Three-dimensional structural analysis of the group B polysaccharide of Neisseria meningitidis 6275 by two-dimensional NMR: the polysaccharide is suggested to exist in helical conformations in solution.
The solution conformations of the group B polysaccharide of Neisseria meningitidis were analyzed by DQF-COSY and pure absorption 2D NOE NMR with three mixing times. The pyranose ring of the sialic acid residue was found to be in the 2C5 conformation. The DQF-COSY analysis indicated that the orientations of H6 and H7 and of H7 and H8 are both gauche. In order to overcome the difficulties in analyzing the NOE data due to the two sets of proton overlaps, molecular modeling of alpha-2,8-linked sialic acid oligomers was carried out to investigate possible conformers, and theoretical NOE calculations were performed by using CORMA (complete relaxation matrix analysis). Our analysis suggests that the polysaccharide adopts helical structures for which the phi (defined by O6-C2-O8-C8) and psi (C2-O8-C8-C7) angles are in the following ranges: phi -60 to 0 degrees, psi 115-175 degrees or phi 90-120 degrees, psi 55-175 degrees. The weak affinity of anti-B antibodies for smaller alpha-2,8-linked oligosaccharides may be due to the fact that such oligomers are more flexible and may not form an ordered structure as the poly(sialic acid) does.


Prevention of Intraoperative Hypothermia in Laparoscopy by the Use of Body-Temperature and Humidified CO 2 : a Pilot Study.
Introduction Hypothermia is defined as a decrease in body core temperature to below 36 °C. If intraoperative heat-preserving measures are omitted, a patient's temperature will fall by 1 - 2 °C. Even mild forms of intraoperative hypothermia can lead to a marked increase in morbidity and mortality. The temperature of the insufflation gas is usually disregarded in the treatment and prevention of hypothermia. This study was conducted to investigate the effect of body-temperature and humidified CO 2 on the intraoperative temperature profile and avoidance of hypothermia in laparoscopic surgery. Material and Methods In this retrospective, non-randomised case control study, 110 patients whose planned operation lasted at least 60 minutes were identified from 376 patients by means of an algorithm. Dry (20% humidity) CO 2 at room temperature was insufflated in 51 patients (control group). 59 patients were insufflated with humidified (98% humidity) CO 2 at body temperature (37 °C) (study group). These conditions were achieved with the HumiGard MR860 Surgical Humidification System (Fisher & Paykel Healthcare Limited, Auckland, New Zealand). The intraoperative temperature profile was evaluated by measurements every 10 minutes. Statistical analysis was performed with IBM ® SPSS ® Statistics 23.0.0. Results The intraoperative temperature in the control group fell steadily, while a continuous rise in temperature was observed in the study group. Warming was demonstrated in the study group with a start-end temperature difference of 0.09 °C, which differed significantly from the control group, in which it was - 0.09 °C (p = 0.011). The middle-end difference of 0.11 °C showed even higher significance in favour of the warmed gas (p = 0.003). The rate of hypothermia at the start of the operation fell from 50 to 36% in the study group and increased from 36 to 42% in the control group. Conclusion These results show that the use of body-temperature and humidified insufflation gas for laparoscopy can help to prevent intraoperative hypothermia.


Up-regulation of telomerase activity in Herpesvirus saimiri immortalized human T-lymphocytes.
Human T-lymphocytes can be transformed to unlimited growth by Herpesvirus saimiri (HVS). We studied the telomerase activity of a recently established HVS immortalized human CD4 T cell clone in comparison to peripheral blood lymphocytes (PBL) and unstimulated or phytohemagglutinin (PHA)-stimulated CD4 T-cells by a Telomeric Repeat Amplification-Protocol (TRAP) -Assay. Telomerase activity in PHA-stimulated CD4 T-cells was seven-fold and in HVS-infected CD4 T-cells 14-fold higher than in untreated CD4 T-cells. The HVS immortalized T-cell clone provides a useful tool for studying the regulation of telomerase activity during carcinogenesis and for testing of telomerase-inhibitory drugs.


Binding characteristics of endothelin isoforms (ET-1, ET-2, and ET-3) in vascular smooth muscle cells.
The existence of distinct endothelin (ET) receptor subtypes has been reported in several tissues. In the present study, we investigated the binding characteristics of the three endothelin isoforms to cultured rat aortic smooth muscle cells. [125I]ET-1, [125I]ET-2, and [125I]ET-3 bound to an apparent single class of binding sites with apparent dissociation constants (Kd) of 111, 123, and 1410 pM and binding capacities (Bmax) of 54.1, 46.0, and 7.9 fmol/10(6) cells, respectively. The binding of the three radiolabeled endothelin isoforms was equally inhibited by ET-1 and ET-2. ET-3 was more effective in competing with [125I]ET-3 than with [125I]ET-1 or [125I]ET-2. In contrast to ET-1 and ET-2, the binding of ET-3 was reversible. Furthermore, 18 h of pre-exposure of the cells to 1 nM ET-1 or ET-2 decreased the ET-1 binding capacity, whereas ET-3 (10 nM) was ineffective. ET-3 binding characteristics were not affected by pretreatment of the cells with any of the endothelin isoforms. These results suggest the presence of two distinct endothelin receptor subtypes in rat aortic smooth muscle cells. The ET-1 and ET-2 preferring receptor (80-85%), sensitive to downregulation or internalization, elicits an irreversible binding. The second subtype (15-20%) binds the three endothelin isoforms with the same affinity in a reversible manner, and is insensitive to downregulation or internalization.


Remote teaching of publication-quality, single-case graphs in Microsoft Excel.
Microsoft Excel is ubiquitous, cost-effective, and can be used to create publication-quality single-case design graphs. We systematically replicated the GraphPad Prism video tutorial by Mitteer et al. (2018) to teach 24 master's students to create multiple-baseline graphs using Excel 2016. Students' mean accuracy on the multiple-baseline graph was 25% in pretraining, 86% with the video tutorial, and 96% with the review checklist. Next, students used the same video tutorial to create multielement and reversal graphs. Students' mean accuracy on the multielement graph was 93% with video tutorial and 94% with review checklist, and accuracy on the reversal graph was 82% with video tutorial and 94% with review checklist. Students reported moderate to high satisfaction with both training components. The results support scientist-practitioners using the video tutorial and review checklists to create three common graphs using Excel 2016, Excel 2019, and Excel Office 365.


Application of draft European Commission reference levels to a regional CT dose survey.
A survey of CT doses in Northern Ireland in the period between October 1995 and March 1997 was carried out. The survey included all but one of the 10 scanners in use at the time, and, additionally, two others that were replacement machines. The method used was to study standard protocols and calculate doses to the NRPB mathematical phantom, so that a direct comparison could be made with other surveys carried out in a similar fashion elsewhere. The survey addressed the patient radiation dose but not image quality or clinical outcomes. It is estimated that in Northern Ireland the contribution to collective dose to the population from CT is about 40% of that from all medical X-rays. The proposed European Commission reference quantities, weighted CT dose index and dose-length product were computed and their potential use evaluated. A full study of mean values of effective dose per examination revealed the average dose per examination was not significantly different from that found in the 1989 UK survey, although several procedures gave rise to doses that were high enough to be investigated with a view to justification or reduction. One of the scanners was found to give consistently high doses. It is likely that a revision of the mAs values used on this scanner will produce a significant reduction in patient doses without compromising image quality. When compared with the draft EC reference levels, fewer procedures were found to have excessively high dose values. The proposed EC reference levels would therefore be useful for continual monitoring of CT dose status, but do not appear to provide as comprehensive an assessment of patient exposure as that given by consideration of effective doses.


Salinosporamide A, a Marine-Derived Proteasome Inhibitor, Inhibits T Cell Activation through Regulating Proliferation and the Cell Cycle.
The appropriate regulation of T cell activity under inflammatory conditions is crucial for maintaining immune homeostasis. Salinosporamide A discovered as a self-resistance product from the marine bacterium Salinospora tropica, has been used as a potent proteasome inhibitor (PI). Although PIs have been developed as novel therapeutics for autoimmune diseases, due to their immunosuppressive effect, whether salinosporamide A inhibits T cell activation remains unknown. The current study finds that salinosporamide A is not cytotoxic, but controls T cell proliferation. Results from our cell cycle arrest analysis revealed that salinosporamide A leads to cell cycle arrest and regulates the expression of cyclin-dependent kinases. Under activated conditions, salinosporamide A abrogated T cell activation by T cell receptor-mediated stimulation, in which the production of cytokines was inhibited by pretreatment with salinosporamide A. Furthermore, we demonstrated that the regulation of T cell activation by salinosporamide A is mediated by suppressing the MAPK pathway. Therefore, our results suggest that salinosporamide A effectively suppresses T cell activation through regulating T cell proliferation and the cell cycle and provides great insight into the development of novel therapeutics for autoimmune diseases or graft-versus-host disease.


Clinical immunoscintigraphy of ovarian carcinoma using iodine-131-labeled 145-9 monoclonal antibody.
The monoclonal antibody (Mab) designated 145-9 recognizes CA125 antigen but binds to a different epitope than that recognized by OC125 antibody. This is a clinical study assessing the safety, kinetics and imaging sensitivity of Mab 145-9. Two milligrams of Mab were labeled with 111 MBq (3.0 mCi) of 131I and infused intravenously in 18 patients with ovarian carcinoma. Immunoscintigraphies were done at three, five, and seven days. There were no adverse reactions to the injection of this Mab. All immunoscintigraphies were considered positive. Immunoscintigraphy detected tumor lesions were confirmed in operative fields, in two patients with normal serum levels of CA125 and in four patients whose sonography and/or x-ray computed tomography showed negative findings. In five patients, immunoscintigraphy was repeated without any adverse reaction and revealed the progress of the carcinoma. Pharmacokinetic studies showed the steady-state volume of distribution (Vdss) to be 2772 +/- 466 ml (mean +/- s.d.), and clearance 51.3 +/- 12.7 ml/hr. In summary, immunoscintigraphies using 131I-labeled Mab 145-9 were done safely in patients with ovarian carcinoma. Preliminary results reveal a high sensitivity compared to radiological methods and tests currently in use.


