Flow injection chemiluminescence determination of dihydralazine sulphate based on permanganate oxidation sensitized by rhodamine B.
A novel flow injection chemiluminescence (CL) method for the determination of dihydralazine sulphate (DHZS) is described. The method is based on the CL produced during the oxidation of DHZS by acidic permanganate solution in the presence of rhodamine B. Rhodamine B is suggested as a fluorescing compound for the energy-transferred excitation. The CL emission allows quantitation of DHZS concentration in the range 5-800 ng/mL, with a detection limit of 1.9 ng/mL (3sigma). The experimental conditions for the CL reaction are optimized and the possible reaction mechanism is discussed. The method has been applied to the determination of DHZS in pharmaceutical preparations and compares well with the high performance liquid chromatography (HPLC) method.


Global analysis of TDP-43 interacting proteins reveals strong association with RNA splicing and translation machinery.
TDP-43 is a highly conserved and ubiquitously expressed member of the heterogeneous nuclear ribonucleoprotein (hnRNP) family of proteins. Recently, TDP-43 was shown to be a major disease protein in the ubiquitinated inclusions characteristic of most cases of amyotrophic lateral sclerosis (ALS), tau-negative frontotemporal lobar degeneration (FTLD), and inclusion body myopathy. In these diseases, TDP-43 is redistributed from its predominantly nuclear location to ubiquitin-positive, cytoplasmic foci. The extent to which TDP-43 drives pathophysiology is unknown, but the identification of mutations in TDP-43 in familial forms of ALS and FTLD-U suggests an important role for this protein in pathogenesis. Little is known about TDP-43 function and only a few TDP-43 interacting proteins have been previously identified, which makes further insight into both the normal and pathological functions of TDP-43 difficult. Here we show, via a global proteomic approach, that TDP-43 has extensive interaction with proteins that regulate RNA metabolism. Some interactions with TDP-43 were found to be dependent on RNA-binding, whereas other interactions are RNA-independent. Disease-causing mutations in TDP-43 (A315T and M337V) do not alter its interaction profile. TDP-43 interacting proteins largely cluster into two distinct interaction networks, a nuclear/splicing cluster and a cytoplasmic/translation cluster, strongly suggesting that TDP-43 has multiple roles in RNA metabolism and functions in both the nucleus and the cytoplasm. Finally, we found numerous TDP-43 interactors that are known components of stress granules, and indeed, we find that TDP-43 is also recruited to stress granules.


Genetic and molecular aspects of acromelic dysplasia.
The acromelic dysplasia group includes three rare disorders: Weill-Marchesani syndrome (WMS), Geleophysic dysplasia (GD) and Acromicric dysplasia (AD) all characterized by short stature, short hands and stiff joints. The clinical overlap between the three disorders is striking. Indeed, in addition to the diagnostic criteria, they all share common features including delayed bone age, cone shaped epiphyses, thick skin and heart disease. In contrast, a microspherophakic lens seems to be a characteristic feature of WMS whereas hepatomegaly and a severe outcome are encountered only in the most severe forms of GD. Finally, WMS is transmitted either by an autosomal dominant or an autosomal recessive (AR) mode of inheritance, GD by an autosomal recessive mode of inheritance and AD by an autosomal dominant mode of inheritance. Using genetic approaches, we have identified the molecular basis of WMS and GD which both involved the same superfamily of proteins, the ADAMTS [A Disintegrin-like And Metalloproteinase domain (reprolysin type) with ThromboSpondin type 1 repeats (TSR)]. We have found ADAMTS10 mutations in the recessive form of WMS and Fibrillin 1 mutations in the dominant form of WMS. More recently, we have identified ADAMTSL2 mutations in GD. The function of ADAMTS1 0 and AD AMTSL 2 are unknown. But the findings of FBN1 and ADAMTS10 mutations in WMS suggest a direct link between the two proteins. Using a yeast double hybrid screen, we have identified LTBP1 (Latent TGFbeta Binding protein 1) as a partner of ADAMTSL2. The combination of these findings suggests that ADAMTS10 and ADAMTSL2 are both involved in the microfibrillar network.


Noninvasive beam-wave spectrometric instrumentation for measuring dielectric constant at microwave frequencies.
From the characteristics of the reflected Gaussian beam-wave for oblique incidence, measured with a spectrometer arrangement, the dielectric properties of a selectively exposed region of a dielectric slab are ascertained at microwave frequencies. For this purpose, a focused (Gaussian) microwave beam is launched from a suitable applicator to irradiate obliquely a selected protion of the test dielectric and the complex reflection coefficient is measured and analyzed. Further, the magnitude of the angular shift involved in the direction of the reflected beam is also used to calculate the dielectric constant. Application of this method to noninvasive measurements of dielectric properties of selective partial-bodies of commercial dielectrics and biological substances is discussed.


Validation of The Slovenian Version of Multiple Sclerosis Quality of Life (MSQOL-54) Instrument.
To cross-culturally adapt and validate Multiple Sclerosis Quality of Life-54 (MSQOL-54) instrument. The study which enrolled 134 Slovenian multiple sclerosis (MS) patients was conducted from March to December 2013. The internal consistency of the MSQOL-54 instrument was evaluated by Cronbach's alpha coefficient (α), and its dimensionality assessed by the principal component analysis (PCA). The whole instrument had high internal consistency (α=0.88), as well as the majority of its twelve subscales (α=0.83-0.94). The results of the PCA showed two components with eigenvalue greater than 1, explaining 59.4% of the cumulative variance. Further results indicated good construct validity of the instrument with the physical health-related-quality-of-life subscales loading highly on the physical component, and mental health-related-quality-of-life subscales loading highly on the mental component. The Slovenian version of the MSQOL-54 instrument proved to be an internally consistent and accurate tool, well accepted by the Slovenian MS patients. The adequate psychometric properties warrant the scientifically sound version of the MSQOL-54 instrument, which is from now on at disposal to all health professionals dealing with MS patients in Slovenia.


The anti-cyclic citrullinated peptide response in tuberculosis patients is not citrulline-dependent and sensitive to treatment.
Patients with tuberculosis (TB) frequently produce anti-citrullinated protein antibodies (ACPA). The objective of this study is to characterize the citrulline-dependence of the ACPA reactivity in sera of patients with mycobacterium infections. Serum samples of 134 patients with untreated mycobacterium infections (122 TB, 12 nontuberculous mycobacterium) were tested for antibodies against both the citrullinated (Cit) and the non-citrullinated (Arg) form of 2 cyclic synthetic peptides. In 33 patients, a follow-up sample was tested six months after starting anti-mycobacterial drugs. A substantial proportion of patients with mycobacterial infections demonstrated antibodies against 0401Cit, 0401Arg, 0722Cit and 0722Arg. Fourteen patients demonstrated anti-0401Cit, 83 anti-0401Arg, 22 anti-0722Cit and 61 anti-0722Arg, while none of these antibodies were detected in the 20 healthy controls. All the patients but one, who were anti-0401Cit and anti-0722Cit positive, demonstrated reactivity against the respective Arg peptide. In the subset of 33 patients with a follow-up test six months after starting treatment, the mean levels of antibodies to 0401Cit, 0401Arg, 0722Cit and 0722Arg significantly decreased after treatment. All the patients who were anti-0401Cit and anti-0722Cit positive turned negative after treatment. The presence of anti-0401Cit/Arg and anti-0722Cit/Arg was found to be significantly correlated with the presence of HIV. ACPA may be found in patients with TB. In most of the cases, the reactivity is citrulline independent. A positive cyclic citrullinated peptide (CCP) test in these patients should therefore be interpreted with care, and preferably followed by a control ELISA with a non-citrullinated antigen.


Basic concepts of fluid responsiveness.
Predicting fluid responsiveness, the response of stroke volume to fluid loading, is a relatively novel concept that aims to optimise circulation, and as such organ perfusion, while avoiding futile and potentially deleterious fluid administrations in critically ill patients. Dynamic parameters have shown to be superior in predicting the response to fluid loading compared with static cardiac filling pressures. However, in routine clinical practice the conditions necessary for dynamic parameters to predict fluid responsiveness are frequently not met. Passive leg raising as a means to alter biventricular preload in combination with subsequent measurement of the change in stroke volume can provide a fast and accurate way to guide fluid management in a broad population of critically ill patients.


Early Time Solvation Dynamics Probed by Spectrally Resolved Degenerate Pump-Probe Spectroscopy.
The dynamic role of solvent in influencing the rates of physico-chemical processes (for example, polar solvation and electron transfer) has been extensively studied using time-resolved fluorescence spectroscopy. Here we study ultrafast excited state relaxation dynamics of three different fluorescent probes (DNTTCI, IR-140 and IR-144) in two polar solvents, ethanol and ethylene glycol, using spectrally resolved degenerate pump-probe spectroscopy. We discuss how time-resolved emission spectra can be directly used for constructing relaxation correlation function, obviating spectral reconstruction and estimation of time-zero spectrum in non-polar solvents. We show that depending on the specific probe used, the relaxation dynamics is governed either by intramolecular vibrational relaxation (for IR140) or by intermolecular solvation (for DNTTCI) or by both (for IR144). We further show (using DNTTCI as a probe) that major differences in solvation by ethanol and ethylene glycol is contributed by early time (<1 ps) dynamics.


Children's perceptions of asthma: establishing normality.
This qualitative research study explores children's perceptions of having asthma. The research methodology utilized a grounded theory approach. The study aimed to identify the beliefs and attitudes held by asthmatic children regarding their illness and to consider how this influences their asthma management. Ten asthmatic children, boys and girls, aged between 9 and 12 years, were interviewed. The transcribed interviews were analysed using the constant comparative method. Analysis revealed four major categories and a core variable identified as 'establishing normality'. These themes influenced each child's appraisal and response to having asthma. The findings show that their concern to establish normality and to be 'normal' does have benefits, but in some circumstances also encourages the acceptance of suboptimal control.


Copper-Catalyzed Aminosulfonylation of O-Homoallyl Benzimidates with Sodium Sulfinates to Access Sulfonylated 1,3-Oxazines.
A facile copper-catalyzed aminosulfonylation of O-homoallyl benzimidates with sodium sulfinates in the presence of tert-butyl peroxybenzoate (TBPB) and XPhos ligand has been developed. By using this protocol, a variety of potentially bioactive 1,3-oxazines were directly synthesized. This method has the merits of a cheap catalyst, easily available and stable sulfone reagents, and simple operation.


