Luminous-flux measurements by an absolute integrating sphere.
We present an original implementation of the absolute-sphere method recently proposed by Ohno. The luminous-flux unit, the lumen, is realized by means of an integrating sphere with an opening calibrated by a luminous-intensity standard placed outside. The adapted experimental setup permits one to measure luminous-flux values between 5 and 2500 lm with a significant improvement with respect to the simulated performances reported in the literature. Traditionally, the luminous-flux unit, the lumen, is realized by goniophotometric techniques in which the luminous-intensity distribution is measured and integrated over the whole solid angle. Thus sphere results are compared with those obtained with the Istituto Elettrotecnico Nazionale goniophotometer. In particular, a set of standards, characterized by luminous-flux values of ~2000 lm, has been calibrated with both techniques. We highlight some of the problems encountered. Experimental results show that the agreement between the two methods is within the estimated uncertainty and suggest promising areas for future research.


Renal renin-angiotensin system dysregulation caused by partial bladder outlet obstruction in fetal sheep.
To determine whether fetal renal obstruction activates the renal renin-angiotensin system (RAS), an important mediator in normal kidney development and obstructive nephropathy, we used a model of fetal partial bladder outlet obstruction (PBOO). Total RNA and protein was extracted from kidney of sheep fetuses with partial bladder outlet obstruction created at 95 days gestation, after 2 (N = 6) and 5 weeks of obstruction (term; N = 6), and from normal fetal sheep at various time points between 60 and 135 days of gestation (total N = 19). Relative levels of mRNA for renin, angiotensinogen, type 1 and 2 angiotensin II (Ang II) receptors (AT-1 and AT-2), and transforming growth factor-beta1 (TGF-beta1) were assessed by semiquantitative reverse transcription-polymerase chain reaction. Expression levels of AT-2 receptor protein were measured by Western blot analysis. Renin mRNA expression was increased (250%) after two weeks of obstruction. In normal fetuses, AT-1 expression was low at 60 to 75 days of gestation and increased toward the end of gestation, whereas AT-2 expression showed a reversed pattern. At 109 days, PBOO caused an increased expression of AT-2 mRNA compared with normals (400%). Correspondingly, AT-2 receptor protein was more abundant in obstructed kidneys. TGF-beta1 mRNA expression was significantly increased in obstructed kidneys at 109 days gestation. These observations confirm the reciprocal developmental regulation of AT-1 and AT-2 receptors' expression, suggesting their functional role in renal development. Partial bladder outlet obstruction produces specific alterations: increased renin expression and altered balance of receptor subtypes, which may induce altered functional and vascular regulation of the obstructed fetal kidney. TGF-beta1, a mediator of Ang II-induced fibrosis, may play a role in inducing and propagating interstitial fibrosis.


Efficacy of dexmedetomidine for prevention of emergence agitation in patients posted for nasal surgery under desflurane anaesthesia: A prospective double-blinded randomised controlled trial.
Nasal surgery under desflurane anaesthesia is more prone to develop emergence agitation (EA). The present study aimed to evaluate the efficacy of dexmedetomidine for prevention of EA. A total of 72 patients were randomised to group C and group D. Group C patients received placebo while group D patients received dexmedetomidine 1.0 μg/kg bolus followed by 0.4 μg/kg/h after induction of anesthesia. End tidal desflurane was adjusted to keep the bispectral index (BIS) 45-55. Study drug was stopped at extubation. EA was evaluated from extubation till the patient was shifted to postanaesthesia care unit (PACU). Primary outcome was incidence of EA. Secondary outcome measures were requirement of desflurane, haemodynamic stability, and recovery after anaesthesia. The results were analyzed using SPSS version 21. Infusion of dexmedetomidine significantly reduced the incidence of EA (Group C 52.8%; Group D 5.6%) by 89.5% (P = 0.00001). The endtidal desflurane concentration was significantly lower and there was an average 28.87% reduction in requirement of desflurane in group D compared to group C (P < 0.001). The mean heart rate was significantly higher in Group C (P < 0.001). In group C time to extubation, time to achieve BIS 90 and time to response on verbal command was significantly lesser compared to group D (P < 0.0001). Dexmedetomidine significantly reduced the incidence of EA and requirement of desflurane in patients undergoing nasal surgery. However, it was associated with delayed extubation, residual sedation, and prolonged PACU stay.


Double blind trial of oral fluticasone propionate v prednisolone in the treatment of active ulcerative colitis.
Fluticasone propionate is a corticosteroid with the potential for topical treatment of ulcerative colitis because of low systemic bioavailability. The drug was compared with prednisolone in the management of active left sided or total ulcerative colitis. Two hundred and five patients were studied in the multicentre four week double blind study. Prednisolone was given in a dose of 40 mg daily orally, reducing over four weeks to 10 or 20 mg. Fluticasone propionate was given in an oral daily dose of 20 mg. The primary end point was the investigator's overall assessment of response. Patient's assessment, sigmoidoscopic appearance, and histology were also studied. Patients improved more rapidly with prednisolone. Differences between the two groups were significant at two weeks. At four weeks differences were not significant, but there was a trend in favour of prednisolone. Corticosteroid side effects were minimal in the fluticasone propionate group, and there was minimal suppression of the hypothalamic pituitary adrenal axis. Fluticasone propionate 20 mg daily is not as effective in the treatment of active ulcerative colitis as prednisolone tapering from 40 mg daily to 10 or 20 mg. The complete absence of suppression of the corticoadrenal axis by fluticasone propionate was encouraging, however, and a higher dosage schedule should be assessed.


Investigation of Abscopal and Bystander Effects in Immunocompromised Mice After Exposure to Pencilbeam and Microbeam Synchrotron Radiation.
Out-of-field effects are of considerable interest in radiotherapy. The mechanisms are poorly understood but are thought to involve signaling processes, which induce responses in non-targeted cells and tissues. The immune response is thought to play a role. The goal of this research was to study the induction of abscopal effects in the bladders of NU-Foxn1 mice after irradiating their brains using Pencil Beam (PB) or microbeam (MRT) irradiation at the European Synchrotron Radiation Facility (ESRF) in Grenoble, France. Athymic nude mice injected with F98 glioma cells into their right cerebral hemisphere 7 d earlier were treated with either MRT or PB. After recovery times of 2, 12, and 48 h, the urinary bladders were extracted and cultured as tissue explants for 24 h. The growth medium containing the potential signaling factors was harvested, filtered, and transferred to HaCaT reporter cells to assess their clonogenic survival and calcium signaling potential. The results show that in the tumor-free mice, both treatment modalities produce strong bystander/abscopal signals using the clonogenic reporter assay; however, the calcium data do not support a calcium channel mediated mechanism. The presence of a tumor reduces or reverses the effect. PB produced significantly stronger effects in the bladders of tumor-bearing animals. The authors conclude that immunocompromised mice produce signals, which can alter the response of unirradiated reporter cells; however, a novel mechanism appears to be involved.


Update on Hereditary Kidney Stone Disease and Introduction of a New Clinical Patient Registry in Germany.
Kidney stone disease is an increasingly prevalent condition with remarkable clinical heterogeneity, with regards to stone composition, age of manifestation, rate of recurrence, and impairment of kidney function. Calcium-based kidney stones account for the vast majority of cases, but their etiology is poorly understood, notably their genetic drivers. As recent studies indicate, hereditary conditions are most likely underestimated in prevalence, and new disease genes are constantly being identified. As a consequence, there is an urgent need of a more efficient documentation and collection of cases with underlying hereditary conditions, to better understand shared phenotypic presentation and common molecular mechanisms. By implementation of a centralized patient registry on hereditary kidney stone disease in Germany, we aim to help closing the vast knowledge gap on genetics of kidney stone disease. In this context, clinical registries are indispensable for several reasons: first, delineating better phenotype-genotype associations will allow more precise patient stratification in future clinical research studies. Second, identifying new disease genes and new mechanisms will further reduce the rate of unknown nephrolithiasis/nephrocalcinosis etiology; and third, deciphering new molecular targets will pave the way to develop drugs for recurrence prevention in severely affected families.


Healthcare Resource Utilisation Associated with Herpes Zoster in a Prospective Cohort of Older Australian Adults.
Herpes zoster (HZ) is a common condition that increases in incidence with older age but vaccines are available to prevent the disease. However, there are limited data estimating the health system burden attributable to herpes zoster by age. In this study, we quantified excess healthcare resource usage associated with HZ during the acute/sub-acute period of disease (21days before to 90 days after onset) in 5952 cases and an equal number of controls matched on age, sex, and prior healthcare resource usage. Estimates were adjusted for potential confounders in multivariable regression models. Using population-based estimates of HZ incidence, we calculated the age-specific excess number of health service usage events attributable to HZ in the population. Per HZ case, there was an average of 0.06 (95% CI 0.04-0.08) excess hospitalisations, 1.61 (95% CI 1.51-1.69) excess general practitioner visits, 1.96 (95% CI 1.86-2.15) excess prescriptions filled and 0.11 (95% CI 0.09-0.13) excess emergency department visits. The average number of healthcare resource use events, and the estimated excess per 100,000 population increased with increasing age but were similar for men and women, except for higher rates of hospitalisation in men. The excess annual HZ associated burden of hospitalisations was highest in adults ≥80 years (N = 2244, 95%CI 1719-2767); GP visits was highest in those 60-69 years (N = 50567, 95%CI 39958-61105), prescriptions and ED visits were highest in 70-79 years (N = 50524, 95%CI 40634-60471 and N = 2891, 95%CI 2319-3449 respectively). This study provides important data to establish the healthcare utilisation associated with HZ against which detailed cost-effectiveness analyses of HZ immunisation in older adults can be conducted.