The effect of low-dose combined hormone therapy (oestradiol and norethindrone acetate) on serum C-reactive protein levels and life quality in natural menopause women.
To assess the effect of low-dose combined oestradiol and norethindrone acetate hormone therapy (HT) on serum C-reactive protein (CRP) levels and life quality in natural menopause women. Forty-five natural menopause women admitted to the clinic during a 1-year period and diagnosed as menopause, who planned to have HT for menopausal symptoms, were enrolled in this prospective study. The serum CRP levels were measured, and vasomotor symptoms scores were graded according to the Blatt-Kupperman menopause index, and life quality scores according to the Menopause-Specific Quality of Life Questionnaire (MENQOL) were recorded before and after (3 months later) hormone therapy. The Blatt-Kupperman menopause index and MENQOL scores were significantly decreased after 3 months of low-dose treatment. No significant difference was found between white blood cell counts and serum CRP levels before and after 3 months of hormone therapy. Considering all HT types and biochemical effects, low-dose HT, which had positive results in terms of quality of life, was a safe treatment and could be preferred to conventional-dose preparations in cases without contraindications. Low-dose combined HT containing oestradiol and norethindrone acetate did not alter the serum CRP level in postmenopausal cases.


Quality control for blood pressure measurement in population studies: Shibata Children's Heart Study.
To investigate the relation between observer performance for blood pressure measurement in a training process and in field conditions, measurement values were studied under training and field conditions among 21 blood pressure observers of 1434 subjects aged 6-15 years in Japan. The observers received training by a videotape, which included six audiovisual presentations of a falling mercury column in a standard sphygmomanometer with Korotkoff sounds. Observer bias was measured for each trainee as the mean difference between the observed and the standard values for each blood pressure reading, including systolic (SBP), fourth-phase diastolic (K4), and fifth-phase diastolic (K5) values. In multiple linear regression analyses, each 1 mmHg increment in observer bias was equivalent to 1.27, 0.88, and 1.25 mmHg difference in actual readings of SBP, K4, and K5, respectively, in the field. This finding indicates that observer performance in videotape training is predictive of measurement behavior in the field.


The possibility of identifying brain hemorrhage in putrefied bodies with PMCT.
This paper aims to demonstrate that post-mortem CT (PMCT) can locate intracranial hemorrhages, even in decomposed cases. This is of relevance in that post-mortem decomposition is particularly damaging to the brain tissue's consistency, resulting in great difficulties to reliably diagnose and locate intracranial hemorrhages. We searched our case database of the last 11 years to find cases with decomposition of the body, where PMCT and an autopsy had been performed. We identified eleven cases according to these criteria. Postmortem interval ranged from 2 days to 2 weeks, and post-mortem radiological alteration index (RAI) was at or above 49. Eight out of eleven cases showed an intraparenchymal hemorrhage whereas the hemorrhage was extra-axial in the remaining three cases. Autopsy validated the presence of intracranial hemorrhage in all eleven cases, but location could not be confirmed due to liquid state of the brain. PMCT identified and localized intracranial hemorrhages in decomposed bodies, and in all of these cases, autopsy validated their presence. The actual cause of the hemorrhage (e.g. tumor, metastasis, vascular malformation, hypertensive hemorrhage) remained obscure. From this case series, it can be concluded that PMCT may add relevant information pertaining to localization of intracranial hemorrhages in decomposed bodies.


Molecular mechanism involved in increased expression of sialyl Lewis antigens in ductal carcinoma of the pancreas.
Increased expression of sialyl Lewis antigens, sLe(a) and sLe(x), is frequent during malignant transformation and tumor progression of gastrointestinal cancers and it is assumed to be correlated with the increased metastatic potential of tumor cells and, consequently, with poor patient survival. To determine the influence of the increased expression of these antigens in disease progression of ductal carcinoma of the pancreas, immunohistochemical expressions of sLe(x) and sLe(a) in 51 ductal carcinomas of the pancreas were examined. We also examined the expression of glycosyltransferase genes, which are involved in the synthetic pathways of these antigens to understand the molecular mechanism involved in the increased expression of these antigens. Of the 51 primary ductal carcinomas of the pancreas, 40 (78.4%) were sLe(a)-positive and 11 (21.6%) were sLe(a)-negative; 16 (31.4%) were sLe(x)-positive and 35 (68.6%) were sLe(x)-negative. Although there were no significant differences in any examined clinicopathological factors such as age, sex, histological type, tumor size, presence of lymph node metastasis, or presence of vessel invasion between the positive and negative groups with both the sLe(a) and sLe(x) antigens, patient survival tended to be worse in the antigens-positive group than in the antigens-negative group. Increased expression, however, was not dependent on the increased expression of a single glycosyltransferase gene examined among five such genes, which are postulated to be responsible for the synthesis of the sLe(a) and sLe(x) epitopes in the glycosylation pathway. Furthermore, the increased expression of these antigens was not closely associated with mutations status of the K-ras or p53 genes. These findings suggested that increased expression of sialyl Lewis antigens are involved in pancreatic tumorigenesis and that the accumulation of genetic alterations or epigenetic changes is responsible for the molecular mechanisms of increased expression of the sLe(a) and sLe(x) antigens in ductal carcinomas of pancreas.


Molecular characterization of Cryptococcus neoformans and Cryptococcus gattii from environmental sources and genetic comparison with clinical isolates in Apulia, Italy.
The present study investigated the environmental distribution of Cryptococcus neoformans and C. gattii species complex molecular types, mating types and sequence types in Apulia, a region of Southern Italy. A total of 2078 specimens from arboreal and animal sources were analyzed. The percentage of positive samples was similar among both arboreal and animal specimens: 4.2% vs. 5.1% for C. neoformans species complex and 0.6% vs. 1.4% for C. gattii species complex. Molecular typing identified 78 isolates as VNI (76 αA and two aA), one as AD-hybrid αADa, and 16 as VGI aB. VNI isolates presented 10 different sequence types (STs) and VGI isolates two. The most frequent STs among C. neoformans and C. gattii species complex isolates were ST23 (51%) and ST156 (90%), respectively. Comparison with molecular types and STs results obtained from 21 clinical isolates collected in Apulia showed that one C. neoformans VNI clinical isolate shared an identical sequence type of one arboreal isolate (ST61) and that one C. gattii VGI clinical isolate matched with the main ST (ST156) present in the environment. In addition, molecular type VNIV was found only among clinical isolates and was absent in the investigated environmental area. In conclusion, the present study identified which C. neoformans and C. gattii species complex genotypes are circulating in Apulia, defined their ecological niches and revealed the relationship with clinical cases. It represents a basal study for addressing future investigations and public health interventions in the region.


Fever in pediatric primary care: occurrence, management, and outcomes.
To describe the epidemiology, management, and outcomes of children with fever in pediatric primary care practice. A cohort of 20 585 children 3 to 36 months of age cared for in 11 pediatric offices of a health maintenance organization between 1991 and 1994. Using automated medical records we identified all office visits with temperatures >/=38 degrees C for a random sample of 5000 children, and analyzed diagnoses conferred, laboratory tests performed, and antibiotics prescribed. We also determined the frequency of in-person and telephone follow-up after initial visits for fever. Finally, we reviewed hospital claims data for the entire cohort of 20 585 to identify cases of meningitis, meningococcal sepsis, and death from infection. Among 3819 initial visits of an illness episode, 41% of children had no diagnosed bacterial or specific viral source. Of these, 13% with a temperature of 38 degrees C to 39 degrees C and 36% with a temperature of >/=39 degrees C received laboratory testing. Almost half (43%) received some documented follow-up care in the subsequent 7 days. Among the 26 970 child-years of observation in the entire cohort, 15 children (56 per 100 000 child-years) were treated for bacterial meningitis or meningococcal sepsis. Five had an office visit for fever in the week before hospitalization, but only 1 had documented fever >/=39 degrees C and received neither laboratory testing for occult bacteremia nor treatment with an antibiotic. The majority of febrile children in ambulatory settings were diagnosed with a bacterial infection and treated with an antibiotic. Of highly febrile children without a source, 36% received laboratory testing consistent with published expert recommendations, and short-term follow-up was common. Meningitis or death after an office visit for fever without a source was predictably rare. These data suggest that increased testing and/or treatment of febrile children beyond the rates observed here are unlikely to affect population rates of meningitis substantially.


[Association between neuropathy and peripheral vascular insufficiency in patients with diabetes mellitus type 2].
Diabetes mellitus (DM) can present complications of neuropathy and peripheral arterial disease with high risk for developing foot ulcers and consequent amputations. To identify the association between peripheral vascular disease, and neuropathy in type 2 Diabetes mellitus patients from the Hospital General de Zona No. 1 IMSS in Colima, Mexico. Cross-sectional study of 80 patients with diabetes mellitus evaluated by means of the Edinburgh Claudication Questionnaire, Michigan Neuropathy Screening Instrument, ankle-arm index, Motor Nerve Conduction Velocity and H-reflex. 51 women and 29 men were studied. Mean age was 53.9 +/- 9.6 years, mean diabetes mellitus progression was 8 +/- 6.6 years and mean glucose level was 283 +/- 110 mg/mL. Neuropathy presented in 65 patients (81.2%). Ankle/arm index revealed 19% of patients presented with moderate peripheral vascular insufficiency. Motor Nerve Conduction Velocity was abnormal in 40% of patients and H-reflex was absent in 70%. Grade 2 motor-sensitive polyneuropathy was found in 70-80% of patients and moderate peripheral vascular insufficiency in 19%. It can thus be inferred that the complication of diabetic neuropathy appears before that of peripheral vessel damage.


Transatrial access to the normal pericardial space for local cardiac therapy: preclinical safety testing with aspirin and pulmonary artery hypertension.
The reliability, rapidity, and safety of nonsurgical, transatrial pericardial access for local cardiac therapy have been demonstrated in healthy animals. Since many patients take aspirin or have increased right-sided pressures, we evaluated the procedure's safety under these conditions. Transatrial pericardial access was performed in anesthetized pigs following aspirin administration (162 mg p.o., n = 6) or during experimental pulmonary artery hypertension (n = 4 different animals) and required only 3 minutes following guide catheter positioning. Platelet aggregability testing with arachidonic acid confirmed aspirin effectiveness. Mean pericardial fluid hematocrit was 0.1 +/- 0.1% after 2 days of aspirin therapy and 1.9 +/- 1.1% at sacrifice 24 hours later (NS). Mean pericardial fluid hematocrit was 1.0 +/- 0.5% after 45 minutes of pulmonary artery hypertension and 4.3 +/- 0.8% at sacrifice 30 minutes later (NS). Histologic analysis in both groups revealed a small thrombus and localized inflammation at the site of puncture. Neither aspirin use nor pulmonary artery hypertension causes significant bleeding into the pericardial space following transatrial access and thus does not preclude this route for local cardiac drug delivery.


