Telomerase activity in cervical scrapes of women with high-grade cervical disease: A nested case-control study.
Epidemiological information on telomerase activity (TA) and development of cervical lesions is scarce. A nested case-control study was carried out within a cohort of Colombian women tested for Human Papillomavirus (HPV). Measurement of TA was done in cervical scrapes of 25 women who developed High Grade Squamous Intraepithelial Lesion (HGSIL) during the first 6 years of follow-up and was compared with that of 104 control women who maintained normal cytology during the entire follow-up. TA was measured by a telomerase repeat amplification protocol-ELISA. TA and HPV infections were significantly more frequent in cases than in controls. Likewise, 68% of the cases were positive for both TA and HPV compared with only 7.7% of the controls (P<0.0001). Factors independently associated with increased odds of HGSIL included TA, high risk HPV (hrHPV) infections and multiple parities. When restricted to hrHPV positive women, TA was strongly associated with increased odds of HGSIL (adjusted odds ratio=37.94, 95% confidence interval, 1.64-678.1). In addition to an infection with hrHPV, TA appears to be a significant cofactor for HGSIL.


Pioneers in oral biology: the migrations of Gottlieb, Kronfeld, Orban, Weinmann, and Sicher from Vienna to America.
Following the annexation of Austria by Hitler's Germany in 1938, officials at the eminent University of Vienna Medical School purged faculty ranks of Jews. Among those forced out were several distinguished physician dentists, several of whom emigrated to the United States. The assimilation of foreign-trained dentists raised questions at national meetings of the AADS and the National Association of Dental Examiners. Already existing ties between dental schools in Chicago and the University of Vienna, including the 1928 appointment of Rudolf Kronfeld to the faculty at Loyola, led to the relocation of Balint Orban, Harry Sicher, and Joseph Peter Weinmann in that city. Bernhard Gottlieb, who had been director of the Dental Institute in Vienna, transplanted less easily, but eventually found a niche at the Baylor College of Dentistry in Dallas. The careers of the Vienna dentist-scientists strengthened the scientific foundations of clinical dentistry in the United States, contributed to the development of a stronger research establishment, and enlarged the scope of oral biology.


Simultaneous covalent and noncovalent carbon nanotube/Ag3PO4 hybrids: new insights into the origin of enhanced visible light photocatalytic performance.
Understanding the interfacial interaction is of paramount importance for rationally designing carbon nanomaterial-based hybrids with optimal performance for electronics, optoelectronics, sensing, advanced energy conversion and storage. Here, we firstly reveal that both covalent and noncovalent interactions simultaneously exist in carbon nanotube (CNT)/Ag3PO4 hybrids by studying systematically the electronic and optical properties to elucidate the mechanism of their enhanced photocatalytic performance. Metallic CNT(9,0) may chemically or physically interact with the Ag3PO4(100) surface depending on its relative orientations, whereas semiconducting CNT(10,0) can only noncovalently functionalize Ag3PO4. The C-Ag bond in the covalently bonded hybrid and type-II, staggered, band alignment in noncovalent hybrids lead to a robust separation of photoexcited charge carriers between two constituents, thus enhancing the photocatalytic activity. The small band gap makes the CNT/Ag3PO4 hybrids absorb sunlight from the ultraviolet to infrared region. Moreover, CNTs are not only effective sensitizers, but also highly active co-catalysts in hybrids. The results can be rationalized by the available experiments, thereby partly resolving a debate on the interpretation of the experimental results, and paving the way for developing highly efficient carbon-based nanophotocatalysts.


A novel cloud-point extraction process for preconcentrating selected polycyclic aromatic hydrocarbons in aqueous solution.
A novel but simple cloud-point extraction (CPE) process is developed to preconcentrate the trace of selected polycyclic aromatic hydrocarbons (PAHs) with the use of the readily biodegradable nonionic surfactant Tergitol 15-S-7 as extractant. The concentrations of PAHs, mixtures of naphthalene and phenanthrene as well as pyrene, in the spiked samples were determined with the new CPE process at ambient temperature (23 degrees C) followed by high performance liquid chromatography(HPLC) with fluorescence detection. More than 80% of phenanthrene and pyrene, respectively, and 96% of naphthalene initially present in the aqueous solutions with concentrations near or below their aqueous solubilities were recovered using this new CPE process. Importantly Tergitol 15-S-7 does not give any fluorometric signal to interfere with fluorescence detection of PAHs in the UV range. No special washing step is, thus, required to remove surfactant before HPLC analyses. Different experimental conditions were studied. The optimum conditions for the preconcentration and determination of these selected PAHs at ambient temperature have been established as the following: (1) 3 wt% surfactant; (2) addition of 0.5 M Na2SO4; (3) 10 min for equilibration time; and (4) 3000 rpm for centrifugal speed with duration of 10 min.


Evolutionary Ecology of Organs: A Missing Link in Cancer Development?
There is striking variation in the incidence of cancer in human organs. Malignant tumors are common in the colon and breast but rare in the heart and small bowel. The uterus frequently develops benign fibroid tumors but uterine cancers are relatively rare. The organ-specific difference in cancer prevalence has been explained primarily by the relative roles of intrinsic and extrinsic risk factors. In this opinion article, we propose also considering organs as distinct but connected ecosystems whose different vulnerabilities to malignant transformation may be partially explained by how essential each organ is for survival through the age of reproduction. We present and discuss some of the basic concepts and assumptions of this perspective on evolutionary medicine.


Guillain-Barré syndrome and its relationship to swine influenza vaccination in Michigan, 1976-1977.
Active surveillance to detect all patients with Guillain-Barré syndrome who had had onset of illness from July 1, 1976 through April 30, 1977 was undertaken in Michigan after indications that the syndrome might be associated with the National Influenza Immunization Program of 1976-1977. Hospital record room librarians, neurologists, and neurosurgeons reported the greatest number of cases; coded hospital discharge records were the best means of ascertaining case occurrence. This differed from national surveillance, which relied essentially on reports that neurologists and other clinicians sent to state epidemiologists and then to the Centers for Disease Control; hospital discharge lists were not systemically reviewed nationally. A total of 79 of the Michigan cases were in persons who had not received swine influenza vaccine, while 46 cases were in persons who had received it. For unvaccinated adults, the incidence of Guillain-Barré syndrome during the 10-month surveillance period was 0.36 cases per 10(6) person-weeks; for adults with onset within six weeks of vaccination, it was 2.31 cases per 10(6) person-weeks. After six weeks post-vaccination, the rate decreased to 0.17 cases per 10(6) person-weeks. The attributable risk for acquiring Guillain-Barré syndrome within six weeks after receiving swine influenza vaccine was 11.70 cases per 10(6) persons vaccinated.


[Use of imaging criteria to identify cervical metastases using CT scans in head and neck tumours].
To assess the diagnostic certainty of CT images to identify regional spread of head and neck tumours. A CT study was performed on 86 patients with neoplasms in the larynx and/or pharynx. After this, surgical dissection was performed for 142 neck sides. In the imaging study the following parameters were considered for all patients before suspecting malignant nodes: size of adenopathy bigger than 10-11 mm, irregular borders, central necrosis, spherical shape, capsular enhancement and presence of groups with three or more lymphadenopathies. 48.5 % of dissections were N+. Sensitivity and specificity for physical examination were 59 % and 82 %, respectively, against 73 % and 86 % for CT. Lymph node necrosis was the pattern with the greatest sensitivity and specificity (35.8 % and 100 %, respectively) and its accuracy was 69.7 %. Accuracy was 60.5 % for spherical shape, 59.8 % for node size, and between 54 % and 58 % for the other three criteria. In the histopathological findings, 25 % of neck dissections were N+ when only one pattern had been detected on CT, whereas those neck sides in which four patterns were identified simultaneously showed regional spread in 100 %. The presence of specific morphological imaging criteria for head and neck tumours in cervical lymph nodes and their concomitance increase the accuracy of imaging to predict regional spread.


Renal arterial blood flow measurement by breath-held MRI: Accuracy in phantom scans and reproducibility in healthy subjects.
This study evaluates reliability of current technology for measurement of renal arterial blood flow by breath-held velocity-encoded MRI. Overall accuracy was determined by comparing MRI measurements with known flow in controlled-flow-loop phantom studies. Measurements using prospective and retrospective gating methods were compared in phantom studies with pulsatile flow, not revealing significant differences. Phantom study results showed good accuracy, with deviations from true flow consistently below 13% for vessel diameters 3mm and above. Reproducibility in human subjects was evaluated by repeated studies in six healthy control subjects, comparing immediate repetition of the scan, repetition of the scan plane scouting, and week-to-week variation in repeated studies. The standard deviation in the 4-week protocol of repeated in vivo measurements of single-kidney renal flow in normal subjects was 59.7 mL/min, corresponding with an average coefficient of variation of 10.55%. Comparison of renal arterial blood flow reproducibility with and without gadolinium contrast showed no significant differences in mean or standard deviation. A breakdown among error components showed corresponding marginal standard deviations (coefficients of variation) 23.8 mL/min (4.21%) for immediate repetition of the breath-held flow scan, 39.13 mL/min (6.90%) for repeated plane scouting, and 40.76 mL/min (7.20%) for weekly fluctuations in renal blood flow.


Distribution of microglia/immune cells in the brain of adult zebrafish in homeostatic and regenerative conditions: Focus on oxidative stress during brain repair.
Microglia are macrophage-like cells exerting determinant roles in neuroinflammatory and oxidative stress processes during brain regeneration. We used zebrafish as a model of brain plasticity and repair. First, by performing L-plastin (Lcp1) immunohistochemistry and using transgenic Tg(mpeg1.1:GFP) or Tg(mpeg1.1:mCherry) fish, we analyzed the distribution of microglia/immune cells in the whole brain. Specific regional differences were evidenced in terms of microglia/immune cell density and morphology (elongated, branched, highly branched, and amoeboid). Taking advantage of Tg(fli:GFP) and Tg(GFAP::GFP) enabling the detection of endothelial cells and neural stem cells (NSCs), we highlighted the association of elongated microglia/immune cells with blood vessels and rounded/amoeboid microglia with NSCs. Second, after telencephalic injury, we showed that L-plastin cells were still abundantly present at 5 days post-lesion (dpl) and were associated with regenerative neurogenesis. Finally, RNA-sequencing analysis from injured telencephalon (5 dpl) confirmed the upregulation of microglia/immune cell markers and highlighted a significant increase of genes involved in oxidative stress (nox2, nrf2a, and gsr). The analysis of antioxidant activities at 5 dpl also revealed an upregulation of superoxide dismutase and persistent H2 O2 generation in the injured telencephalon. Also, microglia/immune cells were shown to be a source of oxidative stress at 5 dpl. Overall, our data provide a better characterization of microglia/immune cell distribution in the healthy zebrafish brain, highlighting some evolutionarily conserved features with mammals. They also emphasize that 5 days after injury, microglia/immune cells are still activated and are associated to a persistent redox imbalance. Together, these data raise the question of the role of oxidative stress in regenerative neurogenesis in zebrafish.


