Early open thoracotomy and mediastinopleural irrigation for severe descending necrotizing mediastinitis.
Descending necrotizing mediastinitis (DNM) is a severe infection spreading from the cervical region to the mediastinal connective tissue. The mortality rate was reported as 40% until the 1980s. Since DNM is uncommon, few reports of large series of patients with DNM (i.e. more than 10 cases) have been published. The present aim was to evaluate our treatment strategy for DNM by retrospective chart review. Retrospective chart review was performed in 10 patients with DNM between 1991 and 2003. The mean age was 53.8+/-23.3 years (median 58, range 16-82). The causes of DNM were primary peritonsillar or parapharyngeal abscess in 5 patients, post-extraction odontogenic abscess in 3, cervical abscess of post-tracheostomy in 1, and unknown in 1 patient. In nine cases, the abscess extended from the cervical region to the lower mediastinum. Immediately after the diagnosis of DNM, broad-spectrum antibiotics were administered empirically, and surgical treatments consisting of cervical drainage, thoracotomy with radical surgical debridement of the mediastinum and excision of necrotic tissue, decortication, and irrigation were performed in all cases. Post-operatively, mediastinopleural irrigation with saline was performed once or twice a day until a culture of pleural effusion became negative. The mean duration of chest tube retention was 26.7+/-17.0 days, and the mean hospital stay was 62.3+/-33.9 days. Five patients suffered from severe complications including septic shock, acute respiratory distress syndrome, disseminated intravascular coagulation, and pan-peritonitis due to duodenal perforation. The outcome was favorable in 8 patients. Of those with severe complications, two patients, who were older than 75 and had diabetes, died of multiple organ failure due to septic shock. Therefore, the mortality rate was 20%. Our treatment strategy for severe DNM was efficacious for early treatment and reduced the mortality rate. Early detection of DNM, and immediate thoracotomy and irrigation of the mediastinum and thoracic cavity, are recommended.


Post-secretion neutralization of transgene-derived effect: soluble erythropoietin receptor/IgG1Fc expressed in liver neutralizes erythropoietin produced in muscle.
The regulation of transgene expression is a key issue for the development of safe gene therapy. Various strategies have been used to regulate protein production at the levels of transgene expression, transcription, translation, and secretion. Neutralization following secretion is another important backup system to prevent super-therapeutic levels of a protein from being expressed by gene transfer. We tested whether the soluble human erythropoietin receptor (EpoR)/IgG(1)Fc could neutralize the rat Epo at the post-secretory level and suppress erythrocytosis. To assess whether soluble human EpoR could bind rat Epo in vitro, we used the Epo-dependent human leukemic cell line, AS-E2. EpoR/IgG(1)Fc significantly inhibited the growth of AS-E2 cells in Epo-containing medium. To test this neutralization effect of EpoR/IgG(1)Fc in vivo, we first transferred pCAGGS-Epo into rat muscle by in vivo electroporation, confirmed erythropoiesis for 3 weeks, and then delivered EpoR/IgG(1)Fc by liver-targeted gene transfer via tail-vein injection with hydrodynamics-based transfection. Reticulocyte counts and hematocrit levels in rats that received pCAGGS-EpoR/IgG(1)Fc injections were significantly lower than in rats that received pCAGGS-EpoR, pCAGGS-IgG(1)Fc, or no injection. These results demonstrate that liver-targeted pCAGGS-EpoR/IgG(1)Fc transfer by tail-vein injection with hydrodynamics-based transfection is useful for neutralizing Epo delivered by in vivo electroporation. This backup strategy at the level of post-secretion could facilitate the clinical application of gene therapy in the future.


Hyper-structure mining of frequent patterns in uncertain data streams.
Data uncertainty is inherent in many real-world applications such as sensor monitoring systems, location-based services, and medical diagnostic systems. Moreover, many real-world applications are now capable of producing continuous, unbounded data streams. During the recent years, new methods have been developed to find frequent patterns in uncertain databases; nevertheless, very limited work has been done in discovering frequent patterns in uncertain data streams. The current solutions for frequent pattern mining in uncertain streams take a FP-tree-based approach; however, recent studies have shown that FP-tree-based algorithms do not perform well in the presence of data uncertainty. In this paper, we propose two hyper-structure-based false-positive-oriented algorithms to efficiently mine frequent itemsets from streams of uncertain data. The first algorithm, UHS-Stream, is designed to find all frequent itemsets up to the current moment. The second algorithm, TFUHS-Stream, is designed to find frequent itemsets in an uncertain data stream in a time-fading manner. Experimental results show that the proposed hyper-structure-based algorithms outperform the existing tree-based algorithms in terms of accuracy, runtime, and memory usage.


Comparison of outcome of asymptomatic to symptomatic patients older than 20 years of age with valvular aortic stenosis.
A 2-part prospective study was performed to evaluate the clinical outcome of patients with hemodynamically confirmed asymptomatic valvular aortic stenosis (AS). During phase 1, linear regression analysis showed continuous wave Doppler to be highly accurate in predicting catheterization measured peak systolic aortic valve pressure gradients in 101 consecutive patients aged 36 to 83 years (mean 65 +/- 8) with symptomatic AS. During phase 2, 90 additional patients (51 asymptomatic and 39 symptomatic) with Doppler-derived peak systolic aortic valve gradients greater than or equal to 50 mm Hg (range 50 to 132 [mean 68 +/- 19]) were followed for 1 to 45 months. Both groups of patients in phase 2 had similar Doppler gradients and clinical and auscultatory evidence of moderate to severe AS at baseline. Asymptomatic patients were younger (p = 0.01), had higher ejection fractions (p = 0.001) and were less likely to have an electrocardiographic strain pattern (p = 0.01) and left atrial enlargement (p = 0.02). End-diastolic wall thickness, left ventricular cross-sectional myocardial area and estimated left ventricular mass were 18% (p = 0.0001), 20% (p = 0.0008), and 29% (p = 0.002) greater in symptomatic patients. During 17 +/- 9 months of follow-up, 21 asymptomatic patients (41%) became symptomatic. Dyspnea was the most common initial complaint, occurring 2.5 and 4.8 times more often than angina and syncope, respectively. Compared with the 39 symptomatic patients, the 51 asymptomatic patients had a lower cumulative life table incidence of death from any cause (p = 0.002), and from cardiac causes (p = 0.0001) including sudden death (p = 0.013).(ABSTRACT TRUNCATED AT 250 WORDS)


[Who prescribes? Origin and adequacy of long term prescriptions included in a computerized long term treatment programme at a health center].
To quantify medications not prescribed at the primary level and their suitability for patients included in a programme of compliance and computerised control of long treatments at a Health Centre. Descriptive study. Zumaia Health Centre (Guipúzcoa). The study sampled 75 patients out of a total of 397 in treatment. The total number of drugs studied was 230, out of which 23% were prescribed by the General Practitioner and 77% referred from other care levels. Of these last, the bibliographical sources consulted advised against their use in chronic treatments in one out of every 5 cases, which depended on the pathology which was the cause of referral. Much of the medication included in our long-treatment programme was prescribed at other care levels than our Health Centre. The elaboration of a list of medications excluded from long-treatment programmes should bear in mind the prescription's real origin in order to avoid negative consequences both for the user and the system. The computerisation of prescriptions could be extremely valuable both in the control of our programmes and the analysis of their attributable costs. We propose that the validity of the type of referred medications used for long-treatment patients should be studied as an indicator of a Health Centre's proper functioning.


[Effects of pelvic floor muscle training on quality of life of a group of women with urinary incontinence: randomized controlled trial].
To evaluate the effects of Kinesiotherapy on function and level of pressure of pelvic floor muscle and quality of life (QOL) of a group of women with urinary incontinence (UI). This is a randomized controlled pilot trial. Thirty women (age 60.87±9.05 years) were evaluated, before and after 12 weeks of treatment, for urinary loss, pelvic floor muscle function and pressure; and quality of life (QOL). Volunteers were randomly allocated into two groups: Kinesiotherapy Group and Control Group. The Kinesiotherapy Group protocol consisted of 12 1-hour sessions with exercises to strengthen pelvic floor muscle and information for UI. The Control Group did not receive any treatment during the corresponding time. The data were analyzed by non-parametric Wilcoxon and Mann-Whitney test. The significance level was 5%. The Kinesiotherapy Group presented a significant improvement in urinary loss (p=0.053), pelvic floor muscle function (p<0.006) and pressure (p=0.0014) and in some domains of Kinǵs Health Questionnaire for QOL assessment: incontinence impact (p=0.034), limitations of daily activities (p=0.025), sleep and disposition (p=0.018) and also gravity domains (p=0.004). No differences were found in the control group for any variables. The protocol to strengthen the pelvic floor muscle used by the Kinesiotherapy Group was effective to improve the UI, QOL, function and pressure of pelvic floor muscle contraction.


Interstitial laser coagulation of the prostate: introduction of a volume-based treatment formula with 12-month follow-up.
The objective of the present study was to assess the efficacy of interstitial laser coagulation (ILC) of the prostate using a low-volume treatment formula as a minimally invasive therapy for symptomatic benign prostatic hyperplasia (BPH). A total of 25 men underwent ILC of the prostate for symptomatic BPH between February 1997 and June 1997. The Indigo 830e laser system from Indigo Medical Inc. and the factory preset therapy regimen was used for ILC of the prostate. The number of treatments or punctures was determined by the formula 0.5 x total prostate volume (ml)/8 ml, rounded to the closest even whole number. The treatment outcome was evaluated at 3-, 6-, and 12-month intervals using the American Urological Association's (AUA) BPH symptom score, maximal urinary flow, prostate size, and postvoid residual urine volume. The AUA symptom score decreased from 23.2 (range 17-28) prior to treatment to 9.4 (range 4-14) at 3 months, 6.6 (range 5-12) at 6 months, and 7.2 (range 4-11) at 12 months. The maximal flow rate improved from 8.4 (range 5-10) ml/s pretreatment to 14.1 (range 10-20) ml/s at 3 months, 14.8 (range 10-18) ml/s at 6 months, and 16.8 (range 12-25) ml/s at 12 months after treatment. There was no significant postprocedure complication. The 1-year clinical results suggest that the ILC procedure using the Indigo 830e device in conjunction with a low-volume treatment formula has outcomes similar to those obtained following ILC based on high-volume coagulation.


A novel pH-responsive quaternary ammonium chitosan-liposome nanoparticles for periodontal treatment.
The aim of this study was to evaluate the antibacterial activity and cytocompatibility of novel pH-activated nanoparticles (NPs) in vitro and in vivo. The NPs were synthesized from a quaternary ammonium chitosan, i.e., N,N,N-trimethyl chitosan, a liposome, and doxycycline (TMC-Lip-DOX NPs). The cytocompatibility of the NPs was evaluated. The TMC-Lip-DOX NPs achieved superb inhibition of free mixed bacteria and biofilm formation. They also showed excellent biocompatibility with human periodontal ligament fibroblasts. Animal experiments showed that the NPs strongly inhibited biofilm formation and prevented alveolar bone absorption in vivo. All the results indicate that the TMC-Lip-DOX NPs have good potential for use in the treatment of periodontal and other inflammatory diseases.


