Investigation of dry eye disease and analysis of the pathogenic factors in patients after cataract surgery.
To study dry eye and analyze pathogenic factors in patients after cataract surgery. A total of 37 patients (50 eyes) were studied by using a 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ25) and Ocular Surface Disease Index (OSDI) 3 days before and 1 week, 1 month, and 3 months after cataract surgery. Slit-lamp microscope examination, cornea and conjunctiva fluorescein staining, tear breakup time (BUT), Schirmer test I (STI), and impression cytology (IC) were carried out at the same time. Cytologic specimens for IC were obtained from the upper lid-covered region, explosive region, and lower lid-covered region of the globe conjunctiva. The average density of goblet cells on these 3 regions was measured, and the pathogenic factors of dry eye after cataract surgery were analyzed. After cataract surgery, the incidence of dry eye increased dramatically; NEI-VFQ25 and OSDI indicated that most patients developed this symptom after surgery. The lacrimal river line became narrow, and BUT and STI decreased in patients after cataract surgery. IC suggested the presence of serious squamous metaplasia in the epithelial layer of the globe conjunctiva, especially the lower lid region. Dry eye can develop or deteriorate after cataract surgery if not treated in time. Misuse of eyedrops is one of the major pathogenic factors that causes dry eye after cataract surgery. Eyedrops should be carefully administered before and after cataract surgery to avoid or reduce the occurrence of dry eye postoperatively.


[Ferumoxide labeled Flk1+ CD31- CD34- human bone marrow mesenchymal stem cells and its in vivo tracing in the brains of Macaca Fascicularis].
To explore the method for labeling Flk1+ CD31- CD34- human bone marrow mesenchymal stem cells (hBMSCs) with ferumoxide-PLL and evaluate the feasibility of its tracing after transplantation into the brains of Macaca Fascicularis. The hBMSCs were incubated with ferumoxide-PLL. Trypan blue staining, Prussian blue staining, and transmission electron microscope were performed to show intracellular iron, marking efficiency, and the vigor of the labeled cells. After the hBMSCs were transplanted into the brains of cynomolgus monkeys by stereotaxis, magnetic resonance imaging (MRI) was performed to trace the cells in vivo. Cell survival and differentiation were studied with immunohistochemistry, Prussian blue staining, and HE staining. The marking efficiency of the ferumoxide-PLL was 96%. Iron particles were found intracytoplasmic of the hBMSCs by Prussian blue staining and transmission electron microscopy. The relaxation rates of labeled cells in MRI were 4.4 and 4.2 times higher than those of the unlabeled cells. Hypointensity area was found by MRI three weeks after transplantation. Many hBMSCs and new vessels were found in the transplantation zone by pathological and immunofluorescence methods. Ferumoxide-PLL can effectively label hBMSCs and thus increase its contrast in MRI results. The cells can survive in the brains of cynomolgus monkeys. The labeled hBMSCs can be traced in vivo by MRI.


PFI management called to account.
A recent report by the House of Commons Public Accounts Committee suggests that many public sector authorities are not doing a good job of managing operational PFI deals. The Committee's 36th Report in the 2007-2008 session also suggests many contract managers do not have sufficient commercial expertise, and that the management of contracts is frequently not sufficiently resourced. Health Estate Journal reports on these and other key conclusions.


Pulmonary non-caseating granuloma in Waldenström macroglobulinemia.
Lung involvement is rare in Waldenström macroglobulinemia (WM). We encountered a male patient with WM who complained of breathlessness. Chest X-ray revealed diffuse infiltrative shadow throughout the both lungs. Transbronchial biopsy showed infiltration of atypical plasmacytoid lymphocytes and non-caseating granuloma. We treated the patients with fludarabine phosphate, and both his symptom and X-ray findings were then improved. To our knowledge, this is the first case showing non-caseating granuloma with lung involvement of WM. We discuss a mechanism of non-caseating granuloma formation in this case.


Age of first appearance of simultaneous and successive negative contrast in infant rats.
Simultaneous (SimNC) and successive negative contrast (SNC), two paradoxical effects that are related to shifts in reward magnitude, were studied in rats from 11 to 17 days of age. Experiments 1 and 2 looked at the emergence of SimNC at 11, 14, and 17 days. At all of these ages, rats were able to discriminate between the large (milk suckling) and small (dry suckling) reward odor cues as measured by attachment latencies, but only the 14- and 17-day-olds showed SimNC. At none of the three ages was a discrimination formed to the differential odor cues in the alley in terms of runway speeds. Experiment 3 was designed as a further test of the absence of SimNC at 11 days. In this experiment, the pups were placed directly on the dam's ventrum to facilitate attachment. As in the earlier experiment, the 11-day-old pups discriminated between the odors signaling the two reward conditions but did not show the SimNC effect. In Experiment 4, SNC was measured in pups 14 and 17 days of age. SNC was shown at 17 days but not at 14 days in the attachment latency measure and at neither age in the run measure. These four experiments extend our earlier findings that the paradoxical effects that emerge out of intermittent schedules of reward magnitude occur earlier than those associated with single abrupt shifts in reward magnitude.


Course evaluation and assessment: examples of a learner-centered approach.
Teaching in higher education increasingly requires greater accountability, the utilization of contemporary learner-focused teaching models, and transparent grading methods for nonstandardized learning products. This article describes learner-centered evaluation and assessment strategies and illustrates how these approaches emphasize learners' responsibility for their own learning, foster students' commitment to learning and provide useful information for continuous curriculum improvement. In addition, the article discusses the components of learner-centered assessment models including the course assessment and enhancement model, the Personal Action Plan, and the Gedanken Experiment. Further, a rubric is presented as a tool for systematic and transparent grading of learner-centered assessment products. The need for further validation of these strategies is being discussed.


The diversity and evolution of circadian clock proteins in fungi.
Circadian rhythms are endogenous cellular patterns that associate multiple physiological and molecular functions with time. The Neurospora circadian system contains at least three oscillators: the FRQ/WC-dependent circadian oscillator (FWO), whose core components are the FRQ, WC-1, WC-2, FRH, and FWD-1 proteins; the WC-dependent circadian oscillator (WC-FLO); and one or more FRQ/ WC-independent oscillators (FLO). Little is known about the distribution of homologs of the Neurospora clock proteins or about the molecular foundations of circadian rhythms across fungi. Here, we examined 64 diverse fungal proteomes for homologs of all five Neurospora clock proteins and retraced their evolutionary history. The FRH and FWD-1 proteins were likely present in the fungal ancestor. WC-1 and WC-2 homologs are absent from the early diverging chytrids and Microsporidia but are present in all other major clades. In contrast to the deep origins of these four clock proteins FRQ homologs are taxonomically restricted within Sordariomycetes, Leotiomycetes and Dothideomycetes. The large number of FRH and FWD-1 homologs identified and their lack of concordance with the fungal species phylogeny indicate that they likely underwent multiple rounds of duplications and losses. In contrast, the FRQ, WC-1 and WC-2 proteins exhibit relatively few duplications and losses. A notable exception is the 10 FRQ-like proteins in Fusarium oxysporum, which resulted from nine duplication events. Our results suggest that the machinery required for FWO oscillator function is taxonomically restricted within Ascomycetes. Although the WC proteins are widely distributed, the functional diversity of the few non-Neurospora circadian oscillators suggests that a WC-FLO oscillator is unlikely to fully explain the observed rhythms. The contrast between the diversity of circadian oscillators and the conservation of most of their machinery is likely best explained by considering the centrality of noncircadian functions in which RNA helicase (FRH), F-box (FWD-1), WC-1 and WC-2 (light-sensing) proteins participate in fungi and eukaryotes.


What shapes vaccine policy? The case of hepatitis B in the UK.
Comparison of hepatitis B vaccine policy with other cases in the past is complicated by the restricted modes of transmission of this disease, which affects relatively few people in the UK. Still, considerations of cost, fear of contamination, divisions of opinion within the medical profession, and regional dispersal of authority are all factors--analysed for other vaccines--which help to explain the limited UK central policy on hepatitis B immunization observed through the 1980s. An important issue, in previous debates on vaccine policies, has been the conflict between public health interests and the rights of individuals to eschew health interventions imposed by the state. It is argued here that this question fed into hepatitis B vaccine policy in an oblique manner, via policy on screening for hepatitis B in the 1970s; minimal screening mainly of selected groups of health workers was favoured, maximizing individual rights. Changes to hepatitis B vaccine policy can be traced, linked with international policy, pharmaceutical company pressure, advances in vaccine technology, and questions of legal liability. The most accurate predictor for vaccine policy appears to have been screening policy. Will this apply to AIDS, which is epidemiologically similar to hepatitis B?


In vivo accumulation of self-assembling dye Congo red in an area marked by specific immune complexes: possible relevance to chemotherapy.
Supramolecular micellar structures have been proposed as carriers in aim-oriented drug transportation to a target marked by specific immune complexes. In this study, the self-assembling dye Congo red was used as a model supramolecular carrier and its accumulation in the target was studied in vivo. The target was created in vivo as the local specific inflammation provoked by subcutaneous injection of antigen to the ear of a previously immunized rabbit. The color caused by accumulation of Congo red after its intravenous injection was registered by pictures of the ear with suitably filtered visible light shining through it to distinguish Congo red against the background color of hemoglobin. The results confirmed the expected accumulation and retention of Congo red in the inflammation area marked by deposits of specific immune complexes. The role of albumin and its possible interference with transportation of drugs through the blood by supramolecular carriers was also subjected to preliminary examination. The results revealed that albumin collaborates rather than interferes with drug transportation; this is another factor making the use of supramolecular carriers for aim-oriented chemotherapy highly promising.


Breast augmentation & lactation outcome: a case report.
This article contains two case reports that illustrate the difficulty two mothers experienced when they mechanically expressed their milk for their very preterm infants. Each of the mothers was enrolled in a separate research study and had previously undergone surgery for breast augmentation. Neither of the mothers was able to provide an adequate milk supply for her preterm infant. Preoperative counseling and informed consent for breast augmentation is vital if the mother desires to exclusively provide mother's milk for the infant.