Posttonsillectomy bacteremia and comparison of tonsillar surface and deep culture.
Objective. This study aimed to identify the microorganisms of surface and depth of tonsils and whether these microorganisms bring the menace of bacteremia during tonsillectomy in the children under surgery. Materials and Methods. The culture specimens were taken from surface and depth of tonsil from the patients suffering from chronic tonsillitis at the time of operation. Also, 10 mL venous blood samples were taken 5 minutes before and after the operation for microbiological study. Results. According to the results, 112 (76.1%) and 117 (79.6%) cultures from surface and depth of tonsils represented multiple microorganisms, respectively. Besides, staphylococci coagulase positive was the most common organism in both surface and depth of tonsils. None of the preoperation blood cultures were positive, while 3 postoperation blood cultures (2.1%) were positive. Staphylococci coagulase negative and alpha hemolytic streptococcus were detected in 2 cases (1.4%) and 1 case (0.7%), respectively. Conclusion. In the present study, the two cultured sites were almost similar regarding the types of isolated microorganisms. Our results suggested that bacteremia might occur after tonsillectomy. Therefore, to avoid the possible dramatic outcomes after tonsillectomy, pre- and postoperation attendances are essential.


Captive house sparrows (Passer domesticus) show little evidence of seasonality of neophobia responses.
Neophobia is a behavior characterized by a reluctance to approach novel objects. We measured neophobia in captive wild house sparrows (Passer domesticus) by comparing the time it took for hungry birds to approach their normal food dish compared to one that had been modified with a novel object. We tested the behavior of animals captured at different times of year to test for seasonal variation in neophobia. One group of birds tested in July approached their food dishes much more quickly than all other birds (a matter of seconds rather than minutes whether or not there was a novel object), a response that was not repeated in a subsequent July. When this possible outlier group was removed from the analysis, approach times to novel objects were not affected by season. However, animals captured and tested in October had a stronger motivation to feed (i.e., they approached unmodified food dishes faster) than birds captured at other times of the year. If we define "neophobia" as an increase in latency to approach a novel versus an unmodified food dish, then there is little evidence for underlying seasonal variation in risk assessment, although a general motivation to feed does show a seasonal pattern.


A Review of Organ Transplantation: Heart, Lung, Kidney, Liver, and Simultaneous Liver-Kidney.
Heart, lung, kidney, liver, and simultaneous liver-kidney transplants share many features. They all follow the same 7-step process, the same 3 immunosuppressant medications, and the same reason for organ transplantation. Organs are transplanted because of organ failure. The similarities end there. Each organ has its unique causes for failure. Each organ also has its own set of criteria that must be met prior to transplantation. Simultaneous liver-kidney transplant criteria vary per transplant center but are similar in nature. Both the criteria required and the 7-step process are described by the United Network of Organ Sharing, which is a private, nonprofit organization, under contract with the US Department of Health and Human Services. Its function is to increase the number of transplants, improve survival rates after transplantation, promote safe transplant practices, and endorse efficiency. The purpose of this article is to review the reasons transplant is needed, specifically heart, lung, kidney, liver, and simultaneous liver-kidney, and a brief overview of the transplant process including criteria used, contraindications, and medications prescribed.


Intermediate-term outcome of Aurolab aqueous drainage implant.
To report the intermediate-term safety and efficacy of Aurolab aqueous drainage implant (AADI) in patients with glaucoma. Retrospective review of patients who underwent AADI between January 2013 and December 2016. Patients aged >16 years and with a minimum follow-up of 6 months were included. Success was defined as complete when the intraocular pressure was ≥6 and ≤21 mmHg without antiglaucoma medication and as qualified if those requiring additional antiglaucoma medications were included. The study included 55 patients (55 eyes) with a mean age ± standard deviation (SD) of 47.3 ± 18.1 years with a mean follow-up of 16.7 ± 11.4 months. Mean intraocular pressure reduced from 30.8 ± 11.1 mmHg to 13.1 ± 4.7, 14.1 ± 4.8, 15.7 ± 2.5 (P < 0.001) mmHg at 6 months, 1 year, and 2 years, respectively. The mean number of antiglaucoma medications reduced from 3.4 ± 1 to 0.8 ± 1.2, 0.7 ± 1.1, 0.8 ± 1 (P < 0.001) at 6 months, 1 year, and 2 years, respectively. The cumulative probability of complete and qualified success was 62% and 100% at 6 months, 54% and 92% at 1 year, and 43% and 88% at 2 years, respectively. Four patients failed during the follow-up period. Postoperative complication occurred in 28 eyes (51%), of which 17 eyes (31%) required intervention. AADI is a safe and effective treatment for the control of intraocular pressure in patients with glaucoma.


Toward the Understanding of Selective Si Nano-Oxidation by Atomic Scale Simulations.
The continuous miniaturization of nanodevices, such as transistors, solar cells, and optical fibers, requires the controlled synthesis of (ultra)thin gate oxides (<10 nm), including Si gate-oxide (SiO2) with high quality at the atomic scale. Traditional thermal growth of SiO2 on planar Si surfaces, however, does not allow one to obtain such ultrathin oxide due to either the high oxygen diffusivity at high temperature or the very low sticking ability of incident oxygen at low temperature. Two recent techniques, both operative at low (room) temperature, have been put forward to overcome these obstacles: (i) hyperthermal oxidation of planar Si surfaces and (ii) thermal or plasma-assisted oxidation of nonplanar Si surfaces, including Si nanowires (SiNWs). These nano-oxidation processes are, however, often difficult to study experimentally, due to the key intermediate processes taking place on the nanosecond time scale. In this Account, these Si nano-oxidation techniques are discussed from a computational point of view and compared to both hyperthermal and thermal oxidation experiments, as well as to well-known models of thermal oxidation, including the Deal-Grove, Cabrera-Mott, and Kao models and several alternative mechanisms. In our studies, we use reactive molecular dynamics (MD) and hybrid MD/Monte Carlo simulation techniques, applying the Reax force field. The incident energy of oxygen species is chosen in the range of 1-5 eV in hyperthermal oxidation of planar Si surfaces in order to prevent energy-induced damage. It turns out that hyperthermal growth allows for two growth modes, where the ultrathin oxide thickness depends on either (1) only the kinetic energy of the incident oxygen species at a growth temperature below Ttrans = 600 K, or (2) both the incident energy and the growth temperature at a growth temperature above Ttrans. These modes are specific to such ultrathin oxides, and are not observed in traditional thermal oxidation, nor theoretically considered by already existing models. In the case of thermal or plasma-assisted oxidation of small Si nanowires, on the other hand, the thickness of the ultrathin oxide is a function of the growth temperature and the nanowire diameter. Below Ttrans, which varies with the nanowire diameter, partially oxidized SiNW are formed, whereas complete oxidation to a SiO2 nanowire occurs only above Ttrans. In both nano-oxidation processes at lower temperature (T < Ttrans), final sandwich c-Si|SiOx|a-SiO2 structures are obtained due to a competition between overcoming the energy barrier to penetrate into Si subsurface layers and the compressive stress (∼2-3 GPa) at the Si crystal/oxide interface. The overall atomic-simulation results strongly indicate that the thickness of the intermediate SiOx (x < 2) region is very limited (∼0.5 nm) and constant irrespective of oxidation parameters. Thus, control over the ultrathin SiO2 thickness with good quality is indeed possible by accurately tuning the oxidant energy, oxidation temperature and surface curvature. In general, we discuss and put in perspective these two oxidation mechanisms for obtaining controllable ultrathin gate-oxide films, offering a new route toward the fabrication of nanodevices via selective nano-oxidation.


Study of Relationship Between Depression and Quality of Life in Patients With Chronic Schizophrenia.
Depression is among the personality traits of schizophrenic patients, which results from psychotic features or is a consequence of a period of psychosis. Depression in schizophrenic patients is one of the important factors affecting their quality of life. The study population of this descriptive and analytic study consists of patients with chronic schizophrenia in Zahedan in 2014. The sample included 60 patients who simultaneously suffered from depression and were selected using random sampling (30 males and 30 females). The research instruments included the Schizophrenia Quality of Life Scale (SQLS) and the Beck Depression Inventory (the inventory was filled out by the tester). In order to form a statistics analysis, we used Pearson correlation and regression multivariate. Investigating the study hypotheses showed that there was a negative correlation between the high level of depression and low quality of life. the relationship between depression and the quality of life subscales showed that in women, the variable of symptoms and complications was a significant predictor; however, the other two variables (energy and motivation and psychosocial) were not significant predictors. In case of men, psychosocial variable was a significant predictor; however, the other two variables (energy and motivation and symptoms and complications) were not significant predictors. In general, depression on these patients makes discontent of life on them; therefore, elimination of their depression on their treatment is necessary.


ATR activated by EB virus facilitates chemotherapy resistance to cisplatin or 5-fluorouracil in human nasopharyngeal carcinoma.
Epstein-Barr virus (EBV) infection is closely associated with nasopharyngeal carcinoma (NPC) and increases the chemotherapy resistance of tumor cells. Although the mechanism by which EBV manipulates ataxia telangiectasia mutation (ATM)-mediated DNA damage response in NPC has been extensively studied, the relationship between ATR (ATM and Rad-3 related) and EBV infection is largely unexplored, and also the role of ATR in chemotherapy resistance in EBV-positive NPC has not been specifically reported. Levels of γ-H2AX, latent membrane protein 1 (LMP1), and EBV-encoded RNA in clinical NPC and nasopharyngeal inflammation (NPI) specimens were examined using immunohistochemistry and in situ hybridization. The effects of EBV infection, chemotherapy drugs cisplatin (CDDP) and 5-fluorouracil (5-FU) treatment, and ATR silencing were assessed in NPC cells in vitro using immunofluorescence, Western blot, and flow cytometry. A notable increase of γ-H2AX expression was examined in the EBV-positive NPC clinical specimens. Additionally, we observed that the phosphorylation of ATR/checkpoint kinase 1 (CHK1) pathway protein was gradually activated along with the duration of EBV exposure in NPC cell lines, which was obviously inhibited after ATR depletion. Moreover, EBV infection promoted the resistance of NPC cells to CDDP and 5-FU, whereas the chemosensitivity of cells was significantly enhanced following ATR knockdown. Furthermore, ATR depletion caused both S-phase cell arrest and apoptosis, enhanced p53 phosphorylation, and impaired the formation of Rad51. Our data suggest that EBV activation of ATR-mediated DNA damage response might result in chemotherapy resistance to CDDP and 5-FU in NPC. Accordingly, ATR knockdown may serve as an effective treatment strategy for chemotherapy-resistant, EBV-positive NPC.