Exergy, advance exergy, and exergo-environmental based assessment of alkanol amine- and piperazine-based solvents for natural gas purification.
Purification of Natural gas is vital for utilizing it as a source of energy harvesting for the world. Amine-based chemical absorption technique is the most utilized in the gas field for the purification of gas that ensures the purity of the sweet gas stream with the elimination of carbon dioxide. However, it is considered an energy-intensive process to deal with considerable energy loss and environmental damage to the ecosystem. Five cases have been developed in this study based on various blends comprising mono and tertiary amines in combination with piperazine with a focus on the use of Aqueous Monodiethanolamine (Aq. MDEA), Aqueous Monoethanolamine (Aq. MEA) and piperazine (Pz) for the CO2 sequestration from the sour natural gas extracted from the remote location located in the province of Baluchistan in Pakistan. The use of exergy, advanced exergy, and exergo environment for optimizing and selecting a suitable solvent combination that may result in an effective separation process has been proposed. Five cases have been developed based on various blends such as mono and tertiary amines combined with piperazine. From the results of all the studied scenarios, Case IV, based on the combination of Aqueous monoethanolamine and piperazine, provides reduced exergy destruction of 2551.7 KW. It was observed that the maximum removal of CO2 around 99.87 wt% is achieved in case IV. In addition, advance exergy analysis also highlights that case-IV has a venue of 25% exergy destruction avoidable, which would further enhance its performance. Nevertheless, still, case-IV has 75% exergy destruction unavoidable. The environmental factors show that Case-IV has a reduced exergy destruction factor of 0.96, a highly environmentally benign choice as a solvent with a high value of 1.03, and case-IV has the higher operational stability and higher exergy efficiency with an exergy stability value of 0.40. Therefore, monoethanolamine combined with piperazine to be an effective and efficient solvent blend that could be an energy-effective approach for sweetening the natural gas.


Characterization of Langmuir-Blodgett films of 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine and 1-palmitoyl-2-[10-(pyren-1-yl)decanoyl]-sn-glycero-3-phosphat idylcholine by FTIR-ATR.
Monomolecular films of 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) and 1-palmitoyl-2-[10-(pyren-1-yl)decanoyl]-sn-glycero-3-phosphatidylc holine (PPDPC) were transferred from an air/water interface onto a germanium attenuated total reflection crystal by the Langmuir-Blodgett (LB) technique. The assemblies were thereafter investigated by Fourier transform infrared-attenuated total reflection (FTIR-ATR) spectroscopy. To determine the molecular organization in the deposited layers we monitored the CH2 and C = O stretching and the CH2 bending regions of the infrared spectra of these lipids in detail. Using Fourier self-deconvolution technique, the carbonyl stretching mode was resolved into two models corresponding to the conformational differences in the ester linkages of the phospholipid sn-1 and sn-2 acyl chains. By varying the temperature of the subphase and using different surface pressures, we were able to transfer different conformational states of DPPC onto a germanium ATR crystal. Deposition of DPPC at 40 mN m-1 and at 15 degrees C or at 20 mN m-1 and at 35 degrees C results in LB-assemblies in ordered or disordered states, respectively, as judged by the IR spectra. These structures in LB films correspond to the state of DPPC in liposomes below and above the temperature of the order-disorder phase transition. Irrespective of the surface pressure and subphase temperature used during the deposition, an ordering process was found in DPPC films when the number of the transferred layers was increased from one to five. The pyrene-labelled phosphatidylcholine analogue, PPDPC, behaved differently from DPPC. In the case where one to three layers of PPDPC transferred at 35 mN m-1 and at 20 degrees C only conformational structures resembling those in fully hydrated liposomes above the main transition temperature were observed.


Recurrence rates of cutaneous squamous cell carcinoma of the head and neck after Mohs micrographic surgery vs. standard excision: a retrospective cohort study.
Recurrent cutaneous squamous cell carcinoma (cSCC) has been associated with an increased risk of local functional and aesthetic comorbidity, metastasis and mortality. To compare the risk of recurrence between Mohs micrographic surgery (MMS) and standard excision for cSCC of the head and neck. This was a retrospective cohort study of all patients with a cSCC treated with MMS or standard excision at the departments of dermatology of a secondary or tertiary care hospital in the Netherlands between 2003 and 2012. To detect all recurrences, patients were linked to the Dutch pathology registry. To compare the risk of recurrence between MMS and standard excision, hazard ratios (HRs) were used adjusted for clinical tumour size > 2 cm and deep tumour invasion. A total of 579 patients with 672 cSCCs were included: 380 cSCCs were treated with MMS and 292 with standard excision. The risk of recurrence was 8% (22 of 292) after standard excision during a median follow-up of 5·7 years [interquartile range (IQR) 3·5-7·8], which was higher than the 3% (12 of 380) after MMS during a median follow-up of 4·9 years (IQR 2·3-6·0). The cumulative incidence of recurrence was higher for standard excision than for MMS during the entire follow-up period of 8·6 years. Carcinomas treated with MMS were at a three times lower risk of recurrence than those treated with standard excision when adjusted for tumour size and deep tumour invasion (adjusted HR 0·31, 95% confidence interval 0·12-0·66). MMS might be superior to standard excision for cSCCs of the head and neck because of a lower rate of recurrence.


Use of Blood Lipid Indicators as a Screening Tool of Insulin Resistance among Individuals in Low-Income Country Sides of China: A Multiethnic Region Study.
This study is aimed at evaluating the diagnostic value of blood lipid indicators (BLIs) for insulin resistance (IR) among major ethnic groups in Xinjiang, China, to identify the most valuable indicators and appropriate cut-off points for each ethnic group and to lay the foundation for the early detection, diagnosis, and treatment of metabolic diseases in remote rural areas. Overall, 418 Uygurs, 331 Kazakhs, and 220 Hans were randomly included in our study. The homeostasis model assessment was the gold standard for identifying IR. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value, and the nomogram was utilized to analyze the predictive value. The size of the area under the curve (AUC) reflected the accuracy of screening and prediction. Differences in races were observed in terms of IR and BLIs, and the Kazakhs had the highest IR level at 5.27 mmol/L. The correlation between IR and BLIs differed among the three races. For the Kazakhs and Hans, all BLIs, except total cholesterol (TC), were correlated to IR. However, for the Uygurs, only the triglyceride (TG) level, TG/high-density lipoprotein cholesterol (HDL-C) ratio, and TC/HDL-C ratio were associated with IR. After further adjustment of confounding factors, these indicators were still correlated to IR. BLIs that independently correlated to IR in the three nationalities had a certain diagnostic value for IR. In terms of the AUC size, the TG level was the highest in Uygurs, the TG/HDL-C ratio was the highest for Kazakhs and Hans, and the corresponding best cut-off points for IR were 1.515, 1.230, and 1.495 mmol/L, respectively. In addition, for each race, when the indicators with a certain diagnostic value were combined, the diagnostic value for IR was higher. BLIs had a certain diagnostic value for IR and could be used as a screening tool for IR among Uygurs, Kazakhs, and Hans in Xinjiang. These findings are extremely important for the prevention and treatment of IR and metabolic diseases in remote rural areas.


Influence of UDP-glucuronosyltransferase polymorphisms on mycophenolate mofetil-induced side effects in kidney transplant patients.
Mycophenolate mofetil (MMF) is an immunosuppressive prodrug approved for use in transplantation. Its active metabolite, mycophenolic acid, is mainly metabolized by UDP-glucuronosyltransferase (UGT) enzymes. In this study, we retrospectively analyzed 74 kidney transplant patients who had been prescribed MMF as part of their immunosuppression regimen. Polymorphisms in UGT1A8 (-999C > T, codon 255A > G, codon 277G > A) were correlated with the occurrence of side effects, such as diarrhea, blood disorders, and infections. The infectious episodes were more frequently observed among individuals receiving MMF (2 g/d) who carryied the variant UGT1A8 codon 277A (P = .031), the haplotype UGT1A8H5 (-999C/codon 55A/codon 277A; P = .02), and the diplotype UGT1A8H2/H5 (-999CC/codon 255AA/codon 277GA; P = .015). The molecular data from this study suggest that UGT polymorphisms may be a factor influencing clinical outcomes among patients receiving MMF for transplant therapy; however, larger studies are warranted.


A clinicopathological study of peripheral lymph nodes in HIV-infected patients with special reference to CD4+ T-cell counts: Experience from a tertiary care institution in Darjeeling (India).
HIV/AIDS is a major health burden worldwide. India bears the third highest HIV-patients load globally. In the Darjeeling district, HIV-prevalence is >1% with very little known about the profile of HIV-lymphadenopathy. The aim of this study was to identify the different causes of peripheral lymphadenopathy among HIV-infected patients in this region, correlate them with CD4+ T-cell counts and formulate some common clinico-haematological parameters as potential predictors of CD4+ T-cell count. In the present study, 76 cases were evaluated. Fine Needle Aspiration Cytology (FNAC) was performed as an out-patient procedure in the Department of Pathology. Smears were stained routinely with Haematoxylin-Eosin and Leishman stains. ZN stains were done when indicated by the cytological findings. Immediate CD4+ T-cell count was obtained by referring the patients to the Anti-retroviral therapy centre. Cytological diagnoses included tuberculosis (82.9%), reactive hyperplasia (6.6%), nonspecific granulomatous lesions (3.9%), non-Hodgkin lymphoma (2.6%), histoplasmosis (2.6%) and simultaneous filariasis with toxoplasmosis (1.3%). Statistically, the opportunistic infections and lymphomas significantly concurred with a CD4+ T-cell count <350/μl. Likewise, the number of enlarged lymph nodes and absolute lymphocyte count (ALC) were found to be useful predictors of CD4+ T-cell counts. Lymph node cytology in HIV-infected patients is essential to identify opportunistic infections from neoplastic lesions and; to enable therapeutic strategies. Correlation of lesions with mean CD4+ T-cell count predicts personal immunity, stage of disease and disease activity. Furthermore, enlarged lymph node numbers and ALC can be surrogate markers of CD4+ T-cell count for monitoring the severity of the immune suppression in under-resourced countries like India.


Acute dissection of the innominate artery: a case of report.
A 61-year-old man developed a ruptured innominate artery associated with localized acute dissection. The innominate artery was reconstructed with a bifurcated prosthetic graft without brain complication.