Reactivation of human herpesvirus (HHV) family members other than HHV-6 in drug-induced hypersensitivity syndrome.
Drug-induced hypersensitivity syndrome (DIHS) is characterized by a severe multiorgan hypersensitivity reaction that usually appears after a 3-6-week exposure to certain drugs, including anticonvulsants. There are some reports showing that serum IgG levels often decrease at the early stage of DIHS. Reactivation of human herpesvirus (HHV)-6 has been reported in patients with DIHS, and some other DIHS patients showed reactivation of cytomegalovirus (CMV) or Epstein-Barr virus (EBV). To determine whether reactivation of HHV-6, HHV-7, CMV and/or EBV occurs in patients with DIHS. Titres of IgG and IgM antibodies to HHV-6 and HHV-7 were determined using an indirect immunofluorescence antibody assay on admission and at various times after admission. Anti-CMV IgG and IgM antibody titres and anti-EBV capsid antigen IgG, IgA, IgM, and EBV nuclear antigen and EBV early antigen IgG titres were determined by enzyme immunoassay. Polymerase chain reaction (PCR) procedures for HHV-6, HHV-7, CMV and EBV DNAs were performed using serum samples. IgG antibody titres to HHV-6, HHV-7, CMV and EBV were increased after the onset in seven, six, seven and two of seven patients, respectively. IgG antibody titres to HHV-6 and HHV-7 were elevated simultaneously 21-38 days after the onset. IgG antibody titres to CMV and EBV were elevated 10-21 days after the elevation of HHV-6 and HHV-7 antibody titres. PCR showed that HHV-6, HHV-7, CMV and EBV DNAs became positive in six, five, seven and two of seven patients, respectively. HHV-6 and HHV-7 DNAs were detected 21-35 days after the onset, and CMV DNA was detected 10-21 days after detection of HHV-6 and HHV-7 DNAs. The present study suggests that in addition to HHV-6 reactivation, reactivation of HHV-7, CMV and/or EBV may also occur following drug eruption in some patients with DIHS.


Epigenetic reversal of acquired resistance to 5-fluorouracil treatment.
Acquired and intrinsic resistance still remains a limitation to the clinical use of 5-fluorouracil (5-FU). The contribution of epigenetic changes to the development of drug resistance remains to be elucidated. Several genes that are hypermethylated and silenced have been identified in colorectal cancer. Based on the findings described in the accompanying article, we hypothesized that acquired resistance to "pulse" 5-FU has an epigenetic origin and might be reversed. Here, we present a novel therapeutic approach to circumvent clinical resistance to bolus 5-FU, that is, treatment of bolus 5-FU-resistant colorectal cancer cells with low-dose 5-azadeoxycytidine (DAC), an inhibitor of DNA hypermethylation, restored sensitivity to 5-FU as well as 5-fluorouridine. Moreover, treatment of nude mice bearing a 5-FU-resistant tumor, characterized by decreased levels of UMP kinase (UMPK), with DAC overcame resistance to bolus 5-FU. DAC-mediated restoration of 5-FU sensitivity was associated with increases in UMPK levels. An increase in UMPK protein and mRNA levels following treatment with low-dose DAC was observed in cultured bolus 5-FU-resistant colorectal cancer cells (HCT-8) and in mice bearing these tumors. We conclude that DAC-mediated restoration of sensitivity to bolus 5-FU is mediated at least in part by increased UMPK levels and clinical resistance to 5-FU due to decreased UMPK in colorectal cancer may be overcome by including methylation inhibitors such as DAC.


A longitudinal investigation of racial discrimination, distress intolerance, and psychological well-being in African American college students.
There is robust evidence that racism negatively influences health outcomes for African American college students. However, few studies have longitudinally examined the underlying mechanisms related to the repercussions of racism. The purpose of this study was to examine the longitudinal association between racial discrimination and psychological well-being (PWB), as well as the mediating role of distress intolerance. As part of a larger parent study, a sample of 105 African American first-year undergraduate students (mean age = 18.1) completed three surveys across 1 year. The RMediation program was used to test the indirect effect of racism on PWB through distress intolerance. There was a significant positive indirect effect of racism on PWB through distress intolerance, such that increased racism was associated with increased distress intolerance, which was thus associated with decreased PWB. Intervention efforts may be aimed at preventing racism for African American college students and providing clinical services that reduce distress intolerance.


Brain DNA damage analysis in pesticide exposed wistar albino rats (Rattus norvegicus): a chemometric approach.
Brain the most important organ which controls most of the regulations in the body is composed of neurons and glia. As brain has a high metabolic rate and reduced cell renewal capability, the lipids, proteins and nucleic acids become the major targets of damage. In the present study carbofuran (CF) induced brain DNA damage in male wistar albino rats at sub-lethal doses (Control-A; B-1.0, C-0.5 and D-0.3 mg/kg BW) while the groups B1,C1, D1, B2, C2, D2 and B3, C3, D3 represents the exposure duration 30, 60 and 90 days each respectively. FTIR spectroscopy based chemometric analysis of functional groups in nucleic acids are reported, changes in band area and band frequencies were examined to understand the DNA damage by constructing heat map. Significant changes were observed in the band frequency, band areas, bandwidth and intensity values (p < 0.05, 0.01, 0.001). The principal component analysis was analyzed to study the alterations at the molecular level, which revealed maximum variance of 74% in groups A, B1, C1, D1 and C2 and 13.7% variance in B2, D2, B3, C3 and D3. The present study provides significant details to analyse DNA damage using non-conventional approach and can also be used for detecting DNA damage in several neural diseases and disorders and emphasizes on using FTIR spectral data through chemometric approach to analyse the DNA damage.Communicated by Ramaswamy H. Sarma.


The managerial future of nephrology and dialysis.
The work analyzes the present situation of hemodialysis centers in Campania Region, mainly highlighting the necessity of a Regional Health planning for all the chronic renal failure care centers in order to rationalize all economic resources, quality levels of health care and therapies.


Insurance incentives for ambulatory surgery.
This study is an attempt to address both the extent to which surgical procedures on an outpatient basis substitute cost-effectively for inpatient procedures, and whether or not an insurance policy's financial incentives increase the volume of outpatient surgical procedures. In particular, given an insurance product of a given composition: What is the probability that the insured will have surgery? and if a surgery does take place, what is the probability that it will occur in an outpatient setting? Finally, the article assesses the implication of such products on the total cost of care by quantifying the insurance plans along two parameters, the relative user price for outpatient versus inpatient surgery and the absolute price for the inpatient surgery. The results indicate that insurance policies that offer relatively lower out-of-pocket payments for ambulatory surgery do not increase the probability that surgery will be done in the ambulatory setting. However, higher out-of-pocket payments for surgery, regardless of site, do reduce the surgery rate. There are other patient and market characteristics, especially the availability of freestanding surgery firms, that do influence the location of surgery.


Reports of preventable medical errors from the Alberta Patient Safety Survey 2004.
The Health Quality Council of Alberta (HQCA) is charged with reporting to Albertans on the quality, safety and performance of the healthcare system. In 2004, the HQCA conducted a telephone survey (response rate: 55%) of 1,500 adult Albertans to assess their perceptions of and personal experiences with preventable medical errors (PMEs). A total of 559 (37.3%) respondents reported that they or a family member had ever experienced a PME. The most common PMEs were related to clinical performance (n=128), medication (n=123), diagnosis (n=121) and communication (n=73). Through this research, patients have provided an orientation to interventions to improve patient care and prevent medical errors.


Apatinib and S-1 combination therapy for the treatment of advanced head and neck neoplasms: Three case reports.
Apatinib, one of the novel oral antiangiogenic agents, shows survival benefits in treating advanced or metastatic gastric adenocarcinoma. However, its efficacy in treating advanced head and neck neoplasms has not been reported. Herein, three elderly men with advanced head and neck neoplasms were treated with apatinib and S-1. Their initial diagnoses were hypopharyngeal carcinoma, metastatic squamous cell carcinoma of head and neck, and squamous cell carcinoma of the pyriform sinus. All patients underwent repeated chemotherapy but developed disease progression. As they refused radiotherapy due to its serious adverse reaction, apatinib was administered at a dose of 425 mg daily and S-1 at 60 mg twice daily. Thirty days after apatinib administration, the patients achieved partial response according to the Response Evaluation Criteria in Solid Tumors 1.1 standard. Mild toxicity or drug-related side effect was observed during the treatment. Therefore, apatinib and S-1 could be the new treatment option for advanced head and neck neoplasms. However, clinical trials are required to confirm their efficacy and safety.


The impact of self-selected short sleep on monetary risk taking.
Risky choice has been widely studied in experimental settings, but there is a paucity of research examining the effects of self-selected sleep schedules on risky choices. The current study examined incentivised risky choices of 100 young, healthy adults whose self-selected (at-home) sleep schedules were tracked via actigraphy for 1 week prior to decision making. Average nightly sleep was 6.43 h/night. On each trial of the decision task, individuals chose between two monetary gambles, with separate blocks of trials presenting amounts to gain versus amounts to lose for each paired gamble choice. In general, participants were risk-averse when trying to maximise gains (GAINS) and risk-seeking when trying to minimise losses (LOSSES). These tendencies were amplified in trials where gambles differed more (vs less) in their riskiness. Response times were longer for real choices (vs. dummy trials of random choice), LOSS versus GAINS trials, and when gambles were more similar versus different in risk. Gamble choices were not impacted by actigraphy measured average sleep levels, which suggests self-selected moderate sleep deprivation does not affect risky monetary choices, as has been found in studies of experimentally induced sleep deprivation. However, our data showed that sleep variability increased risk-taking behaviour in the LOSS condition. Thus, risky decision-making may relate more to variability in sleep efficiency than to overall sleep duration or quality in naturalistic settings. The current study gives insight into how decision making in experimental sleep settings may or may not translate to more ecologically valid settings of self-directed sleep.


Targeted disruption of fad24, a regulator of adipogenesis, causes pre-implantation embryonic lethality due to the growth defect at the blastocyst stage.
In previous studies, we identified a novel gene, factor for adipocyte differentiation 24 (fad24), which plays an important role during the early stages of adipogenesis in mouse 3T3-L1 cells. Moreover, overexpression of fad24 increased the number of smaller adipocytes in white adipose tissue and improved glucose metabolic activity in mice, thus indicating that fad24 functions as a regulator of adipogenesis in vivo. However, the physiological roles of fad24 in vivo are largely unknown. In this study, we attempted to generate fad24-deficient mice by gene targeting. No fad24-null mutants were recovered after embryonic day 9.5 (E9.5). Although fad24-null embryos were detected in an expected Mendelian ratio of genotypes at E3.5, none of the homozygous mutants developed into blastocysts. In vitro culture experiments revealed that fad24-null embryos develop normally to the morula stage but acquire growth defects during subsequent stages. The number of nuclei decreased in fad24-deficient morulae compared with that in wild-type ones. These results strongly suggested that fad24 is essential for pre-implantation in embryonic development, particularly for the progression to the blastocyst stage.