Novel analogs targeting histone deacetylase suppress aggressive thyroid cancer cell growth and induce re-differentiation.
To develop novel therapies for aggressive thyroid cancers, we have synthesized a collection of histone deacetylase (HDAC) inhibitor analogs named AB1 to AB13, which have different linkers between a metal chelating group and a hydrophobic cap. The purpose of this study was to screen out the most effective compounds and evaluate the therapeutic efficacy. AB2, AB3 and AB10 demonstrated the lowest half-maximal inhibitory concentration (IC50) values in one metastatic follicular and two anaplastic thyroid cancer cell lines. Treatment with each of the three ABs resulted in an increase in apoptosis markers, including cleaved poly adenosine diphosphate ribose polymerase (PARP) and cleaved caspase 3. Additionally, the expression of cell-cycle regulatory proteins p21(WAF1) and p27(Kip1) increased with the treatment of ABs while cyclin D1 decreased. Furthermore, AB2, AB3 and AB10 were able to induce thyrocyte-specific genes in the three thyroid cancer cell lines indicated by increased expression levels of sodium iodide symporter, paired box gene 8, thyroid transcription factor 1 (TTF1), TTF2 and thyroid-stimulating hormone receptors. AB2, AB3 and AB10 suppress thyroid cancer cell growth via cell-cycle arrest and apoptosis. They also induce cell re-differentiation, which could make aggressive cancer cells more susceptible to radioactive iodine therapy.


Systemic barriers accessing HIV treatment among people who inject drugs in Russia: a qualitative study.
Achieving 'universal access' to antiretroviral HIV treatment (ART) in lower income and transitional settings is a global target. Yet, access to ART is shaped by local social condition and is by no means universal. Qualitative studies are ideally suited to describing how access to ART is socially situated. We explored systemic barriers to accessing ART among people who inject drugs (PWID) in a Russian city (Ekaterinburg) with a large burden of HIV treatment demand. We undertook 42 in-depth qualitative interviews with people living with HIV with current or recent experience of injecting drug use. Accounts were analysed thematically, and supplemented here with an illustrative case study. Three core themes were identified: 'labyrinthine bureaucracy' governing access to ART; a 'system Catch 22' created by an expectation that access to ART was conditional upon treated drug use in a setting of limited drug treatment opportunity; and 'system verticalization', where a lack of integration across HIV, tuberculosis (TB) and drug treatment compromised access to ART. Taken together, we find that systemic factors play a key role in shaping access to ART with the potential adverse effects of reproducing treatment initiation delay and disengagement from treatment. We argue that meso-level systemic factors affecting access to ART for PWID interact with wider macro-level structural forces, including those related to drug treatment policy and the social marginalization of PWID. We note the urgent need for systemic and structural changes to improve access to ART for PWID in this setting, including to simplify bureaucratic procedures, foster integrated HIV, TB and drug treatment services, and advocate for drug treatment policy reform.


Longitudinal correlated changes in conscientiousness, preventative health-related behaviors, and self-perceived physical health.
Previous research has found that conscientiousness has positive associations with preventative health-related behaviors and self-perceived health, but little is known about the links between changes in these variables over time. In the present study, we examined how levels and changes in conscientiousness were linked to levels and changes in both preventative health-related behaviors and self-perceived physical health. Personality and health questionnaires were administered to participants in two waves, with an interval of approximately three years. Participants ranged in age from 19 to 94. To elucidate the tripartite relations between conscientiousness, preventative health-related behaviors, and self-perceived physical health, we used latent change models to estimate levels and changes of these latent constructs over time. Changes in conscientiousness were significantly and positively correlated with changes in preventative health behaviors and changes in self-perceived physical health. Changes in preventative health behaviors partially mediated the relation between changes in conscientiousness and changes in self-perceived physical health. This longitudinal study extends previous research on conscientiousness and health by exploring the relations between latent variables over a 3-year period. It provides evidence that increases in conscientiousness and preventative health-related behaviors are associated with improvements in self-perceived health over the same time period.


A monoclonal antibody to the carboxyterminal domain of procollagen type I visualizes collagen-synthesizing fibroblasts. Detection of an altered fibroblast phenotype in lungs of patients with pulmonary fibrosis.
Excessive collagen deposition plays a critical role in the development of fibrosis, and early or active fibrosis may be more susceptible to therapeutic intervention than later stages of scarring. However, at present there is no simple method for assessing the collagen-synthesizing and secreting activity of fibroblasts in human tissues. Type I procollagen carboxyterminal domains are proteolytically removed during collagen secretion. Thus, antibodies to these domains should stain fibroblasts synthesizing type I collagen but not extracellular collagen fibrils which could mask the signal from the cells. We developed and characterized a monoclonal antibody (Anti-pC) specific for the carboxyterminal propeptide of type I procollagen. To determine the relationship between Anti-pC staining and collagen synthesis, we stained embryonic and adult chicken tendon. Embryonic chick tendon fibroblasts actively synthesizing type I collagen stained heavily with Anti-pC, while quiescent adult tendon fibroblasts did not stain with Anti-pC. Wounded adult tendons developed fibroblasts that stained with Anti-pC at the wound site. Thus, Anti-pC specifically visualized fibroblasts actively synthesizing collagen. Lung biopsies from patients with fibrotic lung disease were stained with Anti-pC. Interstitial and intraalveolar fibroblasts in biopsies from patients with active fibrosis stained intensely with Anti-pC, while normal human lung was unstained. The absence of staining in normal lung supports the hypothesis that fibrosis is associated with an altered collagen-synthesizing phenotype of tissue fibroblasts. Anti-pC may provide a useful clinical tool for assessing fibrogenic activity at sites of tissue injury.


Timing of symptom improvement after parathyroidectomy for primary hyperparathyroidism.
The timing of symptom improvement after parathyroidectomy for primary hyperparathyroidism (PHPT) has not been well characterized. This prospective study involved administering a questionnaire to patients with PHPT who underwent curative parathyroidectomy over an 11-month period. The questionnaire evaluated the frequency of 18 symptoms of PHPT on a 5-point Likert scale and was administered preoperatively and 1 week, 6 weeks, and 6 months postoperatively. Of 197 eligible patients, 132 (67%) participated in the study. The questionnaires were completed at a rate of 91%, 92%, and 86% at 1 week, 6 weeks, and 6 months postoperatively, respectively. The most commonly reported preoperative symptoms were fatigue (98%), muscle aches (89%), and bone/joint pain (87%). Improvement in symptom severity occurred across all symptoms and was separated into three categories based on the timing of improvement. Fatigue and bone/joint pain demonstrated "Immediate Improvement" (>50% of patients reporting improvement by post-operative week 1), whereas the majority of symptoms showed peak improvement at 6 weeks ("Delayed Improvement"). Symptoms categorized as "Continuous Improvement" were those showing progressive improvement up to 6 months postoperatively (polydipsia, headaches, and nausea/vomiting). Symptom improvement was most prominent 6 weeks postparathyroidectomy, although some symptoms showed continued improvement at 6 months.


High-Flow Nasal Cannula versus Conventional Oxygen Therapy in Children with Respiratory Distress.
The aim of this study is to determine the clinical efficacy of high-flow nasal cannula (HFNC) therapy compared with conventional oxygen therapy in children presented with respiratory distress. This was a randomized controlled study. Infants and children aged between 1 month to 5 years who were admitted to our tertiary referral center for respiratory distress (July 1, 2014 to March 31, 2015) and met the inclusion criteria were recruited. Infants and children hospitalized with respiratory distress were randomized into two groups of interventions. All clinical data, for example, respiratory score, pulse rate, and respiratory rate were recorded. The results were subsequently analyzed. A total of 98 respiratory distress children were enrolled during the study period. Only 4 children (8.2%) failed in HFNC therapy, compared with 10 children (20.4%) in conventional oxygen therapy group (P = 0.09). After adjusted for body weight, underlying diseases, and respiratory distress score, there was an 85% reduction in the odds of treatment failure in HFNC therapy group (adjusted odds ratio 0.15, 95% confidence interval 0.03-0.66, P = 0.01). Most children in HFNC therapy group had significant improvement in clinical respiratory score, heart rate, and respiratory rate at 240, 360, and 120 min compared with conventional oxygen therapy (P = 0.03, 0.04, and 0.03). HFNC therapy revealed a potential clinical advantage in management children hospitalized with respiratory distress compared with conventional respiratory therapy. The early use of HFNC in children with moderate-to-severe respiratory distress may prevent endotracheal tube intubation. TCTR 20170222007.


