Prevention of eating disorders in at-risk college-age women.
Eating disorders, an important health problem among college-age women, may be preventable, given that modifiable risk factors for eating disorders have been identified and interventions have been evaluated to reduce these risk factors. To determine if an Internet-based psychosocial intervention can prevent the onset of eating disorders (EDs) in young women at risk for developing EDs. San Diego and the San Francisco Bay Area in California. College-age women with high weight and shape concerns were recruited via campus e-mails, posters, and mass media. Six hundred thirty-seven eligible participants were identified, of whom 157 were excluded, for a total sample of 480. Recruitment occurred between November 13, 2000, and October 10, 2003. Intervention A randomized controlled trial of an 8-week, Internet-based cognitive-behavioral intervention (Student Bodies) that included a moderated online discussion group. Participants were studied for up to 3 years. The main outcome measure was time to onset of a subclinical or clinical ED. Secondary measures included change in scores on the Weight Concerns Scale, Global Eating Disorder Examination Questionnaire, and Eating Disorder Inventory drive for thinness and bulimia subscales and depressed mood. Moderators of outcome were examined. There was a significant reduction in Weight Concerns Scale scores in the Student Bodies intervention group compared with the control group at postintervention (P < .001), 1 year (P < .001), and 2 years (P < .001). The slope for reducing Weight Concerns Scale score was significantly greater in the treatment compared with the control group (P = .02). Over the course of follow-up, 43 participants developed subclinical or clinical EDs. While there was no overall significant difference in onset of EDs between the intervention and control groups, the intervention significantly reduced the onset of EDs in 2 subgroups identified through moderator analyses: (1) participants with an elevated body mass index (BMI) (> or =25, calculated as weight in kilograms divided by height in meters squared) at baseline and (2) at 1 site, participants with baseline compensatory behaviors (eg, self-induced vomiting, laxative use, diuretic use, diet pill use, driven exercise). No intervention participant with an elevated baseline BMI developed an ED, while the rates of onset of ED in the comparable BMI control group (based on survival analysis) were 4.7% at 1 year and 11.9% at 2 years. In the subgroup with a BMI of 25 or higher, the cumulative survival incidence was significantly lower at 2 years for the intervention compared with the control group (95% confidence interval, 0% for intervention group; 2.7% to 21.1% for control group). For the San Francisco Bay Area site sample with baseline compensatory behaviors, 4% of participants in the intervention group developed EDs at 1 year and 14.4%, by 2 years. Rates for the comparable control group were 16% and 30.4%, respectively. Among college-age women with high weight and shape concerns, an 8-week, Internet-based cognitive-behavioral intervention can significantly reduce weight and shape concerns for up to 2 years and decrease risk for the onset of EDs, at least in some high-risk groups. To our knowledge, this is the first study to show that EDs can be prevented in high-risk groups.


[Her-2 amplification and p185 expression in invasive breast cancer cells in women].
The objective of the investigation was to describe p185 protein expression using immunohistochemistry (IHC) and HER-2 gene amplification by fluorescence in situ hybridization (FISH), assessment being semi-quantitative and with the more precise computer image analysis, and to determine whether p185 overexpression is associated with some clinical and morphological parameters such as histological type, histological grade, axillary lymph node status, tumor size, estrogen receptor expression, proliferative index, and age in females with invasive breast carcinoma. Histological preparations from 390 breast carcinomas were studied with the IHC reaction (HercepTest) based on a polyclonal anti-p185 antibody. HercepTest results classified semi-quantitatively as 2+ and 3+ were evaluated using a computer image analyzer and the p185 index was calculated. HER-2 amplification was carried out with FISH using a unique probe (HER-2) with a satellite probe (CEP17). The FISH reaction was assessed routinely by counting red fluorescence signals emitted by the HER-2 gene and additionally with AnalySIS software (AS). The latter method showed that the mean HER-2 amplification index in carcinomas determined as 2+ was significantly lower as compared to carcinomas defined as 3+ (p < 0.0001). On the other hand, the mean amplification indices of carcinomas classified as 3+ and of 2+ cancers which manifested HER-2 amplification did not differ significantly. High HER-2 amplification values (HER-2/CEP17 > 5) were noted in a similar percentage of carcinomas classified by IHC as 2+ (45.5%) or 3+ (55.5%). No correlation was observed between the intensity of the immunohistochemical reaction to p185 as assessed by computer image analysis and the HER-2 amplification index either in breast carcinomas classified semi-quantitatively as 2+ or 3+. The p185 index in 2+ carcinomas without HER-2 amplification might be higher than in some cancers with HER-2 amplification or even higher than in some carcinomas with HER-2 amplification belonging to the 3+ class. Significant differences were noted in p185 expression between ductal and lobular carcinomas (p = 0.0001) and between lobular and medullar carcinomas (p = 0.003). Invasive ductal carcinomas revealed significant differences in p185 expression depending on histological grade (I degree vs III degree p = 0.02; II degree vs III degree p = 0.02), estrogen receptor expression (p = 0.01), and proliferative index (p = 0.02).


Induced delivery of anencephalic fetuses: a response to James L. Walsh and Moira M. McQueen.
James Walsh and Moira McQueen accurately conclude that the early delivery of anencephalic fetuses is morally acceptable, but the reasoning they use to reach that conclusion is flawed. First, the principle of double effect does not require a weighing of good and evil, but rather seeks a sufficient reason for tolerating the physical evil indirectly intended. Second, the principle of double effect requires a clear distinction between physical and moral causality. Third, the Catholic moral tradition will not admit direct and intended killing of the innocent. Rather, early delivery of anencephalic fetuses is permissible because of the pathology associated with delivery of anencephalic fetuses at full term. Thus, the early delivery of an anencephalic infant is acceptable if the purpose of the moral act is avoiding a pathological condition on the part of the mother.


Psychophysical Map Stability in Bilateral Sequential Cochlear Implantation: Comparing Current Audiology Methods to a New Statistical Definition.
The purpose of this study was to establish a statistical definition for stability in cochlear implant maps. Once defined, this study aimed to compare the duration taken to achieve a stable map in first and second implants in patients who underwent sequential bilateral cochlear implantation. This article also sought to evaluate a number of factors that potentially affect map stability. A retrospective cohort study of 33 patients with sensorineural hearing loss who received sequential bilateral cochlear implantation (Cochlear, Sydney, Australia), performed by the senior author. Psychophysical parameters of hearing threshold scores, comfort scores, and the dynamic range were measured for the apical, medial, and basal portions of the cochlear implant electrode at a range of intervals postimplantation. Stability was defined statistically as a less than 10% difference in threshold, comfort, and dynamic range scores over three consecutive mapping sessions. A senior cochlear implant audiologist, blinded to implant order and the statistical results, separately analyzed these psychophysical map parameters using current assessment methods. First and second implants were compared for duration to achieve stability, age, gender, the duration of deafness, etiology of deafness, time between the insertion of the first and second implant, and the presence or absence of preoperative hearing aids were evaluated and its relationship to stability. Statistical analysis included performing a two-tailed Student's t tests and least squares regression analysis, with a statistical significance set at p ≤ 0.05. There was a significant positive correlation between the devised statistical definition and the current audiology methods for assessing stability, with a Pearson correlation coefficient r = 0.36 and a least squares regression slope (b) of 0.41, df(58), 95% confidence interval 0.07 to 0.55 (p = 0.004). The average duration from device switch on to stability in the first implant was 87 days using current audiology methods and 81 days using the statistical definition, with no statistically significant difference between assessment methods (p = 0.2). The duration to achieve stability in the second implant was 51 days using current audiology methods and 60 days using the statistical method, and again no difference between the two assessment methods (p = 0.13). There was a significant reduction in the time to achieve stability in second implants for both audiology and statistical methods (p < 0.001 and p = 0.02, respectively). There was a difference in duration to achieve stability based on electrode array region, with basal portions taking longer to stabilize than apical in the first implant (p = 0.02) and both apical and medial segments in second implants (p = 0.004 and p = 0.01, respectively). No factors that were evaluated in this study, including gender, age, etiology of deafness, duration of deafness, time between implant insertion, and the preoperative hearing aid status, were correlated with stability duration in either stability assessment method. Our statistical definition can accurately predict cochlear implant map stability when compared with current audiology practices. Cochlear implants that are implanted second tend to stabilize sooner than the first, which has a significant impact on counseling before a second implant. No factors evaluated affected the duration required to achieve stability in this study.


Investigation of a foodborne outbreak at a mass gathering in Petaling District, Selangor, Malaysia.
On 6 October 2019, Petaling District Health Office received notification of a possible foodborne outbreak involving a mass gathering event. This report presents the processes of diagnosis verification, case identification, determination of associated risk factors and commencement of control measures in managing the outbreak. Cases were defined as those who attended the mass gathering event on 6 October 2019, consumed the pre-packaged food and subsequently developed vomiting, abdominal pain, diarrhoea or other symptoms (e.g. fever, nausea and dizziness). Epidemiological, environmental and laboratory investigations were performed. Data were analysed using SPSS software (version 24.0). A total of 169 cases were identified. The attack rate was 7.2%, and cases ranged in age from 7 to 50 years, with a median of 20 years. A total of 156 (92.3%) cases had vomiting, 137 (81.1%) had abdominal pain and 83 (49.1%) had diarrhoea. Consuming nasi lemak at the mass gathering was found to be significantly associated with developing illness (odds ratio: 9.90, 95% confidence interval: 6.46-15.16). The samples from suspected food, food handlers and the environment were positive for Bacillus cereus, Staphylococcus aureus or coliforms. The outbreak at this mass gathering was probably caused by food contaminated with B. cereus and S. aureus. To prevent future outbreaks, we recommend mass gathering events use certified catering services that have adequate food safety training.


QsIA disrupts LasR dimerization in antiactivation of bacterial quorum sensing.
The human pathogen Pseudomonas aeruginosa coordinates the expression of virulence factors by using quorum sensing (QS), a signaling cascade triggered by the QS signal molecule and its receptor, a member of the LuxR family of QS transcriptional factors (LasR). The QS threshold and response in P. aeruginosa is defined by a QS LasR-specific antiactivator (QslA), which binds to LasR and prevents it from binding to its target promoter. However, how QslA binds to LasR and regulates its DNA binding activity in QS remains elusive. Here we report the crystal structure of QslA in complex with the N-terminal ligand binding domain of LasR. QsIA exists as a functional dimer to interact with the LasR ligand binding domain. Further analysis shows that QsIA binding occupies the LasR dimerization interface and consequently disrupts LasR dimerization, thereby preventing LasR from binding to its target DNA and disturbing normal QS. Our findings provide a structural model for understanding the QslA-mediated antiactivation mechanism in QS through protein-protein interaction.