[Study on the volatile oil of leaf of red gland Lonicera in guangxi].
To compare volatile oil of Lonicera confusa (red gland Lonicera) fresh leaves with dry leaves and provide evidence for further study of Lonicera confusa leaves. GC-MS was used to identify chemical composition in volatile oil in red gland Lonicera leaves. 93 chemical components were separated in fresh leaves in which 39 chemical components were identified; 88 chemical components were separated in dry leaves in which 51 chemical components were identified. The main components of fresh leaves of red gland Lonicera were n-Hexadecanoic acid (11.90%), Phytol (11.79) and 9,12,15-Octadecatrienoic acid, methyl ester, (Z, Z, Z)(7.08); The main components of dry leaves of red gland Lonicera were 1,6-Octadien-3-ol, 3,7-dimethyl-(27.62%), Phytol (7.57%) and 2, 6, 10, 14, 18, 22-Tetracosahexaene, 2, 6, 10, 15, 19, 23-hexamethyl-, (all-E) (4.70%). There are significant differences between volatile oil between fresh and dry leaves.


A pseudoatomic model of the dynamin polymer identifies a hydrolysis-dependent powerstroke.
The GTPase dynamin catalyzes membrane fission by forming a collar around the necks of clathrin-coated pits, but the specific structural interactions and conformational changes that drive this process remain a mystery. We present the GMPPCP-bound structures of the truncated human dynamin 1 helical polymer at 12.2 Å and a fusion protein, GG, linking human dynamin 1's catalytic G domain to its GTPase effector domain (GED) at 2.2 Å. The structures reveal the position and connectivity of dynamin fragments in the assembled structure, showing that G domain dimers only form between tetramers in sequential rungs of the dynamin helix. Using chemical crosslinking, we demonstrate that dynamin tetramers are made of two dimers, in which the G domain of one molecule interacts in trans with the GED of another. Structural comparison of GG(GMPPCP) to the GG transition-state complex identifies a hydrolysis-dependent powerstroke that may play a role in membrane-remodeling events necessary for fission.


STAT3/HIF-1α/fascin-1 axis promotes RA FLSs migration and invasion ability under hypoxia.
Rheumatoid arthritis (RA) synovium was identified as "tumor-like" tissues because of the hypoxic microenvironment, significant cell proliferation, and invasion phenotypes. It was reported that hypoxia promoted tumor aggressiveness via up-regulated expression of fascin-1 in cancer. However, the role of fascin-1 in RA synovial hyperplasia and joint injury progression remains unknown. In the current study, we first identified that both fascin-1 and HIF-1α were highly expressed in the RA synovium, in which they were widely colocalized, compared to osteoarthritis(OA). As well, levels of fascin-1 in RA fibroblast-like synoviocytes(FLSs) were found significantly higher than those in OA FLSs. Further, it was demonstrated that the mRNA and protein levels of fascin-1 in RA FLSs were up-regulated in hypoxia (3 % O2) and experimental hypoxia induced by cobalt chloride. Mechanistically, the HIF-1α-mediated hypoxia environment activated the gene expression of the fascin-1 protein, which in turn promoted the migration and invasion of RA FLSs. Accordingly, the restoration of FLSs migration and invasion was observed following siRNA-mediated silencing of fascin-1 and HIF-1α expression. Notably, under the experimental hypoxia, we found that the expression levels of fascin-1, HIF-1α, and p-STAT3 were increased in a time-dependent manner, and fascin-1and HIF-1α expressions were dependent on p-STAT3. Our results indicated that hypoxia-induced fascin-1 up-regulation promoted RA FLSs migration and invasion through the STAT3/HIF-1α/fascin-1 axis, which might represent a novel therapeutic target for the treatment of RA.


Experimental studies of biliary excretion of piperacillin.
The nonrecirculating isolated perfused rat liver was used to study biliary antibiotic excretion by the liver in a steady-state, controlled environment in which bile flow, bile salt output, and antibiotic delivery were maintained under constant conditions. The effects of piperacillin, ampicillin, and gentamicin on bile flow and bile salt output were analyzed; none altered bile salt output, and only high concentrations of piperacillin (100 micrograms/mL) increased bile flow. The ratio of antibiotic concentration in bile and perfusate depended on the type of antibiotic and perfusate concentration. Piperacillin infusions at perfusate concentrations of 50 or 100 micrograms/mL (in the presence of 60 microM taurocholate) yielded bile to perfusate ratios of 112 +/- 10 versus 49 +/- 3, respectively. Using similar perfusate, the concentration ratios for ampicillin (20 micrograms/mL) and gentamicin (10 micrograms/mL) were only 3.4 +/- 0.5 and 0.5 +/- 0.1, respectively. By altering the perfusate to contain either 60 microM or 240 microM taurocholate, we found variance in bile salt output from 27 +/- 1 to 115 +/- 2 mumol/h, yet this alteration had little effect on the output of ampicillin (perfusate concentration of 20 micrograms/mL), 73 +/- 7 versus 74 +/- 12 micrograms/h, or piperacillin (perfusate concentration 100 micrograms/mL), 10 +/- 1 versus 11 +/- 2 mg/h. Thus, it appears ampicillin and piperacillin are excreted into bile at high concentrations by bile salt-independent pathways. Partial biliary obstruction (6 cm H2O) results in significant decreases in bile volume. Infusion of 50 micrograms/mL of piperacillin resulted in increased biliary flow that approached nonobstructed values. Obstruction resulted in significant decreases in bile piperacillin concentration. Whether the choleretic effect of high concentrations of piperacillin has any clinical significance in nonobstructed or obstructed conditions remains to be established.


1,3,4-thiadiazole derivatives. Part 9. Synthesis and biological activity of metal complexes of 5-(2-aminoethyl)-2-amino-1,3,4-thiadiazole.
Metal complexes of the title ligand (L) containing Co(II), Ni(II) and Cu(II) were prepared and characterized by elemental analysis, IR, electronic spectroscopy and conductimetry. The new derivatives, possessing the following formulae, CuL(2)(OH)(2), NiL(2)Cl(2), and [Co(2)LCl(4)](n) showed in vitro antifungal activity against Aspergillus and Candida spp.


Control of avian mycoplasma infections in commercial poultry.
Control of pathogenic avian mycoplasmas can consist of one of three general approaches: Maintaining flocks free of infection, medication, or vaccination. Maintaining flocks free of pathogenic mycoplasmas consists of maintaining replacements from mycoplasma-free sources in a single-age, all-in all-out management system. Good biosecurity and an effective monitoring system are necessary aspects of this program. Medication can be very useful in preventing clinical signs and lesions, as well as economic losses, but cannot be used to eliminate infection from a flock and is therefore not a satisfactory long-term solution. Vaccination against Mycoplasma gallisepticum (MG) or M. synoviae (MS) can be a useful long-term solution in situations where maintaining flocks free of infection is not feasible, especially on multi-age commercial egg production sites.


Extraction, identification and antitumor activity in cell cultures of cubebin isolated from dry seeds Piper cubeba (Piperaceae).
The Pipercubeba, it is one spice, widely consumed in Europe, which has several bioactive molecules, between those a lignan named cubebin. Cubebin has several known biological activities, such as analgesic activity and anti-inflammatory, trypanocidal activity, leishmanicidal and antitumor activity. The objective of this study was to evaluate the antiproliferative activity "in vitro" cubebin in eight different human tumor cell lines. It was fully characterized by IR analysis, NMR, mass spectrometry, DSC, TGA, residual solvent and elemental analysis. The antitumor activity of cubebin was evaluated "in vitro" on eight different human tumor cell lineages. Cubebin showed GI50≤30μg/mL for lineage cell U251 (glioma CNS), 786-0 (kidney), PC-3 (prostate), HT-29 (colon rectum). For K562 cells (leukemia), cubebin presented GI50≤to 4.0mg/mL. For the other lineages cells, MCF-7 (breast) and NCI-H460 to cubebin can be considered inactive because of GI50>250mg/mL. Analyzing the selectivity index for cubebin, it can be observed that high selectivity of cubebin to K562 lineage cells (leukemia). Analyzing the cytotoxic potential of cubebin was observed that probably acts cubebin altering metabolism, inhibiting cell growth - a cytostatic effect, showing no cytocidal effect on any lineage cell.


The Use of Intraoperative Ultrasound During Breast Conserving Surgery.
The purpose of this study is to evaluate the utilization of intraoperative ultrasound (IOUS) for tumor localization in breast-conserving surgery and to examine its impact on margin positivity and re-excision rates. Additionally, the study seeks to identify factors contributing to surgeon utilization of IOUS. A retrospective chart review was conducted of patients with preoperative diagnosis of breast cancer undergoing breast-conserving surgery by breast surgeons at multiple centers within a single healthcare system. Characteristics such as lesion size, palpability, histology, receptor status, and use of neoadjuvant chemotherapy were recorded. Re-excision rates were determined based on localization technique and surgeons' status of breast ultrasound certification. A total of 671 cases were performed, with 322 meeting study inclusion. 57 cases utilized IOUS, 250 utilized preoperative wire-guided localization (WGL), 10 used both methods and 5 cases used neither method. There was no significant difference in re-excision rates between IOUS and WGL or among the four surgeons. Ultrasound-certified surgeons were more likely to utilize IOUS, and re-excision rates trended higher for WGL, which may be clinically significant. Increasing familiarity with and utilization of IOUS during breast-conserving surgery may be clinically advantageous over traditional localization techniques. Ultrasound certification may lead to increased use of IOUS among surgeons.


Differential expression of genes involved in the acute innate immune response to intracortical microelectrodes.
Higher order tasks in development for brain-computer interfacing applications require the invasiveness of intracortical microelectrodes. Unfortunately, the resulting inflammatory response contributes to the decline of detectable neural signal. The major components of the neuroinflammatory response to microelectrodes have been well-documented with histological imaging, leading to the identification of broad pathways of interest for its inhibition such as oxidative stress and innate immunity. To understand how to mitigate the neuroinflammatory response, a more precise understanding is required. Advancements in genotyping have led the development of new tools for developing temporal gene expression profiles. Therefore, we have meticulously characterized the gene expression profiles of the neuroinflammatory response to mice implanted with non-functional intracortical probes. A time course of differential acute expression of genes of the innate immune response were compared to naïve sham mice, identifying significant changes following implantation. Differential gene expression analysis revealed 22 genes that could inform future therapeutic targets. Particular emphasis is placed on the largest changes in gene expression occurring 24 h post-implantation, and in genes that are involved in multiple innate immune sets including Itgam, Cd14, and Irak4. STATEMENT OF SIGNIFICANCE: Current understanding of the cellular response contributing to the failure of intracortical microelectrodes has been limited to the evaluation of cellular presence around the electrode. Minimal research investigating gene expression profiles of these cells has left a knowledge gap identifying their phenotype. This manuscript represents the first robust investigation of the changes in gene expression levels specific to the innate immune response following intracortical microelectrode implantation. To understand the role of the complement system in response to implanted probes, we performed gene expression profiling over acute time points from implanted subjects and compared them to no-surgery controls. This manuscript provides valuable insights into inflammatory mechanisms at the tissue-probe interface, thus having a high impact on those using intracortical microelectrodes to study and treat neurological diseases and injuries.