Application of base-catalysed reaction to the synthesis of dinucleotides containing the four common deoxyribonucleosides and of oligodeoxythymidylates.
The phosphorylation of nucleosides by a nucleoside phosphorofluoridate in the presence of potassium tert-butoxide is a very effective reaction for internucleotide bond synthesis in the case of pyrimidine deoxynucleosides. However, for the purine deoxynucleosides, yields are reduced due to competing reactions. The method was applied to the stepwise synthesis of oligothymidylates. The yield of the trinucleotide was good whereas that of the tetranucleotide was reduced due to the insolubility of the intermediate trinucleotide in the presence of potassium tert-butoxide.


The Aggregate behavior of branch points--measuring the number and velocity of atmospheric turbulence layers.
Optical waves propagating through atmospheric turbulence develop spatial and temporal variations in their phase. For sufficiently strong turbulence, these phase differences can lead to interference in the propagating wave and the formation of branch points; positions of zero amplitude. Under the assumption of a layered turbulence model, we show that these branch points can be used to estimate the number and velocities of atmospheric layers. We describe how to carry out this estimation process and demonstrate its robustness in the presence of sensor noise.


The Effects of Public Access Defibrillation on Survival After Out-of-Hospital Cardiac Arrest: A Systematic Review of Observational Studies.
Despite recent advances, the average survival after out-of-hospital cardiac arrest (OHCA) remains <10%. Early defibrillation by an automated external defibrillator is the most important intervention for patients with OHCA, showing survival proportions >50%. Accordingly, placement of automated external defibrillators in the community as part of a public access defibrillation program (PAD) is recommended by international guidelines. However, different strategies have been proposed on how exactly to increase and make use of publicly available automated external defibrillators. This systematic review aimed to evaluate the effect of PAD and the different PAD strategies on survival after OHCA. PubMed, Embase, and the Cochrane Library were systematically searched on August 31, 2015 for observational studies reporting survival to hospital discharge in OHCA patients where an automated external defibrillator had been used by nonemergency medical services. PAD was divided into 3 groups according to who applied the defibrillator: nondispatched lay first responders, professional first responders (firefighters/police) dispatched by the Emergency Medical Dispatch Center (EMDC), or lay first responders dispatched by the EMDC. A total of 41 studies were included; 18 reported PAD by nondispatched lay first responders, 20 reported PAD by EMDC-dispatched professional first responders (firefighters/police), and 3 reported both. We identified no qualified studies reporting survival after PAD by EMDC-dispatched lay first responders. The overall survival to hospital discharge after OHCA treated with PAD showed a median survival of 40.0% (range, 9.1-83.3). Defibrillation by nondispatched lay first responders was associated with the highest survival with a median survival of 53.0% (range, 26.0-72.0), whereas defibrillation by EMDC-dispatched professional first responders (firefighters/police) was associated with a median survival of 28.6% (range, 9.0-76.0). A meta-analysis of the different survival outcomes could not be performed because of the large heterogeneity of the included studies. This systematic review showed a median overall survival of 40% for patients with OHCA treated by PAD. Defibrillation by nondispatched lay first responders was found to correlate with the highest impact on survival in comparison with EMDC-dispatched professional first responders. PAD by EMDC-dispatched lay first responders could be a promising strategy, but evidence is lacking.


Lifespan persistence of ADHD: the life transition model and its application.
The understanding that attention-deficit/hyperactivity disorder (ADHD) often persists throughout life has heightened interest of patients, families, advocates, and professionals in a longitudinal approach to management. Such an approach must recognize and address known patient- and systems-based challenges of long-term mental health treatment, shifting of clinical presentations of ADHD, and commonality of psychiatric comorbidity with ADHD. The ADHD Life Transition Model is a step toward developing criteria to optimize recognition and clinical management of ADHD (eg, response, remission) across an individual's lifespan and across diverse medical subspecialties. To support therapeutic efficiency and adaptability, our proposed model highlights periods when external resources for managing ADHD are reduced, cognitive and behavioral stressors are increased, and individuals may be reevaluating how they perceive, accept, and adhere to ADHD treatment. Such a model aims to support the clinical community by placing in context new findings, which suggest that the prevention of adult psychopathology in individuals with pediatric ADHD may be possible. The ADHD Life Transition Model seeks to improve care for individuals with ADHD by (1) underscoring that ADHD persists beyond childhood in at least two-thirds of patients, (2) raising awareness of the need to approach ADHD from a chronic illness standpoint, and (3) increasing mental health professionals' diligence in symptom recognition and management of ADHD across developmental phases from childhood through adulthood.


Financial analysis of dipping strategies for indigenous cattle under ranch conditions in Uganda.
A financial analysis was performed to assess the performance of three acaricide-treatment groups of indigenous breeds (Zebu and Nganda) of cattle on a ranch in Luwero District, Uganda. The treatments were based on different frequencies: twice-a-week dipping, once-a-month dipping and no tick control. The objective was to evaluate the economic justification for intensive acaricide application for tick and tick-borne disease control in Uganda. Data were collected by monitoring cattle performance over a period of 34 months. Biological data collected included the number of cows at the beginning and end of the study, net starting liveweight, number of calves born, number of animals dying due to tick-borne diseases and other causes, number of animals sold or slaughtered and milk yield. Records of variable costs (acaricides, drugs, labour, etc.) and output prices were assembled and calculated by treatment group. Gross margin and marginal analysis were used in the financial analysis. The exchange rate in 1990-1993 was one US$ to 1200 Uganda shillings. The gross benefits obtained from animal sales, herd value and milk yield were Uganda shillings 1175, 1389 and 1311 per kg of net starting liveweight for animals dipped twice-a-week, once-a-month and not dipped, respectively. The variable costs were Ug. shs. 424, 390 and 360 per kg of net starting liveweight, respectively. Consequently, the gross margins were Ug. shs. 751, 999 and 951 per kg of net starting liveweight. Furthermore, the marginal rate of return (MRR) in changing from no tick control to once-a-month dipping was 160%, while changing from no tick control to twice-a-week dipping was negative (-313%). The above results showed that the value of increased gains in production obtained from twice-a-week dipping strategy does not offset the costs of inputs for intensive dipping. Once-a-month dipping (strategic) therefore appears to be the most-profitable tick-control strategy for the farmer. The need to conduct further studies in different livestock- production systems and to rationalise future tick control policies is discussed.


Duct drainage alone is sufficient in the operative management of pancreatic pseudocyst in patients with chronic pancreatitis.
To test a hypothesis that definitive management of pseudocyst associated with chronic pancreatitis is predicated on addressing pancreatic ductal anatomy. The authors have previously confirmed the impact of pancreatic ductal anatomic abnormalities on the success of percutaneous drainage of pancreatic pseudocyst. The authors have further defined a system to categorize the pancreatic ductal abnormalities that can be seen with pancreatic pseudocyst. The authors have published, as have others, the usefulness of defining ductal anatomy when managing pancreatic pseudocysts associated with chronic pancreatitis. Beginning in 1985, all patients with pseudocyst who were candidates for intervention (operative, percutaneous, or endoscopic) have undergone endoscopic retrograde cholangiopancreatography (ERCP). An associated diagnosis of chronic pancreatitis was established by means of ERCP findings. Patients were candidates for longitudinal pancreaticojejunostomy (LPJ) if they had a pancreatic ductal diameter greater than 7 mm. In a nonrandomized fashion, patients were managed with either combined simultaneous LPJ and pseudocyst drainage or with LPJ alone. Two hundred fifty-three patients with pseudocyst have been evaluated. Among these there have been 103 patients with chronic pancreatitis and main pancreatic duct (MPD) dilatation (>7 mm). Among these 103 patients, 56 underwent combined LPJ/pseudocyst drainage and 47 had LPJ alone. Compared to combined LPJ/pseudocyst drainage, the patients undergoing LPJ alone had a shorter operative time, slightly less transfusion requirement, slightly reduced length of hospital stay, and slightly reduced complication rate. Long-term pain relief was achieved in 90%, and pseudocyst recurrence was less than 1%. Rates of each of these long-term outcomes were nearly incidental among the two groups. Ductal drainage alone (LPJ) is sufficient in patients with chronic pancreatitis (MPD > 7 mm) and an associated pseudocyst. Simultaneous drainage of pseudocyst is not necessary.


A plant viral "reinitiation" factor interacts with the host translational machinery.
The cauliflower mosaic virus transactivator, TAV, controls translation reinitiation of major open reading frames on polycistronic RNA. We show here that TAV function depends on its association with polysomes and eukaryotic initiation factor eIF3 in vitro and in vivo. TAV physically interacts with eIF3 and the 60S ribosomal subunit. Two proteins mediating these interactions were identified: eIF3g and 60S ribosomal protein L24. Transient expression of eIF3g and L24 in plant protoplasts strongly affects TAV-mediated reinitiation activity. We demonstrate that TAV/eIF3/40S and eIF3/TAV/60S ternary complexes form in vitro, and propose that TAV mediates efficient recruitment of eIF3 to polysomes, allowing translation of polycistronic mRNAs by reinitiation, overcoming the normal cell barriers to this process.


Ordered mesoporous metal oxides for electrochemical applications: correlation between structure, electrical properties and device performance.
Ordered mesoporous metal oxides with a high specific surface area, tailored porosity and engineered interfaces are promising materials for electrochemical applications. In particular, the method of evaporation-induced self-assembly allows the formation of nanocrystalline films of controlled thickness on polar substrates. In general, mesoporous materials have the advantage of benefiting from a unique combination of structural, chemical and physical properties. This Perspective article addresses the structural characteristics and the electrical (charge-transport) properties of mesoporous metal oxides and how these affect their application in energy storage, catalysis and gas sensing.