Review of epidemiological risk models for foot-and-mouth disease: Implications for prevention strategies with a focus on Africa.
Foot-and-mouth disease (FMD) is a highly infectious transboundary disease that affects domestic and wild cloven-hoofed animal species. The aim of this review was to identify and critically assess some modelling techniques for FMD that are well supported by scientific evidence from the literature with a focus on their use in African countries where the disease remains enzootic. In particular, this study attempted to provide a synopsis of the relative strengths and weaknesses of these models and their relevance to FMD prevention policies. A literature search was conducted to identify quantitative and qualitative risk assessments for FMD, including studies that describe FMD risk factor modelling and spatiotemporal analysis. A description of retrieved papers and a critical assessment of the modelling methods, main findings and their limitations were performed. Different types of models have been used depending on the purpose of the study and the nature of available data. The most frequently identified factors associated with the risk of FMD occurrence were the movement (especially uncontrolled animal movement) and the mixing of animals around water and grazing points. Based on the qualitative and quantitative risk assessment studies, the critical pathway analysis showed that the overall risk of FMDV entering a given country is low. However, in some cases, this risk can be elevated, especially when illegal importation of meat and the movement of terrestrial livestock are involved. Depending on the approach used, these studies highlight shortcomings associated with the application of models and the lack of reliable data from endemic settings. Therefore, the development and application of specific models for use in FMD endemic countries including Africa is encouraged.


p27 modulates tropism of mesenchymal stem cells toward brain tumors.
Mesenchymal stem cells (MSCs) have inherent tumor-tropic properties in the brain and seem to be a useful tool for cellular therapy for brain tumors. However, the mechanisms involved in MSC migration are not fully understood. The tumor suppressor p27, an inhibitor of cyclin-dependent kinase complexes, not only plays a crucial role in cell cycle regulation but also has cell cycle-independent functions, such as differentiation and migration of cells. In fact, p27 has been alternatively reported to inhibit or stimulate cell migration in cells of different types. Therefore, in the present study, we investigated whether p27 is involved in the tumor-tropic activity of MSCs using MSCs from p27-null mice. It was found that p27-/- MSCs showed a decreased motility in the wound healing assay and displayed increased numbers of stress fibers. To compare the in vivo migratory activity of p27-/- and p27+/+ MSCs toward glioma, we injected C6 glioma cells into one side of the mouse brain and BrdU-labeled p27-/- or p27+/+ MSCs into the other side. Significantly fewer labeled p27-/- MSCs were observed in the tumor area compared with p27+/+ MSCs. The present study suggests that p27 works as a stimulator of the in vitro and in vivo migration process of MSCs toward tumors. These findings are important when the efficacy of stem cell-based strategies for glioma therapy is considered.


Oscillatory correlates of moral decision-making: Effect of personality.
The role of emotion in moral decision-making is still a matter of debate. Greene, Sommerville, Nystrom, Darley, and Cohen (2001) argue that 'personal' moral judgments are driven by emotional responses, while 'impersonal' judgments are largely driven by cognitive processes. In this study, oscillatory correlates of decision-making were compared in moral personal, moral impersonal, and nonmoral conditions, as well as in trials associated with utilitarian (i.e., favoring the 'greater good' over individual rights) and non-utilitarian choices. Event-related synchronization in delta and theta bands was greater in the right temporal lobe in personal than in both nonmoral and impersonal moral condition. Graph-theoretical analysis of connectivity patterns showed the prominent role of the orbitofrontal and cingulate cortices in personal moral decision-making, implying greater emotional and self-processing. Higher conscientiousness and intellect and lower behavioral activation were associated with greater difference in oscillatory responses between utilitarian and non-utilitarian choices in personal than in impersonal condition, indicating that sensitivity to moral issues and the ability to grasp the nuances of moral situation are essential for understanding the implications of utilitarian choices in personal and impersonal conditions.


Inhibition of CD4+ T cell function by the HIV envelope protein, gp120.
The CD4 molecule is functionally involved in the class II MHC-restricted T cell response to Ag. CD4 is also the receptor for HIV-1, the major etiologic agent of AIDS. We have assessed whether the interaction of the HIV-1 envelope protein with the CD4 molecule might interfere with the normal function of CD4, thereby contributing to the immunosuppression observed after HIV infection. Using a murine T cell hybridoma which expresses the human CD4 protein and exhibits a CD4-dependent response to Ag, we demonstrate that the HIV envelope protein gp120 can specifically inhibit this response.


Rectus abdominis diastasis.
Because of the lack of agreement on when rectus diastasis (RD) is pathologic, the aim was to investigate indications for surgical repair. This study presents classifications of RD, current knowledge on the relation to pregnancy, and conservative and surgical management. A systematic search in Pubmed, Embase, Cochrane, and Cinahl revealed 437 studies. Inclusion criteria were applied according to the above mentioned subjects of interest. In total 28 studies were included, representing 3725 patients, 11 of these by assessing reference lists of included studies. Only one RCT was found; most studies were case-series lacking statistical analysis. RD was common in post-partum women. Antepartum activity level may have a protective effect on RD and exercise may improve post-partum symptoms of RD. Repair was done during abdominoplasty or laparoscopically. The patient-satisfaction was high and long-term recurrence was reported by one study, while five reported no recurrence. Overall major complications were few, while minor complications were primarily seroma and wound complications. RD is by itself not a true hernia and, therefore, not associated with the risk of strangulation. Repair is mostly done due to cosmetic reasons. The condition does not necessarily require repair, and conservative management may be an alternative. If done, the protrusion of the abdomen, rather than the diastasis itself should influence the decision of repair. It is recommended that future studies use the established classifications (e.g. Beer, Rath, or Nahas) when reporting RD and long-term outcome of treatment. Comparison of surgical techniques and studies that address and compare conservative management with surgery are needed.


Acute resveratrol supplementation improves flow-mediated dilatation in overweight/obese individuals with mildly elevated blood pressure.
Flow-mediated dilatation of the brachial artery (FMD) is a biomarker of endothelial function and cardiovascular health. Impaired FMD is associated with several cardiovascular risk factors including hypertension and obesity. Various food ingredients such as polyphenols have been shown to improve FMD. We investigated whether consuming resveratrol, a polyphenol found in red wine, can enhance FMD acutely and whether there is a dose-response relationship for this effect. 19 overweight/obese (BMI 25-35 kg m(-2)) men or post-menopausal women with untreated borderline hypertension (systolic BP: 130-160 mmHg or diastolic BP: 85-100 mmHg) consumed three doses of resveratrol (resVida™ 30, 90 and 270 mg) and a placebo at weekly intervals in a double-blind, randomized crossover comparison. One hour after consumption of the supplement, plasma resveratrol and FMD were measured. Data were analyzed by linear regression versus log(10) dose of resveratrol. 14 men and 5 women (age 55 ± 2 years, BMI 28.7 ± 0.5 kg m(-2), BP 141 ± 2/89 ± 1 mmHg) completed this study. There was a significant dose effect of resveratrol on plasma resveratrol concentration (P < 0.001) and on FMD (P < 0.01), which increased from 4.1 ± 0.8% (placebo) to 7.7 ± 1.5% after 270 mg resveratrol. FMD was also linearly related to log(10) plasma resveratrol concentration (P < 0.01). Acute resveratrol consumption increased plasma resveratrol concentrations and FMD in a dose-related manner. This effect may contribute to the purported cardiovascular health benefits of grapes and red wine.


Neural plasticity and neurorehabilitation: teaching the new brain old tricks.
Following brain injury or disease there are widespread biochemical, anatomical and physiological changes that result in what might be considered a new, very different brain. This adapted brain is forced to reacquire behaviors lost as a result of the injury or disease and relies on neural plasticity within the residual neural circuits. The same fundamental neural and behavioral signals driving plasticity during learning in the intact brain are engaged during relearning in the damaged/diseased brain. The field of neurorehabilitation is now beginning to capitalize on this body of work to develop neurobiologically informed therapies focused on key behavioral and neural signals driving neural plasticity. Further, how neural plasticity may act to drive different neural strategies underlying functional improvement after brain injury is being revealed. The understanding of the relationship between these different neural strategies, mechanisms of neural plasticity, and changes in behavior may facilitate the development of novel, more effective rehabilitation interventions for treating brain injury and disease. Readers will be able to: (a) define neural plasticity, (b) understand how learning in the intact and damaged brain can drive neural plasticity, (c) identify the three basic neural strategies mediating functional improvement, and (d) understand how adjuvant therapies have the potential to upregulate plasticity and enhance functional recovery.


Quality of life in relation to upper and lower respiratory conditions among retired 9/11-exposed firefighters with pulmonary disability.
To examine health-related quality of life (HRQoL) and World Trade Center (WTC) cough syndrome conditions in male firefighters who retired due to a 9/11-related pulmonary disability. From 3/1/2008 to 1/31/2009, we contacted 275 disability-retired firefighters and compared their HRQoL and current aerodigestive conditions to those from WTC-exposed non-disabled retired and active firefighters. Relationships between HRQoL and explanatory variable(s) were examined using multivariable linear regression models. Mean physical component summary (PCS) scores were lowest in disabled retirees compared with non-disabled retirees and actives: 36.4 (9.6), 49.4 (8.7), and 53.1 (5.1), respectively (P < 0.0001). Mean mental component summary (MCS) scores were closer: 44.5 (11.9), 48.1 (8.5), and 48.7 (7.4), respectively (P < 0.0001). In multivariable models, after adjustment for many factors, PCS scores were not associated with early WTC arrival, but were inversely associated with disability retirement and all WTC cough syndrome conditions. MCS scores were inversely associated with early WTC arrival and most WTC cough syndrome conditions, but were not associated with disability retirement. WTC cough syndrome conditions predict lower HRQoL scores even 8 years after exposure, independent of retirement status. These data suggest that monitoring physical conditions of individuals with occupational exposures might help identify those at risk for impaired HRQoL.