Influence of pulsed electromagnetic fields on healing of experimental colonic anastomosis.
The study investigated the influence of pulsed electromagnetic fields (PEMFs) on the mechanical strength and collagen content of uncomplicated colonic anastomosis in rats. A standardized left colonic resection was performed 3 cm above the peritoneal reflection, and end-to-end anastomosis was constructed with eight interrupted inverting sutures. Beginning immediately after surgery, randomly assigned groups were exposed to one of the following: 1) 100 Hz (frequency), 1 mT (intensity) PEMFs with 16-hour on/8-hour off cycles (n = 8); 2) 100 Hz, 2 mT PEMFs with 16-hour on/8-hour off cycles (n = 8); 3) 100 Hz, 1 mT PEMFs with 6-hour on/6-hour off cycles (n = 6), whereas the control group (n = 10) received no PEMFs. Relaparatomy was performed at 72 hours postoperatively, and the bursting pressure of the anastomotic segment was recorded in situ. The hydroxyproline contents of the anastomotic and adjacent perianastomotic segments of equal lengths were determined. Mean bursting pressure values of the groups that received 100 Hz, 1 or 2 mT PEMFs with 16-hour on/8-hour off cycles (90.88 +/- 19.13 and 83.88 +/- 7.08 mmHg, respectively) were significantly higher than those of the control group (61.66 +/- 10.6 mmHg) and the group with 6-hour on/6-hour off cycles (64.83 +/- 7.36 mmHg; P < 0.05 for all comparisons). Hydroxyproline contents of the anastomotic and perianastomotic segments were consistently higher in the 16-hour on/8-hour off PEMF groups, compared with those of the corresponding segments of the control group. PEMFs applied externally to unrestrained rats within a "window of PEMF parameters" provided a significant gain in the mechanical strength of the colonic anastomosis, at least 72 hours post-operatively. Associated relative increases in the hydroxyproline contents of the (peri)anastomotic colonic segments suggest that an altered collagen metabolism might contribute to this enhancement of the anastomotic repair. Further investigations based on these preliminary data and the definition of the exact measures regarding the effects of PEMFs on biologic systems, in general, may lead to an efficient and new adjunctive modality in colorectal surgery.


Disodium cromoglycate enhances ongoing immunoglobulin production in vitro in human B cells.
The effect of disodium cromoglycate (DSCG) upon human immunoglobulin (Ig) isotypes and IgG subclasses production by purified B cells was studied. DSCG enhanced IgM, IgG1, IgG2, IgG3, IgG4 and IgA production in a dose-dependent fashion, while DSCG failed to induce IgE production at any concentrations tested by purified B cells. When B cells were separated into small resting and large activated B cells, DSCG failed to induce Ig production from small resting B cells in the presence or absence of Staphylococcus aureus Cowan strain I (SAC). In contrast, in large activated B cells DSCG significantly enhanced all types of Ig production (two-to threefold), especially IgG4 production (seven-to 11-fold), except IgE, which large B cells did not produce. The enhancement of IgG subclass production was not subclass switching, since DSCG failed to enhance IgG1 production in B cells depleted of surface IgG1+ cells (sIgG1+ cells). Similarly, DSCG did not enhance IgG2, IgG3 or IgG4 production from sIgG2-, sIgG3- or sIgG4- B cells, respectively, Interleukin-4 (IL-4) or interleukin-6 (IL-6) also enhanced Ig production except IgG4 from large activated B cells. The enhancing effect of DSCG was not mediated by IL-4 or IL-6 since anti-IL-4 or anti-IL-6 antibody failed to block the DSCG-induced enhancement. DSCG also enhanced IgG2 and IgM production from human B-cell lines GM-1500 and CBL, respectively. These results suggest that DSCG directly and preferentially stimulates activated B cells which are producing Ig and, in addition, enhances their Ig production.


[Studies on the determination of the flux of gaseous pollutant from an area by passive differential optical absorption spectroscopy].
An optical remote sensing method based on passive differential optical absorption spectroscopy (DOAS) for the determination of the flux of SO2 or other gaseous pollutants from an area (such as industrial area, city) which includes many different atmospheric pollution sources was studied in the present paper. Passive DOAS using the zenith scattered sunlight as the light source provides the column density (the integrated concentration of atmospheric absorbers along the light path) and has been successfully applied to the determination of the flux of gaseous pollutants emitted from the volcano or point source. Passive DOAS instrument installed in a car scanned the plume emitted from an area by circling around the area in this paper. Column density of each selected gaseous pollutant was retrieved from zenith scattered sunlight spectra collected by the instrument by spectral analysis method of passive DOAS in their particular absorption spectral range respectively. Combined with the meteorological (wind field) information during the period of measurement, the net flux value of gaseous pollutant from this area during the measurement could be estimated. DOAS method used to obtain the column density of gaseous pollutant in the section plane of the plume emitted from source and the method of net flux calculation of gaseous pollutant from a certain area are described. Also a passive DOAS instrument was developed and installed in a car to scan the gaseous pollutants from the area surrounded by the 5th Ring Road in Beijing city during a field campaign in the summer of 2005. The SO2 net flux 1.13 x 10(4) kg x h(-1) and NO2 net flux 9.3 x 10(3) kg x h(-1) from this area were derived separately after the passive DOAS measured the entire ring road and the wind data were roughly estimated from wind profile radar. The results indicate that this optical remote sensing method based on passive DOAS can be used to rapidly determine the flux of gaseous pollutant (such as SO2, NO2) emitted from an area, especially from a city or an industrial area.


Case Report: Schizophrenia Discovered during the Patient Interview in a Man with Shoulder Pain Referred for Physical Therapy.
The purpose of this case report is to demonstrate the importance of a thorough patient interview. The case involves a man referred for physical therapy for a musculoskeletal dysfunction; during the patient interview, a psychiatric disorder was recognized that was later identified as schizophrenia. A secondary purpose is to educate physical therapists on the recognizable signs and symptoms of schizophrenia.Client description: A 19-year-old male patient with chronic shoulder, elbow, and wrist pain was referred for physical therapy. During the interview, the patient reported that he was receiving signals from an electronic device implanted in his body.Measures and outcome: The physical therapist's initial assessment identified a disorder requiring medical referral. Further management of the patient's musculoskeletal dysfunction was not appropriate at this time. The patient was referred for further medical investigation, as he was demonstrating signs suggestive of a psychiatric disorder. The patient was diagnosed with schizophrenia by a psychiatrist and was prescribed Risperdal. This case study reinforces the importance of a thorough patient interview by physical therapists to rule out non-musculoskeletal disorders. Patients seeking neuromusculoskeletal assessment and treatment may have undiagnosed primary or secondary psychiatric disorders that require recognition by physical therapists and possible medical referral.


Polymorphism of MHC class IIB in an acheilognathid species, Rhodeus sinensis shaped by historical selection and recombination.
Rhodeus sinensis is a bitterling species occurring throughout the numerous freshwater systems on the East Asia. Here, we analyzed the diversity of the MHC class IIB (DAB) genes from this species, which may offer meaningful insights into evolutionary processes in this species as well as other bitterlings. Using cDNA and gDNA samples from 50 individuals, we discovered classical 140 allelic sequences that could be allocated into either DAB1 (Rhsi-DAB1) or DAB3 (Rhsi-DAB3). DAB sequences completely lacking the intron, but identical or similar to Rhsi-DAB1, were also discovered from our gDNA samples, and this intron loss likely originated from the retrotransposition events of processed mDNA. The β1 domain was the most polymorphic in both Rhsi-DAB1 and -DAB3. Putative peptide biding residues (PBRs) in Rhsi-DAB1, but not in Rhsi-DAB3, exhibited a significant dN/dS, presumably indicating that different selection pressures have acted on those two DABs. Recombination between different alleles seemed to have contributed to the increase of diversity in Rhsi-DABs. Upon phylogenetic analysis, Rhsi-DAB1 and -DAB3 formed independent clusters. Several alleles from other species of Cypriniformes were embedded in the clade of Rhsi-DAB1, whereas Rhsi-DAB3 clustered with alleles from the wider range of taxa (Cyprinodontiformes), indicating that these two Rhsi-DABs have taken different historical paths. A great deal of MHC class IIB allelic diversity was found in R. sinensis, and gene duplication, selection and recombination may have contributed to this diversity. Based on our data, it is presumed that such historical processes have commonly or differently acted on the polymorphism of Rhsi-DAB1 and -DAB3.


Computational prediction of cis-regulatory modules from multispecies alignments using Galaxy, Table Browser, and GALA.
One major goal of genomics is to identify all the functional sequences in genomes, including sequences that regulate the expression of genes. Sequence conservation is a good, albeit imperfect, guide to these functional elements. We describe how to use publicly available servers (Galaxy, the UCSC Table Browser, and GALA) to find genomic sequences whose alignments (from blastZ and multiZ) show properties associated with cis-regulatory modules, such as high conservation score, high regulatory potential score, and conserved transcription factor binding sites. Links to these servers can be accessed at http://www.bx.psu.edu/ and http://genome.ucsc.edu/.


Miniaturized thermocontrol devices enable analysis of biomolecular behavior on their timescales, second to millisecond.
To establish general-purpose methods and tools for biological experiments on a short time scale is an essential requirement for future research in molecular biology because most of the functions of living organisms at the molecular level take place on a time scale from 1-second to millisecond. Thermal control with on-chip micro-thermodevices is one of the strongest and most useful ways to realize biological experiments at molecular level on these time scales. Novel biological phenomena revealed by the experiments using micro-thermodevices on a 1-second and millisecond time scale will be shown for the proof. Finally, the advantages and impact of this methodology in molecular biology will be discussed.