Depot fluphenazine decanoate and enanthate for schizophrenia.
Intramuscular injections (depot preparations) offer an advantage over oral medication for treating schizophrenia by reducing poor compliance. The benefits gained by long acting preparations, however, may be offset by a higher incidence of adverse effects. To investigate the clinical effects of fluphenazine decanoate and enanthate. For this update we searched the Cochrane Schizophrenia Group's Register (May 2002). We considered all relevant randomised clinical controlled trials focusing on people with schizophrenia comparing fluphenazine decanoate or enanthate with placebo or oral anti-psychotics or other depot preparations. We reliably selected, quality rated and data extracted studies. For dichotomous data we estimated relative risk (RR) with 95% confidence intervals (CI), and, where possible, the number needed to treat/harm (NNT/H). Analysis was by intention-to-treat. We used the weighted mean difference (WMD) for normal continuous data. Tests of heterogeneity and for publication bias were undertaken. This review now includes 70 randomised studies. Compared with placebo, fluphenazine decanoate did not reduce relapse over 6 months to 1 year, but one longer term study found that relapse was significantly reduced in the fluphenazine arm (n=54, RR 0.35, CI 0.2 to 0.6, NNT 2 CI 2 to 4). Fluphenazine decanoate does not reduce relapse more than oral neuroleptics (n=419, 6 RCTs, RR relapse 26-52 weeks 1.46 CI 0.8 to 2.8) or other depot antipsychotics (n=581, 11 RCTs, RR relapse 26-52 weeks 0.82 CI 0.6 to 1.2). Relapse rates over 6 months to 1 year were not significantly different between standard dosage of fluphenazine decanoate over a low dose group (n=523, 4 RCTs, RR 2.09 CI 0.6 to 7.1). Movement disorders were significantly less for people receiving fluphenazine decanoate compared with oral neuroleptics (n=259, 3 RCTs, RR 0.47 CI 0.2 to 0.9, NNT 14 CI 10 to 82). For fluphenazine enanthate there were limited data but no clear difference in global change (0 to 5 weeks) when compared with oral neuroleptics (n=31, 1 RCTs, RR 0.67 CI 0.3 to 1.7), and in relapse rates over 6-26 weeks between fluphenazine enanthate and other depots. Compared with placebo, giving the enanthate caused no more people to need need anticholinergic drugs (n=25, 1 RCT, RR 9.69 CI 0.6 to 163.0) and movement disorders, tardive dyskinesia, tremor, blurred vision and dry mouth were equally prevalent when enanthate was compared with other depot neuroleptics. There are more data for fluphenazine decanoate than for the enanthate ester. Both are effective antipsychotic preparations. In the context of trials, there is little advantage of these depots over oral medications in terms of compliance but this is unlikely to be applicable to everyday clinical practice.


The effects of genotype and infant weight on adult plasma levels of fibrinogen, factor VII, and LDL cholesterol are additive.
High circulating levels of cholesterol, particularly low density lipoprotein (LDL) cholesterol and the clotting factors fibrinogen and factor VII, are associated with increased risk of myocardial infarction. Variations in the plasma levels of these factors are determined in part by polymorphisms in the genes concerned and also by weight at 1 year (infant weight). We have looked at the possibility of interactions between these genetic factors and infant weight in a sample of 290 men and 192 women from Hertfordshire using the beta-fibrinogen G/A-455, factor VII R353Q, and ApoE polymorphisms. The rare allele frequencies of the three polymorphisms were 0.19 for beta-fibrinogen, 0.10 for factor VII, and 0.07 and 0.13 for the 2 and 4 alleles of ApoE, and these frequencies were not different in subjects of different infant weight. In this sample, the polymorphisms showed the expected effects on plasma levels of fibrinogen, factor VII, and LDL cholesterol. The A-455 allele was associated with higher fibrinogen levels but the effect was only statistically significant in women (p = 0.003). The R353 allele was associated with higher factor VII activity in both men and women (p < 0.0001 for both). The ApoE2 allele was associated with lower levels of LDL cholesterol (p = 0.03 in men, p = 0.006 in women), while the ApoE4 allele was associated with higher levels (p < 0.001 in men, not significant in women). In this sample of men and women the effect of low infant weight was only associated with significant effects on fibrinogen and LDL cholesterol in the group of men (p = 0.005 and p = 0.008 respectively). Compared with the E3E3 subjects, the LDL lowering effect of the E2 allele and the raising effect of the E4 allele was greater in those with low infant weight compared with those with high infant weight (low v high infant weight for E2: 12.7% v 9.4%; for E4 12.7% v 8.5%). Although in this sample the interactive effect did not reach statistical significance, the additive effect of ApoE genotype and low infant weight on determining plasma LDL cholesterol levels, if confirmed, may be of relevance in determining a person's future risk of atherosclerosis.


Ethylperoxy radical: approaching spectroscopic accuracy via coupled-cluster theory.
Interest in peroxy radicals derives from their central role in tropospheric and low-temperature combustion processes; however, their transient nature limits the scope of possible experimental characterization. As a result, theoretical methods (notably, coupled-cluster theory) have become indispensable in the reliable prediction of properties of such ephemeral open-shell systems. Herein, the X[combining tilde] and à state conformers of ethylperoxy radical (C2H5O2) have been structurally optimized at the CCSD(T)/ANO2 level of theory. Relative enthalpies at 0 K [including à ← X[combining tilde] transition origins (T0)] are reported, incorporating CCSD(T) electronic energies extrapolated to the complete basis set limit via the focal point approach. Higher-level computations, employing basis sets as large as cc-pV5Z and post-HF methods up to CCSDT(Q), prove essential in achieving predictions to within 10 cm-1 for experimental T0; we predict 7363 and 7583 cm-1 for the trans and gauche conformers, respectively. Furthermore, predictions of X[combining tilde] state fundamental transitions incorporating CCSD(T)/ANO0 anharmonic contributions are given. For each conformer, all 21 modes were characterized, improving upon the 16 modes reported in the experimental literature, and providing predictions for the 5 remaining modes.


Comparison of novel and existing methods for detecting differentially methylated regions.
Single-probe analyses in epigenome-wide association studies (EWAS) have identified associations between DNA methylation and many phenotypes, but do not take into account information from neighboring probes. Methods to detect differentially methylated regions (DMRs) (clusters of neighboring probes associated with a phenotype) may provide more power to detect associations between DNA methylation and diseases or phenotypes of interest. We proposed a novel approach, GlobalP, and perform comparisons with 3 methods-DMRcate, Bumphunter, and comb-p-to identify DMRs associated with log triglycerides (TGs) in real GAW20 data before and after fenofibrate treatment. We applied these methods to the summary statistics from an EWAS performed on the methylation data. Comb-p, DMRcate, and GlobalP detected very similar DMRs near the gene CPT1A on chromosome 11 in both the pre- and posttreatment data. In addition, GlobalP detected 2 DMRs before fenofibrate treatment in the genes ETV6 and ABCG1. Bumphunter identified several DMRs on chromosomes 1 and 20, which did not overlap with DMRs detected by other methods. Our novel method detected the same DMR identified by two existing methods and detected two additional DMRs not identified by any of the existing methods we compared.


Tubular handling of phosphate along the nephron of thyroparathyroidectomized rats injected with ethane-1-hydroxy-1,1-diphosphonate.
1. Previous studies have shown that in thyroparathyroidectomized rats injection of disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) at doses that inhibit bone mineral retention (0.16 mmol = 10 mg of phosphorus/kg body wt. per day subcutaneously) leads to a decrease in the net tubular reabsorption of phosphate. 2. In the present work the tubular response to EHDP (0.16 mmol/kg body wt.) injected subcutaneously for 9 days has been localized by free-flow micropuncture in thyroparathyroidectomized rats. 3. The results show tht the net tubular reabsorption of phosphate along the first portion of the (early) proximal tubule was markedly depressed in the EHDP-injected thyroparathyroidectomized rats compared with that in the pair-fed thyroparathyroidectomized control animals. In this latter group the delivery of phosphate to the distal tubule was larger than in the final urine, confirming previous reports. In the EHDP-injected thyroparathyroidectomized rats no difference in delivery of phosphate was found between the distal tubule and the final urine, suggesting that diphosphonate inhibited net reabsorption of phosphate in the terminal nephron. 4. The sites of the EHDP-induced changes in the tubular handling of phosphate were similar to those previously determined for the adaptive response to an increase in the supply of phosphate.