Technologies for harvesting the microalgae for industrial applications: Current trends and perspectives.
Microalgae are emerging as a promising source for augmenting the supply of essential products to meet global demands in an environmentally sustainable manner. Despite the potential benefits of microalgae in industry, the high energy consumption for harvesting remains a significant obstacle. This review offers a comprehensive overview of microalgae harvesting technologies and their industrial applications, with particular emphasis on the latest advances in flocculation techniques. These cutting-edge methods have been applied to biodiesel production, food and nutraceutical processing, and wastewater treatment. Large-scale harvesting is still severely impeded by the high cost despite progress has been made in laboratory studies. In the future, cost-effective microalgal harvesting will rely on efficient resource utilization, including the use of waste materials and the reuse of media and flocculants. Additionally, precise regulation of biological metabolism will be necessary to overcome algal species-related limitations through the development of extracellular polymeric substance-induced flocculation technology.


Functional roles of phenylalanine(7) of thymic humoral factor-gamma 2 in the impaired blastogenic response of uremic T-lymphocytes.
The peptide analogs of thymic humoral factor-gamma 2 (THF-gamma 2) in which phenylalanine residue at the 7th position are replaced by phenylglycine (Phg), homophenylalanine (Hph), and 1-naphthylalanine (1-Nal) were synthesized by a solid-phase method and the immunological significance of the aromatic amino acid of this position was comparatively investigated. The in vitro restoring effect of the synthetic peptides on the impaired phytohemagglutinin (PHA) response of T-lymphocytes from uremic patients was tested. The observed activities of these peptides were in order (1-Nal7) thymic humoral factor [THF]-gamma 2 > 4-Fluoro (Phe7) THF-gamma 2 > THF-gamma 2. However, the other two analogs, [Phg7] THF-gamma 2 and [Hph7] THF-gamma 2, had no restoring effect even at a higher concentration.


Comparison of whole-field simultaneous integrated boost VMAT and IMRT in the treatment of nasopharyngeal cancer.
To study the feasibility of using volumetric-modulated arc therapy (VMAT) to deliver whole-field simultaneous integrated boost (WF-SIB) to treat patients with nasopharyngeal cancer (NPC). WF-SIB intensity-modulated radiotherapy (IMRT) plans, one-arc WF-SIB VMAT plans, and two-arc WF-SIB VMAT plans were generated with identical objective functions for 8 patients with NPC of various stages. Isodose distributions and dose-volume histograms were evaluated. Dosimetric and biological quality indices of clinical target volume (CTV) and organs at risk (OARs) were calculated to study the optimization capability of these 3 modalities in the treatment of patients with NPC. The optimization time, delivery time, required monitor units (MUs), and delivery accuracy were also compared to investigate the feasibility of these 3 modalities. There was no significant difference (p = 0.92) in target coverage (TC) between WF-SIB IMRT (99.00 ± 0.79) and two-arc WF-SIB VMAT (97.98 ± 1.29). However, both had higher TC than one-arc VMAT plans (89.92 ± 6.32, p < 0.01). IMRT demonstrated the best protection of the spinal cord, whereas two-arc VMAT showed the minimum Dmax to OARs. No other significant differences were observed among these 3 modalities on CTV coverage and OAR sparing. The delivery and MU efficiency of one-arc and two-arc WF-SIB VMAT were greatly improved compared with WF-SIB IMRT. The optimization time of one-arc and two-arc WF-SIB VMAT plans were 5 and 10 times greater than that of WF-SIB IMRT, respectively. The delivery accuracy of WF-SIB VMAT was not affected by the increased freedom. For patients with NPC, one-arc WF-SIB VMAT might not be able to achieve sufficient TC, whereas two-arc WF-SIB VMAT was able to achieve reasonable TC. No significant advantage on OAR protection was demonstrated by VMAT compared with IMRT. WF-SIB VMAT has significantly shorter delivery times, but WF-SIB IMRT may still be the first treatment choice for patients with NPC.


Travel time to health-care facilities, mode of transportation, and HIV elimination in Malawi: a geospatial modelling analysis.
UNAIDS has prioritised Malawi and 21 other countries in sub-Saharan Africa for fast-tracking the end of their HIV epidemics. UNAIDS' elimination strategy requires achieving a treatment coverage of 90% by 2030. However, many individuals in the prioritised countries have to travel long distances to access HIV treatment and few have access to motorised transportation. Using data-based geospatial modelling, we investigated whether these two factors are barriers to achieving HIV elimination in Malawi and assessed the effect of increasing bicycle availability on expanding treatment coverage. We built a data-based geospatial model that we used to estimate the minimum travel time needed to access treatment, for every person living with HIV in Malawi. We constructed our model by combining a spatial map of health-care facilities, a map that showed the number of HIV-infected individuals per km2, and an impedance map. We quantified impedance using data on road and river networks, land cover, and topography. We estimated travel times for the existing coverage of 70%, and the time that HIV-infected individuals would need to spend travelling in order to achieve a coverage of 90%, whether driving, bicycling, or walking. We identified a quantitative relationship between the maximum achievable coverage of treatment and the minimum travel time to the nearest health-care facility. At 70% coverage, health-care facilities can be reached within approximately 45 min if driving, 65 min if bicycling, and 85 min if walking. Increasing coverage above 70% will become progressively more difficult. To reach 90% coverage, many HIV-infected individuals (who have yet to initiate treatment) will need to travel for almost twice as long as those already on treatment. Bicycling, rather than walking, in rural areas would substantially increase the maximum achievable coverage. The long travel times needed to reach health-care facilities coupled with little motorised transportation in rural areas are substantial barriers to reaching 90% coverage in Malawi. Increased bicycle availability could help eliminate HIV. US National Institute of Allergy and Infectious Diseases.


Exogenous hydrogen sulfide postconditioning protects isolated rat hearts against ischemia-reperfusion injury.
Hydrogen sul fi de (H2S) is an endogenous gaseous mediator, produced by cystanthionine-gamma-lysase (CSE) in the cardiovascular system. Hydrogen sulfide given before ischemia can decrease myocardial ischemia and reperfusion injury. The present study investigated: (1) if hydrogen sulfide given at early reperfusion could decrease myocardial ischemia and reperfusion injury; (2) if the protective effects of hydrogen sulfide were related to mitochondrial ATP-sensitive K+ (KATP) channels opening. In isolated rat heart model, treatment of heart with NaHS (H2S donor) at the onset of reperfusion resulted in a concentration-dependent limitation of infarct size and creatine kinase release. The optimal NaHS concentration for cardioprotection is 1 microM. The cardioprotective effects of NaHS (1, 10 microM) were comparable to those of ischemic postconditioning. The KATP channels blocker, Glibenclamide or 5-hydroxydecanoate, reversed the cardioprotective effects of NaHS. The datum provided further evidence that exogenous H2S postconditioning protected rat heart against ischemia and reperfusion injury. Mitochondrial KATP channel opening is implicated in the postconditioning of H2S.


Shenfu decoction as adjuvant therapy for improving quality of life and hepatic dysfunction in patients with symptomatic chronic heart failure.
Shenfu decoction (SFD) is a water extract of the dried root or root stalk of Panax ginseng C. A. Mey (Asian ginseng) and the lateral root of Aconitum carmichaeli Debx (prepared by Fuzi, Heishunpian in Chinese). It has been used to treat heart failure for over a thousand years. The main active components of SFD, ginsenosides and higenamine, enhance heart contractility, increase the coronary blood supply, improve ischemic myocardial metabolism, scavenge free radicals and protect myocardial ultrastructure. To investigate the effect of SFD on quality of life (QOL) and hepatic function in symptomatic chronic heart failure (CHF) patients. Forty patients enrolled in the study were randomized into two groups: an SFD group (18 cases) and a control group (22 cases). All the patients received standard heart failure therapy, and the SFD group patients were also treated with Shenfu granules for 14 days as an adjunctive therapy. The effects of SFD on QOL, plasma alanine aminotransferase (ALT) level, cardiac function, left ventricular ejection fraction (LVEF) and tumor necrosis factor-α (TNF-α) level were studied. ALT threshold in hepatic injury are 21U/L for men and 17U/L for women. Minnesota Living with Heart Failure Questionnaire (MLHFQ) scores were improved by 35.27±10.72 vs. 23.87±11.96 in the SFD and control groups respectively (p<0.01). Subgroup analysis of the MLHFQ results demonstrated that both physical and emotional scores were significantly higher in the SFD group (21.00±5.66 vs. 16.75±6.25, p<0.05; 4.64±4.84 vs. 1.13±2.85, p<0.05). Circulating ALT was significantly decreased by SFD (13.3IU/L vs. 0.6IU/L, p<0.01). The grading of cardiac function and LVEF were increased by 1.6±0.5 vs. 1.1±0.3 and 18%±13% vs. 8%±8% in the SFD and control groups respectively (p<0.05 and p<0.05). The level of TNF-α declined more in SFD than control group (64.8±5.0 to 57.6±4.1, p<0.05; vs. 61.6±5.9 vs. 57.7±3.2. p>0.05). Compared with standard heart failure treatment, oral SFD as an adjuvant therapy significantly improved QOL and hepatic injury in CHF patients.


Liver transplantation for hepatocellular carcinoma: University Hospital Essen experience and metaanalysis of prognostic factors.
Liver transplantation has become one of the best treatment options for early hepatocellular carcinoma in cirrhosis. The purpose of this study was to correlate pathologic findings with outcomes after liver transplantation for hepatocellular carcinoma and to evaluate associations between various tumor characteristics and patient outcomes. One hundred patients with hepatocellular carcinoma underwent liver transplantation at our center during an 8-year period. Fifty-five patients received deceased donor livers and the remaining 45 received live donor grafts. A systematic literature search was performed. Using the truncated product method and Tippet's method p values from the literature were combined with our own results, for a total of 3,107 patients. For survival, significant associations were found for tumor grading in our series. Tumor recurrence was significantly associated with alpha-fetoprotein levels, tumor grading, vascular invasion, Milan and University of California San Francisco criteria in univariate analysis, and with tumor grading and University of California San Francisco criteria by multivariable analysis. Meta-analysis showed significant associations for all variables evaluated (alpha-fetoprotein, tumor number, tumor size, lobar distribution, vascular invasion, tumor differentiation, Milan criteria, and University of California San Francisco criteria) both for survival and recurrence in the performed univariate truncated product method analyses. Interestingly, metaanalysis of the available multivariable studies showed no significant associations between Milan/University of California San Francisco criteria and survival or tumor recurrence. Although results of this study add some corroborative evidence in this special field of transplantation for malignancy, they also open the discussion about the prognostic power of the current listing criteria.