Specific p53 mutations detected in plasma and tumors of hepatocellular carcinoma patients by electrospray ionization mass spectrometry.
Hepatocellular carcinoma (HCC), a common cause of cancer deaths worldwide, has several major etiological risk factors, including infection with the hepatitis viruses and exposure to aflatoxin B1. A specific missense mutation resulting from a guanine to thymine transversion at the third position of codon 249 in the p53 tumor suppressor gene has been reported in 10-70% of HCCs from areas of high dietary exposure to aflatoxin B1. Short oligonucleotide mass analysis was compared with DNA sequencing in 25 HCC samples for specific p53 mutations. Mutations were detected in 10 samples by short oligonucleotide mass analysis in agreement with DNA sequencing. Analysis of another 20 plasma and tumor pairs showed 11 tumors containing the specific mutation, and this change was detected in six of the paired plasma samples. Four of the plasma samples had detectable levels of the mutation; however, the tumors were negative, suggesting possible multiple independent HCCs. Ten plasma samples from healthy individuals were all negative. This molecular diagnostic technique has implications for prevention trials and for the early diagnosis of HCC.


Olive and grape seed extract prevents post-traumatic osteoarthritis damages and exhibits in vitro anti IL-1β activities before and after oral consumption.
Polyphenols exert a large range of beneficial effects in the prevention of age-related diseases. We sought to determine whether an extract of olive and grape seed standardized according to hydroxytyrosol (HT) and procyanidins (PCy) content, exerts preventive anti-osteoathritic effects. To this aim, we evaluated whether the HT/PCy mix could (i) have in vitro anti-inflammatory and chondroprotective actions, (ii) exert anti-osteoarthritis effects in two post-traumatic animal models and (iii) retain its bioactivity after oral administration. Anti-inflammatory and chondroprotective actions of HT/PCy were tested on primary cultured rabbit chondrocytes stimulated by interleukin-1 beta (IL-1β). The results showed that HT/PCy exerts anti-inflammatory and chondroprotective actions in vitro. The preventive effect of HT/PCy association was assessed in two animal models of post-traumatic OA in mice and rabbits. Diet supplementation with HT/PCy significantly decreased the severity of post-traumatic osteoarthritis in two complementary mice and rabbit models. The bioavailability and bioactivity was evaluated following gavage with HT/PCy in rabbits. Regular metabolites from HT/PCy extract were found in sera from rabbits following oral intake. Finally, sera from rabbits force-fed with HT/PCy conserved anti-IL-1β effect, suggesting the bioactivity of this extract. To conclude, HT/PCy extract may be of clinical significance for the preventive treatment of osteoarthritis.


Inhibition of nucleotide excision repair by high mobility group protein HMGA1.
The mammalian non-histone "high mobility group" A (HMGA) proteins are the primary nuclear proteins that bind to the minor groove of AT-rich DNA. They may, therefore, influence the formation and/or repair of DNA lesions that occur in AT-rich DNA, such as cyclobutane pyrimidine dimers (CPDs) induced by UV radiation. Employing both stably transfected lines of human MCF7 cells containing tetracycline-regulated HMGA1 transgenes and primary Hs578T tumor cells, which naturally overexpress HMGA1 proteins, we have shown that cells overexpressing HMGA1a protein exhibit increased UV sensitivity. Moreover, we demonstrated that knockdown of intracellular HMGA1 concentrations via two independent methods abrogated this sensitivity. Most significantly, we observed that HMGA1a overexpression inhibited global genomic nucleotide excision repair of UV-induced CPD lesions in MCF-7 cells. Consistent with these findings in intact cells, DNA repair experiments employing Xenopus oocyte nuclear extracts and lesion-containing DNA substrates demonstrated that binding of HMGA1a markedly inhibits removal of CPDs in vitro. Furthermore, UV "photo-foot-printing" demonstrated that CPD formation within a long run of Ts (T(18)-tract) in a DNA substrate changes significantly when HMGA1 is bound prior to UV irradiation. Together, these results suggest that HMGA1 directly influences both the formation and repair of UV-induced DNA lesions in intact cells. These findings have important implications for the role that HMGA protein overexpression might play in the accumulation of mutations and genomic instabilities associated with many types of human cancers.


In vivo biosynthesis of two subunit forms of dopamine beta-hydroxylase in rat brain.
In vivo biosynthesis of the 2 subunit forms of dopamine beta-hydroxylase (DBH) was examined in the rat brain. 35S-methionine was injected into the noradrenergic neurons of the locus coeruleus (LC) using a stereotactic device. Several hours later, newly synthesized 35S-Met-labeled DBH was immunoprecipitated and quantitated. Both Mr = 77,000 (77K) and 73,000 (73K) subunit forms were present in near-equal proportions after 4 hr of labeling, and these were indistinguishable from those isolated from rat PC12 pheochromocytoma cells by electrophoretic mobility. Both forms sedimented with the vesicular subcellular fraction of LC homogenates, and a portion of the 73K form could be released by hypotonic lysis of these vesicles. The 77K form predominated in the first 30 min labeling period, while the 73K form appeared more slowly over the next several hours. By 16 hr, the 73K form comprised about 2/3 of the total 35S-Met-labeled DBH present. Inhibition of protein synthesis with puromycin 30 min after 35S-Met injection into the LC did not prevent the subsequent appearance of the 73K form, suggesting that this subunit form was the product of posttranslational modification of the 77K subunit form in a fashion similar to that seen in PC12 cells. Also, newly synthesized 35S-Met-labeled DBH that underwent axonal transport from the LC to the anterior hypothalamus was predominantly the 73K subunit form. A single injection of the catecholamine-depleting drug reserpine (10 mg/kg, i.p.) produced a 17-fold increase in the relative synthesis of DBH 2 d later without affecting the proportion of its 2 subunit forms.


A comparison of the cost effectiveness of one-stage versus two-stage bilateral total hip replacement.
Forty patients underwent 80 bilateral primary total hip replacements (THRs) under the same anesthesia (one-stage). Forty other patients who underwent unilateral primary THRs during the same time interval were selected to match the first 40 patients with regard to age, sex, diagnosis, weight, medical comorbidity, type of prosthesis used, and perioperative management protocol. An assumption was made in that each unilateral case represented the first side of bilateral THRs performed during two separate hospitalizations (two-stage). Analysis of the total hospital charges submitted to the insurance companies was made between the groups. On average, there was a 24% reduction (P<.05) for each case if bilateral THRs were done in one stage. This was primarily due to a significant decrease (P<.05) in the length of hospital stay in the one-stage group. There was no difference between the two groups in the operative time, estimated blood loss, or perioperative complications.


Fabrication of polymer microlens arrays using capillary forming with a soft mold of micro-holes array and UV-curable polymer.
This paper reports a simple and effective method to fabricate microlens arrays with the ultraviolet-curable resins, and a soft mold of micro-holes array. During capillary forming operation, the surface of the soft mold of micro-holes array is being pressed against the ultraviolet-curable resin layer coated on the plastic substrate. An array of convex lense can be formed in the circular holes of the soft mold due to the capillary filling and surface tension. The microlens arrays have smooth surface and uniform focusing function. The shape and height of micolens can be controlled with a proper combination of pressing pressure, pressing duration and UV curing dose. This technique shows great potential for fabricating polymer microlens arrays with high productivity and low cost.


A linguistic analysis of dehumanization toward substance use across three decades of news articles.
Substances and the people who use them have been dehumanized for decades. As a result, lawmakers and healthcare providers have implemented policies that subjected millions to criminalization, incarceration, and inadequate resources to support health and wellbeing. While there have been recent shifts in public opinion on issues such as legalization, in the case of marijuana in the U.S., or addiction as a disease, dehumanization and stigma are still leading barriers for individuals seeking treatment. Integral to the narrative of "substance users" as thoughtless zombies or violent criminals is their portrayal in popular media, such as films and news. This study attempts to quantify the dehumanization of people who use substances (PWUS) across time using a large corpus of over 3 million news articles. We apply a computational linguistic framework for measuring dehumanization across three decades of New York Times articles. We show that (1) levels of dehumanization remain high and (2) while marijuana has become less dehumanized over time, attitudes toward other substances such as heroin and cocaine remain stable. This work highlights the importance of a holistic view of substance use that places all substances within the context of addiction as a disease, prioritizes the humanization of PWUS, and centers around harm reduction.


Thyroid function, cardiovascular events, and mortality in diabetic hemodialysis patients.
In dialysis patients, the prevalence of thyroid disorders and their impact on specific cardiovascular (CV) events and mortality are largely unknown. The aim of the present study was to analyze whether subclinical thyroid disorders were associated with CV events and mortality. Prospective multicenter cohort study. Thyroid status and clinical outcomes were explored in 1,000 diabetic hemodialysis patients from 178 centers in Germany. Thyroid status, defined by the following cutoff values: euthyroidism (thyrotropin [TSH], 0.30-4.0 mIU/L; free triiodothyronine [T3], 2.7-7.6 pmol/L; and free thyroxine [T4], 11.0-24.0 pmol/L), subclinical hyperthyroidism (TSH<0.3 mIU/L and free T3/free T4 within reference ranges), subclinical hypothyroidism (TSH, 4.1-15.0 mIU/L and free T3/free T4 within reference ranges), euthyroid sick syndrome (free T3<2.7 pmol/L and TSH/free T4 low or within reference ranges). During 4 years' follow-up, prespecified adjudicated end points were determined: sudden cardiac death, myocardial infarction, stroke, combined CV events, and overall mortality. Short-term effects within the first 12 months were contrasted to long-term effects (years 2-4). TSH, free T3, and free T4 levels at baseline. Euthyroidism was present in 78.1% of patients; subclinical hyperthyroidism, in 13.7%; and subclinical hypothyroidism, in 1.6%. Euthyroid sick syndrome was exhibited by 5.4% of patients. The adjusted short-term risk of sudden cardiac death was more than doubled (HR, 2.03; 95% CI, 0.94-4.36) in patients with subclinical hyperthyroidism, and similarly for patients with euthyroid sick syndrome (HR, 2.74; 95% CI, 0.94-7.98) compared with patients with euthyroidism. Short-term mortality was increased almost 3-fold for patients with euthyroid sick syndrome (HR, 2.97; 95% CI, 1.66-5.29), but this effect was not seen in the long term. Subclinical hypothyroidism was not associated with CV events or all-cause mortality. Risks of stroke and myocardial infarction were not affected meaningfully by thyroid disorders. Observational study design. Sudden cardiac death may be influenced by subclinical hyperthyroidism and euthyroid sick syndrome in the short term. Furthermore, euthyroid sick syndrome is associated strongly with mortality in hemodialysis patients. Regular assessment of thyroid status may help estimate the cardiac risk of dialysis patients.