Twenty-four percent of patients with clinical chorioamnionitis in preterm gestations have no evidence of either culture-proven intraamniotic infection or intraamniotic inflammation.
Recent studies on clinical chorioamnionitis at term suggest that some patients with this diagnosis have neither intraamniotic infection nor intraamniotic inflammation. A false-positive diagnosis of clinical chorioamnionitis in preterm gestation may lead to unwarranted preterm delivery. We sought to determine the frequency of intraamniotic inflammation and microbiologically proven amniotic fluid infection in patients with preterm clinical chorioamnionitis. Amniocentesis was performed in singleton pregnant women with preterm clinical chorioamnionitis (<36 weeks of gestation). Amniotic fluid was cultured for aerobic and anaerobic bacteria and genital mycoplasmas and assayed for matrix metalloproteinase-8 concentration. Microbial invasion of the amniotic cavity was defined as a positive amniotic fluid culture; intraamniotic inflammation was defined as an elevated amniotic fluid matrix metalloproteinase-8 concentration of >23 ng/mL. Nonparametric and survival techniques were used for analysis. Among patients with preterm clinical chorioamnionitis, 24% (12/50) had neither microbiologic evidence of intraamniotic infection nor intraamniotic inflammation. Microbial invasion of the amniotic cavity was present in 34% (18/53) and intraamniotic inflammation in 76% (38/50) of patients. The most common microorganisms isolated from the amniotic cavity were the Ureaplasma species. Finally, patients without microbial invasion of the amniotic cavity or intraamniotic inflammation had significantly lower rates of adverse outcomes (including lower gestational age at delivery, a shorter amniocentesis-to-delivery interval, acute histologic chorioamnionitis, acute funisitis, and significant neonatal morbidity) than those with microbial invasion of the amniotic cavity and/or intraamniotic inflammation. Among patients with preterm clinical chorioamnionitis, 24% had no evidence of either intraamniotic infection or intraamniotic inflammation, and 66% had negative amniotic fluid cultures, using standard microbiologic techniques. These observations call for a reexamination of the criteria used to diagnose preterm clinical chorioamnionitis.


The Patient Experience of Prior Authorization for Cancer Care.
Prior authorization (PA) requires clinicians and patients to navigate a complex approval pathway. Resultant delays and denials can be particularly problematic for patients with cancer, who often need urgent treatment or symptom management. To investigate the patient perspective of PA for cancer-related care, including perceptions about the process, outcomes (including delays and denials), and patient administrative burden. This cross-sectional, anonymous survey used a convenience sample of patients with PA experience. Participants were recruited using social media and email lists of US-based cancer advocacy organizations from July 1 to October 6, 2022. Prior authorization for any cancer-related service. Delays to care, outcome of PA, communication, and changes in anxiety (measured on a scale of 0-100, with 0 indicating no anxiety and higher scores indicating higher levels of anxiety) and trust. Of 178 respondents (158 women [88%], 151 non-Hispanic White respondents [84%], 164 respondents [92%] <65 years), 112 (63%) reported that their cancer care was approved and given as recommended, and 39 (22%) did not receive recommended care due to delays or denials. Most respondents (123 [69%]) reported a PA-related delay in care; of those with delayed care, 90 (73%) reported a delay of 2 or more weeks. Most respondents (119 [67%]) had to personally become involved in the PA process; 35 (20%) spent 11 or more hours dealing with PA issues. Overall, the PA experience was rated as bad (70 [40%]) or horrible (55 of 174 [32%]); ratings were associated with the length of delay (ρ = 0.36; P < .001) and the time spent on PA (ρ = 0.42; P < .001). Self-reported PA-related anxiety was higher than usual anxiety (mean [SD] score, 74.7 [20.2] vs 37.5 [22.6]; P < .001) and was correlated with delay length (ρ = 0.16; P = .04), time spent on PA (ρ = 0.27; P < .001), and overall PA experience (ρ = 0.34; P < .001). After PA, 159 respondents (89%) trusted their insurance company less, and 148 respondents (83%) trusted the health care system less. Patient involvement in the PA process was associated with increased odds of distrusting their insurance company (β = 6.0; 95% CI, 1.9-19.2) and the health care system (β = 3.3; 95% CI, 1.4-8.1) and of having a negative experience (β = 6.6; 95% CI, 3.1-14.3). This survey-based cross-sectional study of the patient experience with PA highlights an adverse outcome of PA: 22% of patients did not receive the care recommended by their treatment team because of PA. Most respondents experienced a delay in recommended oncology care, and delays were associated with increased anxiety, a negative perception of the PA process, and patient administrative burden.


Nanomaterials-based Drug Delivery Approaches for Wound Healing.
Wound healing is a complex and dynamic process that requires intricate synchronization between multiple cell types within appropriate extracellular microenvironment. Wound healing process involves four overlapping phases in a precisely regulated manner, consisting of hemostasis, inflammation, proliferation, and maturation. For an effective wound healing, all four phases must follow in a sequential pattern within a time frame. Several factors might interfere with one or more of these phases in healing process, thus causing improper or impaired wound healing resulting in non-healing chronic wounds. The complications associated with chronic non-healing wounds, along with the limitations of existing wound therapies, have led to the development and emergence of novel and innovative therapeutic interventions. Nanotechnology presents unique and alternative approaches to accelerate the healing of chronic wounds by the interaction of nanomaterials during different phases of wound healing. This review focuses on recent innovative nanotechnology-based strategies for wound healing and tissue regeneration based on nanomaterials, including nanoparticles, nanocomposites and scaffolds. The efficacy of the intrinsic therapeutic potential of nanomaterials (including silver, gold, zinc oxide, copper, cerium oxide, etc.) and the ability of nanomaterials as carriers (liposomes, hydrogels, polymeric nanomaterials, nanofibers) and therapeutic agents associated with wound-healing applications have also been addressed. The significance of these nanomaterial-based therapeutic interventions for wound healing needs to be highlighted to engage researchers and clinicians towards this new and exciting area of bio-nanoscience. We believe that these recent developments will offer researchers an updated source for the use of nanomaterials as an advanced approach to improve wound healing.


Cognitive and behavioral correlates of low vitamin B12 levels in elderly patients with progressive dementia.
Vitamin B12 deficiency is common in elderly persons, yet its role in dementia and psychiatric illness is unclear. The authors examined the relationship between vitamin B12 serum levels and cognitive and neuropsychiatric symptoms in dementia. Community-dwelling elderly subjects (N=643) meeting NINCDS-ADRDA criteria for probable or possible Alzheimer disease (AD) underwent comprehensive neuropsychiatric evaluation and measurement of vitamin B12 serum levels. Thirty-seven subjects (5.7%) had low B12 serum levels (200 pcg/ml or less). Subjects with low B12 levels were significantly older and had significantly lower scores on the Mini-Mental State Exam and higher scores on the Blessed Dementia Scale, but not a different pattern of cognitive or behavior disturbances compared with the normal-B12 subjects. In AD, the prevalence of low vitamin B12 serum levels is consistent with that found in community-dwelling elderly persons in general but is associated with greater overall cognitive impairment.


3-[2-Hy-droxy-3-(2,4,6-trimethyl-phen-yl)prop-yl]-3-methyl-1-phenyl-thio-urea.
In the title compound, C(20)H(26)N(2)OS, four non-H atoms of the thio-urea unit are approximately planar (r.m.s. deviation = 0.005 Å); the phenyl and benzene rings are twisted out of this plane by 28.55 (7) and 60.00 (7)°, respectively. An intra-molecular N-H⋯O hydrogen bond occurs. The hy-droxy group is hydrogen bonded to the double-bond S atom of an inversion-related mol-ecule, generating a hydrogen-bonded dimer in the crystal structure.


[Loco-regional recurrence of breast cancer].
The treatment of loco-regional recurrence (LRR) after breast cancer is based on the achievement of loco-regional control by radical surgery and adjuvant postoperative radiotherapy. Antiestrogens used as treatment in patients with steroid receptor positive LRR can increase disease free survival. Adjuvant chemotherapy is not applied to patients with LRR who have had radical loco-regional salvage treatment. Further studies are needed to elucidate this issue.


Polymer-clad silica fibers for tailoring modal area and dispersion.
We demonstrate higher-order-mode (Aeff up to ∼2000 μm2) propagation in a 100 μm outer diameter pure-silica fiber with a low-index polymer jacket commonly used for fiber laser pump guidance. This simple structure obviates the need for complex designs deemed necessary for realizing large-mode-area fibers. Modes ranging from HE1,12 to HE1,22 were found to propagate stably over 15 m in this fiber. The index step is approximately 4 times larger than that obtained with fluorine down doping; thus the fiber supports even higher-order modes, which may have implications for building rare-earth-doped fiber lasers or achieving enhanced dispersion tunability for high-energy fiber nonlinear phenomena.


Prognosis of eight Chinese cases of primary vaginal yolk sac tumor with a review of the literature.
Primary vaginal yolk sac tumor is a rare malignancy in the pediatric population, and a diagnostic challenge and appropriate initial treatment remains unsolved. The aim of this study was to investigate the clinicopathologic features, treatment and prognosis of this tumor. Eight cases of primary vaginal yolk sac tumor were reported with a literature review. There were 4 pure yolk sac tumor cases and four mixed germ cell tumors containing yolk sac tumor element, including two cases with embryonal carcinoma and two cases with embryonal carcinoma and dysgerminoma. Partial vaginectomy was performed in four cases and all patients received chemotherapy. 85 cases in literatures were reviewed and 9 cases were misdiagnosed. Follow-up data was available in 77 cases and 5-year overall survival rate was 87.6%. 5-year survival rate of biopsy with chemotherapy, conservative surgery with chemotherapy and radical surgery with chemotherapy was 91.1%, 100% and 28.6%, respectively (p<0.001). Compared to cases without relapse or metastasis after initial treatment, patients with relapse or metastasis had a shorter overall survival (35.6% vs 96.6%, p<0.001). Mixed germ cell tumor containing yolk sac tumor element was not uncommon and partial vaginectomy may be a good choice for primary vaginal mixed yolk sac tumor type to eradicate local tumor cells and provide complete information for pathological diagnosis and postoperative adjuvant therapy.