Overexpression of both CXC chemokine receptor 4 and vascular endothelial growth factor proteins predicts early distant relapse in stage II-III colorectal cancer patients.
CXC chemokine receptor 4 (CXCR4) and vascular endothelial growth factor (VEGF) are implicated in the metastatic process of malignant tumors. However, no data are currently available on the biological relationship between these molecules in colorectal cancer. We studied whether CXCR4 and VEGF expression could predict relapse and evaluated in vitro the contribution of CXCR4 in promoting clonogenic growth, VEGF secretion, and intercellular adhesion molecule-1 (ICAM-1) expression of colorectal cancer cells. CXCR4 and VEGF were studied in colorectal cancer tissues and in Lovo, HT29, and SW620 colorectal cancer cell lines by immunohistochemistry. Correlations with baseline characteristics of patients and tumors were analyzed by chi2 test. VEGF secretion induced by CXCL12 was measured by ELISA. The effect of CXCL12 on ICAM-1 expression was evaluated by flow cytometry. Clonogenic growth induced by CXCL12 was determined by clonogenic assays. Functional effects induced by CXCL12 were prevented by the administration in vitro of AMD3100, a bicyclam noncompetitive antagonist of CXCR4. Seventy-two patients, seen between January 2003 and January 2004, were studied. CXCR4 was absent in 16 tumors (22.2%); it was expressed in < or = 50% of cells in 25 (34.7%) tumors and in >50% of cells in 31 (43.0%) tumors. VEGF was absent in 17 (23.6%) tumors; it was expressed in < or = 50% of cells in 16 (22.2%) tumors and in >50% of cells in 39 (54.2%) tumors. There was a significant association between CXCR4 expression and lymph nodal status (P = 0.0393). There were significant associations between VEGF and tumor invasion (P = 0.0386) and lymph nodal involvement (P = 0.0044). American Joint Committee on Cancer stage (P = 0.0016), VEGF expression (P = 0.0450), CXCR4 expression (P = 0.0428), and VEGF/CXCR4 expression (P = 0.0004) had a significant prognostic value for disease-free survival with univariate analysis. The predictive ability of the American Joint Committee on Cancer stage and of the concomitant and high expression of VEGF and CXCR4 was confirmed by multivariate analysis. Prognosis is particularly unfavorable for patients whose primary tumors express CXCR4 and VEGF in >50% of cells (median disease-free survival in relapsed patients, 5.8 months; hazard ratio of relapse, 8.23; 95% confidence interval, 7.24-14.29). In clonogenic assays, CXCL12 (20 ng/mL/d) significantly increased the number of clones in SW620, HT29, and Lovo cells at 7 and 14 days. Again, CXCL12 was able to stimulate VEGF secretion in SW620, HT29, and Lovo cells as well as up-regulated ICAM-1. These effects were prevented by the administration of AMD3100 (1 micromol/L). We have shown that concomitant and high expression of CXCR4 and VEGF is a strong and independent predictor of early distant relapse in colorectal cancer. CXCR4 triggers a plethora of phenomena, including stimulation of clonogenic growth, induction of VEGF release, and ICAM-1 up-regulation. These data support the inhibition of CXCR4 to prevent the development of colorectal cancer metastasis.


Neuroimaging and neuropathological findings in essential tremor.
Essential tremor is a chronic neurological syndrome of heterogenous clinical phenotypes and multiple etiologies. Numerous studies have been done in order to investigate the pathological, neuroimaging, physiological, and clinical features of essential tremor; however, a clear pathophysiological mechanism has not been identified. One of the brain structures has been extensively investigated at the macroscopic and the microscopic level in the cerebellum. In the present study, we aim to discuss the main neuroimaging and neuropathological changes of the cerebellum in essential tremor.


Evolutionary networks from RADseq loci point to hybrid origins of Medicago carstiensis and Medicago cretacea.
Although hybridization has played an important role in the evolution of many plant species, phylogenetic reconstructions that include hybridizing lineages have been historically constrained by the available models and data. Restriction-site-associated DNA sequencing (RADseq) has been a popular sequencing technique for the reconstruction of hybridization in the next-generation sequencing era. However, the utility of RADseq for the reconstruction of complex evolutionary networks has not been thoroughly investigated. Conflicting phylogenetic relationships in the genus Medicago have been mainly attributed to hybridization, but the specific hybrid origins of taxa have not been yet clarified. We obtained new molecular data from diploid species of Medicago section Medicago using single-digest RADseq to reconstruct evolutionary networks from gene trees, an approach that is computationally tractable with data sets that include several species and complex hybridization patterns. Our analyses revealed that assembly filters to exclusively select a small set of loci with high phylogenetic information led to the most-divergent network topologies. Conversely, alternative clustering thresholds or filters on the number of samples per locus had a lower impact on networks. A strong hybridization signal was detected for M. carstiensis and M. cretacea, while signals were less clear for M. rugosa, M. rhodopea, M. suffruticosa, M. marina, M. scutellata, and M. sativa. Complex network reconstructions from RADseq gene trees were not robust under variations of the assembly parameters and filters. But when the most-divergent networks were discarded, all remaining analyses consistently supported a hybrid origin for M. carstiensis and M. cretacea.


Cost-Effectiveness of Surveillance for Bloodstream Infections for Sepsis Management in Low-Resource Settings.
Bacterial sepsis is a leading cause of mortality among febrile patients in low- and middle-income countries, but blood culture services are not widely available. Consequently, empiric antimicrobial management of suspected bloodstream infection is based on generic guidelines that are rarely informed by local data on etiology and patterns of antimicrobial resistance. To evaluate the cost-effectiveness of surveillance for bloodstream infections to inform empiric management of suspected sepsis in low-resource areas, we compared costs and outcomes of generic antimicrobial management with management informed by local data on etiology and patterns of antimicrobial resistance. We applied a decision tree model to a hypothetical population of febrile patients presenting at the district hospital level in Africa. We found that the evidence-based regimen saved 534 more lives per 100,000 patients at an additional cost of $25.35 per patient, resulting in an incremental cost-effectiveness ratio of $4,739. This ratio compares favorably to standard cost-effectiveness thresholds, but should ultimately be compared with other policy-relevant alternatives to determine whether routine surveillance for bloodstream infections is a cost-effective strategy in the African context.


Long-term follow-up of a non-infantile desmoplastic ganglioglioma.
Desmoplastic gangliogliomas are mixed cerebral tumors traditionally reported in infants. However, a few non-infantile cases have been documented. A case of a desmoplastic ganglioglioma in a 16-year male is presented. The patient reported severe headaches. Radiological examination revealed a large mass occupying the right frontal lobe. The lesion was totally excised. Histopathological examination confirmed the diagnosis of a desmoplastic ganglioglioma. The postoperative course was excellent. At the 10(1/2) year follow-up there was no evidence of tumor recurrence. Although desmoplastic gangliogliomas have aggressive features, complete surgical removal is the treatment of choice obviating the need for adjuvant therapy.


Dual-Subpopulation as reciprocal optional external archives for differential evolution.
Differential Evolution (DE) is powerful for global optimization problems. Among DE algorithms, JADE and its variants, whose mutation strategy is DE/current-to-pbest/1 with optional archive, have good performance. A significant feature of the above mutation strategy is that one individual for difference operation comes from the union of the optional external archive and the population. In existing DE algorithms based on the mutation strategy-JADE and its variants, individuals eliminated from the population are send to the archive. In this paper, we propose a scheme for managing the optional external archive. According to our scheme, two subpopulations are maintained in the population. Each of them regards the other as the archive. In experiments, our scheme is applied in JADE and two of its variants-SHADE and L-SHADE. Experimental results show that our scheme can enhance JADE and its variants. Moreover, it can be seen that L-SHADE with our scheme performs significantly better than four DE algorithms, CoBiDE, MPEDE, EDEV, and MLCCDE.


A Preliminary Assessment of HTST Processing on Donkey Milk.
Due to increasing attention from consumers on non-bovine milk types, and to the increase in the number of small dairy donkey farms in Italy, farmers require more advanced and reliable processing devices, in order to guarantee a safe product of high quality. To this aim, a new small-scale High-Temperature Short-Time (HTST) pasteurizer (72 °C for 15 s), prototyped by the authors, was tested on donkey milk. The efficacy of the HTST device was tested on raw donkey milk microflora by enumeration of total aerobic bacteria, Enterobacteriaceae and Bacillus cereus. The biochemical quality was assessed by determining the protein profile by monodimensional electrophoresis and by measuring lysozyme activity. The HTST apparatus was able to reduce the total bacteria count, and to completely eradicate Enterobacteriaceae. Bacillus cereus, when present, was decreased with low efficiency. Changes in the protein profile were observed in milk pasteurized in accordance with both processes, although HTST seemed to limit casein degradation. Lysozyme activity was not substantially affected in comparison to raw donkey milk. In conclusion, a tailored small-volume HTST device could be safely applied to pasteurize donkey milk in on-farm pasteurization processes on small dairy donkey farms.


The effect of remifentanil on the emergence characteristics of children undergoing FBO for bronchoalveolar lavage with sevoflurane anaesthesia.
The aim of this study was to compare the effects of sevoflurane vs. sevoflurane and remifentanil on cough and agitation during emergence and recovery after fiberoptic bronchoscopy. Children between 2 and 6 years of age undergoing fiberoptic bronchoscopy were enrolled. All patients were premedicated with oral midazolam. Patients were randomly assigned to either group S (sevoflurane alone, n = 25) or group SR (sevoflurane with remifetanil, n = 25). Anaesthesia was induced and maintained with sevoflurane in all patients. Group SR received remifentanil at a bolus dose of 1 microg/kg over 2 min followed by a maintenance infusion of 0.15 microg/kg/min. In addition to routine anaesthesia documentation, agitation scores and cough scores were recorded every 5 min during emergence and recovery. Duration of the procedure, anaesthesia and emergence phases was similar in both groups (P > 0.05). Time until recovery was significantly shorter in group SR than in group S (7.0 +/- 5.5 min and 13.0 +/- 3.5 min, respectively; P = 0.001). Cough scores were not significantly different between the two groups during emergence and recovery (Kruskal-Wallis ANOVA test, P > 0.05). However, the mean agitation score at 5 min in group SR was significantly higher than that in group S (Kruskal-Wallis ANOVA test, P < 0.01). One case of hypoxaemia from thoracic rigidity occurred in a patient in group SR. The addition of remifentanil significantly shortened recovery time in children undergoing fiberoptic bronchoscopy under sevoflurane anaesthesia. In the recovery period, remifentanil did not decrease cough, and increased agitation.


Vagal stimulation induces expiratory lengthening in the in vitro neonate rat.
Respiration is modulated by lung mechanoreceptor feedback in vivo on a cycle-to-cycle basis. We replicated this modulation in vitro and tested four stimulus protocols to identify which of these most closely replicated in vivo responses to lung mechanoreceptor activation in mammals. We activated pulmonary vagal afferent pathways by electrical stimulation or by lung inflation, applied during expiration, which produces expiratory lengthening in vivo. In each modality, transient and tonic stimuli were applied. Stimuli were applied over a range of delays following inspiratory termination. Tonic stimuli were maintained until subsequent inspiratory onset. All stimulus modalities prolonged expiration (P < 0.05). These results indicate that the neural circuitry mediating pulmonary afferent modulation of expiratory duration is retained in vitro.