Cost of mental and behavioural disorders in Kenya.
BACKGROUND: The health and economic impact of mental and behavioural disorders (MBD) is wide-ranging, long-lasting and large. Unfortunately, unlike in developed countries where studies on the economic burden of MBD exist, there is a dearth of such studies in the African Region of the World Health Organization. Yet, a great need for such information exists for use in sensitizing policy-makers in governments and civil society about the magnitude and complexity of the economic burden of MBD. The purpose of this study was to answer the following question: From the societal perspective (specifically the families and the Ministry of Health), what is the total cost of MBD patients admitted to various public hospitals in Kenya? METHODS: Drawing information from various secondary sources, this study used standard cost-of-illness methods to estimate: (a) the direct costs, i.e. those borne by the health care system and the family in directly addressing the problem of MBD; and (b) the indirect costs, i.e. loss of productivity caused by MBD, which is borne by the individual, the family or the employer. The study was based on Kenyan public hospitals, either dedicated to care of MBD patients or with a MBD ward. RESULTS: The study revealed that: (i) in the financial year 1998/99, the Kenyan economy lost approximately US$13,350,840 due to institutionalized MBD patients; (ii) the total economic cost of MBD per admission was US$2,351; (iii) the unit cost of operating and organizing psychiatric services per admission was US$1,848; (iv) the out-of-pocket expenses borne by patients and their families per admission was US$51; and (v) the productivity loss per admission was US$453. CONCLUSIONS: There is an urgent need for research in all African countries to determine: national-level epidemiological burden of MBD, measured in terms of the prevalence, incidence, mortality, and, probably, the disability-adjusted life-years lost; and the economic burden of MBD, broken down by different productive and social sectors and occupations of patients and relatives.


Dermatomycoses and their etiology in the material of the Dermatological Department in Lódź, Poland.
In the period of 1982-1988 mycological examinations were carried out on 4,657 patients suspected of having dermatomycoses. In approximately 60% of patients infections were localized on the feet and hands and in approximately 30% other regions of the glabrous skin were involved. Before treatment, 5,725 examinations were made. The diagnosis was confirmed mycologically in 30% of the cases, most often in tinea cruris (51%) and chronic paronychia (60%). In more than half of the cases the isolated fungi were dermatophytes, the most frequent species being Tr. mentagrophytes, followed by Tr. rubrum and E. floccosum. Among the other fungi, more than 50% were C. albicans and other Candida species.


Urinary schistosomiasis and malaria associated anemia in Ethiopia.
To assess the prevalence of anemia in children with urinary schistosomiasis, malaria and concurrent infections by the two diseases. Urine and blood samples were collected from 387 children (216 males and 171 females) to examine urinary schistosomiasis and malaria and to determine hemoglobin concentration at Hassoba and Hassoba Buri village in Amibara woreda, Afar region, Ethiopia. The overall prevalence of urinary schistosomiasis and Plasmodium falciparum malaria was 24.54% and 6.20% respectively. Only 2.84% of children carried concurrent infections of both parasites. There was high percentage of anemic patients (81.81%) in the coinfected cases than in either malaria (33.3%) or schistosomiasis (38.94%) cases. There was significantly low mean hemoglobin concentration in concurrently infected children than non-infected and single infected (P<0.05). The mean hemoglobin concentration between Plasmodium falciparum and S. haematobium infected children showed no significant difference (P>0.05). The level of hemoglobin was negatively correlated with the number of S. haematobium eggs/10 mL urine (r=-0.6) and malaria parasitemia (r=-0.53). The study showed that anemia is higher in concurrently infected children than non-infected and single infected. Furthermore, level of hemoglobin was negatively correlated with the number of S. haematobium eggs and malaria parsitemia. Therefore, examination of hemoglobin status in patients co-infected with malaria and schistosomiasis is important to reduce the risk of anemia and to improve health of the community.


Successful super-small-for-size graft liver transplantation by decompression of portal hypertension via splenectomy and construction of a mesocaval shunt: a case report.
We performed a successful super-small-for-size graft liver transplantation by decompressing portal hypertension via splenectomy and a mesocaval shunt. A 46-year-old woman with Child-Pugh class C liver cirrhosis associated with Wilson's disease underwent a living donor liver transplantation (LDLT). The donor had an anomalous portal vein, hepatic vein, and bile duct, so we had to use the right lateral segment for the graft. Preoperative computed tomographic (CT) volumetry showed the volume of this area to be 433 mL; graft-to-recipient weight ratio (GRWR) was 0.72; and graft-to-standard liver volume (GV/SLV) was 39.0%. However, the real volume of the resected right lateral segment was 281 g; GRWR was 0.47; and GV/SLV was 25.3%--a super-small-for-size graft. After implantation, congestion of the small graft was severe due to excessive portal hypertension. Therefore, we tried decompressing the portal vein. First, we performed splenectomy which reduced the portal pressure which remained excessive. Second, a mesocaval shunt was constructed decreasing the portal pressure from 38 to 30 cm H2O. Additionally, we initiated continuous portal injection of prostaglandin E1. The postoperative course was not smooth, but the general status slowly recovered. Over 25 cm H2O of portal hypertension was observed until postoperative day 21 when it improved. At last, the recipient was discharged on postoperative day 156. Accurate preoperative CT volumetry is important to obtain sufficient graft volume. Our case may be one of the smallest-for-size grafts that was successfully transplanted. Management of excessive portal hypertension is important for LDLT, especially using a small-for-size graft. Splenectomy and construction of a mesocaval shunt may be useful strategies to decompress the portal vein.


Small-for-gestational-age and predictors of HOMA indices, leptin and adiponectin in infancy.
To assess whether small-for-gestational-age (SGA) - an indicator of poor fetal growth, may affect metabolic health biomarkers in infancy and explore the predictors. This was a nested matched (1:2) prospective observational study of 65 SGA (birth weight < 10th percentile) and 130 optimal-for-gestational-age (OGA, birth weight 25th-75th percentiles, control) infants in the 3D birth cohort with subjects recruited in Canada from 1 May 2010 to 31 August 2012. The outcomes included homeostasis model assessment of insulin resistance (HOMA-IR) and beta-cell function (HOMA-β), circulating leptin and adiponectin concentrations at age 2 years. HOMA-IR, HOMA-β, leptin and adiponectin concentrations were similar in SGA versus OGA infants. Female sex and accelerated growth in length during mid-infancy (3-12 months) were associated with higher HOMA-IR. Caucasian ethnicity and decelerated growth in weight during late infancy (12-24 months) were associated with lower HOMA-IR. Current BMI was positively associated with circulating adiponectin in SGA infants only (+13.4% [4.0%-23.7%] per BMI z score increment). Insulin resistance and secretion, circulating leptin and adiponectin levels were normal in SGA subjects in infancy at age 2 years. The novel observation in SGA-specific positive association between current BMI and circulating adiponectin suggests dysfunctional adiposity-adiponectin negative feedback loop development during infancy in SGA subjects.


Severe neonatal asphyxia. Incidence and prediction of outcome in the Stockholm area.
In Sweden during the 1970's the incidence of severe asphyxia (an Apgar score of 3 or less at 5 min) has decreased significantly from 3.22 to 2.56 per 1000 infants. A follow-up study was undertaken concerning 116 infants (40 preterm, 76 full-term) admitted to St. Göran's Children's Hospital during a 7-year period (1973-79). The mortality rate was 48% in preterm and 21% in full-term infants. Significant sequelae were present in 27% of the surviving full-term and 14% of the preterm infants. The three severely-handicapped preterm infants had other serious diseases as well whereas this applied to only one full-term infant. The predictors of sequelae included perinatal complications, late onset of spontaneous ventilation (greater than 20 min) and postnatal symptoms, such as seizures. Only two of 9 infants with regular breathing after 20 min and three of 16 infants with seizures were considered normal at follow-up.


Diversity and personality assessment: a country boy goes city.
Born and raised in a country community in Northern Indiana, I mainly learn about the greater world through school, especially graduate school. Diversity and its companion, bigotry, have played major roles in my life along with many individuals--mostly women. I have been lucky to have learned from some of the major individuals in the field of personality assessment, particularly Sid Blatt and John Exner. On the verge of retirement, I look back on a career with affection and some trepidation.


Transmission of Chikungunya Virus in an Urban Slum, Brazil.
After a chikungunya outbreak in Salvador, Brazil, we performed a cross-sectional, community-based study of 1,776 inhabitants to determine chikungunya virus (CHIKV) seroprevalence, identify factors associated with exposure, and estimate the symptomatic infection rate. From November 2016 through February 2017, we collected sociodemographic and clinical data by interview and tested serum samples for CHIKV IgG. CHIKV seroprevalence was 11.8% (95% CI 9.8%-13.7%), and 15.3% of seropositive persons reported an episode of fever and arthralgia. Infections were independently and positively associated with residences served by unpaved streets, a presumptive clinical diagnosis of chikungunya, and recall of an episode of fever with arthralgia in 2015-2016. Our findings indicate that the chikungunya outbreak in Salvador may not have conferred sufficient herd immunity to preclude epidemics in the near future. The unusually low frequency of symptomatic disease points to a need for further longitudinal studies to better investigate these findings.


Scaling up adsorption media reactors for copper removal with the aid of dimensionless numbers.
Adsorption media may be used to sorb copper in an aquatic environment for pollution control. Effective design of adsorption media reactors is highly dependent on selection of the hydraulic residence time when scaling up a pilot-scale reactor to a field-scale reactor. This paper seeks to improve scaling-up technique of the reactor design process through the use of the Damköhler and Péclet numbers via a dimensional analysis. A new scaling-up theory is developed in this study through a joint consideration of the Damköhler and Péclet numbers for a constant media particle size such that a balance between transport control and reaction control can be harmonized. A series of column breakthrough tests at varying hydraulic residence times revealed a clear peak adsorption capacity at a Damköhler number of 2.74. The Péclet numbers for the column breakthrough tests indicated that mechanical dispersion is an important effect that requires further consideration in the scaling-up process. However, perfect similitude of the Damköhler number cannot be maintained for a constant media particle size, and relaxation of hydrodynamic similitude through variation of the Péclet number must occur.


Total hip arthroplasty followed by traction and delayed reduction for Crowe IV developmental dysplasia of the hip.
Hip dislocation secondary to developmental dysplasia of the hip is a debilitating condition. Total hip arthroplasty has proven successful in improving pain, restoring joint function, and correcting leg length discrepancies in this select population. Various techniques have been developed to address the increased complexity inherent to the reconstruction of the severely dysplastic hip. Despite this, femoral and/or sciatic nerve palsy remains a potential catastrophic complication after surgery, with reported rates up to five times that in the general population. We present three cases using a previously unreported technique for performing primary total hip arthroplasty via an anterior approach for Crowe IV hip dysplasia. The goal of this technique is to minimize the risk of postoperative nerve palsy following reconstruction of the severely dysplastic hip. A brief discussion of our technique and the topic of nerve dysfunction after total hip arthroplasty for developmental dysplasia of the hip follows.