A 7-year longitudinal study of sexual minority young men's parental relationships and mental health.
While existing research documents the impact of parental rejection on sexual minorities, the present study extends this research to include a subtler, yet potentially more pervasive, challenge facing sexual minorities and their parents, with lasting implications for mental health. Parental unfinished business refers to persistent, unresolved negative thoughts and feelings toward one's parents and is investigated here as a result of parental rejection of their sexual minority sons' sexual orientation. To capture developmental trajectories of parental unfinished business and its prospective predictors (i.e., rejection) and outcomes (i.e., depressive symptoms, social anxiety, alcohol abuse), young sexual minority men (n = 113; baseline Mage = 20.78) reported their experience of these constructs annually for 7 years. Results revealed significantly decreasing trajectories of unfinished business with mothers, but not fathers, over 7 years. Parental rejection of their son's sexual orientation prospectively predicted greater next-year unfinished business. Unfinished business with fathers prospectively predicted next-year depressive symptoms. Prospective effects did not extend to next-year social anxiety or alcohol abuse for unfinished business with either parent. This study positions unfinished business as a novel, distinct, and important component of young sexual minority men's identity development and depression and examines these constructs over seven formative years. Findings can inform theoretical accounts of sexual minority development and clinical case formulation. (PsycINFO Database Record (c) 2018 APA, all rights reserved).


[Assessing forest ecosystem health II. A case study].
On the bases of samples investment and related data collected by others, and with the method of health distance assessment and the ecosystem health index system of Korean pine and broad-leaved mixed forest established in prior paper, this paper attempted to assess the ecosystem health of Korean pine and broad-leaved mixed forest under various human disturbances. The results showed that the health degree was in the order of 20% intensity selective cutting stand (0.21) < 50% intensity selective cutting stand (0.44) < middle and mature birch stand (0.67) < youth birch stand (0.72) < Korean pine plantation (0.74) < larch plantation (0.77).


Probabilistic diagnosis using a reformulation of the INTERNIST-1/QMR knowledge base. I. The probabilistic model and inference algorithms.
In Part I of this two-part series, we report the design of a probabilistic reformulation of the Quick Medical Reference (QMR) diagnostic decision-support tool. We describe a two-level multiply connected belief-network representation of the QMR knowledge base of internal medicine. In the belief-network representation of the QMR knowledge base, we use probabilities derived from the QMR disease profiles, from QMR imports of findings, and from National Center for Health Statistics hospital-discharge statistics. We use a stochastic simulation algorithm for inference on the belief network. This algorithm computes estimates of the posterior marginal probabilities of diseases given a set of findings. In Part II of the series, we compare the performance of QMR to that of our probabilistic system on cases abstracted from continuing medical education materials from Scientific American Medicine. In addition, we analyze empirically several components of the probabilistic model and simulation algorithm.


Rapid automatized naming (RAN) in children with ADHD: An ex-Gaussian analysis.
Children with ADHD demonstrate increased frequent "lapses" in performance on tasks in which the stimulus presentation rate is externally controlled, leading to increased variability in response times. It is less clear whether these lapses are also evident during performance on self-paced tasks, e.g., rapid automatized naming (RAN), or whether RAN inter-item pause time variability uniquely predicts reading performance. A total of 80 children aged 9 to 14 years-45 children with attention-deficit/hyperactivity disorder (ADHD) and 35 typically developing (TD) children-completed RAN and reading fluency measures. RAN responses were digitally recorded for analyses. Inter-stimulus pause time distributions (excluding between-row pauses) were analyzed using traditional (mean, standard deviation [SD], coefficient of variation [CV]) and ex-Gaussian (mu, sigma, tau) methods. Children with ADHD were found to be significantly slower than TD children (p < .05) on RAN letter naming mean response time as well as on oral and silent reading fluency. RAN response time distributions were also significantly more variable (SD, tau) in children with ADHD. Hierarchical regression revealed that the exponential component (tau) of the letter-naming response time distribution uniquely predicted reading fluency in children with ADHD (p < .001, ΔR2 = .16), even after controlling for IQ, basic reading, ADHD symptom severity and age. The findings suggest that children with ADHD (without word-level reading difficulties) manifest slowed performance on tasks of reading fluency; however, this "slowing" may be due in part to lapses from ongoing performance that can be assessed directly using ex-Gaussian methods that capture excessively long response times.


Maximal respiratory pressures in adult Chinese, Malays and Indians.
Maximal static inspiratory and expiratory mouth pressures (PI,max and PE,max, respectively) enable the noninvasive measurement of global respiratory muscle strength. The aim of this study was primarily to obtain normal values of PI,max and PE,max for adult Chinese, Malays and Indians and, secondarily, to study their effect on lung volumes in these subjects. Four hundred and fifty two healthy subjects (221 Chinese, 111 Malays, 120 Indians) were recruited. Measurements of PI,max from residual volume (RV), PE,max from total lung capacity (TLC) and forced vital capacity (FVC) were obtained in the seated position. There were significant ethnic differences in PI,max and PE,max measurements obtained in males, and FVC measurements in both males and females. Chinese males had higher PI,max values (mean (+/-SD) 88.7+/-32.5 cmH2O) and higher PE,max values (113.4+/-41.5) than Malay males (PI,max 74.0+/-22.7 cmH2O, PE,max 94.7+/-23.4 cmH2O). Chinese males had higher PE,max than Indian males (PI,max = 83.7+/-30.0 cmH2O, PE,max 98.4+/-29.2 cmH2O). There were no significant differences among Chinese females (PI,max 53.6+/-2.3 cmH2O, PE,max 68.3+/-24.0 cmH2O), Malay females (PI,max 50.7+/-18.3 cmH2O, PE,max 63.6+/-21.6 cmH2O) and Indian females (PI,max 50.0+/-15.2 cmH2O, PE,max 60.7+/-20.4 cmH2O). In both sexes, the Chinese had a higher FVC compared with Malays and Indians. After adjusting for age, height and weight, race was still a determinant for PE,max in males, and FVC in both sexes. The FVC only correlated weakly with PI,max and PE,max in both sexes. Ethnic differences in respiratory muscle strength, and lung volumes, occur among Asians. However, respiratory muscle strength does not explain the differences in lung volumes in healthy Asian subjects.


Men's knowledge and beliefs about prostate cancer: education, race, and screening status.
African American men die from prostate cancer at higher rates than do White men, a health disparity that may result from differences in knowledge and beliefs about prostate cancer and screening. Studies conflict on whether race or socioeconomic status affects knowledge of prostate cancer and screening. This study compared education, race, and screening status to determine how each factor shapes men's knowledge of prostate cancer and screening. In-depth interviews were conducted with 65 African American and White men, aged 40-64 years, with diverse educational backgrounds. Education, not race or screening status, was associated with knowledge about the prostate gland, prostate cancer symptoms and screening tests, and fear of prostate cancer. The exception was knowledge about the prostate-specific antigen blood test, which was associated with education and screening status. This study suggests that education may be associated with prostate cancer and screening knowledge. Interventions should focus on all men with low education to correct their misconceptions about prostate cancer and to engage them in shared decision-making about screening.


Lung Cancer Screening with Low-Dose CT: a Meta-Analysis.
Randomized controlled trials have evaluated the efficacy of low-dose CT (LDCT) lung cancer screening on lung cancer (LC) outcomes. Meta-analyze LDCT lung cancer screening trials. We identified studies by searching PubMed, Google Scholar, the Cochrane Registry, ClinicalTrials.gov , and reference lists from retrieved publications. We abstracted data on study design features, stage I LC diagnoses, LC and overall mortality, false positive results, harm from invasive diagnostic procedures, overdiagnosis, and significant incidental findings. We assessed study quality using the Cochrane risk-of-bias tool. We used random-effects models to calculate relative risks and assessed effect modulators with subgroup analyses and meta-regression. We identified 9 studies that enrolled 96,559 subjects. The risk of bias across studies was judged to be low. Overall, LDCT screening significantly increased the detection of stage I LC, RR = 2.93 (95% CI, 2.16-3.98), I2 = 19%, and reduced LC mortality, RR = 0.84 (95% CI, 0.75-0.93), I2 = 0%. The number needed to screen to prevent an LC death was 265. Women had a lower risk of LC death (RR = 0.69, 95% CI, 0.40-1.21) than men (RR = 0.86, 95% CI, 0.66-1.13), p value for interaction = 0.11. LDCT screening did not reduce overall mortality, RR = 0.96 (95% CI, 0.91-1.01), I2 = 0%. The pooled false positive rate was 8% (95% CI, 4-18); subjects with false positive results had < 1 in 1000 risk of major complications following invasive diagnostic procedures. The most valid estimates for overdiagnosis and significant incidental findings were 8.9% and 7.5%, respectively. LDCT screening significantly reduced LC mortality, though not overall mortality, with women appearing to benefit more than men. The estimated risks for false positive results, screening complications, overdiagnosis, and incidental findings were low. Long-term survival data were available only for North American and European studies limiting generalizability.


Grey matter changes over time in high risk subjects developing schizophrenia.
Schizophrenia affects approximately 1% of the population and is associated with reductions in brain volume, but when these are first evident is unknown. Magnetic resonance imaging (MRI) has demonstrated abnormalities of brain structure, particularly of the temporal lobes, in schizophrenia. A study of brain structure in individuals destined to develop schizophrenia, before they do so, is crucial to understanding the illness. We used Voxel Based Morphometry (VBM) to map changes in Grey Matter Density (GMD) in 65 young adults at high risk of schizophrenia, for familial reasons, and 19 healthy young adults, over a period of approximately 2 years. All subjects were anti-psychotic naive at both scans. No increases in GMD were found in any of the groups. Within the high-risk group significant declines in GMD were found in the temporal lobes, the right frontal lobe and right parietal lobe. In the control group a decline was found in the right gyrus rectus. No significant differences over time were found between any of the groups. Those individuals at high risk who had transient or isolated psychotic symptoms showed a different spatial pattern of reductions in GMD than those who did not in within group comparisons. In addition, those individuals at high risk who later developed schizophrenia also showed a different spatial pattern of reductions in GMD in the left temporal lobe and right cerebellum, from 2 to 3 years before they were diagnosed. These particular reductions may therefore be able to predict the later onset of schizophrenia.