A comparative study of the effects of adrenoceptor antagonists on platelet aggregation and thromboxane generation.
Platelet aggregation and thromboxane A2 have been implicated in the pathogenesis of several forms of vascular disease. The aim of this study was to determine the effect of a wide range of adrenoceptor antagonists on platelet aggregation, and thromboxane A2 production, from normal human platelet rich plasma in vitro. Labetalol, pindolol and propranolol inhibited platelet aggregation to collagen in a dose dependent manner. Increasing the concentration of collagen "shifted" the dose response curve to the right. These 3 drugs also significantly inhibited thromboxane A2 generation in response to collagen but not to arachidonic acid. This effect was independent of any inhibitory effect of these drugs on platelet aggregation, and occurred at a drug concentration close to that obtained in vivo. Atenolol, metoprolol, prazosin and timolol were similarly assessed but had no effect on either platelet aggregation or thromboxane A2 generation. This ability of labetalol, pindolol, and propranolol to inhibit platelet aggregation and thromboxane generation, may be of clinical benefit in view of the increasing evidence implicating thromboxane A2 in the pathogenesis of vascular disease.


Inferior olive oscillation as the temporal basis for motricity and oscillatory reset as the basis for motor error correction.
The cerebellum can be viewed as supporting two distinct aspects of motor execution related to a) motor coordination and the sequence that imparts such movement temporal coherence and b) the reorganization of ongoing movement when a motor execution error occurs. The former has been referred to as "motor time binding" as it requires that the large numbers of motoneurons involved be precisely activated from a temporal perspective. By contrast, motor error correction requires the abrupt reorganization of ongoing motor sequences, on occasion sufficiently important to rescue the animal or person from potentially lethal situations. The olivo-cerebellar system plays an important role in both categories of motor control. In particular, the morphology and electrophysiology of inferior olivary neurons have been selected by evolution to execute a rather unique oscillatory pace-making function, one required for temporal sequencing and a unique oscillatory phase resetting dynamic for error correction. Thus, inferior olivary (IO) neurons are electrically coupled through gap junctions, generating synchronous subthreshold oscillations of their membrane potential at a frequency of 1-10 Hz and are capable of fast and reliable phase resetting. Here I propose to address the role of the olivocerebellar system in the context of motor timing and reset.


A cellular automata-based mathematical model for thymocyte development.
Intrathymic T cell development is an important process necessary for the normal formation of cell-mediated immune responses. Importantly, such a process depends on interactions of developing thymocytes with cellular and extracellular elements of the thymic microenvironment. Additionally, it includes a series of oriented and tunely regulated migration events, ultimately allowing mature cells to cross endothelial barriers and leave the organ. Herein we built a cellular automata-based mathematical model for thymocyte migration and development. The rules comprised in this model take into account the main stages of thymocyte development, two-dimensional sections of the normal thymic microenvironmental network, as well as the chemokines involved in intrathymic cell migration. Parameters of our computer simulations with further adjusted to results derived from previous experimental data using sub-lethally irradiated mice, in which thymus recovery can be evaluated. The model fitted with the increasing numbers of each CD4/CD8-defined thymocyte subset. It was further validated since it fitted with the times of permanence experimentally ascertained in each CD4/CD8-defined differentiation stage. Importantly, correlations using the whole mean volume of young normal adult mice revealed that the numbers of cells generated in silico with the mathematical model fall within the range of total thymocyte numbers seen in these animals. Furthermore, simulations made with a human thymic epithelial network using the same mathematical model generated similar profiles for temporal evolution of thymocyte developmental stages. Lastly, we provided in silico evidence that the thymus architecture is important in the thymocyte development, since changes in the epithelial network result in different theoretical profiles for T cell development/migration. This model likely can be used to predict thymocyte evolution following therapeutic strategies designed for recovery of the thymus in diseases coursing with thymus involution, such as some primary immunodeficiencies, acute infections, and malnutrition.


The O-2 Generating NADPH Oxidase of Phagocytes: Structure and Methods of Detection
The NADPH oxidase of phagocytic cells of the immune system plays an important role in the destruction of certain types of microbial pathogens during infections. Its inappropriate activation to release reactive oxidants may also contribute to host tissue damage in inflammatory diseases. In this review, the structure of the NADPH oxidase is described and many of the commonly used methods to detect its activation during the respiratory burst are listed. The advantages and disadvantages of each of these methods are critically discussed.


Are muscle weakness and stiffness risk factors of the development of rotator cuff tendinopathy in overhead athletes: a systematic review.
Underlying muscle weakness and stiffness may increase the risk of developing rotator cuff tendinopathy. This systematic review aims to assess existing prospective studies to summarize whether muscle weakness and stiffness are risk factors for the development of rotator cuff tendinopathy in overhead athletes. A systematic search was performed using PRISMA guidelines. Prospective studies measuring muscle strength or stiffness and the incidence of rotator cuff tendinopathy were included. Quality assessment was performed with the Newcastle-Ottawa quality assessment scale. The search yielded six studies, with a total of 523 trained overhead athletes followed up for one season. External rotation (ER) and internal rotation (IR) strength were described as protective factors against the development of rotator cuff tendinopathy. Athletes who did not sustain shoulder injuries had statistically stronger eccentric IR (p < 0.01) and ER (p < 0.05) strength in the pre-season assessment. Muscle stiffness indicated by limited range of motion of <106° for shoulder ER was described as a risk factor with an odds ratio of 1.12 (p < 0.001). Imbalance between ER and IR strength was reported as risk factors for shoulder injuries in two studies, with a relative risk of 2.57 (p < 0.05) reported in one study. Supraspinatus weakness was also reported as a risk factor for shoulder injuries in one study. Limited evidence support ER, IR weakness, limited ER range of motion, and very limited evidence support imbalance in ER/IR strength, and supraspinatus weakness as risk factors for rotator cuff tendinopathy in overhead athletes. No existing studies investigated the general population on this topic. Future cohort studies may improve on existing evidence with investigations on the general public, a longer follow-up time, clearly documented injury history, and a stringent diagnosis to rotator cuff tendinopathy.


Clinical and biological aspects of rotator cuff tears.
Rotator cuff tears are common and are a frequent source of shoulder pain and disability. A wide variation in the prevalence of rotator cuff tears has been reported. The etiology of rotator cuff tear remains multifactorial and attempts to unify intrinsic and extrinsic theories tried to explain the etiopathogenesis of rotator cuff tears. Knowledge of the etiopathogenesis of rotator cuff tears is important to improve our therapies, surgical techniques and promote tendon repair. Several strategies have been proposed to enhance tendon healing and recently research has focused on regenerative therapies, such as Growth Factors (GFs) and Plasma Rich Platelet (PRP), with high expectations of success.


Coated capillaries and additives for the separation of proteins by capillary zone electrophoresis and capillary isoelectric focusing.
Strategies reported for the separation of proteins in capillary zone electrophoresis and capillary isoelectric focusing are reviewed. The strategies are grouped into two categories: coated capillaries and buffer/sample additives. Success attained with each case and also, more importantly, the limitations of the methodology are discussed. Recent results from our own laboratory in the area of capillary isoelectric focusing in uncoated, fused silica capillaries using additives are summarized. The advantages and disadvantages of coated columns vs. additives are delineated.


[Spanish short-stay-units: results according to department designated to manage the unit].
To compare the efficiency of short-stay units (SSUs) managed by different departments within hospitals. Cross-sectional study in 40 hospitals with SSUs. From June 1 to December 31, 2012,we gathered data on clinical caseloads and management. Variables directly related to efficiency were mean length of stay, bed rotation index, and weekend discharge rate. Forty SSUs were studied; 25 (62.5%) were managed by the hospital's emergency department (ED), 9 (22.5%) were managed by the internal medicine department (IMD), 5 (12.5%) were independent, and 1 was jointly managed by the hospital's ED and the IMD. A total of 45 140 patients were discharged from the SSUs. The most common diagnoses were exacerbation of chronic heart or respiratory disease, urinary tract infection, and respiratory infection. Age was the only variable that was related to the hospital department designated to manage these SSUs. The mean ages by management type were as follows: independent SSUs (75.6 years) vs ED-managed SSUs (67.2 years) vs IMD-managed SSUs (57.8 years) (P=.02). Group-by-group comparisons showed that the mean length of stay was shorter in ED-managed SSUs than in IMD-managed units (2.65 vs 3.73 respectively; P=.047), and overall mortality was lower in IMD-managed SSUs than in ED-managed SSUs (0.64% vs 3%; P=.033). However, unforeseen mortality (after excluding patients under palliative care or judged to be in the final hours of life) did not differ significantly between groups. We did not detect important differences between SSUs managed by different departments in the hospitals in this series. However, mean length of stay was found to be shorter in ED-managed SSUs than in IMD-managed units.


Bone signal abnormalities in the posterolateral tibia and lateral femoral condyle in complete tears of the anterior cruciate ligament: a specific sign?
Thirty-two patients with acute, complete tears of the anterior cruciate ligament (ACL) proved at surgery underwent examination with magnetic resonance (MR) imaging. Bone impaction sites were present in the posterolateral tibial plateau in 30 patients (94%) and in the lateral femoral condyle (LFC) in 29 patients (91%). The bone abnormalities had low signal intensity on T1-weighted images and high signal intensity on T2-weighted images when compared with the signal intensity of normal marrow. It is assumed that the bone changes occur during injury when the LFC impacts into the posterior tibia, either during the initial rotary subluxation or as the LFC recoils to return to anatomic alignment. Only one of six partial ACL tears had a bone signal change. In patients with acute knee injury, bone impaction sites in the posterolateral tibia and the LFC suggest that a complete ACL tear is present.


Synthesis and Antimicrobial Characterization of Half-Calycanthaceous Alkaloid Derivatives.
A total of 29 novel tetrahydropyrroloindol-based calycanthaceous alkaloid derivatives were synthesized from indole-3-acetonitrile in good yields. The synthesized compounds were evaluated against nine strains of bacteria and a wide range of plant pathogen fungi. Bioassay results revealed that majority of the compounds displayed similar or higher in vitro antimicrobial activities than the positive control. The biological activities also indicated that substituents at R₄ and R₅ significantly affect the activities. Notably, compound c4 was found to be most active among the tested calycanthaceous analogues and might be a novel potential leading compound for further development as an antifungal agent. The results could pave the way for further design and structural modification of calycanthaceous alkaloids as antimicrobial agents.