Expression of brain nitric oxide synthase in the developing rat pineal gland coincides with the appearance of the adrenergic cyclic guanosine 3',5'-monophosphate response.
In the developing rat pineal gland, norepinephrine (NE)-stimulated cyclic guanosine 3',5'-monophosphate (cGMP) formation appears 2 weeks later than that of cyclic adenosine 3',5'-monophosphate (cAMP) formation. Since NE-stimulated cGMP formation requires formation of nitric oxide (NO) in the adult rat pineal, we investigated the developmental appearance of the NO-forming enzyme brain NO-synthase (NOS) to find out whether the delayed cGMP response results from the late appearance of NOS. In this study, we investigated pineal glands of rats aged 8-21 days and 8 weeks. Western blot analysis revealed that NOS-immunoreactivity (NOS-IR) was barely detectable until day 12. On day 15 NOS-IR exhibited the same intensity as in adult rats. Expression of NOS at this postnatal stage appears to be responsible for the developmental appearance of the adrenergic cGMP response.


Use of a hydroxylapatite-based material and calcium sulfate as artificial floors to repair furcal perforations.
The purpose of this study was to evaluate a hydroxylapatite-based material and calcium sulfate when each was used under a resin-modified glass ionomer cement to repair furcation perforations. Perforations of pulp chamber floors were made in 72 teeth of 9 dogs. Perforations were divided into 3 equal-sized groups and repaired with resin-modified glass ionomer either alone or over an artificial floor. The artificial floor was either a hydroxylapatite-based material or calcium sulfate. Three dogs were killed at each of 3 intervals (1, 3, and 6 months). The tissue response to the tested materials was evaluated clinically, radiographically, and histologically. The hydroxylapatite-based material showed the highest radiographic success; this was followed by calcium sulfate and glass ionomer. From histologic evaluation, the average success rate was found to be 67% for calcium sulfate, 62% for the hydroxylapatite-based material, and 59% for glass ionomer. However, there was no statistical significant difference with the resin-modified glass ionomer when it was used alone and when it was used over a barrier. There was also no significant difference between the hydroxylapatite-based material and the calcium sulfate when they were used as artificial floors. The use of an artificial floor may not be necessary when flowable resin-modified glass ionomer cements are used.


Interaction of RNA with transformed glucocorticoid receptor. I. Isolation and purification of the RNA.
The glucocorticoid receptor (GR) from mouse AtT-20 pituitary tumor cells, when transformed using a variety of in vitro protocols, yields a DNA-binding RNA-containing 6 S form. In order to better understand the physiological role of RNA interaction with the transformed GR, we have isolated and purified the putative RNA from AtT-20 cells. [3H]Triamcinolone acetonide-labeled cytosolic GR was transformed, using Sephadex G-25 filtration, to yield the RNA-containing 6 S GR. The transformed 6 S GR was separated on DEAE-cellulose into the 4 S GR (eluting at about 100 mM KCl) while its associated RNA eluted at 0.30-0.45 M KCl. The addition of only these RNA fractions to the 4 S GR can reconstitute 6 S GR as shown on 5-20% sucrose gradients. RNA (0.3-0.45 M KCl fractions) was further purified by hydroxylapatite chromatography, and the bound RNA (eluted at approximately 70 mM PO4(-2)) was then loaded onto preparative 5-20% sucrose gradients to separate RNA on the basis of size (sedimentation rate). A uniform class of RNA sedimenting at 4 S was obtained and then adsorbed to oligo(dT)-cellulose columns. The unbound fraction (poly(A-)) was capable of shifting 4 S GR to 6 S. Using these chromatographic procedures about 90% of the cellular RNA, incapable of reconstituting the 6 S GR from the 4 S form, was eliminated. The 4 S GR was covalently cross-linked with the purified RNA (termed PIVB RNA) using formaldehyde. The resulting cross-linked GR X RNA complexes were shown to sediment at the density of ribonucleoprotein (1.38 g/cm3) in CsCl gradients and at the 6 S position in high salt sucrose gradients. The hydrolysis of PIVB RNA with ribonuclease A prevented the formation of high salt-resistant ribonucleoprotein complexes, indicating that the GR may be in close contact with PIVB RNA. Electrophoresis of the PIVB RNA on 5% agarose-formaldehyde-denaturing gels yielded one major band with a molecular size of approximately 75 bases. It thus appears that an endogenous 4 S RNA (PIVB RNA) of about 25 kDa specifically interacts with the monomeric 4 S GR to yield the 6 S GR.


Non-parallel enzyme secretion from rat pancreas in vitro studies.
1. The relative variations of rat pancreatic amylase versus lipase and chymotrypsinogen secretions have been studied in vitro with the help of two different techniques: in situ organ perfusion and incubation of pancreatic lobules. 2. In experiments on the perfused pancreas, with 8 C u.kg-1 hr-1 secretin added to the perfusion fluid, cholecystokinin-pancreozymin (8 ID u.kg-1) or pilocarpine (15 mg kg-1) both resulted in a significant change in the enzyme proportions in the juice. 3. In experiments on pancreatic lobules, the addition to the incubation medium of secretin (10(-7) M), alone or associated with cholecystokinin-pancreozymin (8 x 10(-7) M) or pilocarpine (10(-4) M) did not induce any change in the enzyme proportions in secretion. 4. It was concluded that the non-parallelism between enzyme secretions can occur in the rat upon pancreozyminic or cholinergic stimulation in vitro as well as in vivo (Dagorn, 1978) provided basal protein output is low enough. This is not the case when the tissular integrity of the pancreas is lost, such as in experiments on lobules. 5. This work confirms that pancreatic secretion derives from two intrapancreatic pools of different enzymatic composition, and gives a possible explanation for some discrepancies from the literature on the existence of non-parallel secretion.


Detection and quantification of probiotic strain Lactobacillus gasseri K7 in faecal samples by targeting bacteriocin genes.
Lactobacillus gasseri K7 is a probiotic strain that produces bacteriocins gassericin K7 A and K7 B. In order to develop a real-time quantitative PCR assay for the detection of L. gasseri K7, 18 reference strains of the Lactobacillus acidophilus group and 45 faecal samples of adults who have never consumed strain K7 were tested with PCR using 14 pairs of primers specific for gassericin K7 A and K7 B gene determinants. Incomplete gassericin K7 A or K7 B gene clusters were found to be dispersed in different lactobacilli strains as well as in faecal microbiota. One pair of primers was found to be specific for the total gene cluster of gassericin K7A and one for gassericin K7B. The real-time PCR analysis of faecal samples spiked with K7 strain revealed that primers specific for the gene cluster of the gassericin K7 A were more suitable for quantitative determination than those for gassericin K7 B, due to the lower detection level. Targeting of the gassericin K7 A or K7 B gene cluster with specific primers could be used for detection and quantification of L. gasseri K7 in human faecal samples without prior cultivation. The results of this study also present new insights into the prevalence of bacteriocin-encoding genes in gastrointestinal tract.


Draft genome sequence of plant growth-promoting rhizobium Mesorhizobium amorphae, isolated from zinc-lead mine tailings.
Here, we describe the draft genome sequence of Mesorhizobium amorphae strain CCNWGS0123, isolated from nodules of Robinia pseudoacacia growing on zinc-lead mine tailings. A large number of metal(loid) resistance genes, as well as genes reported to promote plant growth, were identified, presenting a great future potential for aiding phytoremediation in metal(loid)-contaminated soil.


Sleep quantity and quality of critically ill children perceived by caregivers and bedside nursing staff: a pilot study.
Sleep is crucial for healing but often impaired in the pediatric intensive care unit due to environmental disruptions. Caregivers and bedside nursing staff are often most aware of these factors and the impact on patient sleep, but studies have not yet compared their perceptions. Caregivers and bedside nursing staff of pediatric patients staying a second night in the pediatric intensive care unit were asked to complete a survey regarding environmental factors (ie, temperature, light, sound, nursing staff room entries), sleep quality, and sleep quantity (ie, sleep duration, number of naps) of the pediatric patient. Caregivers were asked similar questions about their child's sleep at home. The caregivers and nursing staff of 31 pediatric patients participated in this pilot study. There was no significant difference between caregiver and nursing staff ratings of sleep quality, sleep duration, number of naps, room temperature, sound, or light (P > .05 for all). Nursing staff did report significantly more room entries than caregivers (P = .01). Compared to sleep at home, caregivers reported sleep in the hospital to be of lower quality (P = .009) with more frequent room entries (P = .01). Caregivers rate their child's sleep in the pediatric intensive care unit as lower quality than sleep at home. Caregivers and bedside nursing staff largely agree about pediatric patient sleep quality and quantity as well as environmental factors. This agreement may facilitate further research and interventions at improving sleep in the pediatric intensive care unit. Witte MA, Lloyd RM, McGree M, Kawai Y. Sleep quantity and quality of critically ill children perceived by caregivers and bedside nursing staff: a pilot study. J Clin Sleep Med. 2023;19(12):2027-2033.


Surgical versus non-surgical management for patients with malignant bowel obstruction (S1316): a pragmatic comparative effectiveness trial.
Malignant small bowel obstruction has a poor prognosis and is associated with multiple related symptoms. The optimal treatment approach is often unclear. We aimed to compare surgical versus non-surgical management with the aim to determine the optimal approach for managing malignant bowel obstruction. S1316 was a pragmatic comparative effectiveness trial done within the National Cancer Trials Network at 30 hospital and cancer research centres in the USA, Mexico, Peru, and Colombia. Participants had an intra-abdominal or retroperitoneal primary cancer confirmed via pathological report and malignant bowel disease; were aged 18 years or older with a Zubrod performance status 0-2 within 1 week before admission; had a surgical indication; and treatment equipoise. Participants were randomly assigned (1:1) to surgical or non-surgical treatment using a dynamic balancing algorithm, balancing on primary tumour type. Patients who declined consent for random assignment were offered a prospective observational patient choice pathway. The primary outcome was the number of days alive and out of the hospital (good days) at 91 days. Analyses were based on intention-to-treat linear, logistic, and Cox regression models combining data from both pathways and adjusting for potential confounders. Treatment complications were assessed in all analysed patients in the study. This completed study is registered with ClinicalTrials.gov, NCT02270450. From May 11, 2015, to April 27, 2020, 221 patients were enrolled (143 [65%] were female and 78 [35%] were male). There were 199 evaluable participants: 49 in the randomised pathway (24 surgery and 25 non-surgery) and 150 in the patient choice pathway (58 surgery and 92 non-surgery). No difference was seen between surgery and non-surgery for the primary outcome of good days: mean 42·6 days (SD 32·2) in the randomised surgery group, 43·9 days (29·5) in the randomised non-surgery group, 54·8 days (27·0) in the patient choice surgery group, and 52·7 days (30·7) in the patient choice non-surgery group (adjusted mean difference 2·9 additional good days in surgical versus non-surgical treatment [95% CI -5·5 to 11·3]; p=0·50). During their initial hospital stay, six participants died, five due to cancer progression (four patients from the randomised pathway, two in each treatment group, and one from the patient choice pathway, in the surgery group) and one due to malignant bowel obstruction treatment complications (patient choice pathway, non-surgery). The most common grade 3-4 malignant bowel obstruction treatment complication was anaemia (three [6%] patients in the randomised pathway, all in the surgical group, and five [3%] patients in the patient choice pathway, four in the surgical group and one in the non-surgical group). In our study, whether patients received a surgical or non-surgical treatment approach did not influence good days during the first 91 days after registration. These findings should inform treatment decisions for patients hospitalised with malignant bowel obstruction. Agency for Healthcare Research and Quality and the National Cancer Institute. For the Spanish translation of the abstract see Supplementary Materials section.


