analytic self-focus on social anxiety, negative affect, and self-beliefs. Unexpectedly, SAD participants reported no difference between self-focus conditions. Results suggest that experiential processing may have no benefit for SAD individuals proximal to a social threat. Implications of these findings are discussed.


Nestin contributes to skeletal muscle homeostasis and regeneration.
Nestin, a member of the cytoskeletal family of intermediate filaments, regulates the onset of myogenic differentiation through bidirectional signaling with the kinase Cdk5. Here, we show that these effects are also reflected at the organism level, as there is a loss of skeletal muscle mass in nestin-/- (NesKO) mice, reflected as reduced lean (muscle) mass in the mice. Further examination of muscles in male mice revealed that these effects stemmed from nestin-deficient muscles being more prone to spontaneous regeneration. When the regeneration capacity of the compromised NesKO muscle was tested by muscle injury experiments, a significant healing delay was observed. NesKO satellite cells showed delayed proliferation kinetics in conjunction with an elevation in p35 (encoded by Cdk5r1) levels and Cdk5 activity. These results reveal that nestin deficiency generates a spontaneous regenerative phenotype in skeletal muscle that relates to a disturbed proliferation cycle that is associated with uncontrolled Cdk5 activity.


Rhodium(II) Proximity-Labeling Identifies a Novel Target Site on STAT3 for Inhibitors with Potent Anti-Leukemia Activity.
Nearly 40 % of children with acute myeloid leukemia (AML) suffer relapse arising from chemoresistance, often involving upregulation of the oncoprotein STAT3 (signal transducer and activator of transcription 3). Herein, rhodium(II)-catalyzed, proximity-driven modification identifies the STAT3 coiled-coil domain (CCD) as a novel ligand-binding site, and we describe a new naphthalene sulfonamide inhibitor that targets the CCD, blocks STAT3 function, and halts its disease-promoting effects in vitro, in tumor growth models, and in a leukemia mouse model, validating this new therapeutic target for resistant AML.