A spectrophotometric and thermodynamic study of the charge-transfer complexes of N-aryl-N'-isopropyloxycarbonylsulfamides with DDQ and TCNE.
Molecular charge-transfer complexes of three N-aryl-N'-isopropyloxycarbonylsulfamides derivatives with π-acceptors tetracyanoethylene (TCNE), and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), were studied by using zero and second order derivative UV spectrophotometry in different solvents at four different temperatures within the range of 20-35 °C. The stoichiometries of the complexes were found to be 1:1 ratio between donors and acceptors using Job's method. The data were analyzed in terms of their stability constant (K), molar extinction coefficient (εCT), thermodynamic standard reaction quantities (ΔG°, ΔH°, ΔS°), oscillator strength (f), transition dipole moment (μEN) and ionization potential (ID). The results show that the stability constant (K) for the complexes was found to be dependant upon the nature of electron acceptor, electron donor, and polarity of used solvents.


An ecological approach to children's rights and participation: interrelationships and correlates of rights in different ecological systems.
Current knowledge emphasizes either a developmental or a cultural/contextual theoretical framework for understanding children's approaches to the concepts of rights and participation. This study, carried out among 1,753 Israeli adolescents (ages 15-17), uses a socioecological perspective instead to understand children's rights and participation. It examines adolescents' approaches to their rights and participation at 4 ecological levels-family, school, community, and the larger sociopolitical system-as well as a number of possible child, family, and societal correlates. It also looks at the interactions between some of these correlates. The findings show that different correlates have different links with various ecological circles. For example, girls reported higher levels of participation in the family and at school, but no significant differences were found between boys and girls in their participation in the community and at civic-political levels. Israeli Palestinians reported higher levels of participation in their schools and at the civic-political level but lower levels of participation in the family and the community compared with their Jewish counterparts. The significant interaction effect between nation and gender showed that, among Arab students, there were larger gaps between boys and girls in the different participation domains than there were among Jewish students. Furthermore, higher rates of participation in the family and lower rates of civic participation were found among students from single-parent families. This study shows that employing an ecological framework to the efforts to understand children's approaches to rights and participation is a first step in the right direction for fostering children's rights and participation.


Short-term lineage analysis of dorsally derived Olig3 cells in the developing spinal cord.
We examined the migration and differentiation of cells expressing Olig3, a basic helix-loop-helix transcriptional factor, in the developing spinal cord. Distribution of Olig3 lineage cells was demonstrated with in situ hybridization and X-gal staining in an Olig3-lacZ knock-in mouse. Olig3-positive cells first appeared in the dorsal spinal cord, except for the roof plate. Some of the dorsal Olig3 lineage cells co-expressed Islet1/2, Math1, or Brn3a, markers for dorsal interneuron. LacZ-positive cells were observed in the ventral-most part of the E10.5 spinal cord, suggesting that some dorsal Olig3 lineage cells migrate into the ventral-most part by E10.5. Ventral-ward migration of dorsal cells and contribution to commissural interneurons were substantiated by electroporation of EGFP expression plasmid in the dorsal spinal cord of chick embryo. Dorsal midline cells were also LacZ-positive during development. These findings suggest that dorsal Olig3 cells contribute to dorsal midline cells and commissural interneurons at intermediate and ventral levels.


[Current developments in postoperative pain management].
The aim of the postoperative pain therapy is besides the amelioration of the patients well-being, also lessening of unwanted vegetative reactions and avoidance of the need for excessive care situations. There are numerous ways of therapy and medication at our disposal for this purpose. The first line of drugs are the analgesically most active opiates; they can be combined with antiphlogistics and antipyretics, in order to decrease the specific opiate-induced side effects. Besides the parenteral way the epidural application is being used. Local anesthetics are a valuable alternative to the systemic pain relief therapy and can postoperatively be combined with opiates. By this combination the total dose and the relevant side effects can be reduced. During the last years patient-controlled analgesia was the modern way and the nearest approach to ideal dosing. In comparison to the conventional way, its therapeutic success was described as convincing, even overwhelming. Difficulties or deficiencies in the postoperative pain therapy are mostly caused by lack of time and insufficient knowledge and experience of the personnel, on the other hand also by limited technical possibilities of monitoring the patient. A possible solution may be the setting-up of a special service for the treatment of postoperative pain.


Prevention and correction of airway compromise in rhinoplasty.
Recognition of patients who are at high risk for developing postrhinoplasty airway obstruction is essential. These patients may be at risk because of certain anatomic characteristics or may have a preexisting degree of airway obstruction from previous nasal surgery. Every surgeon who performs esthetic or reconstructive rhinoplasty procedures should be familiar with anatomic variants predisposing to airway obstruction and surgical techniques for airway improvement. The author presents case examples illustrating these principles and his methodology for recognizing and correcting airway compromise in primary and secondary rhinoplasty procedures. The use of spreader grafts, columellar graft, batten grafts, and piriform aperture widening are discussed. The author advocates incorporating these techniques to enhance nasal esthetics and function.


Anaplastic lymphoma kinase (ALK) mutations in patients with adenocarcinoma of the lung.
Non-small cell lung cancer (NSCLC) is a major cause of cancer-related death. Approximately 2-16% of NSCLC patients with wild-type epidermal growth factor receptor (EGFR) harbour anaplastic lymphoma kinase (ALK) mutations. Both EGFR and ALK mutations occur most commonly in Asian patients with NSCLC. As targeted therapy is available for NSCLC patients with these mutations, it is important to establish reliable assays and testing strategies to identify those most likely to benefit from this therapy. Patients diagnosed with adenocarcinoma of the lung between 2010 and 2014 were tested for EGFR mutations. Of these, 92 cases were identified as EGFR wild type and suitable candidates for ALK testing utilising immunohistochemistry and the rabbit monoclonal antibody D5F3. The reliability of the IHC was confirmed by validating the results against those achieved by fluorescence in situ hybridisation (FISH) to detect ALK gene rearrangements. Twelve (13%) cases were positive for ALK expression using immunohistochemistry. Of the 18 evaluable cases tested by FISH, there was 100% agreement with respect to ALK rearrangement/ALK expression between the assays, with 11 cases ALK negative and 7 cases ALK positive by both assays. ALK tumour expression was significantly more common in female compared to male patients (29.6% vs. 6.2%, P < 0.001), detected exclusively in patients that had never smoked (P < 0.001) and more frequently in metastases (22.7%) than in primary tumours (10%) (P = 0.047). Detection of ALK expression by IHC is reliable and the most practical way of identifying NSCLC patients likely to benefit from crizotinib treatment.


Laparoscopic Treatment of Gastroesophageal Reflux Disease in Children: How We Do It.
Over decades now, laparoscopic Nissen fundoplication represents the treatment of choice for symptomatic children with gastroesophageal reflux disease (GERD) unresponsive to medication. Although the basic principles of Nissen's technique are still essential today, academic studies of long-term results, complications, and patients benefits have fostered distinct modifications. Identification of surgical factors for wrap migration, dysphagia, and recurrent GERD led to recommendations for "short and floppy" wraps with minimal dissection of the phrenoesophageal membranes. This report summarizes up-to-date information from experts in the field on "how to wrap it right" followed by a critical discussion about long-term benefits for children with GERD and future developments of laparoscopic Nissen fundoplication.


Intestinal permeability in the assessment of intestinal toxicity of cytotoxic agents.
The diagnosis and assessment of the severity of intestinal mucosal damage in cancer patients treated with cytotoxic drugs still rely on anamnestic data. There is cumulative evidence that measurement of intestinal permeability may represent a sensitive indicator of intestinal damage by cytotoxic agents. The intestinal permeability testing is based on differential permeability of tight junctions along the crypt-villus axis to nonmetabolized sugars. Cytotoxic drugs induce flattening of villi, leading to increased exposure of luminal contents to crypts and increased disaccharide absorption. An increased disaccharide/monosaccharide ratio and decreased xylose absorption have been described in patients treated with different cytotoxic drugs across a spectrum of malignant tumors that correlated with clinical manifestations, and were used to monitor the effect of therapeutic interventions.


[Nasal dermoid and sinus cysts in patients with cleft malformations].
Nasal dermoid sinus cysts are uncommon congenital lesions. They are usually isolated occurrences and are not associated with syndromes or additional malformations. The coincidence of both, cleft malformations and nasal dermoid sinus cysts, has seldom been reported. Within the last 2 years two patients with reconstructed cleft lip and palate and additional nasal dermoid sinus cysts underwent surgical removal. One patient with bilateral complete cleft lip exhibited a fistula from the medial third of the nasal dorsum up to the glabella. Another patient with unilateral cleft lip and Peters' plus syndrome had undergone removal of a nasal dermoid sinus cyst 12 years ago and was referred for management of recurrent disease. Concerning the common cleft-dependent nose malformations with no midline nasal masses, there are reasons for the assumption that a coincidence of both anomalies might be accidental. Especially in Peters' plus syndrome no frequent occurrence of nasal dermoids has thus far been documented. However, the proximity and temporal closeness of an embryological pathway of the frontonasal region and lip development could also argue for a unique formation of both lesions. Complete surgical removal and plastic reconstruction simultaneously or in a second step are recommended.