Oxygenator performance and artificial-native lung interaction.
During extracorporeal membrane oxygenation (ECMO), oxygen (O2) transfer (V'O2) and carbon dioxide (CO2) removal (V'CO2) are partitioned between the native lung (NL) and the membrane lung (ML), related to the patient's metabolic-hemodynamic pattern. The ML could be assimilated to a NL both in a physiological and a pathological way. ML O2 transfer (V'O2ML) is proportional to extracorporeal blood flow and the difference in O2 content between each ML side, while ML CO2 removal (V'CO2ML) can be calculated from ML gas flow and CO2 concentration at sweep gas outlet. Therefore, it is possible to calculate the ML gas exchange efficiency. Due to the ML aging process, pseudomembranous deposits on the ML fibers may completely impede gas exchange, causing a "shunt effect", significantly correlated to V'O2ML decay. Clot formation around fibers determines a ventilated but not perfused compartment, with a "dead space effect", negatively influencing V'CO2ML. Monitoring both shunt and dead space effects might be helpful to recognise ML function decline. Since ML failure is a common mechanical complication, its monitoring is critical for right ML replacement timing and it also important to understand the ECMO system performance level and for guiding the weaning procedure. ML and NL gas exchange data are usually obtained by non-continuous measurements that may fail to be timely detected in critical situations. A real-time ECMO circuit monitoring system therefore might have a significant clinical impact to improve safety, adding relevant clinical information. In our clinical practise, the integration of a real-time monitoring system with a set of standard measurements and samplings contributes to improve the safety of the procedure with a more timely and precise analysis of ECMO functioning. Moreover, an accurate analysis of NL status is fundamental in clinical setting, in order to understand the complex ECMO-patient interaction, with a multi-dimensional approach.


Highly sensitive detection of exosomes by 3D plasmonic photonic crystal biosensor.
In this study, two-dimensional (2D), quasi-three-dimensional (3D), and 3D plasmonic photonic crystal (PPC) nanostructures with point-defect cavities were developed and fabricated using direct and reversal nanoimprint lithography. As a result of the hybrid coupling of localized surface plasmon resonance and Fabry-Perot cavity modes, the quasi-3D plasmonic nanoholes showed higher electromagnetic field intensity and sensitivity than the 2D plasmonic nanoholes. Specifically, the sensitivity of the quasi-3D plasmonic nanoholes was 483 nm per refractive index unit (RIU), whereas that of the 2D plasmonic nanoholes was 276 nm RIU-1. In addition, by enhancing electromagnetic field intensity around corners and generating an additional subradiant dark mode, the symmetrical breakage of the quasi-3D plasmonic nanoholes further increased the sensitivity to 946 nm RIU-1. Among all the nanostructures developed in the study, the 3D PPC nanostructures with point-defect cavities showed the highest sensitivity up to 1376 nm RIU-1 and highest figure of merit of 11.6 as the result of the hybrid coupling of plasmonics and photonic crystal modes with multilayered plasmonic nanostructures. The spacing between the 3D PPC nanostructures was comparable with the average size of exosomes derived from fibroblast L cells, which allowed the exosomes to spread around the 3D PPC nanostructures with increased sensing area. This effect further enhanced the detection sensitivity with a large peak shift of 9 nm when using the 3D PPC biosensor to detect exosomes at the concentration of 1 × 104 particles per ml, and the peak shift increased to 102 nm as exosome concentration increased to 1 × 1011 particles per ml.


Classification algorithms using multiple MRI features in mild traumatic brain injury.
The purpose of this study was to develop an algorithm incorporating MRI metrics to classify patients with mild traumatic brain injury (mTBI) and controls. This was an institutional review board-approved, Health Insurance Portability and Accountability Act-compliant prospective study. We recruited patients with mTBI and healthy controls through the emergency department and general population. We acquired data on a 3.0T Siemens Trio magnet including conventional brain imaging, resting-state fMRI, diffusion-weighted imaging, and magnetic field correlation (MFC), and performed multifeature analysis using the following MRI metrics: mean kurtosis (MK) of thalamus, MFC of thalamus and frontal white matter, thalamocortical resting-state networks, and 5 regional gray matter and white matter volumes including the anterior cingulum and left frontal and temporal poles. Feature selection was performed using minimal-redundancy maximal-relevance. We used classifiers including support vector machine, naive Bayesian, Bayesian network, radial basis network, and multilayer perceptron to test maximal accuracy. We studied 24 patients with mTBI and 26 controls. Best single-feature classification uses thalamic MK yielding 74% accuracy. Multifeature analysis yields 80% accuracy using the full feature set, and up to 86% accuracy using minimal-redundancy maximal-relevance feature selection (MK thalamus, right anterior cingulate volume, thalamic thickness, thalamocortical resting-state network, thalamic microscopic MFC, and sex). Multifeature analysis using diffusion-weighted imaging, MFC, fMRI, and volumetrics may aid in the classification of patients with mTBI compared with controls based on optimal feature selection and classification methods. This study provides Class III evidence that classification algorithms using multiple MRI features accurately identifies patients with mTBI as defined by American Congress of Rehabilitation Medicine criteria compared with healthy controls.


Materiomics for Oral Disease Diagnostics and Personal Health Monitoring: Designer Biomaterials for the Next Generation Biomarkers.
We live in exciting times for a new generation of biomarkers being enabled by advances in the design and use of biomaterials for medical and clinical applications, from nano- to macro-materials, and protein to tissue. Key challenges arise, however, due to both scientific complexity and compatibility of the interface of biology and engineered materials. The linking of mechanisms across scales by using a materials science approach to provide structure-process-property relations characterizes the emerging field of 'materiomics,' which offers enormous promise to provide the hitherto missing tools for biomaterial development for clinical diagnostics and the next generation biomarker applications towards personal health monitoring. Put in other words, the emerging field of materiomics represents an essentially systematic approach to the investigation of biological material systems, integrating natural functions and processes with traditional materials science perspectives. Here we outline how materiomics provides a game-changing technology platform for disruptive innovation in biomaterial science to enable the design of tailored and functional biomaterials--particularly, the design and screening of DNA aptamers for targeting biomarkers related to oral diseases and oral health monitoring. Rigorous and complementary computational modeling and experimental techniques will provide an efficient means to develop new clinical technologies in silico, greatly accelerating the translation of materiomics-driven oral health diagnostics from concept to practice in the clinic.


A new unbiased and highly automated approach to find new prognostic markers in preclinical research.
Data acquisition in (pre)clinical studies is often based on a hypothesis. Numerical algorithms, however, may help to find biomarkers from existing data without formulating any hypothesis. By simply assessing whether a statistical relationship exists between two parameters from a (unlimited) database, every (in)conceivable combination of data becomes a hypothesis. The aim was to create an unbiased and highly automated approach for secondary analysis of (pre)clinical research, including the possibility of a non-linear functional relationship. In our example, an almost homogeneous database was formed by overall 45 parameters (vital, blood and plasma parameters) measured in 11 individual experimental studies at 6 different time points using 57 rats without and 63 rats with systemic inflammation following lipopolysaccharide infusion. For each rat, four group classifiers (treatment, survival, study, ID) were used to get valid samples by a later filtering of the statistical base. Any information about the hypothesis leading to the respective studies was suppressed. In order to assess whether a statistical relationship exists, a total of six different functional prototypes (linear and non-linear) were postulated and examined for their regression. Regression quality, correlation and significance were obtained in form of matrices. In our example, ultimately 510 300 regressions were optimized, automatically evaluated and filtered. The developed algorithm is able to reveal statistical relationships from a nearly crude database with low effort by systematic and unbiased analysis. The finding of well-known correlations proves its reliability, whose validity could be increased by clean aggregation of different studies. In addition, new interesting hints for future research could be gained. Thus, unknown markers can be found which are associated with an increased risk of death during systemic inflammation and sepsis. A further development of the program is planned including multiple regressions (more than two parameters could be related to each other) or cluster analysis.


Dichotomous organization of amygdala/temporal-prefrontal bundles in both humans and monkeys.
The interactions of anterior temporal structures, and especially the amygdala, with the prefrontal cortex are pivotal to learning, decision-making, and socio-emotional regulation. A clear anatomical description of the organization and dissociation of fiber bundles linking anterior temporal cortex/amygdala and prefrontal cortex in humans is still lacking. Using diffusion imaging techniques, we reconstructed fiber bundles between these anatomical regions in human and macaque brains. First, by studying macaques, we assessed which aspects of connectivity known from tracer studies could be identified with diffusion imaging. Second, by comparing diffusion imaging results in humans and macaques, we estimated the patterns of fibers coursing between human amygdala and prefrontal cortex and compared them with those in the monkey. In posterior prefrontal cortex, we observed a prominent and well-preserved bifurcation of bundles into primarily two fiber systems-an amygdalofugal path and an uncinate path-in both species. This dissociation fades away in more rostral prefrontal regions.


Risk and type of crash among young drivers by rurality of residence: findings from the DRIVE Study.
Most previous literature on urban/rural differences in road crashes has a primary focus on severe injuries or deaths, which may be largely explained by variations of medical resources. Little has been reported on police-reported crashes by geographical location, or crash type and severity, especially among young drivers. DRIVE is a prospective cohort study of 20,822 drivers aged 17-24 in NSW, Australia. Information on risk factors was collected via online questionnaire and subsequently linked to police-reported crashes. Poisson regression was used to analyse risk of various crash types by three levels of rurality of residence: urban, regional (country towns and surrounds) and rural. Compared to urban drivers, risk of crash decreased with increasing rurality (regional adjusted RR: 0.7, 95% CI 0.6-0.9; rural adjusted RR: 0.5, 95% CI 0.3-0.7). Among those who crashed, risk of injurious crash did not differ by geographic location; however, regional and rural drivers had significantly higher risk of a single versus multiple vehicle crash (regional adjusted RR 1.8, 95% CI 1.3-2.5; rural adjusted RR: 2.0, 95% CI 1.1-3.6), which was explained by speeding involvement and road alignment at the time or site of crash. Although young urban drivers have a higher crash risk overall, rural and regional residents have increased risk of a single vehicle crash. Interventions to reduce single vehicle crashes should aim to address key issues affecting such crashes, including speeding and specific aspects of road geometry.