Preclinical Alzheimer's disease: A systematic review of the cohorts underlying the concept.
Preclinical Alzheimer's disease (AD) is a relatively recent concept describing an entity characterized by the presence of a pathophysiological biomarker signature characteristic for AD in the absence of specific clinical symptoms. There is rising interest in the scientific community to define such an early target population mainly because of failures of all recent clinical trials despite evidence of biological effects on brain amyloidosis for some compounds. A conceptual framework has recently been proposed for this preclinical phase of AD. However, few data exist on this silent stage of AD. We performed a systematic review to investigate how the concept is defined across studies. The review highlights the substantial heterogeneity concerning the three main determinants of preclinical AD: "normal cognition," "cognitive decline," and "AD pathophysiological signature." We emphasize the need for a harmonized nomenclature of the preclinical AD concept and standardized population-based and case-control studies using unified operationalized criteria.


The incidence of scintigraphically viable and nonviable tissue by rubidium-82 and fluorine-18-fluorodeoxyglucose positron emission tomographic imaging in patients with prior infarction and left ventricular dysfunction.
Although reversible perfusion defects, perfusion-metabolism mismatch and match patterns are important for differentiating viable from nonviable myocardium, the frequency of these scintigraphic patterns has not been reported. The study objective was to establish the incidence of these scintigraphic patterns to estimate the clinical need for metabolic positron emission tomography for evaluating tissue viability in patients with prior myocardial infarction (MI). 82Rb perfusion images were interpreted to identify reversible or irreversible defects, followed by determination of their 18F-fluorodeoxyglucose (18F-FDG) uptake pattern. In 155 patients with prior MI, analysis of 613 abnormal segments showed reversible perfusion defects in 13%. The 87% irreversible defects, 18% showed perfusion-metabolism mismatch, whereas 69% showed the match pattern. Reversible perfusion defects and perfusion-metabolism mismatches were noted in 20% (31/155) and 29% (45/155) of patients, respectively, whereas the match pattern was noted in 51% (79/155) of patients. Irreversible perfusion defects were common in our patients with prior MI, and distinction between viable and nonviable tissue was not possible by perfusion imaging alone. The identification of hibernating myocardium was possible only with the additional 18F-FDG imaging in about one third of patients. This indicates a significant clinical demand for 18F-FDG imaging that identifies patients who will benefit from revascularization.


In vivo dosimetry in UK external beam radiotherapy: current and future usage.
Towards Safer Radiotherapy recommended that radiotherapy (RT) centres should have protocols in place for in vivo dosimetry (IVD) monitoring at the beginning of patient treatment courses (Donaldson S. Towards safer radiotherapy. R Coll Radiol 2008). This report determines IVD implementation in the UK in 2014, the methods used and makes recommendations on future use. Evidence from peer-reviewed journals was used in conjunction with the first survey of UK RT centre IVD practice since the publication of Towards Safer Radiotherapy. In March 2014, profession-specific questionnaires were sent to radiographer, clinical oncologist and physics staff groups in each of the 66 UK RT centres. Response rates from each group were 74%, 45% and 74%, respectively. 73% of RT centres indicated that they performed IVD. Diodes are the most popular IVD device. Thermoluminescent dosimeter (TLD) is still in use in a number of centres but not as a sole modality, being used in conjunction with diodes and/or electronic portal imaging device (EPID). The use of EPID dosimetry is increasing and is considered of most potential value for both geometric and dosimetric verification. Owing to technological advances, such as electronic data transfer, independent monitor unit checking and daily image-guided radiotherapy, the overall risk of adverse treatment events in RT has been substantially reduced. However, the use of IVD may prevent a serious radiation incident. Point dose IVD is not considered suited to the requirements of verifying advanced RT techniques, leaving EPID dosimetry as the current modality likely to be developed as a future standard. Advances in knowledge: An updated perspective on UK IVD use and provision of professional guidelines for future implementation.


Effects of sodium perchlorate and 6-propylthiouracil on metamorphosis and thyroid gland histopathology in the European common frog (Rana temporaria).
Several chemicals have been identified as thyroid hormone axis disrupting chemicals (THADCs) able to interfere with the thyroid hormone system during fetal life and early life stages, thereby impairing neurodevelopment in mammals and inducing development and growth disorders in fish and amphibians. However, identification of THADCs is particularly challenging, and thyroid modalities are currently only assessed in vivo by mammalian and amphibian tests. The aquatic African clawed frog (Xenopus laevis/tropicalis) is the model species of the amphibian test guidelines developed by the OECD and the United States Environmental Protection Agency, but as most European amphibians are semi-aquatic, concern has been raised whether the sensitivity of native European species is comparable to Xenopus. A shortened version of the OEDC test guideline 241 (Larval Amphibian Growth and Development Assay, LAGDA) was used to investigate the effects of two model THADCs on the metamorphosis and thyroid histopathology in the European common frog (Rana temporaria). R. temporaria eggs were collected on the field and exposed till metamorphic climax to sodium perchlorate (11.9-426.5 μg/L perchlorate concentrations) and 6-propylthiouracil (PTU: 1.23-47.7 mg/L). PTU severely delayed metamorphosis and affected several thyroid gland histopathological endpoints at slightly lower concentrations compared to Xenopus. As opposed to what was described in similar Xenopus studies, we observed no effect of perchlorate on the investigated endpoints. Interspecies differences may be linked to mechanisms of action.


Zirconium phenylphosphonate-anchored methyltrioxorhenium as novel heterogeneous catalyst for epoxidation of cyclohexene.
Epoxidation of olefins to epoxides is widely recognized as an important unit process in the manufacture of fine chemicals and intermediates. Developing an environmentally benign heterogeneous catalytic system for olefin epoxidation with high activity and selectivity is still a challenge in this research field. Herein, we report our attempts to synthesize novel zirconium phenylphosphonate-anchored methyltrioxorhenium (MTO/ZrPP) heterogeneous catalysts by a conventional impregnation method and evaluate their catalytic performance for epoxidation of cyclohexene using urea-hydrogen peroxide adduct (UHP) as oxidant without the addition of base ligands. The MTO/ZrPP catalyst samples are characterized by powder X-ray diffraction (XRD), Fourier transform infrared (FT-IR), inductively coupled plasma emission spectrometry (ICP-ES), high resolution transmission electron microscopy (HRTEM), X-ray photoelectron spectroscopy (XPS), and solid-state (1)H magic-angle spinning nuclear magnetic resonance ((1)H MAS NMR) techniques. Meanwhile, the density functional theory (DFT) calculation is carried out to further understand the structure feature and interactions of the MTO/ZrPP catalyst. It is revealed that MTO is anchored on support surface by the favored hydrogen-bonding interaction between two oxo ligands of MTO and two H atoms from the adjacent phenyls of ZrPP. MTO/ZrPP catalyst displays excellent catalytic activity for cyclohexene epoxidation. Moreover, only cyclohexene oxide production can be obtained under the employed reaction conditions.


Evidence that subcellular localization of a bacterial membrane protein is achieved by diffusion and capture.
Bacteria lack an endoplasmic reticulum, a Golgi apparatus, and transport vesicles and yet are capable of sorting and delivering integral membrane proteins to particular sites within the cell with high precision. What is the pathway by which membrane proteins reach their proper subcellular destination in bacteria? We have addressed this question by using green fluorescent protein (GFP) fused to a polytopic membrane protein (SpoIVFB) that is involved in the process of sporulation in the bacterium Bacillus subtilis. SpoIVFB-GFP localizes to a region of the sporulating cell known as the outer forespore membrane, which is distinct from the cytoplasmic membrane. Experiments are presented that rule out a mechanism in which SpoIVFB-GFP localizes to all membranes but is selectively eliminated from the cytoplasmic membrane by proteolytic degradation and argue against a model in which SpoIVFB-GFP is selectively inserted into the outer forespore membrane. Instead, the results are most easily compatible with a model in which SpoIVFB-GFP achieves proper localization by insertion into the cytoplasmic membrane followed by diffusion to, and capture in, the outer forespore membrane. The possibility that diffusion and capture is a general feature of protein localization in bacteria is discussed.


[Therapy of chronic antero-lateral instability of the upper ankle and its results].
From 1970 to 1980, 157 modified Watson-Jones grafts were performed at the BG Unfallklinik Tübingen. The advantages and disadvantages of this procedure are discussed and compared with other surgical procedures. Follow-up examinations were possible in 119 patients. In all patients a significant improvement of the stability could be attained. The functional reduction of mobility appeared minimal. 46 of 64 athletes resumed full sports activities. 90% of the patients stated to be satisfied with the results.


[112 cases of sporadic and genetically determined pheochromocytoma: a comparative pathologic study].
The aim of this study was to compare 64 genetically determined pheochromocytomas (PH) (49 MEN IIa, 3 MEN IIb, 6 Von Recklinghausen diseases, 1 von Hippel-Lindau disease, 5 familial pheochromocytomas) and 48 sporadic PH. Genetically determined PH were more often observed among men and more frequently bilateral and multicentric than sporadic PH. Sporadic tumors had more often adrenal capsular invasion, necrosis and pseudocysts. Genetically determined PH were more differentiated with an insular pattern, hyaline globules and a higher percentage of polyhedric cells. Sporadic tumors were less differentiated with more frequently a diffuse pattern and small cells. Adrenal medullar hyperplasia was significantly associated with genetically determined PH. Adrenal cortical hyperplasia was not associated with a particular type of PH. The PS100 and chromogranin immunodetection was equivalent in both groups.


Inhibitors of dihydropteroate synthase: substituent effects in the side-chain aromatic ring of 6-[[3-(aryloxy)propyl]amino]-5-nitrosoisocytosines and synthesis and inhibitory potency of bridged 5-nitrosoisocytosine-p-aminobenzoic acid analogues.
We previously reported that 6-(methylamino)-5-nitrosoisocytosine (5) is a potent inhibitor (I50 = 1.6 microM) of Escherichia coli dihydropteroate synthase. It was noted that 6-amino substituents larger than methyl were detrimental to binding, although the adverse steric effect could be overcome by a positive ancillary binding contribution of a phenyl ring attached at the terminus of certain 6-alkylamino substituents. We selected the 6-[[3-(aryloxy)propyl]amino]-5-nitrosoisocytosine structure as a parent system and explored the effects of aromatic substituents on synthase inhibition. The nature of the aryl substitution influences binding, as shown by a 30-fold range of inhibitory potencies observed for the 15 aryl analogues (I50 values = 0.6-18 microM), although there is no apparent correlation between synthase inhibition and the electronic or hydrophobic characteristics of the aryl substituents. To explore the possibility that the aryl ring of these inhibitors might interact with the synthase binding site for the substrate p-aminobenzoic acid (PABA), three compounds were synthesized in which a PABA analogue is bridged to the nitrosoisocytosine moiety by linkage to an amino group at C-6 of the isocytosine. The bridged analogues significantly inhibited the synthase (I50 values = 2.5-8.9 microM) but were of unexceptional potency compared with other members of the (aryloxy)propyl series. Structure-activity considerations and inhibition kinetics did not support the PABA binding site as the synthase region that interacts with the aryl ring of these inhibitors. Despite the potent synthase inhibition exhibited by many of the nitrosoisocytosines studied, none of the 18 new analogues showed significant antibacterial activity.