Relative survival of striatal projection neurons and interneurons after intrastriatal injection of quinolinic acid in rats.
An excitotoxic process mediated by the NMDA type glutamate receptor may be involved in striatal neuron death in Huntington's disease (HD). To explore this possibility, we have injected an NMDA-receptor-specific excitotoxin, quinolinic acid (QA), into the striatum in adult rats and 2-4 months postlesion explored the relative patterns of survival for the various different types of striatal projection neurons and interneurons and for the striatal efferent fibers in the different striatal projection areas. The perikarya of specific types of striatal neurons were identified by neurotransmitter immunohistochemical labeling or by retrograde labeling from striatal target areas, while the striatal efferent fiber plexuses were identified by neurotransmitter immunohistochemical labeling. The pattern of survival for the perikarya of each neuron type as a function of distance from the center of the injection site was determined, and the relative survival of each type was compared. For the fibers in target areas, computer-assisted image analysis was used to determine the degree of fiber loss for each projection target. In the study of perikaryal vulnerability, we found that the somatostatin-neuropeptide Y (SS/NPY) interneurons were the most vulnerable to QA and the cholinergic neurons were invulnerable to QA. The perikarya of all projection neuron types (striatopallidal, striatonigral, and striato-entopeduncular) were less vulnerable than the SS/NPY interneurons and more vulnerable than the cholinergic interneurons. Among projection neuron perikarya, there was evidence of differential vulnerability, with striatonigral neurons appearing to be the most vulnerable. Examination of immunolabeled striatal fibers in the striatal target areas indicated that striato-entopeduncular fibers better survived intrastriatal QA than did striatopallidal or striatonigral fibers. The apparent order of vulnerability observed in this study among projection neurons and/or their efferent fiber plexuses and the invulnerability observed in this study of cholinergic interneurons is similar to that observed in HD. The vulnerability of the SS/NPY interneurons to QA is, however, in stark contrast to their invulnerability in HD. The results thus suggest that although the excitotoxin hypothesis of striatal neuron death in HD has merit, QA injections into adult rat striatum do not strictly mimic the outcome in HD. This suggests that either adult rats are not a completely suitable subject for mimicking HD or the HD excitotoxic process does not involve a freely circulating excitotoxin such as QA.


Headspace solid-phase microextraction gas chromatography/mass spectrometry in the analysis of the aroma constituents of 'Cannonau of Jerzu' wine.
"Cannonau of Jerzu" wine is a typical Sardinian product, obtained from only one particular grape variety. Its aroma profile is highly characteristic from the organoleptic point of view but, until now, no analytical investigation of the aroma components has been reported. This aspect has been studied by headspace solid-phase microextraction coupled with gas chromatography/mass spectrometry (GC/MS). Using this approach, 76 abundant aroma components were identified. The results thus obtained show on one hand that the terpene profile is, as expected, dependent on the quality of the grapes (in terms of selection before vintage), and, on the other, that some components are strongly dependent on the production and ageing method.


Tautomers of a Fluorescent G Surrogate and Their Distinct Photophysics Provide Additional Information Channels.
Thienoguanosine ((th) G) is an isomorphic nucleoside analogue acting as a faithful fluorescent substitute of G, with respectable quantum yield in oligonucleotides. Photophysical analysis of (th) G reveals the existence of two ground-state tautomers with significantly shifted absorption and emission wavelengths, and high quantum yield in buffer. Using (TD)-DFT calculations, the tautomers were identified as the H1 and H3 keto-amino tautomers. When incorporated into the loop of (-)PBS, the (-)DNA copy of the HIV-1 primer binding site, both tautomers are observed and show differential sensitivity to protein binding. The red-shifted H1 tautomer is strongly favored in matched (-)/(+)PBS duplexes, while the relative emission of the H3 tautomer can be used to detect single nucleotide polymorphisms. These tautomers and their distinct environmental sensitivity provide unprecedented information channels for analyzing G residues in oligonucleotides and their complexes.


Mapping novel aphid resistance QTL from wild soybean, Glycine soja 85-32.
Two novel QTLs conferring aphid resistance were mapped and validated on soybean chromosomes 8 and 16, respectively. Closely linked markers were developed to assist breeding for aphid resistance. Soybean aphid, Aphis glycines Matsumura, is a highly destructive pest for soybean production. E08934, a soybean advanced breeding line derived from the wild soybean Glycine soja 85-32, has shown strong resistance to aphids. To dissect the genetic basis of aphid resistance in E08934, a mapping population (070020) consisting of 140 F3-derived lines was developed by crossing E08934 with an aphid-susceptible line E00003. This mapping population was evaluated for aphid resistance in a greenhouse trial in 2010 and three field trials in 2009, 2010, and 2011, respectively. The broad-sense heritability across the field trials was 0.84. In the mapping population 070020, two major quantitative trait loci (QTL) were detected as significantly associated with aphid resistance, and designated as Rag6 and Rag3c, respectively. Rag6 was mapped to a 10.5 centiMorgan (cM) interval between markers MSUSNP08-2 and Satt209 on chromosome 8, explaining 19.5-46.4% of the phenotypic variance in different trials. Rag3c was located at a 7.5 cM interval between markers MSUSNP16-10 and Sat_370 on chromosome 16, explaining 12.5-22.9% of the phenotypic variance in different trials. Rag3c had less resistance effect than Rag6 across all the trials. Furthermore, Rag6 and Rag3c were confirmed in two validation populations with different genetic backgrounds. No significant interaction was detected between Rag6 and Rag3c in either the mapping population or the validation populations. Both Rag6 and Rag3c were indicated as conferring antibiosis resistance to aphids by a no-choice test. The new aphid-resistance gene(s) derived from the wild germplasm G. soja 85-32 are valuable in improving soybeans for aphid resistance.


Estimating input parameters from intracellular recordings in the Feller neuronal model.
We study the estimation of the input parameters in a Feller neuronal model from a trajectory of the membrane potential sampled at discrete times. These input parameters are identified with the drift and the infinitesimal variance of the underlying stochastic diffusion process with multiplicative noise. The state space of the process is restricted from below by an inaccessible boundary. Further, the model is characterized by the presence of an absorbing threshold, the first hitting of which determines the length of each trajectory and which constrains the state space from above. We compare, both in the presence and in the absence of the absorbing threshold, the efficiency of different known estimators. In addition, we propose an estimator for the drift term, which is proved to be more efficient than the others, at least in the explored range of the parameters. The presence of the threshold makes the estimates of the drift term biased, and two methods to correct it are proposed.


Synthesis and Evaluation of Cytosolic Phospholipase A(2) Activatable Fluorophores for Cancer Imaging.
Activatable fluorophores selective to cytosolic phospholipase A2 (cPLA2) were synthesized and evaluated for their ability to image triple negative breast cancer cells. The activatable constructs were synthesized by esterification of a small molecule fluorophore with a fatty acid resulting in ablated fluorescence. Selectivity for cPLA2 was generated through the choice of fluorophore and fatty acid. Esterification with arachidonic acid was sufficient to impart specificity to cPLA2 when compared to esterification with palmitic acid. In vitro analysis of probes incorporated into phosphatidylcholine liposomes demonstrated that a nonselective phospholipase (sPLA2 group IB) was able to hydrolyze both arachidonate and palmitate coupled fluorophores resulting in the generation of fluorescence. Of the four fluorophores tested, DDAO (7-hydroxy-9H-(1,3-dichloro-9,9-dimethylacridin-2-one)) was observed to perform optimally in vitro and was analyzed further in 4175-Luc+ cells, a metastatic triple negative human breast cancer cell line expressing high levels of cPLA2. In contrast to the in vitro analysis, DDAO arachidonate was shown to activate selectively in 4175-Luc+ cells compared to the control DDAO palmitate as measured by fluorescence microscopy and quantitated with fluorescence spectroscopy. The addition of two agents known to activate cPLA2 enhanced DDAO arachidonate fluorescence without inducing any change to DDAO palmitate. Inhibition of cPLA2 resulted in reduced fluorescence of DDAO arachidonate but not DDAO palmitate. Together, we report the synthesis of a cPLA2 selective activatable fluorophore capable of detecting cPLA2 in triple negative breast cancer cells.


Vaping and Commitment Flu-B Infection Is a Deadly Combination for Spontaneous Pneumomediastinum.
Vaping or E-cigarettes were created to deliver nicotine-containing aerosol to users with a flavoring agent without agents such as tars, oxidant gases, and carbon monoxide smoke found in traditional tobacco cigarettes. The use of E-cigarettes is steadily increasing in the United States, especially among the young population. Electronic cigarettes seem capable of causing various injury patterns in the lungs, collectively called E-cigarettes or vaping-associated lung injury (EVALI). Spontaneous pneumomediastinum (SPM) is a rare finding in EVALI. Here, we report a case of spontaneous pneumomediastinum secondary to vaping in a young man with no past medical history except for daily vaping and a recent untreated influenza infection.


Influence of Friedreich ataxia GAA noncoding repeat expansions on pre-mRNA processing.
The intronic GAA repeat expansion in the frataxin (FXN) gene causes the hereditary neurodegenerative disorder Friedreich ataxia. Although it is generally believed that GAA repeats block transcription elongation, direct proof in eukaryotic systems is lacking. We tested in hybrid minigenes the effect of GAA and TTC repeats on nascent transcription and pre-mRNA processing. Unexpectedly, disease-causing GAA(100) repeats did not affect transcriptional elongation in a nuclear HeLa Run On assay, nor did they affect pre-mRNA transcript abundance. However, they did result in a complex defect in pre-mRNA processing. The insertion of GAA but not TTC repeats downstream of reporter exons resulted in their partial or complete exclusion from the mature mRNAs and in the generation of a variety of aberrant splicing products. This effect of GAA repeats was observed to be position and context dependent; their insertion at different distances from the reporter exons had a variable effect on splice-site selection. In addition, GAA repeats bind to a multitude of different splicing factors and induced the accumulation of an upstream pre-mRNA splicing intermediate, which is not turned over into mature mRNA. When embedded in the homologous frataxin minigene system, the GAA repeats did not affect the pre-mRNA transcript abundance but did significantly reduce the splicing efficiency of the first intron. These data indicate an association between GAA noncoding repeats and aberrant pre-mRNA processing because binding of transcribed GAA repeats to a multitude of trans-acting splicing factors can interfere with normal turnover of intronic RNA and thus lead to its degradation and a lower abundance of mature mRNA.


Breit interaction contribution to parity violating potentials in chiral molecules containing light nuclei.
The importance of the Breit interaction for an accurate prediction of parity violating energy differences between enantiomers is studied within electroweak quantum chemical frameworks. Besides two-electron orbit-orbit and spin-spin coupling contributions, the Breit interaction gives rise to the spin-other-orbit coupling term of the Breit-Pauli Hamiltonian. The present numerical study demonstrates that neglect of this latter term leads in hydrogen peroxide (H(2)O(2)) to relative deviations in the parity violating potential (V(pv)) by about 10%, whereas further relativistic corrections accounted for within a four-component Dirac-Hartree-Fock-Coulomb (DHFC) framework remain smaller, below 5%. Thus, the main source of discrepancy between previous one-component based (coupled perturbed) Hartree-Fock (HF) and four-component Dirac-Hartree-Fock results for parity violating potentials in H(2)O(2) is the neglect of the Breit contribution in DHFC. In heavier homologs of hydrogen peroxide the relative contribution of the spin-other-orbit coupling term to V(pv) decreases with increasing nuclear charge, whereas other relativistic effects become increasingly important. As shown for the H(2)X(2) (X = O,S,Se,Te,Po) series of molecules and for CHBrClF, to a good approximation these other relativistic influences on V(pv) can be accounted for in one-component based HF calculations with the help of relativistic enhancement factors proposed earlier in the theory of atomic parity violation.