Merits of expanding the Utstein case definition for out of hospital cardiac arrest.
The Utstein population is defined by non-traumatic, bystander-witnessed out-of-hospital cardiac arrest (OHCA) presenting with ventricular fibrillation (VF). It is used to compare resuscitation performance across emergency medical services (EMS) systems. We hypothesized a system-specific survival correlation between the current Utstein population and other VF populations defined by unwitnessed VF OHCA and VF OHCA after EMS arrival (EMS-witnessed). Expanding performance metrics to this more comprehensive population would make the Utstein definition more representative of the actual community burden and response to VF OHCA. We performed a cohort investigation of all non-traumatic, VF OHCA in the Cardiac Arrest Registry to Enhance Survival from 1/1/2013-12/31/2018 among EMS agencies that treated > = 100 VF OHCA. We evaluated sample size and survival with the addition of the new VF populations. We used Pearson coefficient to assess whether there was a correlation of agency-specific survival outcomes between the current Utstein population and unwitnessed and EMS-witnessed VF OHCA. A total of 107 EMS agencies treated 38,836 VF arrests: 22,918 current Utstein, 11,297 unwitnessed VF, and 4621 EMS-witnessed VF OHCA. Overall, survival was 29.8% (11,567/38,836): 33.9% (7774/22,918) among current Utstein, 17.2% (1942/11,297) among unwitnessed VF, and 40.1% (1851/4621) among EMS-witnessed VF. For agency-specific survival outcome, the Pearson correlation was 0.52 between the current Utstein population versus combined unwitnessed and EMS-witnessed groups. For survival with Cerebral Performance Category 1-2, the Pearson correlation was 0.61. Expanding the Utstein population to include unwitnessed and EMS-witnessed VF OHCA achieves a simpler, more inclusive case definition that minimizes variability in case determination and increases the number of survivors and eligible population by ∼50%, while still achieving a distinguishing metric of system-specific performance.


Investigation of path loss and modeling for digital terrestrial television over Nigeria.
Accurate prediction of path losses is a key factor in Digital Terrestrial Television (DTTV) to ensure Quality of Service (QoS). This study investigates the path losses of three Digital Terrestrial Television Base Stations (DTTBS) in Lagos, Kaduna and Katsina cities of Nigeria. The Received Signal Strength (RSS) of the DTTBS was measured at intervals along selected routes around the stations using a digital signal strength meter. So also, the transmitter-receiver distances of data points with their corresponding geographic coordinates and heights were measured using a hand held GPS receiver. Also measured concurrently were some of the location's - based surface meteorological parameters such as temperature, atmospheric pressure and humidity, using a compact wireless weather station. In addition, the corresponding surface radio refractivity values along the routes were computed using the meteorological parameters recorded. Data were collected during dry and wet season months' covering a period of three years. Path losses were calculated using Okumura-Hata model. Results for all the routes and seasons revealed that path loss increases with increase in trans-receiver distances, however path losses were higher during wet compared to dry season's month. Path losses estimated were highest in Kaduna followed by Ikorodu-Lagos and least in Katsina. Average high positive correlation coefficients of 0.76, 0.75 and 0.74 were obtained between path losses and line of sight for Lagos (Coastal zone), Kaduna (Sudan Savannah) and Katsina (Sahel Savannah) respectively. In the same order, negative correlation coefficients of -0.72, -0.79 and -0.63 were obtained between path losses and RSS. In addition, Modified Okumura Hata Model(s) (MOHPL) that incorporates the effect of the specified tropospheric parameters were proposed. Results also revealed that path losses obtained by Okumura-Hata model increase with increase in LOS separation distance from the base station following a consistent exponential rise while the Modified Okumura-Hata Model (MOHPL) followed similar trend with few exceptions of crests and troughs depicting the influence of the incorporated location's-based tropospheric parameters. Another finding is that Okumura Hata model under estimated the path losses associated with digital terrestrial television channel over the study locations. In order to ensure high reliability of power budgets and link's design, the proposed models are recommended for use over the study locations. The overall findings of this work will be useful for the accurate prediction of path losses and the design of power budgets and links over digital terrestrial television and similar wireless channels on the UHF band.


New research development on trans fatty acids in food: Biological effects, analytical methods, formation mechanism, and mitigating measures.
The trans fatty acids (TFAs) in food are mainly generated from the ruminant animals (meat and milk) and processed oil or oil products. Excessive intake of TFAs (>1% of total energy intake) caused more than 500,000 deaths from coronary heart disease and increased heart disease risk by 21% and mortality by 28% around the world annually, which will be eliminated in industrially-produced trans fat from the global food supply by 2023. Herein, we aim to provide a comprehensive overview of the biological effects, analytical methods, formation and mitigation measures of TFAs in food. Especially, the research progress on the rapid, easy-to-use, and newly validated analytical methods, new formation mechanism, kinetics, possible mitigation mechanism, and new or improved mitigation measures are highlighted. We also offer perspectives on the challenges, opportunities, and new directions for future development, which will contribute to the advances in TFAs research.


Multiport-illumination-system-assisted phacoemulsification in eyes with dense vitreous hemorrhage during combined cataract and vitreous surgery.
We describe the use of a multiport illumination system to enhance the red reflex during combined phacoemulsification and pars plana vitrectomy in 10 patients with cataract and vitreous hemorrhage. This method improves illumination and visualization of the lens structures and the instruments, which may reduce the risk of complication. To our knowledge, this approach has not been reported.


Cost-Effectiveness of Single-Inhaler Triple Therapy (FF/UMEC/VI) versus Tiotropium Monotherapy in Patients with Symptomatic Moderate-to-Very Severe COPD in the UK.
For patients with chronic obstructive pulmonary disease (COPD) who remain symptomatic despite maintenance treatment, clinical management guidelines recommend a stepwise escalation from monotherapy to dual therapy, and from dual therapy to triple therapy. However, in clinical practice, patients are often escalated directly from monotherapy to triple therapy based on disease severity. This study evaluated the cost-effectiveness of once-daily, single-inhaler fluticasone furoate, umeclidinium, and vilanterol (FF/UMEC/VI) triple therapy compared with long-acting muscarinic antagonist monotherapy with once-daily tiotropium (TIO) in patients with symptomatic moderate-to-very severe COPD, from a UK National Health Service perspective. The validated GALAXY-COPD disease progression model was populated with patient baseline characteristics and treatment effect data from the 12-week GSK Study 207626 comparing FF/UMEC/VI with TIO in patients with moderate-to-very severe COPD. UK unit costs and drug costs (British Pound, 2021) were applied to healthcare resource utilization and treatments. The base case analysis was conducted over a lifetime horizon, and costs and health outcomes (except for life years [LYs]) were discounted at 3.5% per year. Model outputs included exacerbation rates, healthcare costs, LYs, quality-adjusted LYs (QALYs), and incremental cost-effectiveness ratios. Overall, treatment with FF/UMEC/VI resulted in increased clinical benefit (reduction in total exacerbations and increased overall survival and QALYs), coupled with cost savings (derived from lower maintenance and exacerbation healthcare costs) compared with TIO monotherapy. In the base case analysis, FF/UMEC/VI provided an additional 0.393 LYs (95% range: 0.176, 0.655) and 0.443 QALYs (0.246, 0.648), at a cost saving of £880 (£54, £1608) versus TIO. FF/UMEC/VI remained the cost-effective (dominant) treatment option across sensitivity and scenario analyses. FF/UMEC/VI offers greater clinical benefits and is a cost-effective treatment option compared with TIO for the treatment of adult patients with COPD with persistent symptoms and/or who are at risk of exacerbation in the UK.


Gene expression during activation of Paracoccidioides brasiliensis conidia.
This study focuses on gene expression during crucial biological phenomena of the dimorphic fungal human pathogen Paracoccidioides brasiliensis, the conidia-to-yeast (C-Y) transition and the conidia-to-mycelia (C-M) germination. We studied 10 genes involved in different cellular functions: oxidative stress response (alternative oxidase (AOX), superoxide dismutase (SOD), flavodoxin, conserved hypothetical protein (Y20)); cell metabolism (glyceraldehyde-3-phosphate dehydrogenase (GADPH), cholestenol Delta-isomerase (ChDI), glycine dehydrogenase (GDh)) and heat shock response (Heat shock protein 90 (HSP90)), and cell synthesis and wall structure (glucan synthase-1 (GS-1), α-1,3-glucan synthase (αGS), and mannosyltransferase (MT)). Gene expression was measured during the first 72 h and 96 h of C-Y and C-M, respectively, previously shown to be a fundamental time frame for the consolidation of these cellular processes. The gene expression of AOX, GAPDH, HSP90, MT, αGS, and GDh was significantly increased during the C-Y transition, while SOD, ChDI, GAPDH, MT, GDh, and GS-1 were increased during C-M germination. Additionally, some were highly expressed in each process: AOX, HSP90, and αGS during C-Y; SOD, ChDI, and GS-1 during C-M. Altogether, these data add new information regarding gene expression during the C-Y and C-M processes. Future research will be targeted to further characterize the true relevance of the studied genes during the morphological transition, either during adaptation to the environment or to the infected host.