Infectious Laryngotracheitis Virus Viral Chemokine-Binding Protein Glycoprotein G Alters Transcription of Key Inflammatory Mediators In Vitro and In Vivo.
Infectious laryngotracheitis virus (ILTV) is an alphaherpesvirus that infects chickens, causing upper respiratory tract disease and significant losses to poultry industries worldwide. Glycoprotein G (gG) is a broad-range viral chemokine-binding protein conserved among most alphaherpesviruses, including ILTV. A number of studies comparing the immunological parameters between infection with gG-expressing and gG-deficient ILTV strains have demonstrated that expression of gG is associated with increased virulence, modification of the amount and the composition of the inflammatory response, and modulation of the immune responses toward antibody production and away from cell-mediated immune responses. The aims of the current study were to examine the establishment of infection and inflammation by ILTV and determine how gG influences that response to infection. In vitro infection studies using tracheal organ tissue specimen cultures and blood-derived monocytes and in vivo infection studies in specific-pathogen-free chickens showed that leukocyte recruitment to the site of infection is an important component of the induced pathology and that this is influenced by the expression of ILTV gG and changes in the transcription of the chicken orthologues of mammalian CXC chemokine ligand 8 (CXCL8), chicken CXCLi1 and chicken CXCLi2, among other cytokines and chemokines. The results from this study demonstrate that ILTV gG interferes with chemokine and cytokine transcription at different steps of the inflammatory cascade, thus altering inflammation, virulence, and the balance of the immune response to infection.IMPORTANCE Infectious laryngotracheitis virus is an alphaherpesvirus that expresses gG, a conserved broad-range viral chemokine-binding protein known to interfere with host immune responses. However, little is known about how gG modifies virulence and influences the inflammatory signaling cascade associated with infection. Here, data from in vitro and in vivo infection studies are presented. These data show that gG has a direct impact on the transcription of cytokines and chemokine ligands in vitro (such as chicken CXCL8 orthologues, among others), which explains the altered balance of the inflammatory response that is associated with gG during ILTV infection of the upper respiratory tract of chickens. This is the first report to associate gG with the dysregulation of cytokine transcription at different stages of the inflammatory cascade triggered by ILTV infection of the natural host.


Syndecans, signaling, and cell adhesion.
Syndecans are transmembrane proteoglycans which can participate in diverse cell surface interactions, involving extracellular matrix macromolecules, growth factors, protease inhibitors, and even viral entry. Currently, all extracellular interactions are believed to be mediated by distinct structures within the heparan sulfate chains, leaving the roles of chondroitin sulfate chains and extracellular portion of the core proteins to be elucidated. Evidence that syndecans are a class of receptor involved in cell adhesion is mounting, and their small cytoplasmic domains may link with the microfilament cytoskeleton, thereby mediating signaling events. The molecular details are unknown, but the conservation of regions of syndecan cytoplasmic domains, and a strong tendency for homotypic association, support the idea that the ligand-induced clustering may be a discrete source of specific transmembrane signaling from matrix to cytoskeleton, as proposed for other classes of adhesion receptors.


Interleukin-2 activation of haematopoietic stem cells.
Recent findings concerning the role of immunity in the eradication of residual malignant disease after autologous haematopoietic stem cell transplantation have led to extensive studies of T-cell and natural killer (NK) mediated anti-tumour effects. Interleukin 2 (IL-2) activation of autologous bone marrow (BM) or peripheral blood stem cells (PBSC) before transplantation is one of the methods of adoptive cell therapy. Autologous BM of patients with chronic myelogenous leukaemia (n = 11) and PBSC of patients with multiple myeloma (n = 14) were activated by IL-2 in laboratory conditions with the aim of evaluating the feasibility of this method, the activation of T and NK cells, recovery of active progenitor cells, microbial contamination, and reduction of malignant cell content. Samples of BM (mean 2.6 x 10(6) cells) and PBSC (mean 10.3 x 10(6) cells) were cultured in complete culture medium with IL-2 (6000 Ul/ml) for 24 h. The recovery of CD34+ cells and CFU-GM was 82.5% and 51.5%, respectively, for BM, and 85% and 86%, respectively, for PBSC (mean values). No purging effect was detected by flow cytometry and a small decline in malignant cell contamination was observed by quantitative PCR in BM samples. No microbial contamination occurred during the sample processing. The described in vitro activation of BM and peripheral blood stem cells using IL-2 was evaluated as a safe and reliable method suitable for clinical application.


[Clinical characteristics and prognosis of brain-heart interaction in patients with acute severe stroke].
To investigate and analyze the clinical characteristics and prognosis of brain-heart interaction (BHI) in patients with acute severe stroke. The patients with acute severe stroke admitted to Neurointensive Care Unit of Xuanwu Hospital, Capital Medical University from January 1st, 2015 to December 31st, 2017 were enrolled. The clinical data, indicators related to BHI and prognosis were collected. Patients were divided into BHI group and non-BHI group according to the presence or absence of BHI. The differences of each index were compared between two groups. The independent risk factors of BHI were analyzed using multivariate Logistic regression analysis. In addition, subgroup analysis was performed for patients in the BHI group based on the presence or absence of Takotsubo syndrome (TTS), and multivariate Logistic regression was used to analyze independent risk factors for TTS. 119 patients with acute severe stroke were analyzed, BHI occurred in 91 cases (76.5%), and 17 cases (14.3%) TTS were included in the BHI group. Compared with non-BHI group, BHI group had lower rates of cerebrovascular disease history (20.9% vs. 42.9%, P = 0.020), lower smoking history (25.3% vs. 50.0%, P = 0.013), lower statin use (16.5% vs. 50.0%, P = 0.000), lower total cholesterol [TC (mmol/L): 3.97±1.05 vs. 4.43±0.88, P = 0.039], and lower low density lipoprotein [LDL (mmol/L): 2.30±0.76 vs. 3.00±0.84, P = 0.000]. Multivariate Logistic regression showed that the use of statins [odds ratio (OR) = 0.222, 95% confidence interval (95%CI) = 0.075-0.658, P = 0.007] and the history of cerebrovascular diseases (OR = 0.321, 95%CI = 0.113-0.912, P = 0.033) were protective factors of BHI. Compared with non-TTS subgroup, TTS subgroup had a lower percentage of diabetes history (0% vs. 37.8%, P = 0.002), lower glycated hemoglobin [HbA1c: 0.055 (0.050, 0.056) vs. 0.064 (0.056, 0.075), P = 0.000], higher TC (mmol/L: 4.70±1.16 vs. 3.80±0.95, P = 0.001), first day mean arterial pressure [MAP (mmHg, 1 mmHg = 0.133 kPa): 114 (98, 122) vs. 103 (94, 108), P = 0.042], third day diastolic blood pressure [DBP (mmHg): 82 (77, 94) vs. 67 (59, 86), P = 0.002], and third day MAP [mmHg: 106 (95, 114) vs. 94 (80, 106), P = 0.015]. Multivariate Logistic regression analysis showed that increased MAP on the third day of admission was an independent risk factor for TTS (OR = 11.833, 95%CI = 1.113-125.779, P = 0.040), increased HbA1c was protective factor of TTS (OR = 0.022, 95%CI = 0.001-0.345, P = 0.006). The rate of poor outcome at discharge of all the BHI patients were higher than those of the non BHI patients (34.1% vs. 14.3%, P = 0.045). Acute severe stroke patients with high incidence of acquiring BHI and having BHI is associated with poor outcome after discharge. Using statins, ischemic preconditioning and control blood pressure, the occurrence of BHI can be reduced and might be beneficial to patients.


Design, synthesis and anti-TMV activity of novel α-aminophosphonate derivatives containing a chalcone moiety that induce resistance against plant disease and target the TMV coat protein.
Plant viral diseases, known as "plant cancer", with high contagiosity can substantially reduce crop quality and yield. To identify potential anti-tobacco mosaic virus (TMV) agents with different mechanisms, a series of novel α-aminophosphonate derivatives containing a chalcone moiety were designed and synthesized. Bioassay results revealed that some target compounds exhibited improved curative activity against TMV in vivo, and the EC50 value of compound B3 was 356.7 mg L-1. The activities of the defensive enzymes POD and CAT from tobacco leaves treated with B3 and B17 showed that these target compounds could improve the photosynthetic ability of the leaves and activate plant host resistance against TMV infection. The binding constant between B3 and TMV Coat Protein (CP) (2.51 × 108 M-1), calculated by the fluorescence titration experiment and docking results, revealed that B3 has a strong interaction with TMV CP. Further docking analysis revealed that B3 was embedded between two layers of the TMV CP, which was consistent with the 2:1 binding mode of TMV CP and B3 determined by the binding affinity experiment. The TEM morphological study of TMV treated with B3 and B17 indicated that this series of target compounds may trigger the disassembly of TMV by interacting directly with TMV CP. This study provides new insight for the discovery of antiviral compounds with two different mechanisms of action.


Laser surface treatment on Yttria-stabilized zirconia dental implants: Influence on cell behavior.
Yttria-stabilized zirconia (YSZ) is being proposed as an alternative material to Titanium for dental implants due to its aesthetic and biocompatibility properties. However, is it yet to define the optimal surface treatment to improve YSZ bioactivy. Texturization is a promising approach, but the biological role of patterned YSZ surfaces in cell cultures is yet to be determined. Thus, cellular behavior of osteoblasts and fibroblasts in contact with groove-texturized YSZ surfaces was investigated. YSZ discs were groove-textured by conventional milling and Nd:YAG laser. All samples including control were sandblasted and acid-etched. Human osteoblasts and fibroblasts were cultured on discs for 14 days. Morphology and cellular adhesion were observed. Cell viability, interleukin-1β, osteopontin, collagen type I prodution, alkaline phosphatase activity, and interleukin-8 were measured. YSZ texturization by conventional milling improved osteoblasts viability and differentiation when compared to laser texturization. Fibroblasts behavior did not seem to be influenced by the texturing technique. Compared to sandblasting and acid etching currently used as gold standard for zirconia dental implants no superiority of macrotexturization was found.