Effects of Orbicularis Oculi Flap Suspension on Transcutaneous Lower Blepharoplasty.
The purpose of this study was to analyze the clinical effects of orbicularis oculi muscle suspension in conjunction with transcutaneous blepharoplasty in patients 60 years of age or older. A retrospective study was conducted on patients aged 60 or older who underwent orbicularis oculi flap suspension in conjunction with transcutaneous blepharoplasty to treat lower lid festoons, lower lid fat prolapse, and lid laxity at Korea University Guro Hospital. The outcomes were surgical success rate, recurrence rate, postoperative complications, and patient satisfaction. In total, 39 patients (18 males and 21 females) were included, with an average age of 67.5 years (60-86 y) and a follow-up period of 145.7 days (95-195 d). In all patients, eyelid laxity was effectively corrected, and there was no recurrence of eyelid laxity after surgery. Three patients suffered postoperative complications, transient skin edema in 2 patients, and transient ectropion in 1 patient. Subjective satisfaction score following surgery was high, with an average score of 2.56 out of 3 points. Orbicularis oculi flap suspension with transcutaneous blepharoplasty can shorten operation time due to surgical ease. It also has the advantage of not involving conjunctival-related complications such as conjunctival edema since it does not pass through the conjunctiva. Finally, it can successfully treat lid laxity and could be used in lower blepharoplasty procedures.


Adapting to Space Limitations During Prone Real-Time Magnetic Resonance Imaging-Guided Stereotaxic Laser Ablation: Technical Pearls.
New techniques of intraoperative magnetic resonance imaging (MRI)-guided stereotaxy enable minimally invasive approaches to intracranial pathology. Laser interstitial thermal therapy (LITT), convection-enhanced drug delivery, and stereotactic biopsy can be performed with a real-time confirmation of location and the ability to adjust for intracranial shift during the procedure. However, these procedures are constrained by patient positioning and the need for trajectories that avoid collision between stereotactic elements and the small MRI bore. To our knowledge, this is the first report to outline the technical details of safe intraoperative MRI (iMRI)-guided stereotaxy, performed with prone positioning. To present technical pearls to guide the safe conduction of iMRI-guided stereotaxy and LITT while in the prone position. The details of the positioning and trajectories for a series of patients who underwent Clearpoint® (MRI Interventions Inc) frameless real-time MRI-guided stereotaxis using a posterior approach were reviewed. In this series, 5 patients underwent selective amygdalohippocampectomy, and 2 underwent tumor biopsy/ablation while in the prone position without any complications. Prone iMRI procedures can be performed safely even in a 60-cm MRI bore.


[Diagnosis of wrist joint lesions by arthrosonography in early rheumatoid arthritis].
To assess joint and extraarticular wrist lesions in RA patients with arthrosonography in the disease duration up to 6 months. 38 RA patients aged 40 +/- 10.5 years (25 females and 13 males) entered the study. These patients and 20 controls without musculoskeletal pathology matched by age and sex have undergone sonographic examination of the wrists and extrajoint structures. The following ultrasonographic signs of intra- and extra-articular inflammation were determined: joint cavity expansion, the presence of anechoic/hypoechoic synovial fluid, effusions, synovial thickening, digital flexor and extensor tenosynovitis, incongruous articular surfaces, bone erosions. Wrist arthrosonography is an informative diagnostic method in early RA as it detects bone erosions, alterations in the cartilages, muscles, tendons and ligaments.


Silane and Germane Molecular Electronics.
This Account provides an overview of our recent efforts to uncover the fundamental charge transport properties of Si-Si and Ge-Ge single bonds and introduce useful functions into group 14 molecular wires. We utilize the tools of chemical synthesis and a scanning tunneling microscopy-based break-junction technique to study the mechanism of charge transport in these molecular systems. We evaluated the fundamental ability of silicon, germanium, and carbon molecular wires to transport charge by comparing conductances within families of well-defined structures, the members of which differ only in the number of Si (or Ge or C) atoms in the wire. For each family, this procedure yielded a length-dependent conductance decay parameter, β. Comparison of the different β values demonstrates that Si-Si and Ge-Ge σ bonds are more conductive than the analogous C-C σ bonds. These molecular trends mirror what is seen in the bulk. The conductance decay of Si and Ge-based wires is similar in magnitude to those from π-based molecular wires such as paraphenylenes However, the chemistry of the linkers that attach the molecular wires to the electrodes has a large influence on the resulting β value. For example, Si- and Ge-based wires of many different lengths connected with a methyl-thiomethyl linker give β values of 0.36-0.39 Å-1, whereas Si- and Ge-based wires connected with aryl-thiomethyl groups give drastically different β values for short and long wires. This observation inspired us to study molecular wires that are composed of both π- and σ-orbitals. The sequence and composition of group 14 atoms in the σ chain modulates the electronic coupling between the π end-groups and dictates the molecular conductance. The conductance behavior originates from the coupling between the subunits, which can be understood by considering periodic trends such as bond length, polarizability, and bond polarity. We found that the same periodic trends determine the electric field-induced breakdown properties of individual Si-Si, Ge-Ge, Si-O, Si-C, and C-C bonds. Building from these studies, we have prepared a system that has two different, alternative conductance pathways. In this wire, we can intentionally break a labile, strained silicon-silicon bond and thereby shunt the current through the secondary conduction pathway. This type of in situ bond-rupture provides a new tool to study single molecule reactions that are induced by electric fields. Moreover, these studies provide guidance for designing dielectric materials as well as molecular devices that require stability under high voltage bias. The fundamental studies on the structure/function relationships of the molecular wires have guided the design of new functional systems based on the Si- and Ge-based wires. For example, we exploited the principle of strain-induced Lewis acidity from reaction chemistry to design a single molecule switch that can be controllably switched between two conductive states by varying the distance between the tip and substrate electrodes. We found that the strain intrinsic to the disilaacenaphthene scaffold also creates two state conductance switching. Finally, we demonstrate the first example of a stereoelectronic conductance switch, and we demonstrate that the switching relies crucially on the electronic delocalization in Si-Si and Ge-Ge wire backbones. These studies illustrate the untapped potential in using Si- and Ge-based wires to design and control charge transport at the nanoscale and to allow quantum mechanics to be used as a tool to design ultraminiaturized switches.


Determination of the disulfide bridges in factor Va heavy chain.
The M(r) = 94,000 heavy chain of bovine factor Va contains 10 cysteine residues which are distributed in the 2 A domains which make up this portion of the factor V molecule. The A1 domain contains four cysteines while the A2 domain contains six cysteines. The locations of disulfide bridges and free cysteines in bovine factor Va heavy chain were analyzed using iodo[14C]acetamide-labeled factor Va heavy chain digested with trypsin, plasmin, V-8 protease, and cyanogen bromide. Following HPLC separation of the resulting peptides, free cysteines were identified by the incorporation of radioactivity while disulfide-containing peptides were detected using an SBD-F fluorometric assay after reduction. All cysteine-containing peptides were analyzed by amino acid sequence analysis. The four cysteines in the A1 domain are associated with two disulfide bonds, Cys139-Cys165 and Cys220-Cys301. One disulfide bond was explicitly identified in the A2 domain; Cys471-Cys497, and a free cysteine was found in the A2 domain at Cys538. Significant difficulties were encountered in preparing identifiable or soluble peptides which would permit the explicit identification of the three remaining cysteines in the A2 domain. On the basis of homology, it is likely that Cys589 is a free SH while a disulfide bridge exists between Cys579 and Cys660. Thus, three major disulfide bonding patterns, characterized as "alpha", "beta", and "gamma" loops, are found in factor V. Each A domain contains a 26 residue "alpha loop at positions 139-165, 471-497, and 1684-1710. The A1 and A2 domains each contain 81 amino acid residue "beta" loops at 220-301 and 579-660.(ABSTRACT TRUNCATED AT 250 WORDS)


[Comparison of short-term result between high-flex and conventional posterior-stabilized prosthesis in total knee arthroplasty].
To compare the short-term result between the high-flex (HF) and conventional posterior-stabilized (PS) prosthesis in total knee arthroplasty (TKA). From April 2005 to October 2007, 23 cases (27 knees) underwent TKA by HF prosthesis (HF group), and 35 cases (41 knees) underwent TKA by PS prosthesis (PS group). In HF group, there were 2 males (3 knees) and 21 females (24 knees) aged (64.3 +/- 5.6) years, including 20 cases (23 knees) of osteoarthritis and 3 cases (4 knees) of rheumatoid arthritis; body mass index (BMI) was 27.3 +/- 3.9; the course of disease was (5.3 +/- 5.6) years; the Hospital for Special Surgery Scoring System (HSS) score was 58.4 +/- 7.9; the Western Ontario and McMaster universities osteoarthritis index (WOMAC) score was 49.4 +/- 6.9; the maximum knee flex degree was (107.6 +/- 8.3) degrees; and the range of knee motion was (103.5 +/- 7.7) degrees. In PS group, there were 3 males (3 knees) and 32 females (38 knees) aged (65.1 +/- 5.9) years, including 33 cases (39 knees) of osteoarthritis and 2 cases (2 knees) of rheumatoid arthritis; BMI was 27.1 +/- 4.1; the course of disease was (5.1 +/- 4.9) years; HSS score was 60.1 +/- 10.4; WOMAC score was 47.9 +/- 7.2; the maximum knee flex degree was (108.4 +/- 9.7) degrees; and the range of knee motion was (105.9 +/- 11.4) degrees. There were no significant differences in general data between two groups (P > 0.05). All incisions achieved healing by first intention. No complication of ankylosis, blood vessel and nerve injuries, and prosthesis loosening occurred. All patients were followed up for 24-54 months (average 32.8 months). There were no significant differences in the HSS score, WOMAC score, the maximum knee flex degrees, and the range of knee motion at 3, 12, and 24 months after operation between two groups (P > 0.05), but there were significant differences between pre- and post-operation (P < 0.05). Anterior knee pain occurred in 1 case of HF group and 4 cases of PS group after 24 months, the incidence rates were 3.70% in HF group and 9.76% in PS group, showing significant difference (P < 0.05). The X-ray films showed that no lucent zone around prosthesis and no patella baja were observed, and the force line was excellent. There is no significant difference in the range of knee motion and clinical scores between the HF prosthesis and the PS prosthesis, but the former's incidence rate of anterior knee pain is lower.