Activation of mitochondrial STAT-3 and reduced mitochondria damage during hypothermia treatment for post-cardiac arrest myocardial dysfunction.
While therapeutic hypothermia improves the outcomes of individuals in cardiac arrest, the hemodynamic responses and mechanisms which underlie hypothermia-induced cardioprotection are not fully understood. Therefore, we investigated the mechanism by which induced hypothermia preserves cardiac function and protects against mitochondrial damage following cardiac arrest. Cardiac arrest was induced in adult male Wistar rats by asphyxiation for 8.5 min. Following resuscitation, the animals were randomly assigned to a hypothermia (32 °C) or normothermia (37 °C) group. Monitoring results showed that cardiac output at the fourth hour after resuscitation was significantly better in rats treated with hypothermia when compared to rats treated with normothermia (P < 0.01). Examinations by transmission electron microscopy showed that mitochondria in the left ventricle of rats in the hypothermia group were significantly less swollen compared to such mitochondria in the normothermia group (P < 0.001). Additionally, opening of mitochondrial permeability transition pores occurred less frequently in the hypothermic group. While complex I/III activity in the electron transport reaction was damaged after cardiac arrest and resuscitation, the degree of injury was ameliorated by hypothermia treatment (P < 0.05). The amount of STAT-3 phosphorylated at tyrosine 705 and its expression in mitochondria were significantly higher under hypothermia treatment compared to normothermia treatment. In vitro studies showed that inhibition STAT-3 activation abolished the ability of hypothermia to protect H9C2 cardiomyocytes against injury produced by simulated ischemia and reperfusion. Therapeutic hypothermia treatment can ameliorate cardiac dysfunction and help preserve both mitochondrial integrity and electron transport activity.


Landau-Zener transitions in a dissipative environment: numerically exact results.
We study Landau-Zener transitions in a dissipative environment by means of the numerically exact quasiadiabatic propagator path integral. It allows to cover the full range of the involved parameters. We discover a nonmonotonic dependence of the transition probability on the sweep velocity which is explained in terms of a simple phenomenological model. This feature, not captured by perturbative approaches, results from a nontrivial competition between relaxation and the external sweep.


Phase-specific protein expression in the dimorphic yeast Saccharomyces cerevisiae.
In oxygen-limited continuous culture, Saccharomyces cerevisiae formed pseudohyphae by unipolar budding. We developed a continuous cultivation sequence to discriminate phase-specific from metabolically regulated proteins during dimorphism. Computer-aided substractive analysis of 2D-PAGE protein patterns allowed the detection of proteins specifically expressed during yeast and pseudohyphal phases. Image analysis resolved 3 spots that were specific to the pseudohyphal phase and 2 spots that were specific to yeast phase. In addition to phase-specific proteins, important regulation of protein expression took place. A group of 9 proteins was highly over-expressed during the yeast phase when another group of 12 was underexpressed. This phenomenon was reversed during the pseudohyphal phase. These experiments showed that dimorphism in S. cerevisiae is associated with the expression of specific proteins and suggest that yeast phase-specific proteins maintain the yeast form or repress pseudohyphae formation.


Teenage pregnancy antenatal and perinatal morbidity: results from a tertiary centre in Greece.
We present the experience of a tertiary referral hospital in Greece, evaluating obstetric and perinatal outcomes among teenage and average maternal age (AMA) women. We retrospectively assessed all singleton pregnancies during a twelve-month period (January-December 2012). A total of 1,704 cases were reviewed and divided into two groups: one of AMA mothers (20-34 years old) (1,460 women) and the other of teenage mothers (12-19 years old) (244 women). We observed significantly higher incidence rates of preterm births (p < 0.001), preterm premature rupture of the membranes (p < 0.001), gestational hypertension (p < 0.001), preeclampsia (p = 0.043) and Apgar scores < 7 at 5 min (p = 0.015) among teenage mothers. Antenatal surveillance was decreased among teenage mothers (p < 0.001), while rates of anaemia were higher (p < 0.001). Teenage pregnancy is accompanied by significant antenatal and perinatal complications that need specific obstetrical attention. Obstetricians should be aware of these complications in order to ameliorate the antenatal outcome of childbearing teenagers.


Experimental Shwartzman phenomenon in the heart muscle.
Intravenous injection of E. coli culture caused a sudden death in rabbits which were injected Streptococcus culture into the myocardium 24 h before the experiment. Pretreatment of animals with Trasylol-R, before injection of E. coli culture, caused an increase of survival time. In isolated Langendorff perfused heart from myocardially Streptococcus culture injected animals, E. coli culture filtrate caused a transitory increase and then a continuous decrease in coronary perfusion pressure together with an increase in heart rate. These findings are shown to be prevented by previous addition of Trasylol to the perfusion medium. According to these results it is speculated that a Shwartzman-like phenomenon can also occur in the heart muscle. The possible role of the activation of tissue kallikrein system in the production of this phenomenon is discussed.


Review of Molecular Simulations of Methane Storage in Metal-Organic Frameworks.
Methane storage in porous materials is one of the hot issues because it can replace dangerous high-pressure compressed natural gas (CNG) tanks in natural gas vehicles. Among the diverse adsorbents, metal-organic frameworks (MOFs) are considered to be promising due to their extremely high surface areas and low crystal densities. Molecular simulation has been considered as an important tool for finding an appropriate MOF for methane storage. We review several important roles of molecular modeling for the studies of methane adsorption in MOFs.


Prostate-specific membrane antigen-directed nanoparticle targeting for extreme nearfield ablation of prostate cancer cells.
Almost all biological therapeutic interventions cannot overcome neoplastic heterogeneity. Physical ablation therapy is immune to tumor heterogeneity, but nearby tissue damage is the limiting factor in delivering lethal doses. Multi-walled carbon nanotubes offer a number of unique properties: chemical stability, photonic properties including efficient light absorption, thermal conductivity, and extensive surface area availability for covalent chemical ligation. When combined together with a targeting moiety such as an antibody or small molecule, one can deliver highly localized temperature increases and cause extensive cellular damage. We have functionalized multi-walled carbon nanotubes by conjugating an antibody against prostate-specific membrane antigen. In our in vitro studies using prostate-specific membrane antigen-positive LNCaP prostate cancer cells, we have effectively demonstrated cell ablation of >80% with a single 30-s exposure to a 2.7-W, 532-nm laser for the first time without bulk heating. We also confirmed the specificity and selectivity of prostate-specific membrane antigen targeting by assessing prostate-specific membrane antigen-null PC3 cell lines under the same conditions (<10% cell ablation). This suggests that we can achieve an extreme nearfield cell ablation effect, thus restricting potential tissue damage when transferred to in vivo clinical applications. Developing this new platform will introduce novel approaches toward current therapeutic modalities and will usher in a new age of effective cancer treatment squarely addressing tumoral heterogeneity.


Cost-effectiveness of population based BRCA testing with varying Ashkenazi Jewish ancestry.
Population-based BRCA1/BRCA2 testing has been found to be cost-effective compared with family history-based testing in Ashkenazi-Jewish women were >30 years old with 4 Ashkenazi-Jewish grandparents. However, individuals may have 1, 2, or 3 Ashkenazi-Jewish grandparents, and cost-effectiveness data are lacking at these lower BRCA prevalence estimates. We present an updated cost-effectiveness analysis of population BRCA1/BRCA2 testing for women with 1, 2, and 3 Ashkenazi-Jewish grandparents. Decision analysis model. Lifetime costs and effects of population and family history-based testing were compared with the use of a decision analysis model. 56% BRCA carriers are missed by family history criteria alone. Analyses were conducted for United Kingdom and United States populations. Model parameters were obtained from the Genetic Cancer Prediction through Population Screening trial and published literature. Model parameters and BRCA population prevalence for individuals with 3, 2, or 1 Ashkenazi-Jewish grandparent were adjusted for the relative frequency of BRCA mutations in the Ashkenazi-Jewish and general populations. Incremental cost-effectiveness ratios were calculated for all Ashkenazi-Jewish grandparent scenarios. Costs, along with outcomes, were discounted at 3.5%. The time horizon of the analysis is "life-time," and perspective is "payer." Probabilistic sensitivity analysis evaluated model uncertainty. Population testing for BRCA mutations is cost-saving in Ashkenazi-Jewish women with 2, 3, or 4 grandparents (22-33 days life-gained) in the United Kingdom and 1, 2, 3, or 4 grandparents (12-26 days life-gained) in the United States populations, respectively. It is also extremely cost-effective in women in the United Kingdom with just 1 Ashkenazi-Jewish grandparent with an incremental cost-effectiveness ratio of £863 per quality-adjusted life-years and 15 days life gained. Results show that population-testing remains cost-effective at the £20,000-30000 per quality-adjusted life-years and $100,000 per quality-adjusted life-years willingness-to-pay thresholds for all 4 Ashkenazi-Jewish grandparent scenarios, with ≥95% simulations found to be cost-effective on probabilistic sensitivity analysis. Population-testing remains cost-effective in the absence of reduction in breast cancer risk from oophorectomy and at lower risk-reducing mastectomy (13%) or risk-reducing salpingo-oophorectomy (20%) rates. Population testing for BRCA mutations with varying levels of Ashkenazi-Jewish ancestry is cost-effective in the United Kingdom and the United States. These results support population testing in Ashkenazi-Jewish women with 1-4 Ashkenazi-Jewish grandparent ancestry.


Novel flat-panel cone-beam CT compared to multi-detector CT for assessment of acute ischemic stroke: A prospective study.
Cone beam CT (CBCT) imaging assessment of acute ischemic stroke (AIS) patients with large-vessel occlusion (LVO) in the angiosuite may improve stroke workflow and decrease time to recanalization. In order for this workflow to gain widespread acceptance, current CBCT imaging needs further development to improve image quality. Our study aimed to compare the image quality of a new CBCT protocol performed directly in the angiosuite with imaging from multidetector CT as a gold standard. AIS patients with an LVO who were candidates for endovascular treatment were prospectively included in this study. Following conventional multidetector CT (MDCT), patients underwent unenhanced cone beam CT (XperCT, Philips) imaging in the angiosuite, using two different protocols: a standard 20.8 s XperCT and/or an improved 10.4 s XperCT protocol. Images were evaluated using both qualitative and quantitative methods. We included 65 patients in the study. Patients received CBCT imaging prior to endovascular treatment; 18 patients were assessed with a standard 20.8 s protocol scans and 47 with a newer 10.4 s scan. The quantitative analysis showed that the mean contrast-to-noise ratio (CNR) was significantly higher for the newer 10.4 s protocol compared with the 20.8 s protocol (2.08 +/- 0.64 vs. 1.15 +/- 0.27, p < 0.004) and the mean image noise was significantly lower for the 10.4 s XperCTs when compared with the 20.8 s XperCTs (6.30 +/- 1.34 vs. 7.82 +/- 2.03, p=<0.003). Qualitative analysis, including 6 measures of image quality, demonstrated that 74.1 % of the 10.4 s XperCT scans were ranked as 'Acceptable' for assessing parenchymal imaging in AIS patients(scoring 3-5 points on a 5-point Likert-scale), compared with 32.4 % of the standard 20.8 s XperCT and 100 % of the MDCT scans. Compared to the MDCT studies, 83 % of the 10.4 s XperCT scans were deemed sufficient image quality for a direct-to-angiosuite selection, compared to only 11 % for the standard 20.8 s scans. The largest image quality improvements included grey/white matter differentiation (59 % improvement), and reduction of image noise and artefacts (63 % & 50 % improvement, respectively). Continued advances in cone-beam CT allow marked improvements in image quality for the assessment of brain parenchyma, which supports a direct-to-angiosuite approach for AIS patients eligible for thrombectomy treatment.