Light coagulation of the eye.
A brief description is given of the history and early application of light coagulation in ophthalmology. The technique was originally developed by Meyer-Schwickerath in 1949 following clinical observation of macular damage sustained from watching an eclipse. A variety of different light sources were attempted in the prototype instruments before Carl Zeiss (Oberkochen) developed the first commercial model using a high-pressure Xenon lamp in combination with an ophthalmoscopic view of the funds. The ophthalmological clinical procedure originally advocated by Meyer-Schwickerath for light coagulation is briefly outlined and its potential application as a prophylactic treatment in certain specified pathologies is indicated.


An ethical insight into nursing research in Turkey.
Scientific and technological improvements are accomplished only because of much research. The increase in the number of research studies causes a rise in ethical problems. Nursing research is no exception to this. The aim of this study is to identify and analyse ethical problems in nursing studies. This research is descriptive and partly analytical. It is retrospective in the sense that 169 Master of Science and 66 doctoral theses written between 1972 and 1998 in the Department of Nursing, Institute of Health Sciences, Hacettepe University, Ankara, Turkey, were examined. The following ethical rules were used as criteria: that no harm should be caused to the subject; the subject was informed about the research topic; permission was obtained from the subject; and the privacy of the subject was maintained. The evaluation was carried out by distributing the theses among background variables and by employing nonparametric tests. The research associated with the theses was not harmful to the participants in 93.2%, while 6.8% were considered to have caused harm. In 72.7% of the theses the subjects were not informed of the research; in 73.6%, the researchers did not obtain permission from the subjects; and in 8.5% their privacy was not kept. An ethical score was assigned to each thesis, which varied between 0 and 15. The mean score was 5.02.


Factors Associated with Dual-Fluency Walk Speed Improvement after Rehabilitation in Older Patients.
Walk speed measured under dual-task conditions (neurocognitive tasks) could reflect patient performance in real-life. Rehabilitation programs are effective in increasing walk speed, but few studies have evaluated the associations between geriatric factors and rehabilitation efficacy under dual-task conditions. Our objective was to investigate the association between geriatric factors and an increase in dual-task walk speed (threshold of 0.1 m/s), after a multidisciplinary rehabilitation program. We performed a retrospective cohort study that included patients aged 75 years and over, who underwent a complete rehabilitation program and who had a neurocognitive assessment at baseline. The primary outcome was the increase in the dual-task (fluency verbal task) walking speed between pre- and post-rehabilitation assessments. In this study, 145 patients were included, with a mean age of 83.6 years old. After rehabilitation, dual-task walk speed increase in 62 (43%) patients. In multivariate analysis, the following factors were associated with an increase in dual-task walk speed: IADL (OR 2.50, 95% CI [1.26; 4.94], p = 0.009), vitamin D level (OR 0.83, 95% CI [0.72; 0.95], p = 0.008), severe sarcopenia (OR 0.00, 95% CI [0.00; 0.32], p = 0.016), depression (OR 15.85, 95% CI [1.32; 190.40], p = 0.029), number of drugs (OR 1.41, 95% CI [1.04; 1.92], p = 0.027), initial dual-fluency walk speed (OR 0.92, 95% CI [0.86; 0.98], p = 0.014) and time interval between initial and final assessments (OR 0.98, 95% CI [0.96; 1.00], p = 0.06). Identifying patients that are less resilient to rehabilitation may promote a centered-patient approach for an individualized and optimized rehabilitation care.


Gestational and lactational exposition to Di-N-butyl-phthalate (DBP) increases inflammation and preneoplastic lesions in prostate of wistar rats after carcinogenic N-methyl-N-nitrosourea (MNU) plus testosterone protocol.
In the present study, it was evaluated the susceptibility of prostatic lesions in male adult rats exposed to Di-N-butyl-phthalate during fetal and lactational periods and submitted to MNU plus testosterone carcinogenesis protocol. Pregnant females were distributed into four experimental groups: CN (negative control); CMNU (MNU control); TDBP100 (100 mg/kg of DBP); TDBP500 (500 mg/kg of DBP). Females from the TDBP groups received DBP, by gavage, from gestation day 15 (GD15) to postnatal day 21 (DPN21), while C animals received the vehicle (corn oil). CMNU, TDBP100, and TDBP500 groups received a single intraperitoneal injection of MNU (50 mg/kg) on the sixth postnatal week. After that, testosterone cypionate was administered subcutaneously two times a week (2 mg/kg) for 24 weeks. The animals were euthanized on PND220. Distal segment fragments of the ventral (VP) and dorsolateral prostate (DLP) were fixed and processed for histopathological analysis. Protein extracts from ventral prostate were obtained, and western blotting was performed to AR, ERα, MAPK (ERK1/2), and pan-AKT. Stereological analysis showed an increase in the epithelial compartment in TDBP100 and TDBP500 compared to CN. In general, there was increase in the incidence of inflammation and metaplasia/dysplasia in the DBP-treated groups, mainly in DLP, compared to CN and CMNU. Proliferation index was significant higher in TDBP500 and PIN (prostatic intraepithelial neoplasia) was more frequent in this group compared to CMNU. Western blot assays showed an increase in the expressions of AR and MAPK (ERK1/2) in the TDBP100 compared to CN, and ERα and AKT expressions were higher in the TDBP500 group compared do CN. These results showed that different doses of DBP during prostate organogenesis in Wistar rats could increase the incidence of premalignant lesions in initiated rats inducing distinct biological responses in the adulthood. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1185-1195, 2016.


A critical review of marital therapy outcome research.
This review critically examines conceptual and methodological issues of outcome research designed to evaluate the efficacy of marital therapy (MT). Behavioural marital therapy (BMT), cognitively orientated marital therapy (COMT), emotionally focused marital therapy (EFMT), and insight-oriented marital therapy (IOMT) have provided evidence for efficacy. The initial literature search involved the use of the MEDLINE and Psychlit CD-ROM data bases. A secondary literature search based on citations in articles discovered in the initial search was also conducted. Three broad categories involving the delineation of the client sample, study design considerations, and determination of treatment effects were addressed to investigate the quality of evidence concerning the efficacy of MT. None of the 4 approaches has proven superiority in efficacy, and the research does not provide evidence for the superiority of any one approach in distinct types of marital discord. There is some evidence to indicate that future outcome research should avoid the use of "waiting list control groups," since their use appears to be neither ethical nor humane in marital discord research. The authors suggest that the concept of treatment efficiency may be more clinically relevant to outcome research. A gold standard for "efficiency" would suggest that a marital therapy approach should produce subjective and objective improvement in 50% of eligible couples, and this improvement should be maintained in half of these couples at the one-year follow-up assessment. This standard would be comparable to the data on the 4 effective approaches described in this review.


Synthesis and characterization of a zwitterionic hydrogel blend with low coefficient of friction.
Hydrogels display a great deal of potential for a wide variety of biomedical applications. Often times the performance of these biomimetic materials is limited due to inferior friction and wear properties. This manuscript presents a method inspired by the tribological phenomena observed in nature for enhancing the lubricious properties of poly(vinyl alcohol) (PVA) hydrogels. This was achieved by blending PVA with various amounts of zwitterionic polymer, poly([2-(methacryloyloxy) ethyl] dimethyl-(3-sulfopropyl) ammonium hydroxide) (pMEDSAH). Our results indicate that pMEDSAH acts as an effective boundary lubricant, allowing for reduction in coefficient of friction by more than 80%. This reduction in friction coefficient was achieved while maintaining comparable mechanical and physical properties to that of the neat material. Also, these zwitterionic blends were found to be cytocompatible. Analysis of the structure to property relationships within this system indicate that the zwitterionic polymer served as a boundary lubricant and promoted a reduction in friction through hydration lubrication. This novel approach provides a promising platform for further investigations enhancing the tribological properties of hydrogels for biomedical applications. The novelty of this work stems from showing that zwitterionic polymers can be used as an extremely effective hydrogel boundary lubricant. This work will have significant scientific impact because to date, design of hydrogels has emphasized replication of mechanical properties, but in order for these types of materials to be fully utilized as biomaterials it is imperative that they possess improved tribological and lubrication properties, because ignoring the surface and boundary lubrication mechanism, make these potential load-bearing substitutes incompatible with other natural articulating surfaces, leading the constructs to wear, fail, and damage healthy tissue. Our work also provides unique insight to the structure-property-function relationships of these biomaterials which will be of great interest to the readership of the journal.


TrkB as a potential synaptic and behavioral tag.
Late-phase long-term potentiation (L-LTP), a cellular model for long-term memory (LTM), requires de novo protein synthesis. An attractive hypothesis for synapse specificity of long-term memory is "synaptic tagging": synaptic activity generates a tag, which "captures" the PRPs (plasticity-related proteins) derived outside of synapses. Here we provide evidence that TrkB, the receptor of BDNF (brain-derived neurotrophic factor), may serve as a "synaptic tag." TrkB is transiently activated by weak theta-burst stimulation (TBS) that induces only early-phase LTP (E-LTP). This TrkB activation is independent of protein synthesis, and confined to stimulated synapses. Induction of L-LTP by strong stimulation in one synaptic pathway converts weak TBS-induced E-LTP to L-LTP in a second, independent pathway. Transient inhibition of TrkB around the time of weak TBS to the second pathway diminished L-LTP in that pathway without affecting the first one. Behaviorally, weak training, which induces short-term memory (STM) but not LTM, can be consolidated into LTM by exposing animals to novel but not familiar environment 1 h before training. Inhibition of TrkB during STM training blocked such consolidation. These results suggest TrkB as a potential tag for synapse-specific expression of L-LTP and LTM.


Hepatitis E virus infection as a new probable cause of de novo membranous nephropathy after kidney transplantation.
Hepatitis E virus (HEV) has been identified as a cause of chronic viral hepatitis in immunocompromised patients. Some glomerular diseases were found to be associated with this infection. We report the first case, to our knowledge, of a kidney transplant recipient who developed an HEV infection and de novo membranous nephropathy (MN) concomitantly. The patient displayed a hepatic cytolysis first and a nephrotic syndrome occurred 3 months later. HEV infection was diagnosed upon positive polymerase chain reaction on plasma and stool samples, and renal allograft biopsy revealed de novo MN. Typical causes of MN were definitively excluded. A 3-month course of ribavirin monotherapy allowed the patient to mount a sustained viral response that was rapidly followed by complete remission of the nephrotic syndrome. The chronology of the onset and remission of both diseases is highly suggestive of a causal relationship between hepatitis E and MN.