The Clifton Assessment Schedule - further validation of a psychogeriatric assessment schedule.
This paper is concerned with the further evaluation of the Clifton Assessment Schedule (CAS), a brief psychogeriatric assessment procedure, providing a cross-validation study on a second sample of acute elderly psychiatric admissions. Additionally, further work is reported on its use with a psychogeriatric population resident within the hospital. The results suggest the usefulness of the CAS across a broad range of psychogeriatric patients, providing significant differentiation between groups receiving varying degrees of care and with differing outcome expectations.


Empathy and 'empathism'.
The author begins by tracing the history of the concept of empathy in psychoanalysis, noting that, largely through the influence of Kohut, it began to feature prominently in the literature from the late 1950s on and has since tended, wrongly in his opinion, to be regarded as an all-purpose instrument to be deployed at will. What is often described in theoretical contributions as empathy should in the author's view more properly be called concordance. On the clinical level, the idea that the analyst must deliberately seek to empathise with the patient is stated to have gained currency, but the author argues that such an attempt to achieve empathy by force can lead only to 'empathism', which is a dogmatic, hyperconcordant attitude whereby the inexperienced analyst in particular thinks he can control the process better. Clinical material is presented to show how some patients set out to induce 'empathism' in the analyst for defensive reasons and how the analyst's concordance, until analysed, may lead to an impasse. The author stresses that genuine empathy is a state of complementary conscious-preconscious contact based on separateness and sharing; covering not only the patient's ego-syntonic subjectivity but also his defensive ego and split-off parts, its achievement requires prolonged hard work on the countertransference and a capacity for contact with the analyst's own primitive aspects. The paper ends with a consideration of the possible obstacles to empathic contact.


Mass spectrometry of the white adipose metabolome in a hibernating mammal reveals seasonal changes in alternate fuels and carnitine derivatives.
Mammalian hibernators undergo substantial changes in metabolic function throughout the seasonal hibernation cycle. We report here the polar metabolomic profile of white adipose tissue isolated from active and hibernating thirteen-lined ground squirrels (Ictidomys tridecemlineatus). Polar compounds in white adipose tissue were extracted from five groups representing different timepoints throughout the seasonal activity-torpor cycle and analyzed using hydrophilic interaction liquid chromatography-mass spectrometry in both the positive and negative ion modes. A total of 224 compounds out of 660 features detected after curation were annotated. Unsupervised clustering using principal component analysis revealed discrete clusters representing the different seasonal timepoints throughout hibernation. One-way analysis of variance and feature intensity heatmaps revealed metabolites that varied in abundance between active and torpid timepoints. Pathway analysis compared against the KEGG database demonstrated enrichment of amino acid metabolism, purine metabolism, glycerophospholipid metabolism, and coenzyme A biosynthetic pathways among our identified compounds. Numerous carnitine derivatives and a ketone that serves as an alternate fuel source, beta-hydroxybutyrate (BHB), were among molecules found to be elevated during torpor. Elevated levels of the BHB-carnitine conjugate during torpor suggests the synthesis of beta-hydroxybutyrate in white adipose mitochondria, which may contribute directly to elevated levels of circulating BHB during hibernation.


[Andreas Dudith's thoughts on medicine].
The author analyses the scientific, first of all medical conceptions of András Dudith, the Hungarian humanist of the 16th century. His attitude to medicine is reconstructed from his wide-ranging correspondence. It is pointed out that without taking into consideration the metaphysical notions of Dudith, his views on epidemiology cannot be discussed. His epistemological considerations and value orientation deduced from his metaphysical notions give the key to the author to explore the relation of Dudith to natural sciences and medicine, and to make statements concerning his religion as well. The author demonstrates that in Dudith's opinion the world could be described as a chain of causes conceived as one-direction influence. In order to avoid infinite regression, he separated three spheres of causes and effects, out of which it is the sphere of immediate causes where medicine has reason for existence. Dudith's epidemiological views are based on his causal conceptions and are free of any irrational element in spite of the fact that they took shape in a speculative way. He held the view that the cause of plague is infection, in opposition to the general belief attributing plague to the effect of infected air. Dudith considered the sporadic cases and the epidemic form of plague identical diseases. He possessed several empirical facts concerning the way of spreading from man to man, which solved the problem of two kinds of occurrence and made it possible for him to set up a chain of causation. The cause is the infection (rot), the effect is the disease, which is the cause of the epidemic. Dudith elucidated medical problems on a conceptual basis, consistently increasing the level of abstraction, then, after determining the gaps in knowledge, he raised new questions and tried to answer them on an empirical ground to be able to apply the same method again. ...


[Not Available].
In the past 50 years, Soviet forensic psychiatry has directed its main endeavours towards solution of the problems of organization of forensic psychiatric expert examination, finding the most appropriate forms of handling law offenders--mental patients--as well as towards elucidation of the phenomenology of the morbid process under conditions of preliminary inquest, with prison, and finding with greatest precision the criteria for irresponsibility and incapacity in various diseases.


Effect of Electroacupuncture on the Expression of Glycyl-tRNA Synthetase and Ultrastructure Changes in Atrophied Rat Peroneus Longus Muscle Induced by Sciatic Nerve Injection Injury.
Glycyl-tRNA synthetase (GlyRS) is one of the key enzymes involved in protein synthesis. Its mutations have been reported to cause Charcot-Marie-Tooth disease which demonstrates muscular atrophy in distal extremities, particularly manifested in peroneus muscles. In this situation, the dysfunctions of mitochondria and sarcoplasmic reticulum (SR) affect energy supply and excitation-contraction coupling of muscle fibers, therefore resulting in muscular atrophy. Although the treatment of muscular atrophy is a global urgent problem, it can be improved by electroacupuncture (EA) treatment. To investigate the mechanism underlying EA treatment improving muscular atrophy, we focused on the perspective of protein synthesis by establishing a penicillin injection-induced sciatic nerve injury model. In our model, injured rats without treatment showed decreased sciatic functional index (SFI), decreased peroneus longus muscle weight and muscle fiber cross-sectional area, aggregated mitochondria with vacuoles appearing, swollen SR, and downregulated mRNA and protein expression levels of GlyRS and myosin heavy chain IIb (MHC-IIb). The injured rats with EA treatment showed significant recovery. These results indicated that EA stimulation can alleviate peroneus longus muscular atrophy induced by iatrogenic sciatic nerve injury through promoting the recovery of GlyRS and muscle ultrastructure and increasing muscle protein synthesis.


On the Existence of Constant Accrual Rates in Clinical Trials and Direction for Future Research.
Many clinical trials fall short of their accrual goals. This can be avoided with accurate accrual prediction tools. Past researchers provide important methodological alternative models for predicting accrual in clinical trials. One model allows for slow accrual at the start of the study, which eventually reaches a threshold. A simpler model assumes a constant rate of accrual. A comparison has been attempted but we wish to point out some important considerations when comparing these two models. In fact, we can examine the reasonableness of a constant accrual assumption (simpler model) which had data 239 days into a three-year study. We can now update that and report accumulated from the full three years of accrual data and we can demonstrate that constant accrual rate assumption was met in this particular study. We will use this report to frame future research in the area of accrual prediction.


Induction of H-2-restricted contact hypersensitivity by hapten-derivatized skin grafts. Evidence that the immunogenic signal includes H-2 determinants derived from the skin.
Contact hypersensitivity has been induced in mice grafted with skin derivatized with dinitrofluorobenzene. At optimal concentration of epicutaneously applied hapten (0.02%), it was found that syngeneic, but not allogeneic, skin grafts induced sensitivity. Genetic identity of graft donors and recipients at class I or class II loci of H-2 was essential and sufficient for induction of sensitization. The fact that Ia antigens on haptenated grafts restricted the response indicates that Langerhans cells, the only Ia-bearing cells of the normal murine epidermis, function as antigen presenting cells. Nonvital syngeneic, but not allogeneic, grafts were able to induce contact hypersensitivity, so it is proposed that the immunogenic signal derived from haptenated skin grafts consists of hapten and a class I or class II MHC gene product, but need not necessarily be delivered on a viable cell.


In vivo evidence of gamma-tocotrienol as a chemosensitizer in the treatment of hormone-refractory prostate cancer.
gamma-Tocotrienol (gammaT3) is known to selectively kill prostate cancer (PCa) cells and to sensitize the cells to docetaxel (DTX)-induced apoptosis. In the present study, the pharmacokinetics of gammaT3 and the in vivo cytotoxic response of androgen-independent prostate cancer (AIPCa) tumor following gammaT3 treatment were investigated. Here, we investigated these antitumor effects for PCa tumors in vivo. The pharmacokinetic and tissue distribution of gammaT3 after exogenous gammaT3 supplementation were examined. Meanwhile, the response of the tumor to gammaT3 alone or in combination with DTX were studied by real-time in vivo bioluminescent imaging and by examination of biomarkers associated with cell proliferation and apoptosis. After intraperitoneal injection, gammaT3 rapidly disappeared from the serum and was selectively deposited in the AIPCa tumor cells. Administration of gammaT3 alone for 2 weeks resulted in a significant shrinkage of the AIPCa tumors. Meanwhile, further inhibition of the AIPCa tumor growth was achieved by combined treatment of gammaT3 and DTX (p < 0.002). The in vivo cytotoxic antitumor effects induced by gammaT3 seem to be associated with a decrease in expression of cell proliferation markers (proliferating cell nuclear antigen, Ki-67 and Id1) and an increase in the rate of cancer cell apoptosis [cleaved caspase 3 and poly(ADP-ribose) polymerase]. Additionally, the combined agents may be more effective at suppressing the invasiveness of AIPCa. Overall, our results indicate that gammaT3, either alone or in combination with DTX, may provide a treatment strategy that can improve therapeutic efficacy against AIPCa while reducing the toxicity often seen in patients treated with DTX.


Response of an in vivo-in vitro tumour to X-rays and cytotoxic drugs: effect of tumour disaggregation method on cell survival.
EMT-6/UW tumours were treated in vivo with X-rays, cyclophosphamide, or bleomycin. Cell survival was assayed in vitro following tumour disaggregation with trypsin or an enzyme cocktail (EC) consisting of pronase, collagenase and DNase which gives a 10-20 x higher cell yield. Surviving fraction was lower after cyclophosphamide treatment for cells isolated with EC than for cells prepared with trypsin. The opposite result was obtained with bleomycin; trypsin-isolated cells appeared more sensitive. In attempting to determine the basis for this discrepancy, it was found that both dissociation methods isolate a non-representative cell sample with fewer cells in DNA synthesis (12-13%) than in the original tumour (approximately 22%). The specific nature of the interaction between the injury caused by drug and enzyme remains to be elucidated.