Changes in the lower Drava River water quality parameters over 24 years.
The goal of this study was to analyse 13 physico-chemical and microbiological parameters of the Drava River water at three sampling sites in the lower Drava region (eastern Croatia) over two distinct periods: the pre-war period between 1985 and 1992 and the post-war period between 1993 and 2008. Over both periods, most parameters kept within the tolerable water quality limits, while NO3-N, NH4-N and BOD5 were higher. The lower Drava showed slight organic pollution with high concentrations of dissolved oxygen. High levels of total coliforms and heterotrophic bacteria in the post-war period were only found downstream of the town of Osijek. Upstream of Osijek, the river showed a tendency for improvement.


Implementing a discharge assessment tool in palliative home care.
With an aging population and limited health care resources, reflection on end-of-life care is essential. While terminally ill cancer patients spend much of their last year in the home, the literature reveals that the majority of these patients would also prefer to die at home. Despite patients' and families' cited preference for home deaths, dying at home continues to be infrequent. In Edmonton's Capital Health Region (CHR) only 16% of cancer patients died at home in 1999. While many reasons for the low incidence of home death are cited, little data exists regarding discharges from the palliative home care program in the CHR. As such, it is difficult to assess where resources are needed in the community. The implementation of a discharge assessment tool for use in the Capital Health Palliative Home Care program may provide insight into potential correlates of home death. Not only providing information on individual patients, the inclusion of such data in the palliative home care database would allow for trends to be monitored over time.


GTW inhibits the Epithelial to Mesenchymal Transition of Epithelial Ovarian Cancer via ILK/AKT/GSK3β/Slug Signalling Pathway.
Background: Epithelial ovarian cancer (EOC) accounts for the most lethal of all gynaecological cancers which is attributed to metastasis, invasiveness and drug resistance. A crucial link has been found between epithelial-mesenchymal transition (EMT) and cancer metastasis and chemo-resistance. Previous studies have confirmed that one of the main components of tripterygium glycosides (GTW)-triptolide (TPL) has anticancer effects. Methods: The purpose of this study is to determine whether GTW could inhibit EMT in A2780/DPP cells in vitro and in vivo, and explore the underlying mechanism. Results: In vitro results showed that GTW inhibited cell proliferation, invasion and migration, and intensified the sensitivity of A2780/DDP cells to cisplatin (DDP). GTW, especially GTW+DDP, significantly inhibited the expression of N-cadherin, integrin-linked kinase (ILK), phospho-protein kinase B/AKT (PKB/p-AKT), phospho-glycogen synthase kinase (p-GSK3β) and Slug, while it increased E-cadherin levels by inhibiting EMT via the ILK/AKT/GSK3β/Slug signalling pathway. Animal results indicated that GTW, especially GTW+DDP, significantly reduced tumour burden, prolonged the life span of mice, and down-regulated the levels of tumour markers CA125 and HE4 by regulating EMT through the ILK/AKT/GSK3β/Slug signalling pathway. Conclusion: Our results highlighted the significance of EMT in EOC metastasis, invasiveness and resistance to DDP and investigated the potential role of GTW as an adjuvant therapeutic agent in chemo-resistant EOC.


Medication problems occurring at hospital discharge among older adults with heart failure.
Medication reconciliation problems are common among older adults at hospital discharge and lead to adverse events. The purpose of this study was to examine the rates and types of medication reconciliation problems among older adults hospitalized for acute episodes of heart failure who were discharged home. This secondary analysis of data generated from a transitional care intervention included 198 hospital discharge medical records, representing 162 patients. A retrospective chart review comparing medication lists between hospital discharge summaries and patient discharge instructions was completed to identify medication reconciliation problems. Most hospital discharges (71.2%) had at least one type of reconciliation problem and frequently involved a high-risk medication (76.6%). Discrepancies were the most common problem (58.9%), followed by incomplete discharge summaries (52.5%) and partial patient discharge instructions (48.9%). More attention needs to be given to the quality of discharge instructions, and the problem of vague phrases (e.g., "take as directed") can be addressed by adding it to "do not use" lists to promote safer transitions in care.


Quantitative versus qualitative risk assessment of meat and its products: what is feasible for Sub-Saharan African countries?
Prevalent risks in meat value-chains of sub-Saharan African (SSA) countries are increasingly attributed to microbial rather than chemical hazards. Resource constraints and lack of capacity has limited the utilization of risk assessment tools in the instituting of food controls to mitigate the risks. The review sought to bring to light the focus of risk assessment studies in SSA while generating evidence of feasible options to further the contribution of this component in risk mitigation. The informal street vending sector emerges as a priority in the meat value chain with a vendor population that are unwilling to abandon it. Campylobacter and Staphylococcus aureus are prevalent risks that have bedeviled this sector. However, limited risk assessment studies with capacity to inform proper food controls for the sector have been done. Evidence in place indicate that the incorporation of qualitative aspects in quantitative approaches serve as less-costly and effective ways of generating risk estimates. Limitations of capacity and gaps in epidemiological data are also circumvented. Considering that the street-vending sector is robust and its dynamics of operation are not fully in the picture of policy actors; incorporation of a participatory approach that combines qualitative and quantitative aspects of risk assessment is highly recommended.


Influence of rotating-oscillating, sonic and ultrasonic action of power toothbrushes on abrasion of sound and eroded dentine.
This in vitro study aimed to evaluate the susceptibility of sound and eroded dentine to brushing abrasion performed by different rotating-oscillating, sonic and ultrasonic toothbrushes. Toothbrushing abrasion (20 cycles, each 30 s) was applied to bovine dentine samples (each subgroup n = 10) exhibiting both a demineralized (each cycle: 1% citric acid, pH: 2.3, 60 s; 30 min remineralization in artificial saliva) and a sound surface area. Toothbrushing was performed in an automatic brushing machine with the rotating-oscillating, sonic and ultrasonic toothbrushes either (a) activated, supplemented by 20 strokes/min of the brushing machine, (b) inactivated, supplemented by 20 strokes/min of the brushing machine or (c) inactivated, supplemented by 80 strokes/min of the brushing machine. A manual toothbrush was applied with 20, 80 or 100 linear strokes/min. Specimens of the control group were not brushed after erosion. After each cycle, the samples were stored in artificial saliva for 4 h. After 20 cycles, loss of sound and softened dentine was determined by profilometry. Mann-Whitney-Wilcoxon test and Bonferroni corrections were applied to the data (p < 0.05). For all groups, demineralized dentin areas exhibited significantly higher abrasion values than the respective sound dentine surfaces. However, mean dentine loss of both softened and sound dentine was higher after use of the rotating-oscillating, sonic and ultrasonic brushes with the activated regime [(a) eroded dentine: 9.94-16.45 microm; sound dentine: 3.31-5.47 microm] than after brushing with the inactivated regimes [(b) eroded dentine: 5.10-5.62 microm; sound dentine: 1.16-1.81 microm; (c) eroded dentin: 7.64-8.89 microm; sound dentine: 1.38-1.69 microm]. The results indicate that rotating-oscillating, sonic or ultrasonic action of the power toothbrushes leads to an increased loss of demineralized and sound dentine.


Activation of the interferon-inducible (2'-5') oligoadenylate synthetase by the Epstein-Barr virus RNA, EBER-1.
The 2'-5' oligoadenylate synthetases and the protein kinase PKR are both interferon-induced, double-stranded RNA-dependent proteins that play important roles in the antiviral effects of the interferons and in cellular growth control. Both enzymes are activated by natural or synthetic dsRNAs and by single-stranded RNAs that possess extensive secondary structure. This report describes the effects of the small Epstein-Barr virus-encoded RNA EBER-1 on the regulation of 2-5(A) synthetase activity. We demonstrate that EBER-1 RNA binds to and activates the human 40-kDa 2-5(A) synthetase in a dose-dependent manner. The efficiency of EBER-1 as an activator of 2-5(A) synthetase is approximately 25% of that of the synthetic double-stranded RNA poly(I)/poly(C), and poly(I)/poly(C) further stimulates enzyme activity even in the presence of a high concentration of EBER-1. Conversely, EBER-1 neither stimulates nor inhibits 2-5(A) synthetase that has been activated by a high concentration of poly(I)/poly(C). Competitive binding assays suggest that the relative affinity of the enzyme for poly(I)/poly(C) is considerably higher than that for EBER-1. Our data indicate that EBER-1, like VAI RNA of adenovirus, TAR RNA of HIV-1, and Rex-RE RNA of HTLV-1, is able to activate the 2-5(A) synthetases. The significance of why several viruses may activate the 2-5(A) synthetase/RNase L-mediated RNA degradation pathway is discussed.


The aliphatic chain of cholesterol modulates bilayer interleaflet coupling and domain registration.
Cholesterol is a necessary component and critical regulator of liquid-ordered membrane domains. However, the structural features that determine its unique physicochemical behaviors are not fully understood. In particular, very little is known about the specific functions of the terminal aliphatic chain of cholesterol, as previous studies have focused mainly on the rigid sterol ring structure and its hydroxyl head. In the current work, we used coarse-grained molecular dynamics simulations to investigate the effect of cholesterol aliphatic chain length on the dynamics and structure of coexisting lipid domains. We found that the aliphatic chain has no appreciable effect on phase separation per se, but it significantly affects the rate of cholesterol flip-flop and intermonolayer interaction. These effects are accompanied by changes in domain dynamics, lateral pressure, and interleaflet coupling. Our study provides useful insight into how biological sterols modulate communication between the outer and inner surfaces of the plasma membrane and, therefore, cellular signaling.


A study on the prevalence of gram-negative bacteria in bulk tank milk.
Bulk tank milk from 131 dairy herds in eastern South Dakota and western Minnesota were examined for coliforms and noncoliform bacteria. Coliforms were detected in 62.3% of bulk tank milk samples. Counts ranged from 0 to 4.7 log10 cfu/ml. The mean count was 3.4 log10 cfu/ml. Gram-negative noncoliform bacteria were observed in 76.3% of bulk tank milk. Counts ranged from 0 to 6.2 log10 cfu/ml. The mean count was 4.8 log10 cfu/ml. A total of 234 isolates from bulk tank milk were examined to species level; 205 isolates belonged to 28 species. Coliforms and gram-negative noncoliform bacteria accounted for 32.9 and 67.1% of the total isolates, respectively. Organisms such as Agrobacterium radiobacter, Bordetella spp., Comamonas testosteroni, Listonella damsela, Ochrobactrum anthropi, and Oligella urethralis were isolated from bulk tank milk in this study. These organisms have not been reported previously in bulk tank milk. A total of 116 isolates of Pseudomonas spp. were isolated from raw milk; 98 isolates belonged to nine Pseudomonas spp., and the remaining 18 isolates could not be identified to their species level. Pseudomonas was the most predominant genus. Pseudomonas fluorescens was the most predominant species isolated from bulk tank milk and accounted for 29.9% of all isolates examined. The results of the study suggest that counts of coliforms and noncoliform bacteria in bulk tank milk vary considerably. The isolates represent a wide variety of Gram-negative bacterial species. Examination of bulk tank milk for coliforms and noncoliform bacteria could provide an indication of current and potential problems associated with bacterial counts and milk quality.