Plant-herbivore interactions in a North American mixed-grass prairie : II. Responses of bison to modification of vegetation by prairie dogs.
Studies were conducted during the 1979 growing season to examine how North American bison (Bison bison) use prairie dog (Cynomys ludovicianus) colonies in Wind Cave National Park, South Dakota. Objectives included (1) determining whether bison selected for prairie dog towns parkwide; (2) characterizing in greater detail bison use patterns of a 36-ha colony in Pringle Valley as a function of time since prairie dog colonization; and (3) relating these bison use patterns to measured changes in structure and nutritional value of vegetation on and off the dog town.During midsummer, prairie dog towns were one of the most frequently used habitats by bison parkwide. Day-long observations at Pringle Valley revealed that bison exerted strong selection (nearly 90% of all habitat use and feeding time) for the dog town, which occupied only 39% of the valley. While there, they partitioned their use of the colony by grazing in moderately affected areas (occupied <8 years by prairie dogs) and by resting in the oldest area (>26 years occupation).Prairie dogs facilitate bison habitat selection for a shortgrass successional stage in this mixed-grass community by causing a broad array of compositional, structural, and nutritional changes in the vegetation.


Latitudinal and voltinism compensation shape thermal reaction norms for growth rate.
Latitudinal variation in thermal reaction norms of key fitness traits may inform about the response of populations to climate warming, yet their adaptive nature and evolutionary potential are poorly known. We assessed the contribution of quantitative genetic, neutral genetic and environmental effects to thermal reaction norms of growth rate for populations of the damselfly Ischnura elegans. Among populations, reaction norms differed primarily in elevation, suggesting that time constraints associated with shorter growth seasons in univoltine, high-latitude as well as multivoltine, low-latitude populations selected for faster growth rates. Phenotypic divergence among populations is consistent with selection rather than drift as Q(ST) was greater than F(ST) in all cases. Q(ST) estimates increased with experimental temperature and were influenced by genotype by environment interactions. Substantial additive genetic variation for growth rate in all populations suggests that evolution of trait means in different environments is not constrained. Heritability of growth rates was higher at high temperature, driven by increased genetic rather than environmental variance. While environment-specific nonadditive effects also may contribute to heritability differences among temperatures, maternal effects did not play a significant role (where these could be accounted for). Genotype by environment interactions strongly influenced the adaptive potential of populations, and our results suggest the potential for microevolution of thermal reaction norms in each of the studied populations. In summary, the observed latitudinal pattern in growth rates is adaptive and results from a combination of latitudinal and voltinism compensation. Combined with the evolutionary potential of thermal reaction norms, this may affect populations' ability to respond to future climate warming.


Federal, state, and foundation initiatives around evidence-based practices for child and adolescent mental health.
This article is a survey of many of the initiatives developed by federal and state agencies and foundations focusing on evidence-based mental health practices for children and adolescents. The article intends to show the tremendous interest in the development, dissemination, and implementation of evidence-based practice in child and adolescent mental health that is held by a wide variety of agencies and organizations. Several "next steps" for the field are suggested that might be developed in a subsequent series of initiatives. These steps include a better understanding of dissemination and implementation processes, increased clarity around definitions and terms, increased efforts to build infrastructure and support policy change, and the potential for an aggregation of data already gathered on the implementation of evidence-based practices.


Apoptosis disables CD31-mediated cell detachment from phagocytes promoting binding and engulfment.
Macrophage recognition and ingestion of 'self' cells undergoing apoptosis in vivo protects tissues from the toxic contents of dying cells and modulates macrophage regulation of inflammatory and immune responses. However, the complex molecular mechanisms mediating macrophage discrimination between viable and apoptotic cells are poorly understood. In particular, little is known of why viable nucleated cells are not engulfed by macrophages. To reveal active repulsion of viable cells and to seek specific capture or 'tethering' of apoptotic cells, we studied macrophage binding of viable and apoptotic leukocytes under conditions of flow. We found that homophilic ligation of CD31 (ref. 4) on viable leukocytes promoted their active, temperature-dependent detachment under low shear, whereas such CD31-mediated detachment was disabled in apoptotic leukocytes, promoting tight binding and macrophage ingestion of dying cells. Here we propose that CD31 (also known as platelet-endothelial cell adhesion molecule-1, PECAM-1) is an example of a cell-surface molecule that prevents phagocyte ingestion of closely apposed viable cells by transmitting 'detachment' signals, and which changes function on apoptosis, promoting tethering of dying cells to phagocytes.


Effects of Caffeine and Lycopene in Experimentally Induced Diabetes Mellitus.
Diabetes mellitus (DM) is a global epidemic with increasing prevalence. The disease is chronic in nature, and patients must use antidiabetic drugs or insulin during their lifespan. Because of the difficulty of using injectable insulin preparations, patients and practitioners prefer to use oral antidiabetic drugs for prophylaxis and treatment. There are, however, numerous adverse effects of antidiabetic drugs and rapidly increasing attention is being paid to new nutraceutical drugs with fewer adverse effects. The purpose of this study was to evaluate the effects of caffeine and lycopene on streptozotocin (STZ)-induced DM in rats. Caffeine and lycopene were administered to the study groups by oral gavages for 1 month whereafter experimental diabetes was induced in 90 rats in 6 groups. There were no pathological effects of lycopene and caffeine on the pancreas. Marked vacuolization and degeneration were observed in STZ-treated groups. Caffeine and lycopene decreased the pathological findings and lowered the blood and urine glucose levels in the rats with STZ-induced DM, whereas these compounds increased serum insulin levels. This study showed that caffeine and lycopene provided protective effects against experimentally induced DM. The protective effects of lycopene were observed to be much greater than those of caffeine.


Environmental health disparities: a framework integrating psychosocial and environmental concepts.
Although it is often acknowledged that social and environmental factors interact to produce racial and ethnic environmental health disparities, it is still unclear how this occurs. Despite continued controversy, the environmental justice movement has provided some insight by suggesting that disadvantaged communities face greater likelihood of exposure to ambient hazards. The exposure-disease paradigm has long suggested that differential "vulnerability" may modify the effects of toxicants on biological systems. However, relatively little work has been done to specify whether racial and ethnic minorities may have greater vulnerability than do majority populations and, further, what these vulnerabilities may be. We suggest that psychosocial stress may be the vulnerability factor that links social conditions with environmental hazards. Psychosocial stress can lead to acute and chronic changes in the functioning of body systems (e.g., immune) and also lead directly to illness. In this article we present a multidisciplinary framework integrating these ideas. We also argue that residential segregation leads to differential experiences of community stress, exposure to pollutants, and access to community resources. When not counterbalanced by resources, stressors may lead to heightened vulnerability to environmental hazards.


Sodium Citrate Inhibits Endoplasmic Reticulum Stress in Rats with Adenine-Induced Chronic Renal Failure.
Endoplasmic reticulum stress (ERS) is an important self-protective cellular response to harmful stimuli that contribute to various diseases, including chronic renal failure (CRF). Sodium citrate plays an important role in antioxidant and cellular immunity, but whether it improves ERS in CRF is unclear. The rats were randomly divided into five groups: the control group, the sodium citrate control group, the model group, model rats with low dose sodium citrate (216 mg/kg), and model rats with a high dose of sodium citrate (746 mg/kg). The rats were euthanized at 6, 8, 12, and 16 weeks with their blood and renal tissue in detection. The increased concentrations of blood urea nitrogen and serum creatinine in the model group were significantly decreased by sodium citrate treatment. Hematoxylin-eosin and Masson staining showed that sodium citrate treatment apparently improved renal pathological changes in CRF rats. Western blot analysis showed that sodium citrate treatment decreased the protein levels of transforming growth factor-beta 1 and collagen type IV, which were increased in model rats. Moreover, immunohistochemical staining demonstrated that sodium citrate could effectively reduce the protein expression of glucose-regulated protein 78 kDa and CCAAT/enhancer-binding protein homologous protein in the model rats, which was consistent with western blot results. Additionally, the high dose of sodium citrate had a stronger protective effect in CRF rats than the low dose of sodium citrate. Sodium citrate has a protective effect on CRF through its effects on ERS.


Virtual microscopy in virtual tumor banking.
Many systems have already been designed and successfully used for sharing histology images over large distances, without transfer of the original glass slides. Rapid evolution was seen when digital images could be transferred over the Internet. Nowadays, sophisticated virtual microscope systems can be acquired, with the capability to quickly scan large batches of glass slides at high magnification and compress and store the large images on disc, which subsequently can be consulted through the Internet. The images are stored on an image server, which can give simple, easy to transfer pictures to the user specifying a certain magnification on any position in the scan. This offers new opportunities in histology review, overcoming the necessity of the dynamic telepathology systems to have compatible software systems and microscopes and in addition, an adequate connection of sufficient bandwidth. Consulting the images now only requires an Internet connection and a computer with a high quality monitor. A system of complete pathology review supporting biorepositories is described, based on the implementation of this technique in the European Human Frozen Tumor Tissue Bank (TuBaFrost).