Pharmacokinetics of mercaptopurine.
The anatomical distribution of mercaptopurine was investigated in rats at dose levels of 2.5 and 25 mg/kg iv. The plasma and tissues were analyzed by radioisotopic dilution and spectrofluorometric techniques. The tissue-plasma ratios were: liver-plasma, approximately 4.0; kidney-plasma, approximately 2.4; spleen-plasma, approximately 1.7; muscle-plasma, approximately 1.4; gut lumen-plasma, approximately 3; and bone marrow-plasma, approximately 0.35. Physiologically based pharmacokinetic models were developed to simulate concentrations of mercaptopurine in plasma, kidneys, liver, muscle, spleen, bone marrow, and gut lumen. The agreement between experimental and predicted plasma and tissue profiles was good. Human plasma levels of mercapto-purine were predicted and, when compared with clinical data, demonstrated reasonable agreement.


Perforated Meckel's diverticulum.
We report a patient with diffuse peritonitis due to perforation of Meckel's diverticulum. This patient was referred to the operating room and underwent bowel resection segment encompassing the area of the diverticulum and terminoterminal primary enteroanastomosis on two levels with good evolution. The diverticulum complications are often related to the presence of ectopic mucosa, specially the gastric and pancreatic type. Since preoperative diagnosis is difficult and infrequent, in most cases this anomaly is confirmed only during surgery. Surgical resection of the affected intestinal segment is the mainstay of treatment in both diverticula diagnosed incidentally, as the complicated by inflammation, bleeding, obstruction or perforation. We conclude that in cases of acute abdomen punctured, the diagnosis of Meckel's diverticulum should be considered.


Constitutive activation of STAT3 signaling regulates hTERT and promotes stem cell-like traits in human breast cancer cells.
Mounting clinical data suggest that high telomerase activity is tightly associated with cancer progression and poor outcomes. Constitutively activated STAT3 is found in ∼60% of human malignancies and shows a dismal prognosis. We previously reported that activated STAT3 promoted epithelial-mesenchymal transition (EMT) and cancer stem cell phenotype in human breast cancer. However, little is known how STAT3 is regulated in the cancer stem cell and by which mechanisms STAT3 contributes to poor prognosis in aggressive breast cancer. Here we demonstrate that STAT3 physically interacts with CD44 and NF-kB and activates the catalytic subunit of telomerase (hTERT) in human breast cancer stem cells. STAT3 plays a role as a signal transducing molecule between CD44 and NF-kB. In addition to functioning as a catalytic subunit of telomerase, hTERT has been reported to function as a transcription co-factor which drives EMT and cancer stem cell phenotype in human cancer. We observed that activated hTERT increases CD44 (+) subpopulation, whereas targeted knock-down of hTERT abolished cancer stem cell phenotype. Targeted STAT3 knock-down cells also down-regulated hTERT and decreased CD44 subpopulation. Finally, CD44 knock-down resulted in the abrogation of cancer stem cell phenotype and concurrent down-regulation of pSTAT3 and hTERT. Our study delineates the signaling pathway where STAT3 functions as a modulator for CD44 and hTERT, promoting a cancer stem cell phenotype. The constitutive activation of STAT3 signaling that leads to regulation of hTERT pathway may provide novel therapeutic targets for human breast cancer stem cells.


Nanoscale Three-Dimensional Network Structure of a Mesoporous Particle Unveiled via Adaptive Multidistance Coherent X-ray Tomography.
Mesoporous nanoparticles provide rich platforms to devise functional materials by customizing the three-dimensional (3D) structures of nanopores. With the pore network as a key tuning parameter, the noninvasive and quantitative characterization of these 3D structures is crucial for the rational design of functional materials. This has prompted researchers to develop versatile nanoprobes with a high penetration power to inspect various specimens sized a few micrometers at nanoscale 3D resolutions. Here, with adaptive phase retrievals on independent data sets with different sampling frequencies, we introduce multidistance coherent X-ray tomography as a noninvasive and quantitative nanoprobe to realize high-resolution 3D imaging of micrometer-sized specimens. The 3D density distribution of an entire mesoporous silica nanoparticle was obtained at 13 nm 3D resolution for quantitative physical and morphological analyses of its 3D pore structure. The morphological features of the whole 3D pore network and pore connectivity were examined to gain insight into the potential functions of the particles. The proposed multidistance tomographic imaging scheme with quantitative structural analyses is expected to advance studies of functional materials by facilitating their structure-based rational design.


Estrogen and Environmental Enrichment Differentially Affect Neurogenesis, Dendritic Spine Immunolabeling and Synaptogenesis in the Hippocampus of Young and Reproductively Senescent Female Rats.
Studies examining the ability of estrogen replacement therapy (ERT) to enhance memory in women, and in animal models, have not produced consistent results. However, studies examining the effects of activity and exposure to novel environments consistently find enhancement of memory. An animal model of reproductive aging was used to determine if estradiol (E2) replacement, activity, and/or exposure to an enriched environment could act synergistically to improve memory, and neural correlates of memory. Young (3 months) and reproductively senescent (12 months) female rats were ovariectomized and received either vehicle or E2 treatment. Rats were assigned to 1 of 3 exposures; control: rats remained in their cage; maze control: rats were put into a pen where they could move and explore; enriched maze: rats were put into a pen with various items to climb on or investigate. The amount of time rats were active in each environment was measured. On the third day of exposure, one of the items in the enriched environment was exchanged, and the amount of time animals spent investigating the new item was used as a measure of memory. E2 increased activity, immunostaining for proliferating cell nuclear antigen, and synaptic markers, synaptophysin and spinophilin, in the hippocampus of all animals. However, E2- and activity-induced changes in these markers were more pronounced in young rats. Only young rats displayed improved recognition in response to E2. Older rats may need an extended period of ERT or increased activity before the benefits on memory become apparent.


Imaging characteristic analysis of metastatic spine lesions from breast, prostate, lung, and renal cell carcinomas for surgical planning: Osteolytic versus osteoblastic.
Surgeons treating metastatic spine disease can use computed tomography (CT) imaging to determine whether lesions are osteolytic, osteoblastic, or mixed. This enables treatment that considers the structural integrity of the vertebral body (VB), which is impaired with lytic lesions but not blastic lesions. The authors analyzed CT imaging characteristics of spine metastasis from breast, lung, prostate, and renal cell carcinomas (RCCs) to determine the metastasis patterns of each of these common tumors. The authors identified patients with metastatic spine disease treated during a 3-year period. Variables studied included age, sex, and cancer type. Lesions from breast, lung, prostate, and RCC primary lesions were selected for imaging analysis. Sixty-six patients were identified: 17 had breast metastasis, 14 prostate, 18 lung, and 17 RCC. Breast cancer metastasis involved 33% of VBs with 56%, 20%, and 24% osteolytic, osteoblastic, and mixed, respectively. Prostate cancer metastasis involved 35% of VBs with 14%, 62%, and 24% osteolytic, osteoblastic, and mixed, respectively. Lung cancer metastasis involved 13% of VBs with 64%, 33%, and 3% osteolytic, osteoblastic, and mixed, respectively. RCC metastasis involved 11% of VBs with 91%, 7%, and 2% osteolytic, osteoblastic, and mixed lesions, respectively. To improve surgical planning, we advocate the use of CT prior to surgery to evaluate whether spine metastases are osteolytic or osteoblastic. In cases of osteolytic lesions, the concern is of segmental instability requiring reconstruction and the risk for screw pull out should instrumentation be considered. In cases of osteoblastic lesions, surgeons should consider debulking dense bone.


Reversion of somatic mutations of the respiratory syncytial virus-specific human monoclonal antibody Fab19 reveal a direct relationship between association rate and neutralizing potency.
The role of affinity in determining neutralizing potency of mAbs directed against viruses is not well understood. We investigated the kinetic, structural, and functional advantage conferred by individual naturally occurring somatic mutations in the Ab H chain V region of Fab19, a well-described neutralizing human mAb directed to respiratory syncytial virus. Comparison of the affinity-matured Ab Fab19 with recombinant Fab19 Abs that were variants containing reverted amino acids from the inferred unmutated ancestor sequence revealed the molecular basis for affinity maturation of this Ab. Enhanced binding was achieved through mutations in the third H chain CDR (HCDR3) that conferred a markedly faster on-rate and a desirable increase in antiviral neutralizing activity. In contrast, most somatic mutations in the HCDR1 and HCDR2 regions did not significantly enhance Ag binding or antiviral activity. We observed a direct relationship between the measured association rate (Kon) for F protein and antiviral activity. Modeling studies of the structure of the Ag-Ab complex suggested the HCDR3 loop interacts with the antigenic site A surface loop of the respiratory syncytial virus F protein, previously shown to contain the epitope for this Ab by experimentation. These studies define a direct relationship of affinity and neutralizing activity for a viral glycoprotein-specific human mAb.


Adrenal cancer in neurofibromatosis type 1: case report and DNA analysis.
Adrenal cortical carcinoma (ACC) has previously only been reported in eight patients with type 1 neurofibromatosis (NF1). There has not been any clear evidence of a causal association between NF1 gene mutations and adrenocortical malignancy development. We report the case of a 49-year-old female, with no family history of endocrinopathy, who was diagnosed with ACC on the background of NF1, due to a novel germline frame shift mutation (c.5452_5453delAT) in exon 37 of the NF1 gene. A left adrenal mass was detected by ultrasound and characterised by contrast computerised tomography (CT) scan. Biochemical tests showed mild hypercortisolism and androgen excess. A 24-h urinary steroid profile and (18)flouro deoxy glucose PET suggested ACC. An open adrenalectomy was performed and histology confirmed ACC. This is the first reported case with DNA analysis, which demonstrated the loss of heterozygosity (LOH) at the NF1 locus in the adrenal cancer, supporting the hypothesis of an involvement of the NF1 gene in the pathogenesis of ACC. LOH analysis of the tumour suggests that the loss of neurofibromin in the adrenal cells may lead to tumour formation. ACC is rare but should be considered in a patient with NF1 and adrenal mass when plasma metanephrines are normal.Urinary steroid metabolites and PET/CT are helpful in supporting evidence for ACC.The LOH at the NF1 region of the adrenal tumour supports the role of loss of neurofibromin in the development of ACC.