Phytotoxicity and speciation of copper, zinc and lead during the aerobic composting of sewage sludge.
The content and speciation of heavy metals in composted sewage sludge is the main cause of negative impacts on environment and health of animal and human. An aerobic composting procedure was conducted to investigate the influences of some key parameters on phytotoxicity and speciation of Cu, Zn and Pb during sewage sludge composting. The pH value reached the optimal range for development of microorganisms, and content of organic matter (OM) and dissolved organic carbon (DOC) decreased with the composting age. The total amounts of Cu, Zn and Pb were much lower in the final compost. The results from sequential extraction procedure of heavy metals showed that composting process changed the distribution of five fractions of Cu, Zn and Pb, and reduced the total contents and sum percentages of four mobile fractions (exchangeable (EXCH), carbonate (CAR), reducible iron and manganese (FeMnOX), and organic matter bound (OMB)), indicating that the metal mobility and phytotoxicity decreased after aerobic composting. The seed germination and root growth of Pakchoi (Brassica Chinensis L.) were enhanced with composting age and reached the highest value at the end of compost. The decrease of OM and DOC was significantly correlated to changes of metal distribution and germination index (GI) of Pakchoi. Only for Cu in the compost, the GI could be predictable from the sum mobile metal fractions (EXCH+CAR+FeMnOX+OMB) (R=-0.814(*)). For Zn and Pb, R value was significantly increased by use of other components, such as pH, OM and DOC, which suggested that the transformation of heavy metal speciation and phytotoxicity of sewage sludge during an aerobic composting was rather strongly dependent on multiple components than a single element.


Systemic changes and adverse effects induced by retinopathy of prematurity screening.
To estimate the potential systemic events during and after retinopathy of prematurity (ROP) screening. A prospective and descriptive designed study was conducted to detect the physiologic and pathological changes 24h before, during, and 72h after ROP screening. Control blood pressure (BP), saturation, pulse rate, and body temperature were routinely taken at various time internals before and after screening. Adverse effects pertain to cardiovascular system, respiratory system, gastric system, urinary system and nervous system were retrospect 0-72h after ROP screening at a 24-hour interval. Totally 1254 prematurity babies receiving ROP screening during Jan. 1(st) 2013 to Dec. 31(th) 2013 were enrolled in our survey. Compared to control vital sign data taken before the examination, there was a fluctuation in the diastolic BP with the increased 3.03 mm Hg (P=0.04) after 3 doses of mydriatic drops. Immediately after the examination, there was a further 12.64 mm Hg (P<0.01) increase in systolic BP and a 7.24 mm Hg (P<0.01) in diastolic BP. The mean pulse rate during examination was 22.4 bpm (P<0.01) higher than the 133.3±9.0 bpm control level. The oxygen saturation shared an average drop of 5% (P<0.01) during screening. In prematurity with postconceptional age less than 31wk, the incidence of apnea (23.5%), necrotizing enterocolitis (NEC) (8.7%), gastric residual (25.4%) and upper digestive tract hemorrhage (6.4%) also demonstrated a significant rise (P<0.01). In our study sample, ROP screening was associated with NEC, gastric residual and upper digestive tract hemorrhage. These gastrointestinal side effects, along with breath activity pattern change and vital signs indicators fluctuation, may be results of additional stress responses.


[Cloning and sequence analysis of the gene encoding the second region of MSA1 from three Chinese isolates of Plasmodium falciparum].
Gene encoding the second region of merozoite surface antigen (MSA1-R2) of three Chinese isolates of Plasmodium falciparum from Hainan, Yunnan and Anhui were amplified by PCR, cloned into M13 and sequenced. Comparison among MSA1-R2 sequences from different isolates of P. falciparum shows that there is no difference among the three Chinese isolates. The sequence of MSA1-R2 of the Chinese isolates are highly homologous with that of WELLCOME from West Africa. The sequence flanking the upstream of the tandem repeats is exactly the same as that of MAD-20, but sequence downstream the repeats exhibit the characteristics of K1 allele, indicating that intragenic recombination of the two MSA1 allelic families exists in the Chinese isolates.


Solid-phase synthesis of a nucleopeptide from the linking site of adenovirus-2 nucleoprotein, -Ser(p5'CATCAT)-Gly-Asp-. Convergent versus stepwise strategy.
The synthesis of a nucleopeptide with the sequence -Ser(p5'CATCAT)-Gly-Asp- has been undertaken by either convergent or stepwise solid-phase strategies, both of which use base-labile permanent protecting groups. The coupling of phosphitylated protected peptides onto oligonucleotide-resins did not afford the desired nucleopeptide, which was nevertheless obtained after oligonucleotide elongation at the hydroxyl group of the resin-bound peptide and deprotection under mild basic conditions. A preliminary study on the stability of different nucleopeptides to bases is also reported.


[Effect of exopolysaccharide from Bifidobacterium bifidum on cell of gastric cancer and human telomerase reverse transcriptase].
To study the inhibition of human gastric cancer cell line BGC-823 by exopolysaccharide (B. EPS) extracted from Bifidobacterium bifidum and the effect on the activity of telomerase rate-limiting factor human telomerase reverse transcriptase (hTERT). In vitro human gastric cancer cell line BGC-823 were treated by three concentrations of B. EPS. The inhibition rate of gastric cancer cell line BGC-823, the morphology changes of cells and the apoptosis in the initial stage of cell was observed respectively by MTF, inverted fluorescent microscope and the Annexin V-FITC/PI flow cytometry. In addition, the effect of B. EPS on cell telomerase rate-limiting factor hTERT mRNA was tested by RT-PCR; the changes in the concentration of calcium ions inside the cytoplasm were detected by spectrofluorometer. B. EPS inhibited the growth of gastric cancer cell BGC-823 (P < 0.05), the inhibition rate increased and the concentration of B.EPS showed dose-time response relation. The expression of cell telomerase rate-limiting factor hTERT mRNA decrease after effected by B.EPS (P < 0.05), and showed dose-effect relation with B. EPS. The concentration of calcium ion in cytoplasm was higher than the control apparently (P < 0.05). The apoptosis mechanism of human gastric cancer cell line BGC-823 induced by B. EPS might be relevant with the changes of the hTERT mRNA expression and the calcium ions concentration in cytoplasm.


Direct Observation of Vesicle Transport on the Synaptic Ribbon Provides Evidence That Vesicles Are Mobilized and Prepared Rapidly for Release.
Synaptic ribbons are thought to provide vesicles for continuous release in some retinal nonspiking neurons, yet recent studies indicate that genetic removal of the ribbon has little effect on release kinetics. To investigate vesicle replenishment at synaptic ribbons, we used total internal reflection fluorescence microscopy to image synaptic vesicles and ribbons in retinal bipolar cells of goldfish (Carassius auratus) of both sexes. Analysis of vesicles released by trains of 30 ms depolarizations revealed that most releasable vesicles reside within 300 nm of the ribbon center. A single 30 ms step to 0 mV was sufficient to deplete the membrane-proximal vesicle pool, while triggering rapid stepwise movements of distal vesicles along the ribbon and toward the plasma membrane. Replenishment only becomes rate-limiting for recovery from paired-pulse depression for interstimulus intervals shorter than 250 ms. For longer interstimulus intervals, vesicle movement down the ribbon is fast enough to replenish released vesicles, but newly arrived vesicles are not release-ready. Notably, the rates of vesicle resupply and maturation of newcomers are among the fastest measured optically at any synapse. Lastly, our data show that the delay in vesicle departure increases and vesicle speed decreases with multiple stimuli. Our results support a role for ribbons in the supply of vesicles for release, provide direct measurements of vesicle movement down the ribbon, and suggest that multiple factors contribute to paired-pulse depression.SIGNIFICANCE STATEMENT Synaptic ribbons are macromolecular scaffolds that tether synaptic vesicles close to release sites in nonspiking neurons of the retina and cochlea. Because these neurons release neurotransmitter continuously, synaptic ribbons are assumed to act as platforms for supplying vesicles rapidly in the face of prolonged stimulation. Yet, ribbon synapses suffer from profound paired-pulse depression, which takes seconds to subside. We investigated the mechanistic origin of this phenomenon by directly imaging triggered vesicle movement and release at ribbon sites in retinal bipolar cells, and find that, although ribbon synapses deliver and prime vesicles faster than most conventional synapses, both vesicle absence and vesicle priming contribute to the long recovery from paired-pulse depression.


Granulocyte/macrophage colony-stimulating factor stimulates human polymorphonuclear leukocytes to produce interleukin-8 in vitro.
Interleukin-8 (IL-8) is a potent chemotactic factor for polymorphonuclear leukocytes (PMN). Here we examine whether PMN synthesize and release IL-8 in response to stimulation by selected inflammatory cytokines. PMN isolated from normal heparinized peripheral human blood were incubated in RPMI culture medium at 37 degrees C in 5% CO2, with and without granulocyte/macrophage colony-stimulating factor (GM-CSF). The culture supernatants were tested for chemotactic activity using a modified Boyden chamber. Immunoreactive IL-8 protein was measured by ELISA with a monoclonal antibody specific for IL-8. GM-CSF (0.01 to 50 ng/ml) stimulated PMN to produce chemotactic activity in a dose- and time-dependent manner. The amount of chemotactic activity reached maximal levels after 3 h of incubation with GM-CSF. Treatment of culture media supernatants with rabbit antiserum against IL-8 blocked the GM-CSF-induced chemotactic activity. IL-8 protein concentrations detected by ELISA closely paralleled the chemotactic bioactivity in both the dose-response and kinetic studies. Northern blot analysis of total RNA from PMN using a 30 mer oligonucleotide complementary to mRNA for IL-8 yielded a single 1.6-kb band. Its intensity increased 4-fold 2 h after treatment of PMN with GM-CSF. These data suggest that peripheral blood PMN can be stimulated by GM-CSF to synthesize and secrete bioactive IL-8. Since both IL-8 and GM-CSF accumulate in sites of acute inflammation, PMN may induce IL-8 gene expression in response to GM-CSF and thereby amplify the acute inflammatory response by recruiting additional PMN into inflammatory sites.