Disentangling neglect and hemianopia.
In this paper we report findings which question the diagnosis of a hemianopia in B.Q., a 66-year-old lady who shows unilateral spatial neglect following a lesion to the right parietal lobe. The presence of a hemianopia has been indicated following two independent assessments of B.Q.'s visual fields. We examined B.Q.'s performance on a visuo-spatial task in which single or double stimuli were displayed left and right of a central fixation point. B.Q. failed to report left stimuli when the fixation point was continuously displayed (OVERLAP CONDITION). This performance is consistent with the suggestion of a left hemianopia as indicated by perimetric field testing. In a further condition the fixation point was extinguished prior to stimuli onset (GAP CONDITION). B.Q. consistently responded to left stimuli in the gap condition and also showed improved performance to right stimuli. Eye movements were recorded on a separate testing session, in which B.Q. showed a normal saccadic response to left targets in the gap condition, but not during the overlap condition. These results suggest that B.Q.'s failure to report left stimuli during field plotting is due to her neglecting left stimuli and not because she has a visual field defect. By using a testing procedure which reduces the severity of neglect B.Q. is able to respond to left stimuli. Reducing the severity of B.Q.'s neglect also abolishes the apparent hemianopia. Standard field plotting techniques which use a consistently displayed fixation point may not be appropriate for the testing of neglect patients' visual fields.


Today's and tomorrow's bio-based bulk chemicals from white biotechnology: a techno-economic analysis.
Little information is yet available on the economic viability of the production of bio-based bulk chemicals and intermediates from white biotechnology (WB). This paper details a methodology to systematically evaluate the techno-economic prospects of present and future production routes of bio-based bulk chemicals produced with WB. Current and future technology routes are evaluated for 15 products assuming prices of fermentable sugar between 70 euro/t and 400 euro/t and crude oil prices of US $25/barrel and US $50/barrel. The results are compared to current technology routes of petrochemical equivalents. For current state-of-the-art WB processes and a crude oil price of US $25/barrel, WB-based ethanol, 1,3-propanediol, polytrimethylene terephthalate and succinic acid are economically viable. Only three WB products are economically not viable for future technology: acetic acid, ethylene and PLA. Future-technology ethylene and PLA become economically viable for a higher crude oil price (US $50/barrel). Production costs plus profits of WB products decrease by 20-50% when changing from current to future technology for a crude oil price of US $25 per barrel and across all sugar prices. Technological progress in WB can thus contribute significantly to improved economic viability of WB products. A large-scale introduction of WB-based production of economically viable bulk chemicals would therefore be desirable if the environmental impacts are smaller than those of current petrochemical production routes.


Energy density of foods and diets in Mexico and their monetary cost by socioeconomic strata: analyses of ENSANUT data 2012.
In January 2014, Mexico implemented an 8% tax on non-essential foods with energy density ≥275 kcal/100 g, with a view to prevent obesity. This study explored energy density of foods and diets in Mexico and their monetary cost across population subgroups. Dietary intakes for 3057 adults (ages ≥19 years) were obtained from the nationally representative Encuesta Nacional de Salud y Nutrición (ENSANUT 2012). Energy density (kcal/g) was calculated for foods, food groups and total diets. The mean national retail prices for 153 foods were obtained from the National Institute for Geography and Statistics (INEGI). The monetary cost of total diets (MXN/day) was estimated by attaching food prices to dietary intakes from the ENSANUT food frequency questionnaire. A series of descriptive analyses and regression models examined associations among dietary energy density and diet cost by age, gender, rural or urban residence and socioeconomic status (SES). Energy-dense grains, fats and sweets cost less per calorie than did milk and dairy, meat, vegetables and fruit. Lower cost diets derived more calories from tortillas, tamales, beans and sugar, whereas higher cost diets contained more non-essential energy-dense processed foods and more sugar sweetened beverages, and fruits and vegetables. At each quintile of energy intake, higher dietary energy density was associated with lower energy-adjusted diet costs. Traditional energy-dense tortillas and tamales, also characterised by lower cost, were consumed more by the rural poor. Urban dwellers had more 'western-style' diets. Food patterns in Mexico appear to be driven by monetary cost and SES.


Fish oil in recent onset rheumatoid arthritis: a randomised, double-blind controlled trial within algorithm-based drug use.
The effects of fish oil (FO) in rheumatoid arthritis (RA) have not been examined in the context of contemporary treatment of early RA. This study examined the effects of high versus low dose FO in early RA employing a 'treat-to-target' protocol of combination disease-modifying anti-rheumatic drugs (DMARDs). Patients with RA <12 months' duration and who were DMARD-naïve were enrolled and randomised 2:1 to FO at a high dose or low dose (for masking). These groups, designated FO and control, were given 5.5 or 0.4 g/day, respectively, of the omega-3 fats, eicosapentaenoic acid + docosahexaenoic acid. All patients received methotrexate (MTX), sulphasalazine and hydroxychloroquine, and DMARD doses were adjusted according to an algorithm taking disease activity and toxicity into account. DAS28-erythrocyte sedimentation rate, modified Health Assessment Questionnaire (mHAQ) and remission were assessed three monthly. The primary outcome measure was failure of triple DMARD therapy. In the FO group, failure of triple DMARD therapy was lower (HR=0.28 (95% CI 0.12 to 0.63; p=0.002) unadjusted and 0.24 (95% CI 0.10 to 0.54; p=0.0006) following adjustment for smoking history, shared epitope and baseline anti-cyclic citrullinated peptide. The rate of first American College of Rheumatology (ACR) remission was significantly greater in the FO compared with the control group (HRs=2.17 (95% CI 1.07 to 4.42; p=0.03) unadjusted and 2.09 (95% CI 1.02 to 4.30; p=0.04) adjusted). There were no differences between groups in MTX dose, DAS28 or mHAQ scores, or adverse events. FO was associated with benefits additional to those achieved by combination 'treat-to-target' DMARDs with similar MTX use. These included reduced triple DMARD failure and a higher rate of ACR remission.


Structural analysis of an endoprosthesis designed with graded density lattice structures.
The most common causes of conducting a hip revision surgery after total hip replacement are aseptic loosening (aseptic instability) of the endoprosthesis, bone destruction as a result of contact with the endoprosthesis, and a periprosthetic fracture. These are the effects of load transfer to the bone tissue in arthroplasty resulting due to the difference in stiffness of the endoprosthesis and the bone. Titanium alloy is widely used in endoprostheses manufacturing because of its high biocompatibility, good wear properties, and corrosion resistance, but such endoprostheses are stiffer than the femur. These problems have raised interest in searching for the best materials and topology for a femoral implant. Nowadays additive technology is of great interest as it enables to create materials with graded density. These materials consist of multiple lattice structures with variable parameters and topology. By varying the parameters of lattice structures one can adjust the mechanical properties of the material as required. These materials find their application in hip endoprostheses manufacturing, allowing to adjust the parameters of the lattice structures, and deliver a product with femur-like mechanical properties. The porous structure also ensures bone tissue ingrowth into the prosthesis. The authors designed and simulated an endoprosthesis made of graded density lattice structures with femur-like mechanical properties. Using a numerical simulation software Ansys Mechanical authors determined the effect of the topology on the structural behavior of the femur and defined the endoprosthesis-femur combined performance under various load cases.


[Investigation of the hepatoprotector action of natural flavonoids].
The prophylactic hepatoprotective properties of a series of natural flavonoids (hesperidin from citrus peel, diosmine from Vicia tanuifolia Roth., and diosmine analog from Vicia trunctula) were studied in a group of white male rats with a model of acute CCl4 hepatitis. The effect was evaluated by the ability of tested substances to normalize the biochemical characteristics of the functional state of the liver, in comparison to the reference drug carsil. The most pronounced hepatoprotective action was observed for diosmine analog administered in a dose of 100 mg/kg, which was superior in some respects to the reference hepatoprotector (in equivalent doses). This is probably related to the higher bioaccessibility of diosmine analog ensured by a carbohydrate moiety of this compound, in combination with the C2-C3 double bond present in diosmetin (diosmin aglycon).


Prognostic value of the metabolic bulk volume in patients with diffuse large B-cell lymphoma on baseline 18F-FDG PET-CT.
We retrospectively investigated the prognostic value of the metabolic bulk volume (MBV), defined as the metabolic volume of the largest lesion, in 106 patients with diffuse large B-cell lymphoma who underwent baseline 18FDG PET-CT. Semi-automatically segmented (41% SUVmax) total metabolic tumor volume (TMTV) and MBV underwent receiver operating characteristic analysis, identifying optimal thresholds of 147 cm3 for the TMTV and 41.5 cm3 for the MBV. A low TMTV and a low MBV were significantly associated with longer progression-free survival (PFS) and overall survival (OS). According to Cox multivariate analysis, the TMTV and MBV were independent predictors, respectively, for PFS (HR = 3.501), and OS (HR = 7.242). The TMTV and MBV classification were discordant in 18.9% of patients with a 5-year PFS rate of 100% for patients with low MBV/high TMTV and 74% for high MBV/low TMTV. The baseline MBV can be an efficient tool for the risk stratification of aggressive lymphoma.


PDX1 in ducts is not required for postnatal formation of β-cells but is necessary for their subsequent maturation.
Pancreatic duodenal homeobox-1 (Pdx1), a transcription factor required for pancreatic development and maintenance of β-cell function, was assessed for a possible role in postnatal β-cell formation from progenitors in the pancreatic ducts by selectively deleting Pdx1 from the ducts. Carbonic anhydrase II (CAII)(Cre);Pdx1(Fl) mice were euglycemic for the first 2 postnatal weeks but showed moderate hyperglycemia from 3 to 7 weeks of age. By 10 weeks, they had near-normal morning fed glucose levels but showed severely impaired glucose tolerance and insulin secretion. Yet the loss of Pdx1 did not result in decreased islet and β-cell mass at 4 and 10 weeks of age. Within the same pancreas, there was a mixed population of islets, with PDX1 and MAFA protein expression normal in some cells and severely diminished in others. Even at 10 weeks, islets expressed immaturity markers. Thus, we conclude that Pdx1 is not necessary for the postnatal formation of β-cells but is essential for their full maturation to glucose-responsive β-cells.