Allergen and protein content of latex gloves.
Proteins eluting from surgical gloves and other medical rubber products elicit immediate local and systemic hypersensitivity reactions in latex-allergic subjects but detailed knowledge about the amount and allergenic potential of these proteins is scanty. To protect latex-allergic people and to diminish the risk of sensitization, adequate methods are needed to measure and monitor the allergen content of surgical latex gloves. Extracts of six surgical and one household latex glove brand were studied. Bradford and Lowry methods were used for total protein measurements. Sera from 17 latex-allergic patients were used as a source of latex IgE antibodies. Allergen content of extracts was studied in vitro by immunoblot, crossed radioimmunoelectrophoresis and immunospot methods, and in vivo by skin prick testing in 35 latex-allergic patients. The total protein concentration of the glove extracts varied from 3 to 337 micrograms/g glove. The Bradford method gave lower values than the Lowry method. Immunoblotting showed allergenic rubber proteins in four of the seven glove brands. Ten proteins in two surgical and six proteins in one household glove brand bound latex IgE antibodies in a heterogeneous manner. The results from crossed radioimmunoelectrophoresis and immunospot assays were mostly in line with immunoblotting findings. Extracts from five of the seven glove brands elicited positive prick tests; in all five also the presence of allergens could be shown by in vitro tests. Prick test reactivity and total protein concentration were not directly correlated. In vitro assays showed considerable variation in the total protein and allergen contents of different latex glove brands. The amount of protein eluting from the gloves did not always correlate with their allergenicity in skin prick tests indicating that total protein measurement is not a sufficient method to monitor the allergenic properties of latex gloves.


Erectile dysfunction in hemodialysis patients with diabetes mellitus: association with age and hemoglobin A1c levels.
Erectile dysfunction (ED) is common in patients with diabetes mellitus (DM) as well as those undergoing hemodialysis (HD). The purpose of this study is to investigate the frequency and severity of ED in HD patients with DM and those without DM. In addition, we examined the relationship between erectile function and several risk factors, including presence of DM and hemoglobin A1c levels in HD patients. This study involved 180 patients on HD, including 66 HD patients with DM (DM-HD) and 114 patients without DM (non-DM-HD). We evaluated erectile function using an abridged five-item version of the international index of erectile function (IIEF-5). Logistic regression analysis was used to investigate the relationship between presence of ED and several risk factors. The total score of IIEF-5 in DM-HD patients (9.5 +/- 4.2) was significantly lower than in non-DM-HD patients (13.5 +/- 5.7). The prevalence of severe ED was 42.4% and 18.4% in DM-HD patients and non-DM-HD patients, respectively. Age, cardiovascular disease history, and DM were identified as independent risk factors for the presence of ED. Furthermore, age and elevated hemoglobin A1c levels were identified as independent risk factors for the presence of severe ED. DM-HD patients are more likely to have ED, and particularly severe forms of ED, than non-DM-HD patients. DM and elevated hemoglobin A1c levels were associated with the presence of ED or severe ED, respectively. Aging was identified as an independent factor in both ED and severe ED.


Pattern recognition cytometry for label-free cell classification by 2D light scattering measurements.
We develop a pattern recognition cytometric technique for label-free cell classification. Two dimensional (2D) light scattering patterns from single cells and cell aggregates are obtained with a static cytometer. Good performance of the cytometric setup is verified by comparing yeast cell experimental results with theoretical simulations. Adaptive boosting (AdaBoost) method (a machine learning algorithm) is adopted for the analysis of the 2D light scattering patterns. It is shown that aggregates of three yeast cells can be well differentiated from aggregates of four yeast cells by this pattern recognition cytometric technique. We demonstrate that the pattern recognition cytometry can perform label-free classification of normal cervical cells and HeLa cells with a high accuracy rate.


Rapid divergence of gene duplicates on the Drosophila melanogaster X chromosome.
The recent sequencing of several eukaryotic genomes has generated considerable interest in the study of gene duplication events. The classical model of duplicate gene evolution is that recurrent mutation ultimately results in one copy becoming a pseudogene, and only rarely will a beneficial new function evolve. Here, we study divergence between coding sequence duplications in Drosophila melanogaster as a function of the linkage relationship between paralogs. The mean K(a)/K(s) between all duplicates in the D. melanogaster genome is 0.2803, indicating that purifying selection is maintaining the structure of duplicate coding sequences. However, the mean K(a)/K(s) between duplicates that are both on the X chromosome is 0.4701, significantly higher than the genome average. Further, the distribution of K(a)/K(s) for these X-linked duplicates is significantly shifted toward higher values when compared with the distributions for paralogs in other linkage relationships. Two models of molecular evolution provide qualitative explanations of these observations-relaxation of selective pressure on the duplicate copies and, more likely, positive selection on recessive adaptations. We also show that there is an excess of X-linked duplicates with low K(s), suggesting a larger proportion of relatively young duplicates on the D. melanogaster X chromosome relative to autosomes.


Estimating nitrogen and phosphorus contents using model integrated in small agricultural watersheds.
The Agricultural Nonpoint Source Pollution Model (AGNPS) was applied to estimate the loads of nitrogen and phosphorus according to antecedent soil moisture conditions (AMC) using probable rainfall in a stream draining small agricultural watersheds. Calibration and verification of the model were performed using observed data collected from rainfall events in the Imgo watersheds during 1997-1998. Evaluation of model outputs was based on graphical displays contrasting observed and simulated values for each rainfall-runoff event, and standard statistics such as coefficient of efficiency. The coefficient of efficiency of peak flow, total N, and total P in the estimation were 0.97, 0.93, and 0.74, respectively. Probable rainfall of Imgo watersheds was computed for several return periods using the frequency analysis of Gumbel's extreme value distribution. As the probable flood increase, concentrations of total N and total P generally decrease. Loss of N and P was proportional to the preceding soil water content in the same probable rainfall. The excessive fertilization under AMC-III condition can cause relatively higher outflow of N and P from the soil. It can be concluded that surface runoff and sediment transport influence soil quality and the quality of water absorption and AGNPS can provide realistic estimates of nonpoint source nutrient yields.


Base composition of RNA obtained from motor neurons in amyotrophic lateral sclerosis.
The base composition of RNA obtained from the large motor neurons of the cervical and lumbar swelling was examined in amyotrophic lateral sclerosis (ALS) patients and a similar number of age-matched controls. Spinal cords were obtained at autopsy and immediately fixed in buffered formalin. The single cell technique of Edström was employed to extract, hydrolyze, and electrophoresis the RNA. The base composition obtained for the controls was 17.47% adenine, 28.88% guanine, 28.50% cytidylic acid, and 25.14% uridylic acid. The cervical intumescence revealed higher levels of uridylic acid than the lumbar, 27.23% in the cervical and 23.31% in the lumbar intumescence. The motor neuron cell bodies isolated from patients having had ALS revealed a lower percentage of adenine in both the cervical (13%) and lumbar (10%) intumescences. When the data for these areas were combined, the percentage of adenine was 15.52, compared to 17.47% in the controls (p less than 0.01). The A/U ratio was also significantly reduced in the ALS group. The composition of the remaining bases in ALS appeared to be similar to the controls. The significant change in adenine, coupled with the quantitative reduction in total neuronal RNA, suggests that a disorder of nucleic acid metabolism may relate to the pathogenesis of ALS.


C1-esterase inhibitor reverses functional consequences of superior mesenteric artery ischemia/reperfusion by limiting reperfusion injury and restoring microcirculatory perfusion.
Activated complement contributes significantly to reperfusion injury after ischemia. This study explores functional consequences of C1-esterase inhibitor (C1-INH) treatment after superior mesenteric artery occlusion (SMAO)/reperfusion using intravital microscopy. Thirty anesthetized, spontaneously breathing, male Sprague-Dawley rats underwent SMAO for 60 min followed by reperfusion (4 h). C1-esterase inhibitor (100 and 200 IU/kg body weight) or saline (0.9%) was given as a single bolus before reperfusion. Sham-operated animals (n = 10) without SMAO served as controls. Systemic hemodynamics were monitored continuously, arterial blood gases analyzed intermittently, and leukocyte/endothelial interactions in the mesenteric microcirculation quantified at intervals using intravital microscopy. Ileal lipid-binding protein (I-LBP) levels were determined from serum samples with an enzyme-linked immunosorbent assay at the end of the experiments. C1-esterase inhibitor restored microcirculatory perfusion to baseline levels in a dose-dependent manner and reduced adherent leukocytes after SMAO/reperfusion to similar levels in both C1-INH-treated groups during reperfusion. Furthermore, C1-INH treatment efficiently prevented metabolic acidosis, reduced the need for intravenous fluids to support blood pressure, and decreased I-LBP levels in a dose-dependent manner. Survival rates were 100% in controls and after 200 IU/kg C1-INH, 90% after 100 IU/kg C1-INH, and 30% in saline-treated animals. C1-esterase inhibitor bolus infusion efficiently blunted functional consequences of mesenteric ischemia/reperfusion with I-LBP, proving to be a valuable serum marker mirroring the effect of ischemia/reperfusion and treatment at the end of the experiments.


"The black and white of it": Barbara Grier editing and publishing women of color.
In the 1970s and 1980s, lesbian-feminist writing and publishing expressed new theoretical insights about race and envisioned new, intersectional identities. Using texts published and edited by Grier in The Ladder and subsequent Ladder anthologies published by Diana Press, archival documents from Diana Press, and the Grier-Naiad Press papers, this article explores Grier's editorial practices and compares Grier's work to other lesbian-feminist editors and publishers to illuminate different generational understandings of racial-ethnic and class formations within lesbianism and feminism and highlight some of the strategies that White publishers like Grier utilized to realize a vision of multicultural publishing.