Taxonomic revision of Saffron-billed Sparrow Arremon flavirostris Swainson, 1838 (Aves: Passerellidae) with comments on its holotype and type locality.
The Saffron-billed Sparrow (Arremon flavirostris) complex occurs in the undergrowth of deciduous woodlands and forests from the Andes of Bolivia and northern Argentina to Paraguay and southern, mid-western and interior eastern Brazil. Currently four subspecies are recognized: A. f. flavirostris, A. f. polionotus, A. f. devillii and A. f. dorbignii. We review the taxonomy of this complex by analyzing coloration and morphometrics of a series of 234 skins, and by comparing 101 sound recordings. Our results suggest that under both the Phylogenetic and Biological Species Concept, three species should be recognized in this complex: A. flavirostris, A. polionotus and A. dorbignii. On the other hand, A. devillii should be considered a junior synonym of A. polionotus since these two have no constant differences in morphology and vocalization. These species are diagnosable by their coloration characters, but not by morphometrics. Vocalizations are useful in diagnosing A. flavirostris from A. dorbignii, but do not diagnose A. polionotus from the others. We show that part of the previous taxonomic confusion can be attributed to variation in back color of adult and immature A. polionotus. Finally, we comment on the recently located holotype of A. flavirostris, which was believed to be lost, and its type locality.


Hippocampal NR3C1 DNA methylation can mediate part of preconception paternal stress effects in rat offspring.
Many studies have been shown that maternal stress during pregnancy and in early life period influences offspring in the behavioral and molecular aspects in human and animal models. Recent research has indicated that the environmental condition of males before conception has effects on next generations. We evaluated whether preconception paternal stress (PPS) could influence on hippocampal glucocorticoid receptor gene (GR), (NR3C1) expression, corticosterone response and behavioral outcomes of their offspring. For this purpose, adult male rats were subjected to daily 10min session of forced swimming for 21 consecutive days. Then, two parental breeding groups were formed: stressed father (SF) and non-stressed father (NSF) or control group. 30-day-old pups were tested for anxiety-like behavior by using the elevated plus maze (EPM). Serum corticosterone level was also measured by ELISA. Hippocampal NR3C1 DNA methylation, gene and protein expression were respectively assayed by methylation sensitive restriction enzymes (Real Time PCR), Reverse Transcriptase PCR (RT-PCR) and Western-blotting in all groups. More anxiety-related behavior, serum corticosterone concentration, DNA methylation levels of NR3C1 and lower expression of this gene were significantly observed in paternally stressed pups compared to control pups. As well, molecular changes were more pronounced in male pups compared to female pups. Our results revealed that paternal stress prior to conception has a negative effect on molecular, hormonal and behavioral outcomes in their offspring.


[Dermatomyositis and pregnancy: a case in Gabon].
The purpose of this report is to describe a case of successful pregnancy involving a 30-year-old Afican woman presenting dermatomyositis, without use of immunosuppressive treatment. The child was delivered prematurely by caesarean section at 32 weeks of gestation.


Torpedo Maculopathy in a 6-Month-Old Infant: Early Clinical and Optical Coherence Tomography Findings.
A 6-month-old male infant presented for routine ophthalmologic examination. Indirect ophthalmoscopy revealed a flat, oval, hypopigmented lesion located in the temporal macula in the right eye with the tip pointing toward the fovea, which was compatible with torpedo maculopathy. Optical coherence tomography (OCT) was performed at the time of diagnosis. OCT scans of the lesion revealed slight retinal pigment epithelium hyperreflectivity. This case serves as the earliest OCT finding of the youngest patient diagnosed as having torpedo maculopathy in the literature. [J Pediatr Ophthalmol Strabismus. 2017;54:e54-e57.].


Interventions to ameliorate reductions in muscle quantity and function in hospitalised older adults: a systematic review towards acute sarcopenia treatment.
Assimilate evidence for interventions to ameliorate negative changes in physical performance, muscle strength and muscle quantity in hospitalised older adults. We searched for articles using MEDLINE, Embase, CINAHL and Cochrane library using terms for randomised controlled trials, older adults, hospitalisation and change in muscle quantity, strength or physical performance. Two independent reviewers extracted data and assessed risk of bias. We calculated standardised mean differences for changes in muscle function/quantity pre- and post-intervention. We identified 9,805 articles; 9,614 were excluded on title/abstract; 147 full texts were excluded. We included 44 studies including 4,522 participants; mean age 79.1. Twenty-seven studies (n = 3,417) involved physical activity interventions; a variety were trialled. Eleven studies involved nutritional interventions (n = 676). One trial involved testosterone (n = 39), two involved Growth Hormone (n = 53), one involved nandrolone (n = 29), and another involved erythropoietin (n = 141). Three studies (n = 206) tested Neuromuscular Electrical Stimulation. Evidence for effectiveness/efficacy was limited. Strongest evidence was for multi-component physical activity interventions. However, all studies exhibited at least some concerns for overall risk of bias, and considering inconsistencies of effect sizes across studies, certainty around true effect sizes is limited. There is currently insufficient evidence for effective interventions to ameliorate changes in muscle function/quantity in hospitalised older adults. Multiple interventions have been safely trialled in heterogeneous populations across different settings. Treatment may need to be stratified to individual need. Larger scale studies testing combinations of interventions are warranted. Research aimed at understanding pathophysiology of acute sarcopenia will enable careful risk stratification and targeted interventions.


Large scale production of vesicles by hollow fiber extrusion: a novel method for generating polymersome encapsulated hemoglobin dispersions.
Vesicles, which include both liposomes and polymersomes (polymer vesicles), are being developed as therapeutic drug carriers. In this study, we present a fully scalable low pressure extrusion methodology for preparing vesicles. Vesicles were generated by continuous extrusion through a 200 nm pore diameter hollow fiber (HF) membrane. The first half of this study describes a method for generating empty polymersomes composed of different molecular weight amphiphilic poly(butadiene-b-ethylene oxide) (PBD-b-PEO) diblock copolymers on a large scale (50-100 mL) using a HF membrane. Monodisperse empty polymersomes were formed with particle diameters slightly less than 200 nm, which were close to the rated 200 nm pore size of the HF membrane. The second half of this study describes the successful encapsulation of hemoglobin (Hb) inside the aqueous core of polymersomes using the HF extrusion methodology. We demonstrate that polymersome encapsulated hemoglobin (PEH) particles formed by this technique had similar oxygen affinity, cooperativity coefficient, and methemoglobin (metHb) level compared to PEH particles formed by the 1 mL volume small scale manual extrusion method. Most notably, Hb encapsulation inside the polymer vesicles formed by the HF extrusion method increased 2-fold compared to the manual extrusion method. This work is important, since it will enable facile scale-up of homogeneous vesicle dispersions that are typically required for preclinical and clinical studies as well as industrial use.


Molecular Dynamics Study of Conformational Changes of Tankyrase 2 Binding Subsites upon Ligand Binding.
The interactions between proteins and ligands are involved in various biological functions. While experimental structures provide key static structural information of ligand-unbound and ligand-bound proteins, dynamic information is often insufficient for understanding the detailed mechanism of protein-ligand binding. Here, we studied the conformational changes of the tankyrase 2 binding pocket upon ligand binding using molecular dynamics simulations of the ligand-unbound and ligand-bound proteins. The ligand-binding pocket has two subsites: the nicotinamide and adenosine subsite. Comparative analysis of these molecular dynamics trajectories revealed that the conformational change of the ligand-binding pocket was characterized by four distinct conformations of the ligand-binding pocket. Two of the four conformations were observed only in molecular dynamics simulations. We found that the pocket conformational change on ligand binding was based on the connection between the nicotinamide and adenosine subsites that are located adjacently in the pocket. From the analysis, we proposed the protein-ligand binding mechanism of tankyrase 2. Finally, we discussed the computational prediction of the ligand binding pose using the tankyrase 2 structures obtained from the molecular dynamics simulations.


Acute diaphragmatic shortening: in vitro mechanics and fatigue.
In acute hyperinflation, the occurrence of diaphragmatic shortening may alter the contractile characteristics and function of the diaphragm. The aim of this study was to investigate the effects of acute passive diaphragmatic shortening on in vitro mechanical properties and fatigability. Optimal diaphragmatic length (Lo) was defined as being that length at which peak twitch-tension occurred. Acute shortening (85% Lo, 70% Lo) altered the twitch characteristics. At shorter lengths, the time-to-peak tension and the half-relaxation time were significantly reduced (p less than 0.05). These alterations led to marked alterations in the shape of the force-frequency curve at shorter lengths and in the length-tension properties when assessed at different stimulation frequencies. When normalized with respect to maximal tension, a disproportionate decrease in the generated tension was observed at shorter lengths. Fatigability was assessed by repeatedly stimulating the diaphragmatic bundles and observing the drop in tension with respect to time. For a given fatigue regimen, i.e., same stimulation frequency, the shorter diaphragm (70% Lo) generated more absolute force at any given time period. When the initial tensions were matched at Lo and 70% Lo by increasing the stimulation frequency used to fatigue the shorter muscle, the acutely shortened diaphragm generated less absolute force following 60 s of the fatigue regimen. We conclude that alterations in the contractile characteristics of the diaphragm during acute passive shortening are such that a disproportionately greater excitability is required in order to reach a given submaximal tension as at Lo. This factor may partly account for increased diaphragmatic fatiguability in the acutely shortened state.


Fanconi's anemia. A family study with 20-year follow-up including associated breast pathology.
A brother and sister with Fanconi's anemia, having typical skeletal deformity and characteristic chromosomal breaks in their lymphocytes and who followed the typical clinical course, with progressive bone marrow insufficiency beginning late in the first decade, are described. The natural history of the disease before chemotherapy was available is contrasted with the response to intermittent courses of anabolic steroids during a continuous 20-year follow-up. The female patient developed a carcinoma of the breast at the age of 26, from which she died 5 years later. This neoplasm may reflect increased susceptibility of cells with proven chromosomal abnormality to the influence of carcinogens. Her brother required repeated surgery for painful, but benign, breast masses. The explanation for the latter lesion is unknown but may be related to endocrine disturbances occurring in patients with Fanconi's anemia.