Platinum Twin and Triplet Drugs Improve Chemoimmunotherapy.
Several chemoimmunotherapy regimens have been approved by the U.S. FDA, verifying the great clinical value and potential of the strategy. However, the immunomodulatory function of chemotherapy was insufficient, which did not provide extra overall survival benefits, especially in a head-to-head comparison of chemoimmunotherapy versus immunotherapy. Here, we engineered twin and triplet drugs derived from an immunogenic chemotherapeutic drug (oxaliplatin) and small-molecule inhibitors of negative immunoregulation pathways (COX2 and IDO) in tumors as an improved chemotherapeutic component within chemoimmunotherapy. The twin and triplet drugs exhibited significantly improved synergy with anti-PD-1 in a CT26 colorectal mouse tumor model. Mechanistic analyses revealed that the drug induced immunogenic cell death and restored tumor immune microenvironment toward tumor clearance in vivo, resulting in a great decrease in tumor-infiltrating Tregs and an increase in the CD8+ T/Treg ratio when combined with anti-PD-1. Our work expands the application of platinum twin drugs in combination with an immune checkpoint blockade.


[Mechanisms of impaired perfusion recovery in type 1 diabetic mouse].
To investigate the perfusion restoration of type 1 diabetic mouse under the setting of surgically induced hind limb ischemia and the number and function of bone marrow endothelial progenitor cells (EPCs). Forty mice were randomly divided into two groups: one group was injected with alloxan through tail vein to induce type 1 diabetes mellitus, and another group was set as control group. All mice were surgically induced to hind limb ischemia. Blood flow was monitored with Laser Doppler perfusion imaging for 4 weeks after artery ligation. Ten mice in each group were sacrificed and muscle tissues were harvested for histological detection. The remaining mice were sacrificed 7 days after surgery, bone marrow mesenchymal stem cells were harvested and EPCs were analyzed by flow cytometry and then were collected to culture for functional detection. All mice received alloxan injection showed typical symptoms of type 1 diabetes mellitus. Restoration of blood flow was significantly slower in type 1 diabetic mice with lower level of vascular density in ischemic muscles than control group (P < 0.001, P < 0.05). The number and function of EPCs (CD34 and vascular endothelial growth factor receptor 2 double positive cells) in type 1 diabetic mice were significantly lower than that in control mice (P < 0.05). The spontaneous angiogenesis is attenuated with a decreased number and function of EPCs in the setting of type 1 diabetes mellitus. This may partly explain why diabetic patients with peripheral artery diseases have more aggressive disease and poorer outcome.


Watercress-based electrospun nanofibrous scaffolds enhance proliferation and stemness preservation of human adipose-derived stem cells.
The present study describes the effects of Watercress extract (WE) based electrospun nanofibrous mats on the regulation of adhesion, proliferation, cytoprotection and stemness preservation of adipose-derived stem cells (ADSCs). Watercress (Nasturtium officinale) is one of the most important medicinal plant with a board spectrum of biological functions. For this purpose, WE-loaded PCL-PEG nanofibers were fabricated by electrospinning and characterized using FE-SEM and FTIR. Adhesion, proliferation and cytoprotection of ADSCs on the nanofibers was investigated using FE-SEM and MTT assays. Analysis of cell cycle was carried out by flow-cytometry. Finally, qPCR was applied to measure the expression levels of cell cycle-regulated genes and stemness markers of ADSCs grown on the nanofibers. In this study, we found that WE-loaded PCL-PEG nanofibers had great antioxidant potential and exhibited higher cytoprotection, better adhesion, and significantly increased proliferation of ADSCs. The greater proliferation and preserving stemness ability of ADSCs on WE based nanofibers was further confirmed by higher expression levels of cell cycle-regulated genes and stemness markers. These results demonstrate that WE-loaded PCL-PEG electrospun nanofibrous mats appear suitable to support ADSCs adhesion and proliferation while concurrently preserving the cell stemness, therefore representing a hopeful approach for applying in stem cell based regenerative medicine.


Migraine and breast cancer risk: a meta-analysis of observational studies based on MOOSE compliant.
It has long been speculated that migraine may contribute to an increased risk of breast cancer; however, results from previous studies have been inconclusive. To definitively interrogate this issue, we performed a meta-analysis to assess the correlation between these 2 diseases.Medline and PubMed were searched to identify relevant studies that had been published until October 2015. Based on a random effects model, relative risk (RR) and the corresponding 95% confidence interval (CI) were used to evaluate the pooled risk.A total of 7 studies involving 17,776 cases and 162,954 participants were included. Our study revealed that there was an inverse relationship between migraine and total breast cancer risk, with RR (95%CI) was 0.78 (0.66, 0.92). In subgroup-analysis, such an inverse relationship was also identified in the ductal and lobular carcinoma, case-control studies, and the ER/PR breast cancer. Little evidence indicative of a publication bias was uncovered.In conclusion, our study implicates a statistically significant inverse association between migraine and the risk of breast cancer. However, larger prospective cohort studies concerning other geographic populations to assess the association between migraine and the breast cancer risk are warranted.


Advances in acute lymphoblastic leukemia.
Current literature. Acute lymphoblastic leukemia (ALL) is a stem cell disorder characterized by an overproduction of lymphoblasts in the bone marrow that eventually spill into circulation, producing lymphocytosis. As with the other acute leukemias, the most common symptoms experienced by patients include fatigue, bleeding, and recurrent infections resulting from the suppression of normal hematopoiesis in the bone marrow by the accumulating blasts. ALL primarily affects children and exhibits the best response to standard chemotherapy as compared to acute myeloblastic leukemias (AML). Further, remission rates are highest among ALL patients, many of whom are experiencing sustained remissions suggesting cure. In light of early treatment successes, researchers began to investigate modifications of standard treatment regimens to accommodate variability in weight, age, and response to therapy among children with ALL. Individualized treatment plans were implemented where some patients received a reduced intensity course of therapy to minimize drug toxicity while others received drug intensification to maximize response. More recently, research efforts have been directed at the elucidation of leukemogenic mechanisms implicated in ALL to identify specific protein mutants that can be used to design drugs tailored to interfere with the activity of these mutant protein targets. Identification of chimeric proteins produced from chromosomal translocations and gene expression profiles from microarray analyses are the primary techniques used to identify the potential therapeutic targets. Several reliable prognostic indicators have been identified and are being used to improve therapeutic planning and outcome prediction in ALL patients. Individualized treatment regimens have been developed based on the specific characteristics of each patient to minimize treatment related adverse events and maximize response. Through the use of cytogenetic, molecular, and microarray testing, ALL classification schemes have improved and potential therapeutic targets have been identified. It is anticipated that the next major advance in the treatment of ALL will involve the use of designer therapies developed to specifically interfere with particular molecular abnormalities producing the leukemogenic aberration to the normal signal transduction pathways.


Synthesis and unique photoluminescence properties of nitrogen-rich quantum dots and their applications.
Nitrogen-rich quantum dots (N-dots) were serendipitously synthesized in methanol or aqueous solution at a reaction temperature as low as 50 °C. These N-dots have a small size (less than 10 nm) and contain a high percentage of the element nitrogen, and are thus a new member of quantum-dot family. These N-dots show unique and distinct photoluminescence properties with an increasing percentage of nitrogen compared to the neighboring carbon dots. The photoluminescence behavior was adjusted from blue to green simply through variation of the reaction temperature. Furthermore, the detailed mechanism of N-dot formation was also proposed with the trapped intermediate. These N-dots have also shown promising applications as fluorescent ink and biocompatible staining in C. elegans.


Antimicrobial Activity of Essential Oils against Streptococcus mutans and their Antiproliferative Effects.
This study aimed to evaluate the activity of essential oils (EOs) against Streptococcus mutans biofilm by chemically characterizing their fractions responsible for biological and antiproliferative activity. Twenty EO were obtained by hydrodistillation and submitted to the antimicrobial assay (minimum inhibitory (MIC) and bactericidal (MBC) concentrations) against S. mutans UA159. Thin-layer chromatography and gas chromatography/mass spectrometry were used for phytochemical analyses. EOs were selected according to predetermined criteria and fractionated using dry column; the resulting fractions were assessed by MIC and MBC, selected as active fractions, and evaluated against S. mutans biofilm. Biofilms formed were examined using scanning electron microscopy. Selected EOs and their selected active fractions were evaluated for their antiproliferative activity against keratinocytes and seven human tumor cell lines. MIC and MBC values obtained for EO and their active fractions showed strong antimicrobial activity. Chemical analyses mainly showed the presence of terpenes. The selected active fractions inhibited S. mutans biofilm formation (P < 0.05) did not affect glycolytic pH drop and were inactive against keratinocytes, normal cell line. In conclusion, EO showed activity at low concentrations, and their selected active fractions were also effective against biofilm formed by S. mutans and human tumor cell lines.


A review of compliance to treatment in Alzheimer's disease: potential benefits of a transdermal patch.
Following prescribed medication regimens is essential for the effective treatment of any medical condition. Unfortunately, patients often fail to follow recommendations, and treatment non-compliance represents a widespread, often underestimated problem, placing tremendous burden on the healthcare system. Compliance in Alzheimer's disease (AD), a chronic neurodegenerative disease typically afflicting older adults, is especially challenging. To review factors contributing to poor treatment compliance in AD, considering the prominent role care givers often play in treatment management; and acknowledging strategic approaches, particularly modern transdermal patches, to improve compliance in this particularly susceptible population. Articles were identified by searching MEDLINE in November 2006 (search limits: 1987-2007) using the terms: compliance; Alzheimer's; treatment; and transdermal. Additional resources included bibliographies of identified articles. Strategic approaches to improving treatment compliance include: simplifying treatment regimens, using reminder packaging, and developing more patient- or caregiver-friendly modes of administration. To date, AD therapies have been administered orally. However, recent developments in alternative modes of drug delivery, such as transdermal patches, may offer effective, well-tolerated treatment options with the potential to enhance compliance. A patch containing rivastigmine (Exelon), an established cholinesterase inhibitor, has been developed and demonstrated to have good efficacy and tolerability in patients with AD. In addition, initial caregiver experience suggests preference for the patch over oral administration. Transdermal patches may be an effective way to optimize treatment compliance for AD, as well as an increasing number of other chronic conditions that typically afflict the older population, offering the possibility of more sustained clinical benefits.