Comprehensive structure-function characterization of DNMT3B and DNMT3A reveals distinctive de novo DNA methylation mechanisms.
Mammalian DNA methylation patterns are established by two de novo DNA methyltransferases, DNMT3A and DNMT3B, which exhibit both redundant and distinctive methylation activities. However, the related molecular basis remains undetermined. Through comprehensive structural, enzymology and cellular characterization of DNMT3A and DNMT3B, we here report a multi-layered substrate-recognition mechanism underpinning their divergent genomic methylation activities. A hydrogen bond in the catalytic loop of DNMT3B causes a lower CpG specificity than DNMT3A, while the interplay of target recognition domain and homodimeric interface fine-tunes the distinct target selection between the two enzymes, with Lysine 777 of DNMT3B acting as a unique sensor of the +1 flanking base. The divergent substrate preference between DNMT3A and DNMT3B provides an explanation for site-specific epigenomic alterations seen in ICF syndrome with DNMT3B mutations. Together, this study reveals distinctive substrate-readout mechanisms of the two DNMT3 enzymes, implicative of their differential roles during development and pathogenesis.


Signal Pathways and Intestinal Flora through Trimethylamine N-oxide in Alzheimer's Disease.
The current studies show signs of progress in treating Alzheimer's disease (AD) with the "brain-gut axis." Restoring intestinal flora balance can alleviate neurodegeneration in the central nervous system. However, due to the complex mechanisms involved in the brain-gut axis, the neuroprotective mechanism brought by intestinal flora has not been fully understood. Trimethylamine N-oxide (TMAO) is a microbiota-dependent metabolism production; TMAO has been proven to be a major risk factor for atherosclerosis, thrombosis, type II diabetes, and other diseases. Meanwhile, all the above diseases are associated with AD; thus, we speculate that TMAO and AD are also correlated. Microbiota, such as Firmicutes, Ruminococcaceae, Escherichia coli, Bifidobacterium, Akkermansia, etc., correlate with the production process of TMAO. High choline intake and insulin resistance have also been identified as contributors to TMAO synthesis. With the increasing TMAO in plasma, TMAO can enter the central nervous system, causing neuroinflammation and immune responses and damaging the blood-brain barrier. TMAO can increase the expression of Aβ and the hyperphosphorylation of tau protein, regulate the signal pathways of NLRP3/ASC/caspase1, SIRT1/p53/p21/Rb, PERK/eIF2α/ER-stress, SIRT3-SOD2-mtROS, TXNIP-NLPR3, and PERK/Akt/mTOR, and stimulate the inflammation, apoptosis, endoplasmic reticulum stress, and the ROS. In this mini-review, we have summarized the diseases induced by TMAO through clinical and signal pathways, and intestinal flora correlated with TMAO. Through the analysis of diseases and mechanisms involved in TMAO, we have concluded TMAO to be a potentially important pathological factor of AD.


pH and trace-elements content in raisin extract industrial-scale alcoholic fermentation.
The ability of all kinds of Greek raisins for the industrial-scale fermentation related to pH and trace-element contents is discussed. In the case of raisin extracts of pH 3.2 larger ethanol productivities, yields, and a continuous use of the same yeast culture at a level of 300 batches was obtained. Metals such as Co, Fe, Zn, Cu, Cd, and Pb in all kinds of raisins have been determined using atomic absorption spectroscopy. The raisin variety Trechumena contains the smallest amount of Cu, and the variety Psilla contains 7 times higher concentration than Trechumena. This is in agreement with the fact that Psilla is the worst kind of raisin and Trechumena the best for spirit production. This observation is related with experimental results obtained by alcoholic fermentation in a series of synthetic media containing sacharose and different concentrations of copper.


[Effect of high glucose on the expression of fibronectin and plasminogen activator inhibitor-1 in human peritoneal mesothelial cells].
To evaluate the effect of high glucose on the expression of fibronectin (FN) and plasminogen activator inhibitor-1 (PAI-1) in human peritoneal mesothelial cells (HPMC). The cultured HPMC were exposed to the culture medium containing different concentrations of glucose (1.5%, 2.5%, 4.25%) for 6, 12, 24, 48 hours, and normal culture medium was used as control. FN and PAI-1 in supernatant were detected by enzyme-linked immunoassay(ELISA). The glucose at 1. 5%, 2.5%, 4.25% resulted in a time- and concentration-dependent increase in FN expression in HPMC(P < 0.05). The glucose at 2.5%, 4.25% increased PAI-1 expression in HPMC (P < 0.05), and the effect was time- and concentration-dependent. PAI-1 expression was not affected by 1.5% glucose (P > 0.05). High glucose increases the expression of FN and PAI-1 in HPMC, thus playing a part in the progression of peritoneal fibrosis.


Financial strain and the health and well-being of college students during the COVID-19 pandemic.
Objective: This study examined the associations between COVID-19-related financial strain and the stress, mental health, physical health symptoms, and health behaviors of American university students. Participants: Online data were collected from 485 participants between May 2020 and March 2021. Participants were majority female and majority white. Methods: Participants reported on stress (COVID-19 health stress and work stress), mental health (depression, anxiety, loneliness, social support, and subjective well-being), physical health symptoms, and health behaviors (sleep latency, alcohol consumption, alcohol coping, other substance use, exercise, COVID-19 health behaviors). Results: Both Pearson's correlations and Bayesian correlation indicated more stress and worse mental health, health symptoms, and health behaviors for students who experienced more financial strain. Conclusion: Pandemic-related financial strain could have enduring negative effects for students, many of whom already experience financial challenges. This work highlights a need to allocate resources to promote college student health during and after the COVID-19 pandemic.


Estimation of unconjugated, conjugated, and "delta" bilirubin fractions in serum by use of two coated thin films.
We used two coated thin films to measure the concentrations of unconjugated, conjugated, and total bilirubin as well as bilirubin covalently bound to albumin ("delta" bilirubin) in more than 400 serum samples. We measured the unconjugated and conjugated species by determining their reflection densities at two wavelengths (400 and 460 nm) on a coating designed for the enhanced spectral measurement of bilirubin but which does not register the delta form. Total bilirubin was measured by use of a diazo-based thin film (Clin Chem 29: 37-41, 1983). We estimated the concentration of delta bilirubin by subtracting the sum of unconjugated and conjugated bilirubin from the concentration of total bilirubin. All measurements agree well with those by comparative methods, as shown by linear regression. Slopes ranged from 0.92 to 1.02, correlation coefficients from 0.935 and 0.998. Linear combinations of these values can also be used to compute other results; e.g., the sum of conjugated and delta bilirubin can be considered to be an estimate of "direct"-reacting bilirubin.


The Effect of Osmotherapy and Tight Control of Acidosis on Early Graft Function among Deceased-Donor Kidney Transplant Recipients: A Randomized Controlled Trial.
Reperfusion injury and the acid-base status of the transplant are important factors affecting post-transplantation graft function. We hypothesized that infusing hypertonic saline (HS) or tight control of acid-base status of the blood rushing through renal graft using sodium bicarbonate may have beneficial effects on early graft function. Candidates for deceased-donor kidney transplant were randomized into three groups. HS group (n=33) received 50 mL/kg normal saline (NS) titrated during operation plus 4 mL/kg of 5% HS just within graft reperfusion phase; bicarbonate group (n=37) was administered 60 mL/kg NS while their metabolic acidosis (base excess ≤5 mEq/L) was tightly corrected every 30 min with sodium bicarbonate; and a control group (n=36) that received 60 mL/kg normal saline while they were administered sodium bicarbonate only, if they encountered severe metabolic acidosis (base excess ≤15 mEq/L). The primary outcome was defined as early post-operative renal function evaluated based on serial serum creatinine levels. The study was registered in Iranian Registry of Clinical Trials (IRCT2013122815841N19). Post-operative early graft function improved significantly during the first 3 days in the intervention groups (p<0.05). However, that beneficial effect no longer remained at the same level after the day four. Timely administration of HS or tight control of metabolic acidosis with sodium bicarbonate infusion improve early renal function during renal transplant surgery.


Lack of cytosolic glutamine synthetase1;2 in vascular tissues of axillary buds causes severe reduction in their outgrowth and disorder of metabolic balance in rice seedlings.
The development and elongation of active tillers in rice was severely reduced by a lack of cytosolic glutamine synthetase1;2 (GS1;2), and, to a lesser extent, lack of NADH-glutamate synthase1 in knockout mutants. In situ hybridization using the basal part of wild-type seedlings clearly showed that expression of OsGS1;2 was detected in the phloem companion cells of the nodal vascular anastomoses and large vascular bundles of axillary buds. Accumulation of lignin, visualized using phloroglucin HCl, was also observed in these tissues. The lack of GS1;2 resulted in reduced accumulation of lignin. Re-introduction into the mutants of OsGS1;2 cDNA under the control of its own promoter successfully restored the outgrowth of tillers and lignin deposition to wild-type levels. Transcriptomic analysis using a 5 mm basal region of rice shoots showed that the GS1;2 mutants accumulated reduced amounts of mRNAs for carbon and nitrogen metabolism, including C1 unit transfer in lignin synthesis. Although a high content of strigolactone in rice roots is known to reduce active tiller number, the reduction of outgrowth of axillary buds observed in the GS1;2 mutants was independent of the level of strigolactone. Thus metabolic disorder caused by the lack of GS1;2 resulted in a severe reduction in the outgrowth of axillary buds and lignin deposition.


Expression of organic cation transporter 1 (OCT1): unique patterns of indirect regulation by nuclear receptors and hepatospecific gene regulation.
The organic cation transporter 1 (OCT1) is the dominant carrier of organic cationic drugs and some positively charged endogenous compounds into hepatocytes. OCT1 has unique expression pattern. It has the highest expression among drug transporters in normal human hepatocytes with large interindividual variability, but it has negligible expression in other tissues or their tumors. Nowadays, it is clear that the regulation of SLC22A1 gene encoding OCT1 transporter is rather complex and that transactivation with hepatocyte nuclear factor 4α (HNF4α) and CCAAT-enhancer-binding protein (C/EBPs) transcription factors as well as epigenetic regulation contribute to its unique hepatocyte-specific expression pattern. Unfortunately, species- and tissue-specific regulation of OCT1 and its orthologs as well as significant down-regulation in most immortalized cell lines hamper the study of SLC22A1 gene regulation. In the current review, we summarize our current understanding of human OCT1 transporter hepatic gene regulation and we propose potential post-transcriptional regulation by predicted miRNAs. We also discuss in detail recent findings on indirect regulation of the transporter via farnesoid X receptor (FXR), glucocorticoid receptor and pregnane X (PXR) receptor, which point out to potential novel mechanisms of xenobiotic-transporting and drug-metabolizing proteins regulation in the human liver as well as to potentially novel drug-drug interaction mechanisms. We also propose that comprehensive understanding of mechanisms of SLC22A1 gene regulation could direct research for other drug transporters and drug-metabolizing enzymes highly expressed in hepatocytes and controlled by HNF4α or other liver-enriched transcription factors.