Effect of surgeon experience on femoral component size selection during total knee arthroplasty.
Femoral component size selection during total knee arthroplasty should not vary from surgeon to surgeon for patients with the same bone size. This study explored if systematic variations in femoral component size selection exist. Thirteen surgeons' choices of femoral component size (Duracon, n = 1388; Triathlon, n = 740) were analyzed using a generalized linear model with femoral component size as the dependent variable and surgeon identification, years in practice, and adult reconstruction fellowship training as the independent variables. The model adjusted for differences in bone size. It was found that more experienced surgeons implant larger femoral components. New instruments and training protocols may be necessary to adjust for surgeon experience.


[Plasma erythropoietin levels of kidney transplant patients in the early period after transplantation].
Plasma erythropoietin (EPO) levels were assessed in 51 uraemic patients immediately after kidney transplantations and in 16 healthy subjects. Before transplantation EPO levels were significantly higher than in normals. In patients with acute renal failure of the transplanted kidney, a significant increase of plasma EPO level was noticed. Such an increase of plasma EPO was absent in patients with a normally functioning kidney transplant. In these last patients normalization of plasma EPO was found during the first month after transplantation. No significant correlation was found between plasma EPO level and the haematocrit value in kidney transplant patients. From results obtained in this study it seems, that factors other than EPO are also involved in the pathogenesis of anaemia in patients at the early phase after kidney transplantation.


A Calcium-Deficient Diet in Rat Dams during Gestation Decreases HOMA-β% in 3 Generations of Offspring.
Prenatal malnutrition can affect the phenotype of offspring by altering epigenetic regulation. Calcium (Ca) plays an important role in the pathogenesis of insulin resistance syndrome. We hypothesized that a Ca-deficient diet during pregnancy would alter insulin resistance and secretion in more than 1 generation of offspring. Female Wistar rats consumed either a Ca-deficient or a control diet ad libitum from 3 weeks before conception to 21 days after parturition and were mated with control males. Randomly selected F1 and F2 females were mated with males of each generation on postnatal day 70. The F1 and F2 dams were fed a control diet ad libitum during pregnancy and lactation. All offspring were fed a control diet starting at the time of weaning and were sacrificed on day 180. HOMA-β% decreased in F1 through F3, and levels in F2 and F3 males and females were significantly lower than in controls. The mean levels of insulin and HOMA-IR were higher in F1 males but lower in F3 males than in control males. The HOMA-IR did not differ between any of the female offspring and controls. Maternal Ca restriction during pregnancy and/or lactation influences insulin secretion in 3 generations of offspring.


Linkage studies of Friedreich ataxia by means of blood-group and protein markers.
Friedreich ataxia (FA) is an autosomal recessive, neuro-degenerative disorder in which the pathogenetic mechanism remains unidentified despite extensive biochemical studies. Genetic-linkage studies provide an alternative approach to determining the basic defect. Linkage analysis between FA and 36 polymorphic-blood-group and protein markers has been carried out on three separate patient populations--16 families from the inbred Acadian population of Louisiana, 21 French-Canadian families from Quebec, and nine apparently unrelated British families--in an attempt to determine the chromosomal location of the disease mutation. Neither evidence of linkage to any of the markers investigated nor heterogeneity among the populations was found for any of the comparisons. The negative lod scores exclude the locus for FA from greater than 20% of the genome.


Mutation theory of aging, assessed in transgenic mice and knockout mice.
A vital question in the mutation theory of aging is whether mutation accumulates with age. If it does, what are the causes and consequences of the accumulation of mutation? The recent development of transgenic mice has made it possible to study mutation in different kinds of tissues and at a molecular level. An application of these mice to the study of age-dependent alteration has revealed that mutation does accumulate in the aging process. Studies have also revealed several important characteristics of mutation associated with aging. (1) The rate of age-dependent increase of mutant frequency varies among different types of tissue. (2) The rate is not in parallel with the cell proliferation rate of the tissue. (3) Some types of mutation are unique to specific tissues, suggesting the presence of a mechanism of mutation relative to tissue type. On the other hand, several kinds of knockout mice defective in DNA repair have been shown to exhibit tissue lesions and shortened life span. These characteristics provide a new view on the relationship between aging and the genome maintenance system. Here we review the current status of research on the correlation between mutation and aging undertaken by the use of transgenic and knockout mice.


Model for Short Term Movements in Stapelia variegata Linn.
Recently it was demonstrated that holographic interferometry could be used to quantify minute displacements of a mature Stapelia variegata Linn. The previously unobtainable measurements revealed that the short term response of the stapelia was regular enough so that the dynamics could be evaluated through the use of a highly damped mass, spring, dashpot model. Such a model is derived explicitly and the relationship between movements of the entire plant and the dynamics of individual cells or groups of cells is shown.


[Effect of Pitressin (8-arginine vasopressin) on the lower esophageal sphincter in dogs].
The effect of vasopressin on the lower esophageal sphincter pressure (LESP) is still poorly understood. The present study was designed to determine the effect of I.V. and intra-arterial administration of 8-arginine vasopressin (Pitressin) on the LESP in dogs. A total of 16 anesthetized mongrel dogs were given a continuous perfusion of Pitressin for 20 minutes. Group A (3 dogs): Infused at 2.75 mU/kg/min into the superior mesenteric artery. Group B (3 dogs): 2.75 mU/kg/min into a peripheral vein. Group C (5 dogs): 14 mU/kg/min into a peripheral vein (equivalent to therapeutic dose in humans). Group D (5 dogs): 28 mU/kg/min into a peripheral vein. Esophageal manometry was performed using a triple lumen polyvinyl tube assembly perfused with water at 0.4 ml/min. LESP was checked by the pull-through technique before, immediately and 30 minutes later after termination of the infusion. LESP was monitored at 3 locations during the infusion. No change in LESP was noted when Pitressin (2.75 mU/kg/min) was infused intra-arterial or I.V. I.V. infusion of 14 and 28 mU/kg/min Pitressin caused a significant sustained decrease in LESP (p less than 0.001). After infusion of 28 mU/kg/min, LESP failed to return to control levels in 30 minutes. The results suggest that intravenous administration of a high dose of Pitressin predisposes to gastroesophageal reflux during and shortly after infusion.


[Effects of case management using Resident Assessment Instrument-Home Care (RAI-HC) in home health services for older people].
To evaluate the effects of case management using Resident Assessment Instrument-Home Care (RAI-HC) in home health service for older people. All elders were assessed at baseline and 3 months later using RAI-HC. The change of function in the intervention group was compared with that of a conventional intervention group. Function was measured with Activities of Daily Living (ADL), Instrumental Activities of Daily Living (IADL), Cognitive Performance Scale (CPS), Depression Rating Scale (DRS), Pain and the number of Clinical Assessment Protocols (CAP). Among ninety two elders participated in the program, 59 were allocated to the case management group and 33 to the conventional group. The intervention, home health service by a nurse over a 3 month period, consisted of comprehensive assessment, case conference for care plan, direct care, education and referral, and outcome evaluation. The percent of elders whose function improved in the intervention group was greater than the conventional group for depression (odds ratio [OR]: 10.941, confidence interval [CI]: 2.338-51.206), IADL (OR: 4.423, CI: 1.151-16.999) and the number of CAP (OR: 11.443, CI: 3.805-34.410). Case management was effective for older people in the community. The effect might have resulted from individual, systematic intervention, however, standards of service including eligibility criteria for case management and collaboration of multi-disciplines is required for more effective home health service programs.


[Devices for the prevention of contrast-induced acute kidney injury in interventional cardiology].
Contrast-induced acute kidney injury (CI-AKI) consists in acute decline in renal function following iodinated contrast media exposure. It has a significant impact on long-term prognosis and mortality, development of chronic kidney disease and on the rate of hospitalization due to cardiovascular or renal events. Anamnestic and procedural aspects linked to higher risk of CI-AKI have been investigated and new devices have been designed in order to prevent it. This paper deals with CI-AKI in interventional cardiology, focusing on patients' risk stratification, contrast media agent selection and contrast media volume reduction strategies, in order to suggest a standardized algorithm.


Developing Multiagent E-Learning System-Based Machine Learning and Feature Selection Techniques.
Recently, artificial intelligence (AI) domain increased to contain finance, education, health, mining, and education. Artificial intelligence controls the performance of systems that use new technologies, especially in the education environment. The multiagent system (MAS) is considered an intelligent system to facilitate the e-learning process in the educational environment. MAS is used to make interaction easily among agents, which supports the use of feature selection. The feature selection methods are used to select the important and relevant features from the database that could help machine learning algorithms produce high performance. This paper aims to propose an effective and suitable system for multiagent-based machine learning algorithms and feature selection methods to enhance the e-learning process in the educational environment which predicts pass or fail results. The univariate and Extra Trees feature selection methods are used to select the essential attributes from the database. Five machine learning algorithms named Decision Tree (DT), Logistic Regression (LR), Random Forest (RF), Naive Bayes (NB), and K-nearest neighbors algorithm (KNN) are applied to all features and selected features. The results showed that the learning algorithm that has been measured by the Extra Trees method has achieved the highest performance depending on the evaluation of cross-validation and testing.


[Perinatal herpes infection. Clinical aspects--therapy--follow-up].
Herpes simplex virus may cause serious infections in neonates. In case of foetal infection in the first trimenon, abortions, stillbirth, prematurity, intrauterine growth retardation (not obligatory) and various malformations may result. Neonatal HSV infection is mostly the consequence of intrapartum virus acquisition during passage through the birth canal. The infection is mostly localised on the skin, at the eyes or the mouth or disseminated with or without HSV meningoencephalitis. It is difficult to establish the diagnosis, because neonatal herpes disease in the early stage is not easy to distinguish from other diseases in the newborn such as RDS, NEC or ICH. Antiviral therapy with aciclovir is the treatment of choice and seems to improve the outcome of neonatal herpes. Prognosis depends on early therapy. Treatment should be initiated in relation to clinical findings, because available diagnostic techniques do not always permit an early detection of the disease.