Neurite orientation dispersion and density imaging of the healthy cervical spinal cord in vivo.
Here we present the application of neurite orientation dispersion and density imaging (NODDI) to the healthy spinal cord in vivo. NODDI provides maps such as the intra-neurite tissue volume fraction (vin), the orientation dispersion index (ODI) and the isotropic volume fraction (viso), and here we investigate their potential for spinal cord imaging. We scanned five healthy volunteers, four of whom twice, on a 3T MRI system with a ZOOM-EPI sequence. In accordance to the published NODDI protocol, multiple b-shells were acquired at cervical level and both NODDI and diffusion tensor imaging (DTI) metrics were obtained and analysed to: i) characterise differences in grey and white matter (GM/WM); ii) assess the scan-rescan reproducibility of NODDI; iii) investigate the relationship between NODDI and DTI; and iv) compare the quality of fit of NODDI and DTI. Our results demonstrated that: i) anatomical features can be identified in NODDI maps, such as clear contrast between GM and WM in ODI; ii) the variabilities of vin and ODI are comparable to that of DTI and are driven by biological differences between subjects for ODI, have similar contribution from measurement errors and biological variation for vin, whereas viso shows higher variability, driven by measurement errors; iii) NODDI identifies potential sources contributing to DTI indices, as in the brain; and iv) NODDI outperforms DTI in terms of quality of fit. In conclusion, this work shows that NODDI is a useful model for in vivo diffusion MRI of the spinal cord, providing metrics closely related to tissue microstructure, in line with findings in the brain.


Cross-cultural validation of Harter's self-perception profile for children in the United Arab Emirates.
Harterâs Self-Perception Profile for children (SPPC) is a self-reporting inventory for ascertaining childrenâs perception of themselves in various specific domains of their life, as well as their sense of global selfworth. A few studies have examined the psychometric properties of this instrument in the Western setting, but none have investigated this in an Arabic culture. Psychometric properties of the SPPC were examined, using a sample of 100 schoolchildren aged 8 to 16 years in the United Arab Emirates. The internal consistency reliability was found to be excellent with Chronbachâs alpha, ranging from 0.86 to 0.92. Significant age and gender differences were found with the internal consistency reliability scores, being higher in children aged 13 to 16 years (0.88 to 0.93) when compared to younger children, especially boys aged 8 to 12 years (0.54 to 0.66), suggesting a need to exercise caution while using this scale in young boys in this culture. Behavioral conduct subscale was found to have the highest reliability score and the strongest correlation to global self-worth (r=0.54) for both younger and older children in our sample. This is in contrast to findings from similar studies carried out on American and Dutch samples, where this subscale was found to have the lowest reliability score and the weakest correlation with oneâs global self-worth. The findings indicate that the SPPC is a reliable and internally valid instrument for use in the Arab culture.


Full immersion simulation: validation of a distributed simulation environment for technical and non-technical skills training in Urology.
To evaluate the face, content and construct validity of the distributed simulation (DS) environment for technical and non-technical skills training in endourology. To evaluate the educational impact of DS for urology training. DS offers a portable, low-cost simulated operating room environment that can be set up in any open space. A prospective mixed methods design using established validation methodology was conducted in this simulated environment with 10 experienced and 10 trainee urologists. All participants performed a simulated prostate resection in the DS environment. Outcome measures included surveys to evaluate the DS, as well as comparative analyses of experienced and trainee urologist's performance using real-time and 'blinded' video analysis and validated performance metrics. Non-parametric statistical methods were used to compare differences between groups. The DS environment demonstrated face, content and construct validity for both non-technical and technical skills. Kirkpatrick level 1 evidence for the educational impact of the DS environment was shown. Further studies are needed to evaluate the effect of simulated operating room training on real operating room performance. This study has shown the validity of the DS environment for non-technical, as well as technical skills training. DS-based simulation appears to be a valuable addition to traditional classroom-based simulation training.


Parent's awareness of, and influence on, their 14-17-year-old child's vaping and smoking behaviours; an analysis of 3242 parent-child pairs in Australia.
Vaping by young people in Australia is a rapidly emerging public health issue. Evidence shows that parental behaviours and attitudes can play a key role in influencing adolescent behaviours. Considering the health harms of vaping and evidence that it can be a gateway to tobacco smoking for never-smokers, it is important to understand whether parents' smoking and vaping behaviours influence their teenage children's smoking and vaping behaviours. Online cross-sectional surveys as part of the Generation Vape study, conducted in Australia in 2021/2022, were used to assess parents' influence on, and awareness of, one of their 14-17-year-old child's vaping and smoking behaviours. Participants were 3242 parents and 3242 14-17-year-old teenage children. The risk of vaping and smoking uptake among 14-17-year-old teenagers was 42% (p = 0.003) and 97% (p < 0.001) higher, respectively, if their parent was an ever-vaper. The risk of vaping and smoking uptake among teenagers was 81% (p < 0.001) and 159% (p < 0.001) higher, respectively, if their parent was an ever-smoker. Parents of teenagers who have not vaped were considerably better at correctly predicting this (97% correct) than parents of teenagers who have vaped (70% correct). Compared to parents, teenagers tended to have less agreement with statements suggesting vaping is unsafe or harmful, and more agreement with statements suggesting vaping is relatively safe. Parental smoking and vaping behaviours are associated with those of their children. Hence, it is important that both tobacco and vaping control policies and interventions are designed to influence behaviours of all demographics, consistent with the evidence.


Chronic placental insufficiency affects retinal development in the guinea pig.
Very low birth weight (VLBW) and fetal growth restriction are associated with increased risks of long-term visual impairments, including alterations to contrast sensitivity, a parameter mediated in part by dopaminergic amacrine cells. This study was conducted to determine whether chronic placental insufficiency (CPI), sufficient to cause growth restriction, results in neurochemical alterations to retinal interneurons, specifically amacrine and horizontal cell populations near term. CPI was induced just before midgestation (term approximately 67 days of gestation, dg) in guinea pigs through unilateral ligation of the uterine artery. Growth-restricted (GR, n = 32) and control (n = 29) fetuses were euthanized at 60 dg and retinas prepared for analysis of amacrine cell populations by using antibodies to calbindin, calretinin, cholineacetyltransferase (ChAT), gamma-amino-butyric acid (GABA), dopamine beta-hydroxylase (D beta H), tyrosine hydroxylase (TH, dopaminergic), and NADPH-diaphorase histochemistry (nitrergic). Calbindin immunoreactivity (IR) was also used to identify horizontal cells. HPLC was used to assess concentrations of catecholamines and Western blot analysis to detect total TH levels. In GR compared with control fetuses the total number of TH-IR amacrine (P < 0.02) and calbindin-IR horizontal (P < 0.05) cells was reduced; however, there were no differences in the number of the ChAT, calbindin, calretinin, GABAergic, or nitrergic amacrine cell populations. HPLC revealed a reduction in the concentration of dopamine (P < 0.05) and noradrenaline (P < 0.05), and Western blot analysis revealed a reduction in TH in the retinas of GR compared with control fetuses (P < 0.05). CPI results in alterations to specific populations of retinal neurons. Such effects could contribute to visual impairments reported for VLBW children.


Tracing air flow and diagnosing hypopnoeas in normal subjects.
Hypopnoea is a type of sleep-related breathing disorder (SRBD), and the apnoea plus hypopnoea index (AHI) is usually computed to diagnose this condition. We introduce a new method to diagnose flow with internal thermistors located on the same sensors as we use to diagnose obstructive segments in patients with sleep-related breathing disorders. The aim of this study is to investigate whether internal thermistors are reliable for diagnosis of hypopnoeas. Fifteen volunteers participated in a prospective comparative study in healthy subjects without SRBD. We simultaneously measured minute ventilation by a pneumotachograph and indirectly air flow by internal thermistors in awake subjects was manually analysed from both the pneumotachograph and the internal thermistors. We found a close agreement between the different methods for percentage reduction in air flow both for the hypopnoea and the apnoea data. The mean difference between the percentage reduction in flow from normal breathing to hypopnoea measured by the pneumotachograph and the internal thermistors lying supine was 3.8% (SD 7.4). In the lateral position the corresponding figures were 1.0% and 4.6. This study in awake, normal subjects indicates that internal thermistors are as reliable as the pneumotachograph in diagnosing hypopnoeas and we believe that the reliability of this monitoring method is adequate for clinical use.


Vascular Endothelial Growth Inhibitor, a Cytokine of the Tumor Necrosis Factor Family, is Associated With Epithelial-Mesenchymal Transition in Renal Cell Carcinoma.
Previous studies have revealed that the activation of the epithelial-mesenchymal transition (EMT) endows metastatic properties upon cancer cells to promote invasion and migration. In this study, immunohistochemical analysis was performed in 50 cases of clear cell renal cell carcinoma (RCC) and paired normal kidney tissues. We detected the expression of vascular endothelial growth inhibitor (VEGI) and EMT markers (E-cadherin, fibronectin, and Slug) and recorded the clinical, pathologic, and follow-up (median follow-up: 79.0 mo) information. The expression of VEGI and E-cadherin was significantly lower in RCC tissues compared with normal kidney tissues (P<0.001). However, the expression of fibronectin and Slug was higher in RCC tissues (P<0.05). VEGI and EMT marker expression marginally differed in tumor size and stage. Significant differences were found in the pathologic grade (P<0.05). The Spearman correlation analysis suggested a positive correlation between VEGI and E-cadherin (r=0.451, P<0.01). A negative correlation was shown between VEGI and fibronectin (r=-0.465, P<0.01). There was also a negative correlation between VEGI and Slug (r=-0.758, P<0.01). During the 79.0 months (range, 7 to 119 mo) of follow-up, 6 patients died due to RCC, and the tumor-free survival rate was 88% (44/50). We did not find a significant correlation between VEGI/EMT markers (E-cadherin, fibronectin, and Slug) and overall survival (P>0.05). Our findings indicate that VEGI plays an important role in EMT in RCC. It suggests that VEGI may be investigated as a disease biomarker and therapeutic target in RCC.