The benefit of 3D laser scanning technology in the generation and calibration of FEM models for health assessment of concrete structures.
Terrestrial laser scanning technology (TLS) is a new technique for quickly getting three-dimensional information. In this paper we research the health assessment of concrete structures with a Finite Element Method (FEM) model based on TLS. The goal focuses on the benefits of 3D TLS in the generation and calibration of FEM models, in order to build a convenient, efficient and intelligent model which can be widely used for the detection and assessment of bridges, buildings, subways and other objects. After comparing the finite element simulation with surface-based measurement data from TLS, the FEM model is determined to be acceptable with an error of less than 5%. The benefit of TLS lies mainly in the possibility of a surface-based validation of results predicted by the FEM model.


Vasodilatory effect of nitroglycerin in Japanese subjects with different aldehyde dehydrogenase 2 (ALDH2) genotypes.
The functional genetic polymorphism of aldehyde dehydrogenase 2 (ALDH2) influences the enzymatic activities of its wild type (Glu504 encoded by ALDH2*1) and mutant type (Lys504 encoded by ALDH2*2) proteins. The enzymatic activities of mutant-type ALDH2 are limited compared with those of the wild type. ALDH2 has been suggested as a critical factor for nitroglycerin-mediated vasodilation by some human studies and in vitro studies. Currently, there is no research on direct observations of the vasodilatory effect of nitroglycerin sublingual tablets, which is the generally used dosage form. In the present study, the contribution of ALDH2 to the vasodilatory effect of nitroglycerin sublingual tablets was investigated among three genotype groups (ALDH2*1/*1, ALDH2*1/*2, and ALDH2*2/*2) in Japanese. The results by direct assessments of in vivo nitroglycerin-mediated dilation showed no apparent difference in vasodilation among all genotypes of ALDH2. Furthermore, to analyze the effect of other factors (age and flow-mediated dilation), multiple regression analysis and Pearson's correlation coefficient analysis were carried out. These analyses also indicated that the genotypes of ALDH2 were not related to the degree of vasodilation. These results suggest the existence of other predominant pathway(s) for nitroglycerin biotransformation, at least with regard to clinical nitroglycerin (e.g., a sublingual tablet) in Japanese subjects.


Field evaluation of formalin inactivated Kyasanur forest disease virus tissue culture vaccine in three districts of Karnataka state.
A formalin inactivated Kyasanur forest disease (KFD) virus tissue culture vaccine produced by the health department of the State Government of Karnataka at Shimoga was administered in Shimoga, Uttar Kannada and Chikmangalur districts during 1990-92 KFD epidemic seasons. The selection of places for vaccination was based on the prevalence of KFD activity in previous years; villages adjacent to KFD affected areas and the villages from which mortality in monkeys was reported. A total of 284 villages was covered under vaccination; 26850 individuals received one dose whereas, 61302 received two doses of vaccine. No untoward reaction was observed in any of the vaccinees. In the 72 KFD affected villages there were 14 patients among 9072 and 10 among 21083 vaccinees receiving one and two doses respectively, whereas 325 patients were reported among 37373 unvaccinated individuals during the same period. In 1990-91 the number of males patients was more than females whereas, in 1991-92 the ratio was reserved. On analysis indicated that the vaccine has a highly significant protective effect.


The product: All intravenous immunoglobulins are not equivalent.
The first intravenous formulation of intravenous immunoglobulin (IGIV) was introduced in the United States in the early 1980s. At that time, the only indication was for treatment of primary immunodeficiency. By the mid-1990s, IGIV was mainly used for indications approved by the United States Food and Drug Administration, but as new indications are found, use of IGIVs is increasing. In fact, today, IGIV is mostly used for off-label indications. The specific characteristics of individual IGIV products must be directly addressed in the manufacturing process, as clinical efficacy may be affected. In addition, the safety profile of the ideal IGIV should be maximized by ensuring inactivation of the widest spectrum of viruses and prions. Some IGIV products are more suitable than others for certain patients; the challenge is to understand the different characteristics among products and select the most appropriate IGIV product for each patient. Convenience factors must be considered, for both the health care provider and the patient, without jeopardizing the more important features of the IGIV, such as tolerability and safety.


Metabolic and hormonal side effects in children and adolescents treated with second-generation antipsychotics.
The aim of this study was to evaluate metabolic and hormonal side effects in children and adolescents after 6 months of treatment with 3 different second-generation antipsychotics (SGAs). 66 children and adolescents (44 male [66.7%], mean +/- SD age = 15.2 +/- 2.9 years) treated for 6 months with risperidone (N = 22), olanzapine (N = 20), or quetiapine (N = 24) composed the study sample. 34 patients (51.5%) suffered from schizophrenia or other psychosis (according to DSM-IV criteria). Patients were consecutively attending different programs from March 2005 to October 2006. Prior to enrollment in the study, patients were either antipsychotic-naive (37.9%, N = 25) or had been taking an antipsychotic drug for fewer than 30 days. Significant weight gain was defined as a > or = 0.5 increase in body mass index (BMI) z score (adjusted for age and gender) at 6 months. Based on recent criteria for pediatric populations, patients were considered "at risk for adverse health outcome" if they met at least 1 of the following criteria: (1) > or = 85th BMI percentile plus presence of 1 or more negative weight-related clinical outcomes, or (2) > or = 95th BMI percentile. After the 6 months, BMI z scores increased significantly in patients receiving olanzapine and risperidone. At the 6-month follow-up, 33 patients (50.0%) showed significant weight gain. The number of patients at risk for adverse health outcome increased from 11 (16.7%) to 25 (37.9%) (p = .018). The latter increase was significant only in the olanzapine group (p = .012). Total cholesterol levels increased significantly in patients receiving olanzapine (p = .047) and quetiapine (p = .016). Treatment with quetiapine was associated with a significant decrease in free thyroxin (p = .011). Metabolic and hormonal side effects of SGAs in children and adolescents should be carefully monitored when prescribing these drugs.


Assessment of serum cortisol and thyrotropin correlation in euthyroid and subclinical hypothyroid subjects.
This cross-sectional study was performed on healthy volunteers and those who had been referred with a diagnosis of subclinical hypothyroidism (TSH<10 mIU/L). Subjects with the age of 18-35 years were enrolled. The sera were analyzed for Cortisol, FT4, FT3, TSH, Ani-TPO, and Anti-Tg. Final sample of 36 in group A (TSH<2.5), 45 in group B (TSH: 2.5-4.2), and 71 in group C (TSH: 4.3-10) were included. Cortisol levels were significantly different in the three groups, the lowest for the A group and higher for the C group, and the two-to-two difference in the groups was also significant (p < 0.001). There was a positive and significant correlation between cortisol levels with TSH (r = 0.740; p < 0.001). There was a potential link between TSH and serum cortisol in young people so that with an increase in TSH from 2.5, the serum cortisol level also increases, but this positive correlation in TSH ≤2.5 was not observed.


Protocol of Aerobic Exercise and Cognitive Health (REACH): A Pilot Study.
A growing body of evidence supports that aerobic exercise can decrease the risk of future cognitive impairment and Alzheimer's disease (AD). There is a pressing need to rigorously determine whether cognitively normal yet at-risk individuals stand to benefit from the protective effects of exercise. The present study will test the feasibility of an aerobic exercise intervention in such a population and inform the design of a larger-scale randomized, controlled trial examining the effect of aerobic exercise on biomarkers of AD in late-middle-aged, at-risk individuals. This was a single-site, 1 : 1 block-randomized, parallel, two-arm trial. Cognitively normal participants aged 45-80 with documentation of familial and genetic AD risk factors were randomly assigned to one of two interventions. The Usual Physical Activity group was provided educational materials about exercise. The Enhanced Physical Activity intervention delivered 26 weeks of individualized and supervised aerobic exercise. Exercise duration and intensity were incrementally increased to 150 min/week and 70-80% of heart rate reserve, respectively. Retention and adherence were measured to assess study feasibility. In addition, pre- and post- intervention differences between the two arms were evaluated for cardiorespiratory fitness, physical activity, brain glucose metabolism, cerebral structure, vascular health, memory, executive function, and mood. Data from randomized controlled trials of exercise training are needed to identify the proper exercise prescription for reducing accumulation of AD biomarkers in cognitively normal individuals. The current trial will contribute to filling that gap while informing the design of large-scale trials.


Destabilization of the TAR hairpin affects the structure and function of the HIV-1 leader RNA.
The TAR hairpin of the human immunodeficiency virus type 1 (HIV-1) RNA genome is essential for virus replication. TAR forms the binding site for the transcriptional trans-activator protein Tat and multiple additional TAR functions have been proposed. We previously constructed an HIV-1 variant in which the TAR-Tat transcription control mechanism is replaced by the components of the Tet-ON regulatory system. In this context, the surprising finding was that TAR can be truncated or even deleted, but partial TAR deletions that destabilize the stem structure cause a severe replication defect. In this study, we demonstrate that the HIV-1 RNA genome requires a stable hairpin at its 5'-end because unpaired TAR sequences affect the proper folding of the untranslated leader RNA. Consequently, multiple leader-encoded functions are affected by partial TAR deletions. Upon evolution of such mutant viruses, the replication capacity was repaired through the acquisition of additional TAR mutations that restore the local RNA folding, thus preventing the detrimental effect on the leader conformation.


[Statistical reporting requirements for medical journals: Amplifications and explanations].
Our study aimed to amplify and explain the items of statistical reporting requirements proposed by medical journals, and to improve the statistical reporting quality of medical articles. Statistical reporting requirements were obtained from the reporting standards published by the International Committee of Medical Journal Editors (ICMJE), the Enhancing the QUAlity and Transparency of Health Research (EQUATOR) network, and the editorial board of Chinese Medical Journal, etc. The items involved in statistical reporting requirements were summarized as issues of study design, statistical analysis, and interpretation of results. Each item was amplified based on cases of original articles. It is noticeable that the statistical reporting requirements of English medical journals generally referring to guidance documents, including "Recommendations for the conduct, reporting, editing, and publication of scholarly work in medical journals" proposed by the ICMJE, or the statements for different study types published by the EQUATOR network, where the statistical reporting of medical articles had been detailed specified. The statistical reporting requirements of Chinese medical journals, however, were usually stated by the editorial boards. Although the formats and contents of statistical analysis had been regulated, the requirements of Chinese medical journals were to some extent insufficient and should be enhanced in accordance with the international standards. In conclusion, the amplification and explanation of statistical reporting requirements were expected to help investigators understand the requirements for statistical reporting in medical researches, so as to effectively improve the quality of medical articles.