A meta-analysis of the relationship between symptom severity of Posttraumatic Stress Disorder and executive function.
Some studies of Posttraumatic Stress Disorder (PTSD) find executive dysfunction, whereas others do not. We meta-analytically examined the association between executive function and PTSD and used meta-regression to examine the potential moderating effect of PTSD severity on executive function. We conducted a meta-analysis according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We identified published peer-reviewed articles containing measures of executive function and PTSD symptom severity in subjects with PTSD compared to trauma-unexposed controls or trauma-exposed controls without PTSD, or both. We calculated an effect size for each study containing at least one measure of executive function and PTSD symptom severity. PTSD subjects for whom the Clinician-Administered PTSD Scale (CAPS) score was available had worse executive function compared to both trauma-unexposed controls (g = 0.464, p < .001) and to trauma-exposed controls without PTSD (g = 0.414, p = .001), as did PTSD subjects for whom the Mississippi Scale for Combat-Related PTSD (M-PTSD) score was available (g = 0.390, p < .001). Neither CAPS nor M-PTSD scores significantly moderated the effect size of executive function. PTSD is associated with executive dysfunction, but this association was not moderated by PTSD symptom severity, suggesting that once PTSD occurs, executive dysfunction may occur regardless of PTSD severity.


Postprandial levels of GLP-1, GIP and glucagon after 2 years of weight loss with a Paleolithic diet: a randomised controlled trial in healthy obese women.
Objective To investigate how weight loss by different diets impacts postprandial levels of glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and glucagon. Methods In this single-centre, parallel group 2-year trial, 70 healthy postmenopausal obese women were randomised to the Paleolithic diet or a healthy control diet based on Nordic Nutrition Recommendations. Both diets were without calorie restriction. The primary outcome was the change in fat mass. Here, secondary analyses on GLP-1, GIP and glucagon measured during an OGTT are described. Results In the Paleolithic diet group, mean weight loss compared to baseline was 11% at 6 months and 10% at 24 months. In the control diet group, mean weight loss was 6% after 6 and 24 months (P = 0.0001 and P = 0.049 for the comparison between groups at 6 and 24 months respectively). Compared to baseline, the mean incremental area under the curve (iAUC) for GLP-1 increased by 34 and 45% after 6 and 24 months in the Paleolithic diet group and increased by 59% after 24 months in the control diet group. The mean iAUC for GIP increased only in the Paleolithic diet group. The area under the curve (AUC) for glucagon increased during the first 6 months in both groups. The fasting glucagon increase correlated with the β-hydroxybutyrate increase. Conclusions Weight loss caused an increase in postprandial GLP-1 levels and a further rise occurred during weight maintenance. Postprandial GIP levels increased only after the Paleolithic diet. Reduced postprandial glucagon suppression may be caused by a catabolic state.


An adaptable soft-mold embossing process for fabricating optically-accessible, microfeature-based culture systems and application toward liver stage antimalarial compound testing.
Advanced cell culture methods for modeling organ-level structure have been demonstrated to replicate in vivo conditions more accurately than traditional in vitro cell culture. Given that the liver is particularly important to human health, several advanced culture methods have been developed to experiment with liver disease states, including infection with Plasmodium parasites, the causative agent of malaria. These models have demonstrated that intrahepatic parasites require functionally stable hepatocytes to thrive and robust characterization of the parasite populations' response to investigational therapies is dependent on high-content and high-resolution imaging (HC/RI). We previously reported abiotic confinement extends the functional longevity of primary hepatocytes in a microfluidic platform and set out to instill confinement in a microtiter plate platform while maintaining optical accessibility for HC/RI; with an end-goal of producing an improved P. vivax liver stage culture model. We developed a novel fabrication process in which a PDMS soft mold embosses hepatocyte-confining microfeatures into polystyrene, resulting in microfeature-based hepatocyte confinement (μHEP) slides and plates. Our process was optimized to form both microfeatures and culture wells in a single embossing step, resulting in a 100 μm-thick bottom ideal for HC/RI, and was found inexpensively amendable to microfeature design changes. Microfeatures improved intrahepatic parasite infection rates and μHEP systems were used to reconfirm the activity of reference antimalarials in phenotypic dose-response assays. RNAseq of hepatocytes in μHEP systems demonstrated microfeatures sustain hepatic differentiation and function, suggesting broader utility for preclinical hepatic assays; while our tailorable embossing process could be repurposed for developing additional organ models.


Complex tribomechanical characterization of ZnO nanowires: nanomanipulations supported by FEM simulations.
In the present work, we demonstrate a novel approach to nanotribological measurements based on the bending manipulation of hexagonal ZnO nanowires (NWs) in an adjustable half-suspended configuration inside a scanning electron microscope. A pick-and-place manipulation technique was used to control the length of the adhered part of each suspended NW. Static and kinetic friction were found by a 'self-sensing' approach based on the strain profile of the elastically bent NW during manipulation and its Young's modulus, which was separately measured in a three-point bending test with an atomic force microscope. The calculation of static friction from the most bent state was completely reconsidered and a novel more realistic crack-based model was proposed. It was demonstrated that, in contrast to assumptions made in previously published models, interfacial stresses in statically bent NW are highly localized and interfacial strength is comparable to the bending strength of NW measured in respective bending tests.


Molecular characterization of the oafA locus responsible for acetylation of Salmonella typhimurium O-antigen: oafA is a member of a family of integral membrane trans-acylases.
Lipopolysaccharide (LPS) coats the surface of gram-negative bacteria and serves to protect the cell from its environment. The O-antigen is the outermost part of LPS and is highly variable among gram-negative bacteria. Strains of Salmonella are partly distinguished by serotypic differences in their O-antigen. In Salmonella typhimurium, the O-antigen is acetylated, conferring the 05 serotype. We have previously provided evidence that this modification significantly alters the structure of the O-antigen and creates or destroys a series of conformational epitopes. Here we report the detailed mapping, cloning, and DNA sequence of the oafA gene. The locus contains one open reading frame that is predicted to encode an inner membrane protein, consistent with its role in modification of the O-antigen subunit. The OafA protein shows homology to proteins in a number of prokaryotic and one eukaryotic species, and this defines a family of membrane proteins involved in the acylation of exported carbohydrate moieties. In many of these instances, acylation defines serotype or host range and thus has a profound effect on microbe-host interaction.


Translation of maternal TATA-binding protein mRNA potentiates basal but not activated transcription in Xenopus embryos at the midblastula transition.
Early embryonic development in Xenopus laevis is characterized by transcriptional repression which is relieved at the midblastula stage (MBT). Here we show that the relative abundance of TATA-binding protein (TBP) increases robustly at the MBT and that the mechanism underlying this increase is translation of maternally stored TBP RNA. We show that TBP is rate-limiting in egg extract under conditions that titrate nucleosome assembly. Precocious translation of TBP mRNA in Xenopus embryos facilitates transcription before the MBT, without requiring TBP to be prebound to the promoter before injection. This effect is transient in the absence of chromatin titration and is sustained when chromatin is titrated. These data show that translational regulation of TBP RNA contributes to limitations on the transcriptional capacity before the MBT. Second, we examined the ability of trans-acting factors to contribute to promoter activity before the MBT. Deletion of cis-acting elements does not affect histone H2B transcription in egg extract, a finding indicative of limited trans-activation. Moreover, in the context of the intact promoter, neither the transcriptional activator Oct-1, nor TBP, nor TFIID enable transcriptional activation in vitro. HeLa cell extract, however, reconstitutes activated transcription in mixed extracts. These data suggest a deficiency in egg extract cofactors required for activated transcription. We show that the capacity for activated H2B transcription is gradually acquired at the early gastrula transition. This transition occurs well after the blastula stage when the basal transcription machinery can first be complemented with TBP.


Effects of antibiotics on morphologic characteristics and migration of canine corneal epithelial cells in tissue culture.
To determine effects of commonly used ophthalmic antibiotics on cellular morphologic characteristics and migration of canine corneal epithelium in cell culture. Corneal epithelial cells harvested from corneas of 12 euthanatized dogs and propagated in cell culture. Cells were treated with various antibiotics after a defect was created in the monolayer. Cellular morphologic characteristics and closure of the defect were compared between antibiotic-treated and control cells. Cells treated with ciprofloxacin and cefazolin had the greatest degree of rounding, shrinkage, and detachment from plates. Cells treated with neomycin-polymyxin B-gramicidin and gentamicin sulfate had rounding and shrinkage but with less detachment. Cells treated with tobramycin and chloramphenicol grew similarly to control cells. On the basis of comparisons of defect circumference between control cells and cells exposed to antibiotics, tobramycin affected cellular migration the least. Effects of ciprofloxacin and cefazolin on morphologic characteristics of canine corneal epithelial cells in vitro should be taken into consideration before using these antibiotics for first-line of treatment for noninfected ulcers. Of the antibiotics tested that have a primarily gram-negative spectrum of coverage, gentamicin inhibited corneal epithelial cell migration and had greater cytopathologic effects than tobramycin did. For antibiotics with a gram-positive coverage, chloramphenicol had no cytopathologic effects on cells in comparison to cefazolin, which caused most of the cells to shrink and detach from the plate. Polymyxin B-neomycin-gramicidin was midrange in its effects on cellular morphologic characteristics and migration.