The effect of methylation outside the recognition sequence of restriction endonuclease PvuII on its cleavage efficiency.
This study is to extend our earlier observation that Dam and Dcm methylation outside the PvuII recognition sequence inhibited PvuII cleavage in one of the three PvuII sites of pGEM4Z-ras DNA. In this paper, a new recombinant plasmid DNA, pGEM4-SV40ori-anti-ras, was constructed which has only two PvuII sites, I and II. The Dam and Dcm-methylated and unmethylated DNAs were produced in Escherichia coli and linearized by ScaI. The DNA molecules were digested with different amounts of PvuII. The results show that by comparing the DNA fragment number and intensity of the partial and final products in agarose gel, PvuII site I on the methylated DNA molecule was digested four- to eight-fold more slowly than site II. In the unmethylated plasmid DNA, the two PvuII sites were cleaved at about the same rate. The difference was caused only by methylation of Dam and Dcm sites outside the PvuII recognition sequence. A methylated Dam site immediately adjacent to the less efficiently cut PvuII site I may be responsible for the inhibitory effect. We suggest that a new parameter, involving methylation of sites outside the recognition sequence, be considered in kinetic experiments on cleavage.


Intracellular transport and processing of Sindbis virus glycoproteins.
The intracellular transport and processing of Sindbis virus envelope glycoproteins were studied in cells infected with Sindbis virus using the mannose-specific enzyme, endoglycosidase H (endo H). In pulse/chase labeling experiments of hamster cells with [35S]methionine, Sindbis glycoproteins PE2 and E1 became endo H resistant in two steps at 12.5 and 20.0 min after a 5-min pulse, suggesting that the glycoproteins required this period of time to be transported to the Golgi compartments containing the enzymes which process the high mannose side chains acquired in the endoplasmic reticulum. E2 could be detected at the end of a 5-min pulse and the E2 produced early was found to be endo H sensitive. The rate at which PE2 was converted to E2, relative to the acquisition of endo H resistance, suggests the independence of this proteolytic event from cellular protein transport and raises the possibility that the proteolytic function is of viral origin.


Minimum Distance of Suture Anchors Used for Rotator Cuff Repair Without Decreasing the Pullout Strength: A Biomechanical Study.
To investigate the minimum distance between the anchors without decreasing the pullout strength using the polyurethane foams and the porcine bones. Metal screw-type anchors and PEEK (polyether ether ketone) coil-type anchors were used. Two same-type suture anchors were placed into the polyurethane foams and porcine bones. The polyurethane foams were 3 different densities simulating severe osteoporosis, osteoporosis, and normal bone. The distances between the centers of anchors were set at 4, 6, 8, and 10 mm. The pair of anchors were loaded to failure if they had not been pulled out after cyclic loading from 50 to 200 N, 10 cycles per each 50-N increment. Mode of failure, ultimate load to failure, displacement of the anchor, and number of cycles completed were recorded. In all polyurethane foams of 3 different densities with use of metal screw-type anchors, the 4-mm group demonstrated a significantly lower ultimate load to failure compared with the 6-, 8-, and 10-mm groups (P < .01). There were no significant differences in the load to failure among the 6-, 8-, and 10-mm groups. Porcine bone or PEEK coil-type anchor showed results similar to those of the metal screw-type anchors. For the 2 tested anchors, the minimum distance between the anchors without decreasing the pullout strength was 6 mm (center to center) regardless of bone density in a biomechanical study. Although it has been thought that the minimum distance between the anchors without decreasing the pullout strength was 1 cm (center to center), our data showed that it was 6 mm.


What is the preferred number of consecutive night shifts? results from a crossover intervention study among police officers in Denmark.
Among police officers in Denmark, we studied (i) how many consecutive night shifts participants preferred at baseline; (ii) preferences regarding three intervention conditions (two, four, and seven consecutive night shifts followed by the same number of days off/day shifts: '2 + 2', '4 + 4', '7 + 7') at follow-up; (iii) characteristics of participants preferring each of these intervention conditions. Questionnaire data from a crossover intervention study were used (baseline: n = 73; follow-up: n = 68). At baseline, 49% preferred four consecutive night shifts. At follow-up, 57% preferred '4 + 4', 26% preferred '2 + 2' and 26% preferred '7 + 7'. Participants, who preferred longer spells of night work experienced that night work was less demanding, found it easier to sleep at different times of the day, and were more frequently evening types compared with participants who preferred shorter spells of night work. The participants' preferences are likely to be influenced by their previous shift work experience. Practitioner Summary: We investigated police officers' preferences regarding the number of consecutive night shifts. The majority preferred four consecutive night shifts. Those who preferred the longer spells of night work found night work less demanding, found it easier to sleep at different times of the day, and were more frequently evening types.


The pleasantness and unpleasantness of an object distinctively drives its grasping prediction: behavioral evidence.
Action and perception share a common sensorimotor network permitting a functional action-perception coupling. This coupling would permit to predict the outcome of others' actions. Moreover, recent findings suggest that action-perception linkage could be sensitive to emotional content of the visual scene. The present study sought to address how emotion inherent to an object (pleasantness and unpleasantness) affects action prediction processing. To this end, we compared the participants' temporal estimative of the hand contact with emotional objects in occlusion and full vision conditions. We found that the emotion strongly interfered in the prediction of its grasping. Indeed, the participants highly anticipated the touch instant for unpleasant valence compared to pleasant and neutral ones. Moreover, the visual conditions (i.e., occlusion and full vision) affect the magnitude of the predictive error except to unpleasant object. Accordingly, the present results unveil that pleasantness and unpleasantness of an object distinctively drive the prediction of its touch instant.


Haploid all the way: a new style of asexuality revealed in animals.
Weeks et al(1) recently reported that they had found a species of mites where the parthenogenetic females are haploid. They show that this is caused by intracellular bacteria that turn genetic haploid males into haploid females. I discuss these findings and attempt to place these observations in evolutionary context.


Novel in-office peroxide-free tooth-whitening gels: bleaching effectiveness, enamel surface alterations, and cell viability.
To evaluate the bleaching ability, the effect on enamel surface and cytotoxicity of novel tooth-whitening formulations containing papain, ficin, or bromelain. Forty bovine dental discs (6 cm ×4 cm) were pigmentated and randomly allocated into the following groups (n = 10): Group 1, 20 wt% carbamide peroxide (control); group 2, 1% papain-based whitening; group 3, 1% ficin-based whitening; and group 4, 1% bromelain-based whitening. The whitening gels were prepared and applied on the enamel three times per day once a week, for 4 weeks. Color measurement was obtained by CIEDE2000. Enamel Knoop microhardness and roughness were evaluated. The WST-1 assay was used to evaluate the cell viability of mouse fibroblast cells (L929). Data were statistically analyzed by one-way analysis of variance (ANOVA) and Student Newman Keuls's post hoc test at α = 0.05 significance level. Bromelain, ficin-based, and carbamide peroxide bleaching gels showed a similar color change (p < 0.001). Higher enamel hardness decrease and higher enamel roughness were caused by the carbamide peroxide (p < 0.05). The experimental whitening gels did not affect cell viability. Tooth bleaching gels containing bromelain, papain, or ficin have substantial clinical potential to be used in the development of peroxide-free tooth whitening gels.


Arsenic trioxide therapy for relapsed or refractory Japanese patients with acute promyelocytic leukemia: need for careful electrocardiogram monitoring.
Recent studies have shown that arsenic trioxide (As(2)O(3)) can induce complete remission in patients with acute promyelocytic leukemia (APL). We tested the efficacy and safety of As(2)O(3) for the treatment of patients with APL who had relapsed from or become refractory to all-trans retinoic acid (ATRA) and conventional chemotherapy in a prospective study. As(2)O(3) at a dose of 0.15 mg/kg was administered until the date of bone marrow remission to a maximum of 60 days. In patients who achieved complete remission (CR), one additional course of As(2)O(3) was administered using the same dose for 25 days. Of 14 patients, 11 (78%) achieved CR. Six of 10 patients who achieved CR showed disappearance of PML-RARalpha transcript by RT-PCR assay. The duration of As(2)O(3)-induced CR ranged from 4 to 22 months (median, 8 months) at a median follow-up of 17 months. Adverse events included 13 electrocardiogram abnormalities (13 QTc prolongation, eight ventricular premature contraction, four nonsustained ventricular tachycardia and two paroxysmal supraventricular tachycardia), seven nausea and vomiting, four pruritus, three peripheral neuropathy, three fluid retention and one APL differentiation syndrome. Four patients received antiarrhythmic agents. Hyperleukocytosis developed in five patients and in three cytotoxic drugs were necessary. Other adverse events were relatively mild. As(2)O(3) treatment is effective and relatively safe in relapsed or refectory patients with APL. Cardiac toxicities in patients with QTc prolongation should be carefully monitored.


Characterization of Extracellular Vesicles from Cilia and Epithelial Cells of Ductuli Efferentes in a Turtle (Pelodiscus sinensis).
The ductuli efferentes (DE) form a transit passage for the passage of spermatozoa from the rete testis to the epididymis. After spermiation, various epithelial secretory proteins are transferred via extracellular vesicles (EVs) to the spermatozoa for their maturation and long-term viability. The aim of the present study was to investigate the distribution, classification, and source of multivesicular bodies (MVBs) and their EVs in the epithelia of the efferentes duct in a turtle species, the soft-shelled freshwater turtle Pelodiscus sinensis by using light and transmission electron microscopy. The results showed that CD63 as a classical exosome marker was strongly immunolocalized within the apical and lateral cytoplasm of the ciliated cells (CC) and moderate to weak in the non-ciliated cells (NCC) of DE. The ultrastructure revealed that early endosome was present at the basement membrane and perinuclear cytoplasm of both CC and NCC, whereas MVBs were located over the nucleus in the cytoplasm of NCC and adjacent to the basal bodies of cilia within the CC. Many EVs, as sources of MVBs, were located within the blebs that were attached to the cilia of CC, within the apical blebs from NCC, and the lateral spaces of CC and NCC. There was ultrastructure evidence of EVs associated with spermatozoa in the lumens of DE. Collectively, the present study provides cytological evidence that the DE epithelium secreted EVs to the lumen by (1) apical blebs, (2) ciliary blebs, and (3) from the basolateral region. These EVs were associated with spermatozoa in the DE lumen of this turtle. Characterization and cellular distribution of these EVs in the DE of a turtle may provide a study model to further investigate the transferring of micromolecules via EVs to the spermatozoa.


The Adult Carotid Body: A Germinal Niche at the Service of Physiology.
The carotid body is the most relevant oxygen sensor in mammalian organisms. This organ helps to detect acute changes in PO2, but it is also crucial for the organismal adaptation to a maintained hypoxemia. Profound angiogenic and neurogenic processes take place in the carotid body to facilitate this adaptation process. We have described a plethora of multipotent stem cells and restricted progenitors, from both vascular and neuronal lineages, existing in the quiescent normoxic carotid body, ready to contribute to organ growth and adaptation upon the arrival of the hypoxic stimulus. Our deep understanding of the functioning of this stunning germinal niche will very likely facilitate the management and treatment of an important group of diseases that course with carotid body over-activation and malfunction.