A Randomized, Controlled Trial Exploring Collaborative Nursing Intervention on Self-Care Ability and Blood Glucose of Patients with Type 2 Diabetes Mellitus.
For determining the impacts of collaborative nursing intervention (CNI) on self-care ability and blood glucose (BG) of patients with type 2 diabetes mellitus (T2DM). The study enrolled 72 T2DM patients, who are referred to our hospital between April 2017 and September 2019. Of them, 35 cases given routine nursing were set as the control group (CG) and 37 cases given CNI were set as the research group (RG). The Exercise of Self-Care Agency (ESCA) scale scores and the levels of fasting plasma glucose (FPG) as well as glycosylated hemoglobin (HbAlc) were observed pre- and postintervention. The scores of SAS and HAMD and Morisky pre- and postnursing intervention as well as postnursing SF-36 scores and patients' satisfaction toward the nursing content were recorded. After intervention, RG presented notably lower serum HbAlc and FPG levels than CG (P < 0.05); RG presented evidently lower SAS and HAMD scores while distinctly higher Morisky, SF-36, and ESCA scores than CG (P < 0.05); the nursing satisfaction in RG and CG was 97.30% and 51.43%, respectively. In view of the fact that CNI can decrease HbAlc and FPG levels in patients with T2DM and enhance their self-care ability, it is worth popularizing in the clinic.


Theoretical study on the structures and properties of mixtures of urea and choline chloride.
In this work, we investigated in detail the structural characteristics of mixtures of choline chloride and urea with different urea contents by performing molecular dynamic (MD) simulations, and offer possible explanations for the low melting point of the eutectic mixture of choline chloride and urea with a ratio of 1:2. The insertion of urea molecules was found to change the density distribution of cations and anions around the given cations significantly, disrupting the long-range ordered structure of choline chloride. Moreover, with increasing urea concentration, the hydrogen bond interactions between choline cations and Cl(-) anions decreased, while those among urea molecules obviously increased. From the hydrogen bond lifetimes, it was found that a ratio of 1:2 between choline chloride and urea is necessary for a reasonable strength of hydrogen bond interaction to maintain the low melting point of the mixture of choline chloride with urea. In addition, it was also deduced from the interaction energies that a urea content of 67.7 % may make the interactions of cation-anion, cation-urea and anion-urea modest, and thus results in the lower melting point of the eutectic mixture of choline chloride and urea. The present results may offer assistance to some extent for understanding the physicochemical properties of the eutectic mixture of choline chloride and urea, and give valuable information for the further development and application of deep eutectic solvents.


Urinary antispasmodic use and the risks of ventricular arrhythmia and sudden death in older patients.
The introduction of new medications to treat overactive bladder has resulted in a significant increase in the number of individuals with this condition who use medications for symptoms. Formal epidemiological studies of the safety of these medications in typical patient populations are lacking, particularly studies of serious events. We sought to determine whether the use of urinary antispasmodics increases the risk of ventricular arrhythmias or sudden death. Retrospective cohort study. Retrospective analysis of data of participants in community, hospital or nursing home setting. Fourteen thousand six hundred thirty-eight subjects with a diagnosis of urinary incontinence made between January 1, 1991, and June 30, 1995; all were aged 65 and older and enrolled in Medicare and Medicaid or the Pharmacy Assistance for the Aged and Disabled programs of New Jersey. Filled prescriptions for oxybutynin (Ditropan), flavoxate (Urispas), hyoscyamine (Cystospas), and hyoscyamine sulfate (Cystospas-M) were used to define days of exposure to these drugs. We also identified all use of nonsedating antihistamines and cytochrome P450 3A4 inhibitors, and their concurrent use, to serve as a positive control exposure. Two outcomes were then defined: a new diagnosis of ventricular arrhythmia combined with initiation of an antiarrhythmic medication and sudden death. Other covariates, including clinical, demographic, medication use, and healthcare utilization variables, were also assessed. Adjusted risk ratios of ventricular arrhythmia and sudden death were derived from multivariable Cox proportional hazards models. There was no significant association between periods of use of urinary antispasmodics and the development of ventricular arrhythmias (adjusted risk ratio (RR) = 1.23, 95 confidence interval (CI) = 0.87-1.75) or sudden death (adjusted RR = 0.70, 95% CI = 0.28-1.74). A significantly increased risk of ventricular arrhythmia was observed for the positive control regimen, concurrent use of nonsedating antihistamines and cytochrome P450 3A4 inhibitors (adjusted RR = 5.47; 95% CI = 1.34-22.26), but not for use of either drug group alone. Concurrent use of nonsedating antihistamines and cytochrome P450 3A4 inhibitors was also associated with a significant increase in the risk of sudden death (adjusted RR = 21.50, 95% CI = 5.23-88.37). Other variables significantly associated with ventricular arrhythmia included ischemic heart disease and congestive heart failure, whereas nursing home use before the index date was associated with a decreased likelihood of receiving a diagnosis of and treatment for ventricular arrhythmia. Other variables significantly associated with sudden death included male gender, black race, and congestive heart failure. Antimuscarinic urinary antispasmodics available before 1996 were not associated with an increased risk of ventricular arrhythmias and sudden death. Additional study will be required to confirm these results, exclude the possibility of unmeasured confounders contributing to any lack of an observed relationship, and extend these findings to newer agents such as tolterodine.


Reactive Oxygen Species-Mediated Mechanisms of Action of Targeted Cancer Therapy.
Targeted cancer therapies, involving tyrosine kinase inhibitors and monoclonal antibodies, for example, have recently led to substantial prolongation of survival in many metastatic cancers. Compared with traditional chemotherapy and radiotherapy, where reactive oxygen species (ROS) have been directly linked to the mediation of cytotoxic effects and adverse events, the field of oxidative stress regulation is still emerging in targeted cancer therapies. Here, we provide a comprehensive review regarding the current evidence of ROS-mediated effects of antibodies and tyrosine kinase inhibitors, use of which has been indicated in the treatment of solid malignancies and lymphomas. It can be concluded that there is rapidly emerging evidence of ROS-mediated effects of some of these compounds, which is also relevant in the context of drug resistance and how to overcome it.


LRP and H-NS--cooperative partners for transcription regulation at Escherichia coli rRNA promoters.
The synthesis of ribosomal RNAs in bacteria is tightly coupled to changes in the environment. This rapid adaptation is the result of several intertwined regulatory networks. The two proteins FIS and H-NS have previously been described to act as antagonistic transcription factors for rRNA synthesis. Here we provide evidence for another player, the regulatory protein LRP, which binds with high specificity to all seven Escherichia coli rRNA P1 promoter upstream regions (UAS). Comparison of the binding properties of LRP and H-NS, and characterization of the stabilities of the various complexes formed with the rRNA UAS regions revealed different binding modes. Binding studies with LRP and H-NS in combination demonstrated that the two proteins interacted with obvious synergism. The efficiency of LRP binding to the rRNA regulatory region is modified by the presence of the effector amino acid leucine, as has been shown for several other operons regulated by this transcription factor. The effect of LRP on the binding of RNA polymerase to the rrnB P1 promoter and in vitro transcription experiments indicated that LRP acts as a transcriptional repressor, thus resembling the activity of H-NS described previously. The results show for the first time that LRP binds to the regulatory region of bacterial rRNA promoters, and very likely contributes in combination with H-NS to the control of rRNA synthesis. From the known properties of LRP a mechanism can be inferred that couples rRNA synthesis to changes in nutritional quality.


Data-driven analysis of the electronic-structure factors controlling the work functions of perovskite oxides.
Tuning the work functions of materials is of practical interest for maximizing the performance of microelectronic and (photo)electrochemical devices, as the efficiency of these systems depends on the ability to control electronic levels at surfaces and across interfaces. Perovskites are promising compounds to achieve such control. In this work, we examine the work functions of more than 1000 perovskite oxide surfaces (ABO3) using data-driven (machine-learning) analysis and identify the factors that determine their magnitude. While the work functions of the BO2-terminated surfaces are sensitive to the energy of the hybridized oxygen p bands, the work functions of the AO-terminated surfaces exhibit a much less trivial dependence with respect to the filling of the d bands of the B-site atom and of its electronic affinity. This study shows the utility of interpretable data-driven models in analyzing the work functions of cubic perovskites from a limited number of electronic-structure descriptors.


Regulatory T cell subsets in peripheral blood of celiac disease patients and TLR2 expression: correlation with oxidative stress.
The study was carried out to study expression of Toll like receptors 2 (TLR2), natural/inducible Treg and Interferon-γ alongside oxidative stress and understand their significance in pediatric samples. Influence of oxidative stress on Celiac Disease was analysed by evaluating lipid peroxidation, reduced glutathione, Glutathione peroxidase, etc. A comparison was performed among CD patients, CD patients on gluten free diet (GFD), and healthy controls. Peripheral nTregs exhibited a similar pattern of reduced numbers in CD and GFD cases when compared to healthy controls. On the other hand, inducible Tregs were much lower in GFD patients as compared to CD patients. Expression of TLR2 on iTregs was elevated in CD and GFD, however, expression on nTregs was unaltered in all the three groups. The inflammatory cytokine IFN-γ positive Treg cells were found to be elevated in CD as compared to control group. Oxidative stress was elevated in CD as compared to healthy controls while that in GFD samples was lower in comparison to CD. The levels of LPO, activities of enzymes SOD and Catalase were higher in CD and GFD samples when compared to controls. However, enzyme Glutathione peroxidase and reduced glutathione levels declined in both CD and GFD groups as compared to controls. This report highlights the effect of elevated oxidative stress in CD on reduced traffic of iTregs toward periphery. A strong correlation was observed between the cytokine IFN-γ and TLR2 expression in movement of iTregs in CD patients.


Ferroelectric and ferroelastic domain wall motion in unconstrained Pb(Zr,Ti)O3 microtubes and thin films.
Ferroelectric polarization switching of high aspect ratio (>80:1) PbZr(0.52)Ti(0.48)O(3) (PZT) microtubes with a wall thickness of ~200 nm was investigated. A charge-based technique was used to assess the dielectric and ferroelectric properties of individual mechanically-unconstrained PZT microtubes with interdigitated electrodes. An enhancement in the degree of ferroelastic (non-180 degrees ) domain wall motion was observed in the tubes relative to films of similar thickness on rigid substrates. The dielectric response of the tubes showed a Rayleigh-like ac field dependence over a wide temperature range; the extent of the extrinsic contribution to the dielectric response dropped as the temperature approached 10K, but remained finite. This work demonstrates a general methodology for directly electrically addressing small, unconstrained ferroelectric devices, extending the range of driving fields and temperatures over which these materials can be probed.