Associations between brain-derived neurotrophic factor plasma levels and severity of the illness, recurrence and symptoms in depressed patients.
There is increasing evidence that the brain-derived neurotrophic factor (BDNF) is involved in the pathophysiology of mood disorders and that its peripheral levels represent a reliable mirror of its concentration in the brain. The aim of the present study was to measure BDNF plasma levels in patients affected by major depression and to explore the possible relationship between the biological parameter and characteristics of the illness. BDNF plasma levels were evaluated in 30 inpatients suffering from major depression, according to DSM-IV criteria, by means of a commonly employed ELISA method. The clinical characteristics were assessed by the Hamilton Rating Scale for Depression (HRSD) and the Clinical Global Impression Scale. BDNF plasma levels were significantly lower in the patients with the severest illness compared with the others, and the same was true for patients with dissociative symptoms, severe sleep disturbance and recurrent depression. A significant and negative correlation was observed between the biological parameter and the retardation factor score of the HRSD. These findings suggest that low BDNF levels are related to both recurrence and severity of depression, as well as to symptoms typical of dysfunctions of the hypothalamic-pituitary-adrenal axis.


Mitochondrial dynamics associated with oxygen-glucose deprivation in rat primary neuronal cultures.
Our objective was to investigate the mitochondrial dynamics following oxygen-glucose deprivation (OGD) in cultured rat cortical neurons. We documented changes in morphology, protein expression, and DNA levels in mitochondria following OGD and examined the roles of mitochondrial fission [dynamin-related protein 1 (Drp1), fission protein-1 (Fis1)] and fusion [mitofusin-1 (Mfn1), mitofusin-2 (Mfn2), and optic atrophy-1 protein (OPA1)] proteins on mitochondrial biogenesis and morphogenesis. We tested the effects of two Drp1 blockers [15-deoxy-Δ12,14-Prostaglandin J2 (PGJ2) and Mitochondrial Division Inhibitor (Mdivi-1)] on mitochondrial dynamics and cell survival. One hour of OGD had minimal effects on neuronal viability but mitochondria appeared condensed. Three hours of OGD caused a 60% decrease in neuronal viability accompanied by a transition from primarily normal/tubular and lesser number of rounded mitochondria during normoxia to either poorly labeled or small and large rounded mitochondria. The percentage of rounded mitochondria remained the same. The mitochondrial voltage-dependent anion channel, Complex V, and mitoDNA levels increased after OGD associated with a dramatic reduction in Drp1 expression, less reduction in Mfn2 expression, an increase in Mfn1 expression, with no changes in either OPA1 or Fis1. Although PGJ2 increased polymerization of Drp1, it did not reduce cell death or alter mitochondrial morphology following OGD and Mdivi-1 did not protect neurons against OGD. In summary, mitochondrial biogenesis and maintained fusion occurred in neurons along with mitochondrial fission following OGD; thus Mfn1 but not Drp1 may be a major regulator of these processes.


Body mass index determines sunbathing habits: implications on vitamin D levels.
Vitamin D is crucial for calcium and bone metabolism. Overweight people have been found to have lower levels of this vitamin. The aim of the paper was to test if sun exposure habits might differ according to weight and body fat per cent in a random population-based sample, and have an impact on vitamin D levels. The analysis of 367 persons showed that, among other established factors, differences in sunbathing also explain the lower vitamin D levels in overweight and elderly individuals.


Understanding frailty in the geriatric population.
Clinicians who work with the frail elderly know what frailty looks like, but until recently, they have had no science-based definition of this condition. Frailty is classified as a medical syndrome, and Fried et al. were among the first to standardize the definition of frailty as a distinct syndrome with biologic underpinnings. Their definition describes a clinical phenotype of decreased reserve and resistance to stressors, with clinical manifestations of a mutually exacerbating cycle of negative energy balance, sarcopenia, diminished strength, and exertion intolerance. Age is no longer considered a defining characteristic, although frailty is still considered primarily a geriatric problem. Approximately two-thirds of affected individuals enter frailty in a slow, progressive way, while one-third become frail cataclysmically. Weakness is a common early sign, and exhaustion and weight loss are often late manifestations. Observing early behavioral changes before frailty develops could provide insight into its development and suggest early interventions. Since frailty is clearly associated with adverse outcomes, a healthy, active lifestyle is the cornerstone of prevention, and many researchers suggest that resistance training can reverse some muscle loss and improve functioning. When the health care team proposes any change in care, including a new medication, it should be prepared to describe how the intervention may affect cognition, memory, energy, or function.


Trainability of young athletes and overtraining.
Exercise adaptations to strength, anaerobic and aerobic training have been extensively studied in adults, however, young people appear to respond differently to such exercise stimulus in comparison to adults. In addition, because overtraining in young athletes has received little attention, this important area is also discussed. Resistance training in children can be safe and effective. It has the potential to improve sport performance, enhance body composition and reduce the rate of sport incurred injury. Furthermore, with the appropriate stimulus, prepubertal and adolescent athletes can show significant increments in muscle strength (13 - 30%). Children can improve anaerobic power (3%-10% Mean Power and 4%-20% in Peak Power), although the mechanisms responsible for the improvements in children remain unclear. Children show a 'reduced' trainability of peak VO2 in comparison to adults. Nevertheless, their aerobic power is trainable, with improvements reported at approximately 5%. Moreover, improvements in other variables like exercise economy or lactate threshold may occur without significant changes in peak VO2 The limited evidence available indicates that overtraining is occurring in young athletes (30% prevalence), highlighting the importance of further research in to all the possible contributing factors - physiological, psychological and emotional - when investigating overtraining. Key pointsChildren's strength, anaerobic and aerobic power is trainable, although the improvements may be smaller than seen in adults.Children can demonstrate significant gains in muscle strength with resistance training (13 - 30%).Improvements in mean power (3 - 10%) and peak power (4 - 20%) are reported in children.Aerobic fitness can improve with training in children by approximately 5%.Limited available evidence indicates an occurrence of overtraining in young athletes of around 30%.


Small bowel transplantation.
Intestinal transplantation is gradually becoming a therapeutic intervention rather than an experimental procedure. In the long term, the best outcome for patients with intestinal failure remains total parenteral nutrition, but where this is unlikely to allow long-term survival because of loss of venous access sites or severe cholestasis, intestinal transplantation should be considered. The technical aspects of the procedure are well described and advances in recent years in both immunosuppression and antimicrobial therapy have led to improved outcomes, particularly in the larger centers. Graft monitoring and the profound sepsis that accompanies graft dysfunction due to bacterial translocation remain major challenges, whereas the issues of denervation, lymphatic disruption, graft-versus-host disease (GVHD), and nonphysiological venous drainage have not proved to be major problems. Whether intestinal transplantation will become an alternative for the stable patient on total parenteral nutrition rather than a salvage procedure for when total parenteral nutrition fails remains to be seen.


[Diagnostic strategy of metachromatic leukodystrophy in Tunisia].
We recruited a 44-year-old woman who had a dementia with behavioral and personality troubles. A biochemical analysis which includes a qualitative study of urinary sulfatides by thin layer chromatography followed by the determination of the enzymatic activity of arylsulfatase A (ARSA) was performed. The Molecular analysis concerned the research of the most frequent mutations (459 +1 G> A, p.P426L, p.I179S). The profile that has revealed the presence of 3-O-sulfogalactosylceramide fraction was in favor of metachromatic leukodystrophy. The activity of arylsulfatase A was collapsed in the index case which confirmed the phenotype of the adult form of the diagnosed MLD. The molecular study showed the presence of the mutation p.I179S in the homozygous state in the index case.


Long-term results of the FemSoft urethral insert for the management of female stress urinary incontinence.
A 5-year ongoing, controlled multicenter study enrolled 150 women. Outcome measures included pad weight tests (PWT), voiding diary (VD), quality of life (QOL) and satisfaction questionnaires. Outcome measures during the baseline period were compared to evaluations during follow-up. Concurrent evaluations with and without device use were also performed. Safety evaluations included urinalysis and culture, leak-point pressure (LPP) and cystoscopy. Adverse events (AE) were recorded throughout the study. One to 2 years of follow-up were collected on all study participants (mean 15 months). Statistically significant reductions in overall daily incontinence episodes (P<0.001) and PWT urine loss (P<0.001) were observed with the device at all follow-up intervals, and 93% of women had a negative PWT at 12 months. Women were satisfied with ease of use of the device, comfort and dryness, and significant improvements in QOL were observed (P<0.001). Subgroup analysis revealed that the insert was effective, despite the presence of urgency, low LPP, failed surgery and advanced age. AE included symptomatic urinary tract infection in 31.3%, mild trauma with insertion in 6.7%, hematuria in 3.3%, and migration in 1.3% of women. The results of PWT and VD demonstrated device efficacy. Women were satisfied and significant improvements in QOL were observed. AE were transient and required minimal or no treatment. The urethral insert should be considered as an option for the management of SUI.


The ORVAC trial: a phase IV, double-blind, randomised, placebo-controlled clinical trial of a third scheduled dose of Rotarix rotavirus vaccine in Australian Indigenous infants to improve protection against gastroenteritis: a statistical analysis plan.
The purpose of this double-blind, randomised, placebo-controlled, adaptive design trial with frequent interim analyses is to determine if Australian Indigenous children, who receive an additional (third) dose of human rotavirus vaccine (Rotarix, GlaxoSmithKline) for children aged 6 to < 12 months, would improve protection against clinically significant all-cause gastroenteritis. Up to 1000 Australian Aboriginal and Torres Strait Islander (hereafter Indigenous) infants aged 6 to < 12 months will be recruited from all regions of the Northern Territory. The intervention is the addition of a third scheduled dose of human monovalent rotavirus vaccine. ORVAC has two co-primary outcomes: (1) anti-rotavirus IgA seroconversion, defined as serum anti-rotavirus IgA ≥ 20 U/ml 28 to 55 days post Rotarix/placebo, and (2) time from randomisation to medical attendance for which the primary reason for presentation is acute gastroenteritis or acute diarrhoea illness before age 36 months. Secondary outcomes include (1) change in anti-rotavirus IgA log titre, (2) time from randomisation to hospitalisation with primary admission code presumed or confirmed acute diarrhoea illness before age 36 months, (3) time from randomisation to hospitalisation for which the admission is rotavirus confirmed diarrhoea illness before age 36 months and (4) time from randomisation to rotavirus infection (not necessarily requiring hospitalisation) meeting the jurisdictional definition before age 36 months. A detailed, prospective statistical analysis plan is presented for this Bayesian adaptive design. The plan was written by the trial statistician and details the study design, pre-specified adaptative elements, decision thresholds, statistical methods and the simulations used to evaluate the operating characteristics of the trial. As at August 2020, four interim analyses have been run, but no stopping rules have been triggered. Application of this SAP will minimise bias and supports transparent and reproducible research. Clinicaltrials.gov NCT02941107. Registered on 21 October 2016 ORIGINAL PROTOCOL FOR THE STUDY: https://doi.org/10.1136/bmjopen-2019-032549.