Dental trauma: prevalence and risk factors in schoolchildren.
This cross-sectional study aimed to determine the prevalence of traumatic injury to the permanent incisors in 8- to 12-year-old children and to test associations between dental trauma and nutritional status and physical activity level, with adjustment for demographic, behavioral, and psychosocial variables. Differences in risk factors between sexes were also assessed. Two-stage cluster sampling was used to select 1210 children in 20 public and private schools in Pelotas, Brazil, for study participation. Dental trauma was assessed using the O'Brien criteria. Parents provided information about socioeconomic characteristics and their children's history of trauma in early childhood via questionnaire. Children were interviewed to obtain demographic and psychosocial information and to assess physical activity level. Anthropometric measures were collected for body mass index calculation. Hierarchical Poisson regression was used for data analyses. The prevalence of dental trauma was 12.6% [95% confidence interval (CI), 10.8-14.7%] in the entire sample; it increased with age from 7.2% at 8 years to 21.5% at 12 years. In the adjusted analysis, dental trauma was more prevalent in boys [prevalence ratio (PR) = 0.71; 95% CI, 0.50-0.99], older children (PR = 3.57; 95% CI, 1.73-7.34), those with inadequate lip coverage (PR = 2.03; 95% CI, 1.22-3.38), and those with histories of trauma in the primary dentition (PR = 2.60; 95% CI, 1.80-3.75). In a sex-stratified analysis, dental trauma was more prevalent in overweight/obese boys (PR = 1.65; 95% CI, 1.10-2.92). No significant association was found with socioeconomic variables, psychosocial characteristics, physical activity level, or school retention among boys or girls. The pronounced increase in the prevalence of dental trauma with age highlights the need to establish preventive strategies among schoolchildren. The risk of dental injury was increased in overweight/obese boys and children with histories of dental trauma in early childhood, confirming the existence of accident-prone children.


Cloning and characterization of 4.5S and 5S RNA genes in tobacco chloroplasts.
Tobacco chloroplast 4.5S and 5S RNAs were shown to hybridize with a 0.9 . 10(6) dalton EcoRI fragment of tobacco chloroplast DNA. Recombinant plasmids were constructed from fragments produced by partial digestion of the chloroplast DNA with EcoRI and the pMB9 plasmid as a vector. Five recombinants containing the 4.5S and 5S genes were selected by the colony hybridization technique. One of these plasmids contained also the 16S and 23S RNA genes and was mapped using several restriction endonucleases as well as DNA-RNA hybridization. The order of rRNA genes is 16S-23S-4.5S-5S and the four rRNA genes are coded for by the same DNA strand.


[Development of a program of prevention of drug dependence in school children].
To promote healthy habits of behaviour among school-children so that they reject drug-taking and learn to identify high-risk situations. Quasi-experimental study. The Amorós private school in Carabanchel, in Madrid's Health District XI. 45 pupils from the eighth year of basic, aged between 13 and 14. Quantitative and qualitative methods. Quantitative indicators were: number of students who attended the activities organised, their level of participation, the number of new terms, increase in knowledge. Qualitative indicators were the oral poll of class leaders, attainment of objectives, later evaluation of changes in attitude towards drug-takers and collages among the initiatives after the course. Drug-taking usually starts in the family context, leisure situations and peers. In this study isolated consumption was also detected. Most commonly consumed drugs were: caffeine, tobacco (mainly Virginia), alcohol occasionally, and cannabis. The type and form of drug-taking found is very similar to that of other, Spaniards of the same age. We found children who were not drug-takers, but were anxious about this because they "wanted to try out drugs".


Analysis of the primary sequence and microtubule-binding region of the Drosophila 205K MAP.
We have sequenced cDNA clones encoding the Drosophila 205K microtubule-associated protein (MAP), a protein that may be the species specific homologue of mammalian MAP4. The peptide sequence deduced from the longest open-reading frame reveals a hydrophilic protein, which has basic and acidic regions that are similar in organization to mammalian MAP2. Using truncated forms of the 205K MAP, a 232-amino acid region could be defined that is necessary for microtubule binding. The amino acid sequence of this region shares no similarity with the binding motif of MAP2 or tau. We also analyzed several embryonic cDNA clones, which show the existence of differentially spliced mRNAs. Finally, we identified several potential protein kinase target sequences. One of these is distal to the microtubule-binding site and fits the phosphorylation consensus sequence of proteins phosphorylated by the mitosis specific protein kinase cdc2. Our data suggest that the 205K MAP uses a microtubule-binding motif unlike that found in other MAPs, and also raise the possibility that the activities of the 205K MAP may be regulated by alternative splicing and phosphorylation.


Prognostic factors after relapse in nonmetastatic rhabdomyosarcoma: a nomogram to better define patients who can be salvaged with further therapy.
Previous studies suggest poor outcome in children with relapsed rhabdomyosarcoma (RMS). A better understanding is needed of which patients can be salvaged after first relapse. The analysis included children with nonmetastatic RMS and embryonal sarcoma enrolled onto the International Society of Paediatric Oncology (SIOP) Malignant Mesenchymal Tumor (MMT) 84, 89, and 95 studies who relapsed after achieving complete local control with primary therapy. All patients included in the analysis had follow-up for ≥ 3.0 years after the last event. The clinical features, initial treatment characteristics, and features of the relapse were correlated with survival in univariate and multivariate analyses. In all, 474 eligible patients were identified for the study. At ≥ 3.0 years from the last event, 176 (37%) were alive ("cured"). In a full-model multivariate analysis, the factors identified at first relapse that most strongly associated with poor outcome were metastatic relapse (odds ratio [OR], 4.19; 95% CI, 2.0 to 8.5), prior radiotherapy treatment (OR, 3.64; 95% CI, 2.1 to 6.4), initial tumor size > 5 cm (OR, 2.53; 95% CI, 1.5 to 4.1), and time of relapse < 18 months from diagnosis (OR, 2.20; 95% CI, 1.3 to 3.6). Unfavorable primary disease site, nodal involvement at diagnosis, alveolar histology, and previous three- or six-drug chemotherapy were also independently associated with poor outcome. To estimate chance of cure for individual patients, a nomogram was developed, which allowed for weighting of these significant factors. Some children with relapsed RMS remain curable. It is now possible to estimate the chance of salvage for individual children to direct therapy appropriately toward cure, use of experimental therapies, and/or palliation.


RNA-Seq profiling of circular RNAs in mice with lipopolysaccharide-induced acute lung injury.
Acute lung injury (ALI) is a serious illness that develops suddenly, progresses rapidly, has a poor treatment response and a high mortality rate. Studies have found that circular RNAs (circRNA) play a critical role in several diseases, but their role in ALI remains unclear. The aim of this study was to identify circRNAs that are associated with ALI and investigate their potential molecular mechanisms. A comparison of lung circRNA and microRNA expression profiles in mice with ALI and controls was performed by RNA-sequencing. A bioinformatic analysis was conducted to identify differentially expressed (DE) RNAs, to construct competitive endogenous RNA (ceRNA) networks, and to analyze their function and pathways. Then, a protein-protein interaction (PPI) network was generated by the Search Tool for the Retrieval of Interacting Genes database, and hub genes were identified using Cytoscape. Furthermore, a key ceRNA subnetwork was constructed based on these hub genes. Overall, we found 239 DE circRNAs and 42 DE microRNAs in ALI mice compared to controls. Additionally, the molecular mechanism of ALI was further understood by building ceRNA networks based on these DE genes. ALI-induced circRNAs are mostly function in the inflammatory response and metabolic processes. Moreover, DE circRNAs are primarily involved in the nuclear factor (NF)-kappa B and PI3K-Akt signaling pathways. Seven hub genes were derived from the PPI network of 191 genes, followed by the construction of circRNA-miRNA-hub gene subnetworks. In this study, circRNA profiles are remarkably changed in mice with LPS-triggered ALI, and their potential contribution to the disease is revealed.


Locally formed dopamine inhibits Na+-K+-ATPase activity in rat renal cortical tubule cells.
Dopamine, generated locally from L-dopa, inhibits Na+-K+-ATPase in permeabilized rat proximal tubules under maximum transport rate conditions for sodium. To determine whether locally formed dopamine inhibits Na+-K+-ATPase activity in intact cortical tubule cells we studied the effect of L-dopa on ouabain-sensitive oxygen consumption rate (QO2) and 86Rb uptake in renal cortical tubule cell suspensions. L-Dopa (10(-4) M) did not affect ouabain-insensitive QO2 or mitochondrial respiration. However, L-dopa inhibited ouabain-sensitive QO2 in a concentration-dependent manner, with half-maximal inhibition (K0.5) of 5 x 10(-7) M and a maximal inhibition of 14.1 +/- 1.5% at 10(-4) M (P less than 0.05). L-Dopa also blunted the nystatin-stimulated QO2 in a concentration-dependent manner, with a K0.5 of 5 x 10(-8) M and a maximal inhibition of 21.8 +/- 1.2% at 10(-5) M (P less than 0.05), indicating that L-dopa directly inhibits Na+-K+-ATPase activity and not sodium entry. Ouabain-sensitive 86Rb uptake was also inhibited by L-dopa (16.0 +/- 2.4%, P less than 0.05). Carbidopa (10(-4) M), an inhibitor of the conversion of L-dopa to dopamine, eliminated the effect of L-dopa on ouabain-sensitive QO2 and 86Rb uptake, indicating that dopamine rather than L-dopa was the active agent. The finding that the L-dopa concentration-response curve was shifted to the left by one order of magnitude in the presence of nystatin suggests that the inhibitory effect is enhanced when the intracellular sodium concentration is increased.(ABSTRACT TRUNCATED AT 250 WORDS)


Technical note: A novel boundary condition using contact elements for finite element based deformable image registration.
Deformable image registration is an important tool for image-guided radiotherapy. Physics-model-based deformable image registration using finite element analysis is one of the methods currently being investigated. The calculation accuracy of finite element analysis is dependent on given boundary conditions, which are usually based on the surface matching of the organ in two images. Such a surface matching, however, is hard to obtain from medical images. In this study, we developed a new boundary condition to circumvent the traditional difficulties. Finite element contact-impact analysis was employed to simulate the interaction between the organ of interest and the surrounding body. The displacement loading is not necessarily specified. The algorithm automatically deforms the organ model into the minimum internal energy state. The analysis was performed on CT images of the lung at two different breathing phases (exhalation and full inhalation). The result gave the displacement vector map inside the lung. Validation of the result showed satisfactory agreement in most parts of the lung. This approach is simple, operator independent and may provide improved accuracy of the prediction of organ deformation.