Genetic structure of Sesamia nonagrioides (Lefebvre) populations in the Mediterranean area.
The Mediterranean corn borer, Sesamia nonagrioides (Lefebvre) (Lepidoptera: Noctuidae), is a major pest of maize in the Mediterranean area. Transgenic Bt maize expressing the Cry1Ab toxin from the bacterium Bacillus thuringiensis can effectively control this pest. The characterization of S. nonagrioides population structure, at a large geographical scale, would provide some insight in decision making for resistance management. The genetic relationships among nine populations from Spain, one from France, one from Italy, three from Greece, and one from Turkey were assessed using Random Amplyfied Polymorphic DNA (RAPD) markers. Populations from France and Spain formed a cluster independent from a cluster of populations collected in Italy, Turkey, and Greece in a unweighted pair-group method with arithmetic average dendrogram constructed from Nei's genetic distances. Average genetic differentiation among samples was significant for all geographical groupings analyzed (F (ST) = 0.160 +/- 0.014 for Spanish populations; 0.133 +/- 0.022 for Spanish and French populations; and 0.095 +/- 0.010 for Greek, Italian, and Turkish populations). Genetic differentiation was also significant for all paired comparisons of populations, including two Spanish populations separated by only 15 km with no apparent geographical barriers. No pattern of isolation by distance was observed among Mediterranean corn borer populations collected in Spain and France. These results suggest a limited genetic exchange between relatively distant S. nonagrioides populations in Europe, which might contribute to decreased rate of spread of resistance alleles once resistance has developed at a certain site.


Study of the Relationship between Entropy and Hardness in Laser Cutting of Hardox Steel.
The article presents the findings of a study on the machining of 10 mm thick Hardox 400 steel plates using the CO2 laser. The purpose of the investigation was to investigate the relationship between the entropy and the hardness of machined surfaces. For this purpose, a new mathematical model is established to estimate the entropy, and its influence on the hardness is determined. The mathematical model is statistically and experimentally validated. An entropy variation ΔS = -330 mJ/K between 2 K is found, causing a decrease in hardness compared to the standard value. The influences of input parameters (laser power, cutting speed, and auxiliary gas pressure) on hardness are determined. It is demonstrated that the surface hardness is strongly influenced by the auxiliary gas pressure. The combination of laser power P = 4200 W with gas pressure p = 0.45 bar at average cutting speed v = 1400 mm/min leads to a hardness of 38 HRC, extending the life and wear resistance of the cut parts.


Structure-function relationships for the IL 2-receptor system. IV. Analysis of the sequence and ligand-binding properties of soluble Tac protein.
The Tac protein is one of at least two glycoproteins known to bind the growth and differentiation factor interleukin 2 (IL 2). In addition to its location on the cell surface, where it plays a part in high and low affinity IL 2 receptors, Tac is released from activated lymphocytes in a soluble form. We observed this release both for Tac protein labeled biosynthetically and for Tac protein labeled by surface iodination of intact cells. Competitive binding studies indicated that the soluble Tac protein retained an ability to bind IL 2 with a low affinity (Kd of 11.1 nM). In addition, structural analysis revealed that the polypeptide chain began at position 1 and ended at or just before Cys-192 of the full-length molecule. Thus, the protein was missing its normal transmembrane and intracytoplasmic segments, accounting for its solubility and cellular release. The apparent lack of modification in the amino acid sequence and the termination at Cys-192 are inconsistent with a mechanism of cellular release dependent only on alternate mRNA splicing. Instead, the results suggest that proteolysis may accompany the release of soluble Tac protein from cells expressing IL 2 receptors.


[Gallstones in a retained gastric antrum].
Retained gastric antrum arises when there is incomplete excision of the gastric antrum during Billroth II gastrectomy for peptic ulcer disease. We report the case of a patient with gallstones in a retained gastric antrum, without biliodigestive fistula. This finding is extremely rare and we have found no previously reported cases in the literature.


Factors related to urinary incontinence in community-dwelling women.
Urinary incontinence (UI) is one of the most prevalent and costly health problems in the United States. Women participating in two clinical trials had experienced UI for a mean of 7.2 +/- 7.6 SD years. Hormone status, gynecologic surgery, alcohol intake, age, and educational attainment were significantly related to amount of urine loss. Amount of urine loss was also related to episodes of urine loss, caffeine and fluid intake, and quality of life.


Fibrillar vs crystalline full-length beta-2-microglobulin studied by high-resolution solid-state NMR spectroscopy.
Elucidating the fine structure of amyloid fibrils as well as understanding their processes of nucleation and growth remains a difficult yet essential challenge, directly linked to our current poor insight into protein misfolding and aggregation diseases. Here we consider beta-2-microglobulin (beta2m), the MHC-1 light chain component responsible for dialysis-related amyloidosis, which can give rise to amyloid fibrils in vitro under various experimental conditions, including low and neutral pH. We have used solid-state NMR to probe the structural features of fibrils formed by full-length beta2m (99 residues) at pH 2.5 and pH 7.4. A close comparison of 2D (13)C-(13)C and (15)N-(13)C correlation experiments performed on beta2m, in both the crystalline and fibrillar states, suggests that, in spite of structural changes affecting the protein loops linking the protein beta-strands, the protein chain retains a substantial share of its native secondary structure in the fibril assembly. Moreover, variations in the chemical shifts of the key Pro32 residue suggest the involvement of a cis-trans isomerization in the process of beta2m fibril formation. Lastly, the analogy of the spectra recorded on beta2m fibrils grown at different pH values hints at a conserved architecture of the amyloid species thus obtained.


Outpatient bowel preparation for elective colon resection.
To determine the safety and cost-effectiveness of outpatient preoperative bowel preparation with polyethylene glycol-electrolyte lavage solution, we retrospectively analyzed 726 cases of colectomy done by colon and rectal surgeons between July 1987 and July 1991. Included were 319 patients who had elective segmental or total abdominal colectomy with primary anastomosis. Patients who required protective proximal stoma were excluded. Patients requiring emergency surgery, colostomy closure, and restorative proctocolectomy were excluded. Patients were separated into two groups equally matched by age, sex, procedure done, and comorbidity: 145 had bowel preparation as outpatients and 174 as inpatients. Both groups had similar numbers of days hospitalized, days receiving nothing by mouth, and days requiring nasogastric intubation or gastrostomy tube, as well as similar postoperative complications. There was one wound infection, one anastomotic leak, and one death in each group. Cost of outpatient preparation was approximately $40. Cost of inpatient preparation, including a semiprivate room, was approximately $400. Outpatient preparation with polyethylene glycol-electrolyte lavage solution and oral antibiotics before elective colon resection can be done with equivalent safety and at a substantial cost savings.


Building the Bridge From Aquatic Nanotoxicology to Safety by Design Silver Nanoparticles.
Nanotechnologies have rapidly grown, and they are considered the new industrial revolution. However, the augmented production and wide applications of engineered nanomaterials (ENMs) and nanoparticles (NPs) inevitably lead to environmental exposure with consequences on human and environmental health. Engineered nanomaterial and nanoparticle (ENM/P) effects on humans and the environment are complex and largely depend on the interplay between their peculiar properties such as size, shape, coating, surface charge, and degree of agglomeration or aggregation and those of the receiving media/body. These rebounds on ENM/P safety and newly developed concepts such as the safety by design are gaining importance in the field of sustainable nanotechnologies. This article aims to review the critical characteristics of the ENM/Ps that need to be addressed in the safe by design process to develop ENM/Ps with the ablility to reduce/minimize any potential toxicological risks for living beings associated with their exposure. Specifically, we focused on silver nanoparticles (AgNPs) due to an increasing number of nanoproducts containing AgNPs, as well as an increasing knowledge about these nanomaterials (NMs) and their effects. We review the ecotoxicological effects documented on freshwater and marine species that demonstrate the importance of the relationship between the ENM/P design and their biological outcomes in terms of environmental safety.


Benzylic C-H trifluoromethylation of phenol derivatives.
Phenol derivatives were trifluoromethylated using copper/Togni reagent. In dimethylformamide, the benzylic C-H bond at the para position of the hydroxyl group was selectively substituted with a CF3 group. In contrast, aromatic C-H trifluoromethylation occurred in alcoholic solvents. Practical utility of the reactions was demonstrated by application to the synthesis of a potent enoyl-acyl carrier protein reductase (FabI) inhibitor.


[Local hyperthermia of malignant brain tumors].
In glioblastoma multiforme and high-grade astrocytomas the following procedure has been implemented to try and prevent recurrence: after extirpation of the tumour its bed is lined with metal powder and the patient's head is exposed to a high-frequency magnetic field every 4 weeks. As a result the temperature is raised by induction to +45 degrees C at the boundary between metal and brain tissue. This ought to be sufficient to prevent tumour recurrence. Varied results were achieved using this technique in 103 patients.


Population pharmacokinetics of brodalumab in patients with moderate to severe plaque psoriasis.
Brodalumab is a fully human monoclonal antibody targeting the IL-17 receptor A leading to an inhibition of the biological effect of IL-17A, IL-17F, IL-17A/F heterodimer, IL-17C and IL-17E isoforms. It has shown to be efficacious in the treatment of moderate to severe plaque psoriasis (210 mg administered subcutaneously at weeks 0, 1 and 2 followed by 210 mg every 2 weeks [Q2W+1]). A population pharmacokinetic model based on psoriasis patients only from six clinical trials was developed to describe the pharmacokinetics and identify sources of variability. In patients with psoriasis, Brodalumab exhibits non-linear pharmacokinetics due to target-mediated drug disposition resulting in concentration-dependent clearance. The pharmacokinetics was best described by a two-compartment model with linear absorption and combined linear and Michaelis-Menten elimination. The subcutaneous bioavailability of Brodalumab was 55%, absorption rate was 0.30 day-1 , and body-weight was found to affect the volume of distribution and clearance. For a reference patient with plaque psoriasis (body-weight of 90 kg), the estimates were 0.16 L/d for linear serum clearance, 6.1 mg/d for the maximum non-linear clearance rate, and 4.7 and 2.4 L for central and peripheral volume of distribution, respectively. For the approved dosing regimen, time to maximum concentration was 4 days and 90% of steady-state was achieved after 10 weeks for a reference patient. Following last dose at steady-state, 90% of the population of reference patients will reach serum concentrations below lower limit of quantification after 45 days.