Rare species are valued big time.
It has recently been postulated that the value humans place on rarity could cause the extinction of rare species. This is because people are willing to pay the high costs of exploiting the last individuals. Many hobbies, such as ecotourism or the keeping of exotic pets may cause this effect--known as the anthropogenic Allee effect. However, the entire theory relies on the insofar undemonstrated assumption that people do value rarity. In order to quantify how much people valued rare species relative to common ones, we created online slideshows of photographs of either rare or common species on an Internet web site. The slideshow with photographs of rare species attracted more visitors, and visitors spent, in general, more time waiting to view it. We provide evidence that people value rare more than common species. As we did not target consumers of a specific market, this finding suggests that the anthropogenic Allee effect is likely be driven by a large part of the population. Given the substantial participation in our online experiment, we highlight the potential of the world wide web resource as a tool for conservation action. However, the evidence presented here that the general public value rare species, combined with the assumption that anthropogenic Allee effect is operating, implies that conservationists should be prudent when using rarity to promote conservation.


Oral health of high-cost patients and evaluation of oral health measures as predictors for high-cost patients in South Korea: a population-based cohort study.
To examine the oral health conditions and oral health behaviour of high-cost patients and evaluate oral health measures as predictors of future high-cost patients. A retrospective, population-based cohort study using administrative healthcare records. The National Health Insurance Service (NHIS) medical check-up database (a.k.a. NHIS-national health screening cohort database) in South Korea. 131 549 individuals who received biennial health check-ups including dental check-ups in 2011 or 2012, aged 49-88. Current and subsequent year high-cost patient status. High-cost patients, on average, incur higher dental costs, suffer more from periodontal disease, brush their teeth less and use secondary oral hygiene products less. Some of the self-reported oral health behaviours and oral symptom variables show statistically significant associations with subsequent year high-cost patient indicators, even after adjusting for demographic, socioeconomic, medical conditions, and prior healthcare cost and utilisation. We demonstrate that oral health measures are associated with an increased risk of becoming a high-cost patient.


Fructose 2,6-bisphosphate, carbohydrate partitioning, and crassulacean Acid metabolism.
Fructose 2,6-bisphosphate (F 2,6-P(2)) was detected in the CAM species, Ananas comosus and Bryophyllum tubiflorum, and in C(3)- and CAM-Mesembryanthemum crystallinum. In both Mesembryanthemum tissues, F 2,6-P(2) was located outside the chloroplast. The levels of F 2,6-P(2), malate, starch, or soluble sugars were measured during various periods during the day-night cycle in the leaves of Ananas, a species which stores carbohydrate in an extrachloroplastic compartment, and in Bryophyllum, a species which stores carbon as starch in the chloroplast. In both species, the levels of F 2,6-P(2) were correlated with the stages of the day-night CAM cycle. Immediately following the dark-light transition the F 2,6-P(2) levels exhibited a rapid transient increase followed by a decrease. F 2,6-P(2) reached a daily minimum soon after the onset of deacidification and remained low until the malic acid pools approached their daily minima; the levels of F 2,6-P(2) then began a slow increase which accelerated during the period of afternoon CO(2) uptake. Immediately following the light-dark transition F 2,6-P(2) levels fluctuated. The levels were usually low after the fluctuations had ceased. The pools then increased as the rate of malate synthesis increased, remained at relatively constant high levels when the rates of malate synthesis were constant, and decreased as malate synthesis decreased towards the end of the dark period. The absolute levels of F 2,6-P(2) were always higher in Ananas than in Bryophyllum. The ratios of the activity of pyrophosphate fructose-6-phosphate l-phosphotransferase to cytoplasmic fructose 1,6-bisphosphatase and to phosphofructokinase were also far higher in Ananas than in Bryophyllum or in C(3)- or CAM-Mesembryanthemum.


Remote diagnosis in ophthalmology.
In cooperation with the C.H.U.-Lille (Eye Department) we set up an interregional and european project. We explain the possibilities and difficulties of remote diagnosis. The aim is to build up a network between different ophthalmological centers and so to give access to different centers of expertise to have a faster and more reliable diagnosis for the benefit of the patient.


A novel small peptide as an epidermal growth factor receptor targeting ligand for nanodelivery in vitro.
The epidermal growth factor receptor (EGFR) serves an important function in the proliferation of tumors in humans and is an effective target for the treatment of cancer. In this paper, we studied the targeting characteristics of small peptides (AEYLR, EYINQ, and PDYQQD) that were derived from three major autophosphorylation sites of the EGFR C-terminus domain in vitro. These small peptides were labeled with fluorescein isothiocyanate (FITC) and used the peptide LARLLT as a positive control, which bound to putative EGFR selected from a virtual peptide library by computer-aided design, and the independent peptide RALEL as a negative control. Analyses with flow cytometry and an internalization assay using NCI-H1299 and K562 with high EGFR and no EGFR expression, respectively, indicated that FITC-AEYLR had high EGFR targeting activity. Biotin-AEYLR that was specifically bound to human EGFR proteins demonstrated a high affinity for human non-small-cell lung tumors. We found that AEYLR peptide-conjugated, nanostructured lipid carriers enhanced specific cellular uptake in vitro during a process that was apparently mediated by tumor cells with high-expression EGFR. Analysis of the MTT assay indicated that the AEYLR peptide did not significantly stimulate or inhibit the growth activity of the cells. These findings suggest that, when mediated by EGFR, AEYLR may be a potentially safe and efficient delivery ligand for targeted chemotherapy, radiotherapy, and gene therapy.


[Changes of total RNA and mRNA differential expressions in leaves of Pinellia ternata under high temperature stress].
To study the total RNA and mRNA differential expression in leaves of Pinellia ternata under high temperature, provide more information of the molecular mechanism of the sprout tumble. The total RNA and mRNA differential expression in leaves of P. ternata at different stress time was analyzed. The results showed that the trend of total RNA content was divided into three descending stages and two ascending stages, the total RNA content was the highest at 0, 6 h, but it was the lowest at and 42 h, as well as when the sprout tumbled. The differential display showed that the polymorphism and type of bands of the sample at 6 h were similar to those at 0 h. But the bands numbers at other time were far less than those at 0, 6 h. And there were some different mRNA differential expression bands between the different samples. In the process of the sprout tumble caused by high temperature stress, the RNA and mRNA differential expression in leaves of P. ternata changed.


Purification of KorA protein from broad host range plasmid RK2: definition of a hierarchy of KorA operators.
The KorA protein of promiscuous plasmid RK2 is encoded in the central control operon, which coordinates expression of genes for replication, transfer and partitioning. KorA is known to repress transcription from seven promoters on the plasmid genome but at the trfA promoter, for the vegetative replication genes, it also causes derepression of trbAp, the first promoter for the operon whose genes are required primarily for mating pair formation prior to conjugative transfer. We have overproduced and purified KorA (101 amino acid residues). Crosslinking indicates that it exists largely as a dimer in solution. Western blotting with specific antibodies suggests that there are approximately 4000 monomers per cell in exponential phase and about 600 in stationary phase. Footprinting confirmed the expected location of the KorA operator, and indicated that KorA and RNA polymerase can bind simultaneously in promoter regions. Gel retardation experiments with DNA fragments carrying each of the seven KorA operators revealed that there is a hierarchy of binding affinities. Highest affinity (Kapp = 12 to 20 nM) occurs with operators containing the 12 bp inverted repeat GTTTAGCTAAAC (klaAp, korAp and trfAp), while lower affinities (Kapp = 136 to 272 nM) occur with less perfect repeats (klcA, kleA, kleC, kfrA). In addition, specific DNA sequences flanking the 12 bp are necessary for the characteristic type I KorA binding affinity. This hierarchy may be important in providing a graded response in expression of the operons controlled by KorA as its concentration varies, as for example on transition from exponential to stationary phase.


The Effects of Different Blood Sample Types on Quantitative Detection of Procalcitonin.
Procalcitonin (PCT) has been recommended and widely used for the prognosis, diagnosis, and monitoring of sepsis. Currently, a majority of PCT detection products are limited to using serum samples, which requires the tedious pre-treatment process, as well as a large sample volume for analysis. Hence, there is an increasing need to replace serum with plasma or whole blood samples. In this work, we evaluated the effects of different blood sample types on PCT quantitative detection by measuring PCT levels in clinically homogenous whole blood, plasma, and serum samples, in hope of extending the application of PCT detection in more sample types. Ninety patients from Tong Ren Hospital of Shanghai Jiao Tong University, School of Medicine with different PCT levels volunteered for this study. Clinically homogenous samples, including EDTA- K2 anticoagulant whole blood, centrifuged serum and procoagulant plasma, were collected and analyzed using i-Reader S automatic immunoanalyzer and its supporting reagent kits. Passing and Bablok regression analysis, Bland-Altman plotting, and Kappa test were used for consistency analysis and the determination of consistency intensity, respectively. Correlation analysis showed that PCT concentrations measured from EDTA-K2 anticoagulated plasma samples had a good linear regression relationship with PCT from serum samples, with a slope of 0.8741, r = 0.958, p < 0.05. A similar correlation was observed between whole blood and serum, with a slope of 0.9234, r = 0.965, p < 0.05. A good correlation was found from the quantitative results of different sample types obtained from the same patient. In detail, PCT levels in EDTA-K2 anticoagulant whole blood and plasma are well correlated with that in the serum (r = 0.831, p < 0.05; r = 0.814, p < 0.05). There was no significant difference among different sample types (p > 0.05). Variation in PCT quantification induced by different sample types has no statistical influence on positive/negative decision (p > 0.05). Bland-Altman analysis for assessing PCT concentration agreement showed there was no outlier ratio between whole blood and plasma within the range of the detection system, as well as no outlier between serum and plasma. Kappa coefficient of PCT concentration between serum and homologous EDTA-K2 anticoagulated plasma was 0.8942 (p < 0.001), and for serum and homologous whole blood it was 0.6954 (p < 0.001). We concluded that quantitative PCT detection can be conducted in different sample types with good correlation and consistency, which means that it is feasible to replace serum samples with whole blood and/or plasma samples for PCT detection in clinical use. These findings reduce the sample volume and turnover time of PCT detection in clinical labs, greatly improving the process of PCT detection and promoting the application of PCT as an important inflammatory biomarker for disease diagnosis.


Assessing the validity of a computer-generated cognitive screening instrument for patients with multiple sclerosis.
Neuropsychological testing requires considerable time, expense, and expertise to administer. These factors can limit patient access. Computerized cognitive testing has been proposed as an alternative. The objective of this paper is to validate a brief, simple-to-use computer-generated cognitive assessment screening battery for multiple sclerosis (MS) patients that has minimal motor involvement. A sample of 96 MS patients and 98 healthy controls completed a computer-generated battery that included the Stroop, Symbol Digit Modalities Test (C-SDMT), a two- and four-second visual analog of the Paced Auditory Serial Addition Test (PVSAT-2, PVSAT-4), and simple and choice reaction time tests. The Minimal Assessment of Cognitive Function in MS was used to define cognitive impairment in the MS sample. Each newly developed test successfully distinguished between cognitively impaired patients and healthy controls as well as cognitively intact patients. A combination of three computerized tests (C-SDMT, PVSAT-2, PVSAT-4) with a mean administration time of 10 minutes had a sensitivity of 82.5% and specificity of 87.5% in detecting cognitive impairment. Good test-retest reliability was obtained for each measure. Good sensitivity and specificity, brevity, ease of administration, and a limited motor component highlight the feasibility of introducing this computer-generated cognitive screening instrument in a busy MS clinic.


Structural and functional analysis of peptidyl oligosaccharyl transferase inhibitors.
The peptide cyclo(hex-Amb(1)-Cys(2))-Thr(3)-Val(4)-Thr(5)-Nph(6)-NH2 was previously shown to be a slow, tight-binding inhibitor (Ki = 37 nM) of the yeast oligosaccharyl transferase (OT) [Hendrickson et al. (1996) J. Am. Chem. Soc. 118, 7636-7637]. This enzyme catalyzes the transfer of a carbohydrate moiety to an asparagine residue in the consensus sequence Asn-Xaa-Thr/Ser. Herein we present a study of the contribution of the residues in positions 1, 3, 4, and 5 to OT binding. Replacement of the threonine (residue 3) by valine or (S)-2-aminobutyric acid dramatically reduced the potency of the inhibitor while, surprisingly, the incorporation of an additional methylene into the side chain of residue 1 [(S)-2,3-diaminobutyric acid changed to ornithine] had very little effect. Variants with acidic, basic, hydrophilic/polar, and hydrophobic side chains in positions 4 and 5 were also evaluated for both yeast and porcine liver OT inhibition. This aspect of the study reveals that basic (lysine) and acidic (glutamic acid) residues are detrimental to the binding, whereas hydrophobic (valine) and polar/hydrophilic (threonine) residues are both well tolerated. The kinetic behavior of substrate analogs [cyclo(hex-Asn(1)-Cys(2))-Thr(3)-Xaa(4)-Yaa(5)-Nph-NH2] corresponding to inhibitors of weak, medium, and strong potency was also examined in order to provide insight into the nature of these inhibitors.


Intrathecal baclofen for generalized dystonia: a case report.
Dystonia is an abnormal movement characterized by sustained muscle contractions, frequently causing twisting and repetitive movements or abnormal postures. Primary generalized dystonia usually evolves to a debilitating condition, often unresponsive to oral pharmacologic regimens or physical rehabilitation. We present the case of a patient with idiopathic adult-onset generalized dystonia who was recalcitrant to oral therapies. This patient was treated with intrathecal baclofen therapy and responded dramatically with improved functional abilities, resolution of chronic pain, and an improved rating on the dystonia scale.


Prognostic Impact of a Nutritional Index Including Muscle Volume in Stage 4 Colorectal Cancer.
Nutritional status influences cancer prognosis. Measurement of the area of the psoas muscle on computed tomography is useful for evaluation of skeletal muscle mass and prediction of prognosis. The psoas muscle index (PMI) was determined in 42 patients undergoing surgery for stage 4 colorectal cancer. Patients were classified into high and low PMI groups using a cutoff of 5.5×10-4 cm2 m-2 Relationships of PMI with prognosis, chemotherapy period, and postoperative complications were examined. The 3-year overall survival rate was 24.0%. PMI was significantly associated with 3-year OS in univariate (high vs. low PMI: 43.0% vs. 12.9%, p=0.0415) and multivariate (p=0.0146) analyses. A low PMI was associated with a shorter period of chemotherapy. A reduction in PMI was a predictor of a poor prognosis. PMI status is related to the period of chemotherapy and is an independent prognostic factor in patients with stage 4 colorectal cancer.


Incidence, Clinical Features, and Outcomes of Langerhans Cell Histiocytosis in the United States.
Langerhans cell histiocytosis (LCH) is a disorder with highly diverse clinical manifestations. We explored if age, sex, race, organ system involved, and therapy approaches determine patient survival in the era of modern treatments. LCH patient data reported to the Surveillance, Epidemiology, and End Results (SEER) program in 2010-2016 (n=1282; age: 0 to 100 y) was analyzed. Age-specific LCH incidence flattening to a low level suggests an age cutoff for pediatric patients of 20 years. The overall survival probability is lower for patients 21 to 100 years old ( P <0.0001), irrespective of sex and race. The commonest sites involved in the 0- to 20-year age group were bone, skin, and bone marrow; this shifted to lung, bone, and skin as the commonest disease sites in patients 21 to 100 years of age. The treatments applied differed between age groups, as younger versus older patients were more likely to receive chemotherapy-based treatment (48.4% vs. 17%; P <0.0001). There also was a trend toward nonwhite versus white patients being less likely to receive chemotherapy-based treatment (31.7% vs. 38.2%; P =0.067). Whereas there are treatment disparities related to LCH patient age and perhaps race, patient age is the strongest predictor of survival, with patients 21 to 100 years of age with lung, lymph node, skin, and bone marrow disease having the worst outcomes ( P <0.0001).


[Relations between parameters of lipid metabolism and hemostasis in vascular diseases].
In 98 patients with arterial insufficiency of arteriosclerotic and diabetic genesis correlation analyses were carried out between total cholesterol, HDL cholesterol, triglycerides, creatinine, blood pressure, platelet counts, platelet function and antithrombin III. Besides the known relations between the parameters of lipid metabolism and blood pressure, correlations were found and analysed between antithrombin III, platelet function, renal function and between platelet counts and HDL cholesterol. The importance of the findings for the diagnosis of vascular insufficiency and the relation to normal values are discussed.


Anchoring screening of defects interaction in a nematic liquid crystal.
The relaxation dynamic of a dipole of +1/2 and -1/2 parallel disclination lines in a confined geometry is measured. The confinement and the planar anchoring conditions force the disclinations to be normal to the glass plates. In a first asymptotic regime, the direct elastic interaction between disclination is completely screened out by the anchoring energy. In a second regime, corresponding to the final annihilation steps, the dynamic follows the square-root law predicted by de Gennes for two isolated and parallel disclinations. The annihilation dynamic, in the asymptotic regime, is in good agreement with an elastic model based on an electrostatic analogy.


Frontal Lobe Hemodynamic Responses to Painful Stimulation: A Potential Brain Marker of Nociception.
The purpose of this study was to use functional near-infrared spectroscopy (fNIRS) to examine patterns of both activation and deactivation that occur in the frontal lobe in response to noxious stimuli. The frontal lobe was selected because it has been shown to be activated by noxious stimuli in functional magnetic resonance imaging studies. The brain region is located behind the forehead which is devoid of hair, providing a relative ease of placement for fNIRS probes on this area of the head. Based on functional magnetic resonance imaging studies showing blood-oxygenation-level dependent changes in the frontal lobes, we evaluated functional near-infrared spectroscopy measures in response to two levels of electrical pain in awake, healthy human subjects (n = 10; male = 10). Each subject underwent two recording sessions separated by a 30-minute resting period. Data collected from 7 subjects were analyzed, containing a total of 38/36 low/high intensity pain stimuli for the first recording session and 27/31 pain stimuli for the second session. Our results show that there is a robust and significant deactivation in sections of the frontal cortices. Further development and definition of the specificity and sensitivity of the approach may provide an objective measure of nociceptive activity in the brain that can be easily applied in the surgical setting.


Exploring the Impacts of Conditioning on Proton Exchange Membrane Electrolyzers by In Situ Visualization and Electrochemistry Characterization.
For a proton exchange membrane electrolyzer cell (PEMEC), conditioning is an essential process to enhance its performance, reproducibility, and economic efficiency. To get more insights into conditioning, a PEMEC with Ir-coated gas diffusion electrode (IrGDE) was investigated by electrochemistry and in situ visualization characterization techniques. The changes of polarization curves, electrochemical impedance spectra (EIS), and bubble dynamics before and after conditioning are analyzed. The polarization curves show that the cell efficiency increased by 9.15% at 0.4 A/cm2, and the EIS and Tafel slope results indicate that both the ohmic and activation overpotential losses decrease after conditioning. The visualization of bubble formation unveils that the number of bubble sites increased greatly from 14 to 29 per pore after conditioning, at the same voltage of 1.6 V. Under the same current density of 0.2 A/cm2; the average bubble detachment size decreased obviously from 35 to 25 μm. The electrochemistry and visualization characterization results jointly unveiled the increase of reaction sites and the surface oxidation on the IrGDE during conditioning, which provides more insights into the conditioning and benefits for the future GDE design and optimization.


Asymmetric synthesis of 2-alkenyl-1-cyclopentanols via tin-lithium exchange and intramolecular cycloalkylation.
[reaction: see text] We report a method for the synthesis of chiral cyclopentanes using tin-lithium exchange and cycloalkylation reactions. The sec-butyllithium/(-)-sparteine-mediated deprotonation of an alkyl carbamate and subsequent substitution furnishes a highly enantioenriched stannane as a stable carbanion equivalent. It was transformed into suitable cyclization precursors, which underwent tin-lithium exchange and stereoselective cycloalkylation when reacted with n-butyllithium, giving highly enantioenriched cyclopentanes in very good yields. A kinetic resolution was observed with a higher substituted stannane.


Chemical synthesis and characterization of branched oligodeoxyribonucleotides (bDNA) for use as signal amplifiers in nucleic acid quantification assays.
The divergent synthesis of bDNA structures is described. This new type of branched DNA contains one unique oligonucleotide, the primary sequence, covalently attached through a comb-like branching network to many identical copies of a different oligonucleotide, the secondary sequence. The bDNA comb molecules were assembled on a solid support using parameters optimized for bDNA synthesis. The chemistry was used to synthesize bDNA comb molecules containing 15 secondary sequences. The bDNA comb molecules were elaborated by enzymatic ligation into branched amplification multimers, large bDNA molecules (a total of 1068 nt) containing an average of 36 repeated DNA oligomer sequences, each capable of hybridizing specifically to an alkaline phosphatase-labeled oligonucleotide. The bDNA comb molecules were characterized by electrophoretic methods and by controlled cleavage at periodate-cleavable moieties incorporated during synthesis. The branched amplification multimers have been used as signal amplifiers in nucleic acid quantification assays for detection of viral infection. It is possible to detect as few as 50 molecules with bDNA technology.