Measurements of milli-Newton surface tension forces with tilted fiber Bragg gratings.
Small lateral forces (lower than 0.1 N) cannot normally be measured with conventional single-mode fiber-based sensors because of the high value of their Young modulus (>70 GPa). Here we demonstrate the measurement of lateral forces in the range from 0.2 to 1.4×10-3 N with a tilted fiber Bragg grating (TFBG) in conventional single-mode fiber pushed against the surface tension (ST) of a bead of water. The measured transmission changes of individual cladding mode resonances of the TFBG corresponding to these force values are of the order of 29 dB. Separate measurements of the contact angle between the surface of the water and the fiber are used to calibrate the sensor with help from the known value of ST for water. Once calibrated, a TFBG can be used to measure unknown forces in the same range or to measure an unknown ST, provided a separate force measurement is available.


From hydra regeneration to human brain structural plasticity: a long trip through narrowing roads.
Regeneration is a strategy to maintain form and function throughout life. Studies carried out on animal models throughout the phylogenetic tree have flourished in the last decades in search of mechanisms underlying the regenerative processes. The development of such studies is strictly linked with stem cell research and both are viewed as one of the most promising outcomes for regenerative medicine; yet, regeneration, stem cells, and tissue repair do not seem to follow a logical path through the different animal species and tissues. As a result, some mammalian organs, e.g., kidney and brain, have lost most of their regenerative capacity. The human nervous system, although harboring neural stem cells, is placed at the extreme of "perennial" tissues. In addition, it is affected by neurodegenerative diseases, whose heavy burden is heightened by enhanced life spans. This review, starting from the basic principles of tissue regeneration viewed in a comparative context, tries to answer this question: To which extent can regenerative medicine be figured out in a mammalian brain equipped with many anatomical/evolutionary constraints?


Interleukin 4-inducible phosphorylation of HMG-I(Y) is inhibited by rapamycin.
The non-histone chromosomal protein HMG-I(Y) participates in repression of transcription directed by a promoter which confers interleukin 4 (IL-4)-inducible activation in transfected B cell lines. Metabolic labeling, phosphoamino acid analyses, and in vitro phosphorylation studies demonstrate that IL-4 induces serine phosphorylation of HMG-I(Y) in B lymphocytes. Phosphopeptide mapping shows that the predominant site of phosphorylation contains a casein kinase II consensus motif. The immunosuppressive agent rapamycin has been shown preferentially to inhibit IgE production by IL-4-treated human B cells. It is shown here that rapamycin inhibits both activation of the human germ line epsilon promoter by IL-4 and IL-4-inducible phosphorylation of HMG-I(Y). These findings demonstrate a rapamycin-sensitive pathway that transduces signals from the IL-4 receptor to nuclear factors that regulate inducible transcription. The affinity of normal nuclear HMG-I(Y) for DNA is increased by dephosphorylation in vitro, whereas in vitro kinase reactions using casein kinase II decrease recombinant HMG-I(Y) binding to DNA. These data further suggest a novel mechanism in which phosphorylation triggered by IL-4 or other cytokines could regulate the effects of HMG-I(Y) on gene transcription.


Prenatal stress and hemodynamics in pregnancy: a systematic review.
Maternal prenatal stress is associated with preterm birth, intrauterine growth restriction, and developmental delay. However, the impact of prenatal stress on hemodynamics during pregnancy remains unclear. This systematic review was conducted in order to assess the quality of the evidence available to date regarding the relationship between prenatal stress and maternal-fetal hemodynamics. The PubMed/Medline, EMBASE, PsycINFO, Maternity and Infant Care, Trip, Cochrane Library, and CINAHL databases were searched using the search terms pregnancy; stress; fetus; blood; Doppler; ultrasound. Studies were eligible for inclusion if prenatal stress was assessed with standardized measures, hemodynamics was measured with Doppler ultrasound, and methods were adequately described. A specifically designed data extraction form was used. The methodological quality of included studies was assessed using well-accepted quality appraisal guidelines. Of 2532 studies reviewed, 12 met the criteria for inclusion. Six reported that prenatal stress significantly affects maternal or fetal hemodynamics; six found no significant association between maternal stress and circulation. Significant relationships between prenatal stress and uterine artery resistance (RI) and pulsatility (PI) indices, umbilical artery RI, PI, and systolic/diastolic ratio, fetal middle cerebral artery PI, cerebroplacental ratio, and umbilical vein volume blood flow were found. To date, there is limited evidence that prenatal stress is associated with changes in circulation. More carefully designed studies with larger sample sizes, repeated assessments across gestation, tighter control for confounding factors, and measures of pregnancy-specific stress will clarify this relationship.


Effluent carbonaceous biochemical oxygen demand (CBOD) characterization for modern pulp and paper facilities.
As receiving water quality models are being used to address dissolved oxygen issues requiring an increased degree of resolution, a more refined characterization of effluent CBOD can become an important aspect of the analysis. The selection and use of kinetic models to identify effluent specific parameters can have a significant impact on this characterization. This study modeled effluents from six pulp and paper facilities in order to reassess the kinetic models, the data, and experimental design used for a typical effluent characterization. The dual first order model fit these effluents with significantly less error than the traditional first order model suggesting a significant fraction of the CBOD is slowly degradable. Because the dual first order model produces a more refined characterization of CBOD kinetics than the first order model, it places an increased demand upon the data used to inform the parameter estimates. Therefore, analysis of the precision of the parameter estimates and methods for improving estimation precision via experimental design are also discussed.


Experience-dependent and cell-type-specific spine growth in the neocortex.
Functional circuits in the adult neocortex adjust to novel sensory experience, but the underlying synaptic mechanisms remain unknown. Growth and retraction of dendritic spines with synapse formation and elimination could change brain circuits. In the apical tufts of layer 5B (L5B) pyramidal neurons in the mouse barrel cortex, a subset of dendritic spines appear and disappear over days, whereas most spines are persistent for months. Under baseline conditions, new spines are mostly transient and rarely survive for more than a week. Transient spines tend to be small, whereas persistent spines are usually large. Because most excitatory synapses in the cortex occur on spines, and because synapse size and the number of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors are proportional to spine volume, the excitation of pyramidal neurons is probably driven through synapses on persistent spines. Here we test whether the generation and loss of persistent spines are enhanced by novel sensory experience. We repeatedly imaged dendritic spines for one month after trimming alternate whiskers, a paradigm that induces adaptive functional changes in neocortical circuits. Whisker trimming stabilized new spines and destabilized previously persistent spines. New-persistent spines always formed synapses. They were preferentially added on L5B neurons with complex apical tufts rather than simple tufts. Our data indicate that novel sensory experience drives the stabilization of new spines on subclasses of cortical neurons. These synaptic changes probably underlie experience-dependent remodelling of specific neocortical circuits.


Rac1 and Cdc42 capture microtubules through IQGAP1 and CLIP-170.
Linkage of microtubules to special cortical regions is essential for cell polarization. CLIP-170 binds to the growing ends of microtubules and plays pivotal roles in orientation. We have found that IQGAP1, an effector of Rac1 and Cdc42, interacts with CLIP-170. In Vero fibroblasts, IQGAP1 localizes at the polarized leading edge. Expression of carboxy-terminal fragment of IQGAP1, which includes the CLIP-170 binding region, delocalizes GFP-CLIP-170 from the tips of microtubules and alters the microtubule array. Activated Rac1/Cdc42, IQGAP1, and CLIP-170 form a tripartite complex. Furthermore, expression of an IQGAP1 mutant defective in Rac1/Cdc42 binding induces multiple leading edges. These results indicate that Rac1/Cdc42 marks special cortical spots where the IQGAP1 and CLIP-170 complex is targeted, leading to a polarized microtubule array and cell polarization.


Modeling Sex Differences in Pharmacokinetics, Pharmacodynamics, and Disease Progression Effects of Naproxen in Rats with Collagen-Induced Arthritis.
Naproxen (NPX) is a frequently used nonsteroidal anti-inflammatory drug for rheumatoid arthritis (RA). Lack of quantitative information about the drug exposure-response relationship has resulted in empirical dosage regimens for use of NPX in RA. Few studies to date have included sex as a factor, although RA predominates in women. A pharmacokinetic, pharmacodynamic, and disease progression model described the anti-inflammatory effects of NPX in collagen-induced arthritic (CIA) male and female rats. Three groups of rats were included for each sex: healthy animals, CIA controls, and CIA rats given a single 50-mg/kg dose of NPX intraperitoneally. Paw volumes of healthy rats indicated natural growth, and disease status was measured by paw edema. An innovative minimal physiologically based pharmacokinetic (mPBPK) model incorporating nonlinear albumin binding of NPX in both plasma and interstitial fluid (ISF) was applied. Arthritic rats exhibited lower plasma and ISF albumin concentrations and reduced clearances of unbound drug to explain pharmacokinetic profiles. The unbound ISF NPX concentrations predicted by the mPBPK model were used as the driving force for pharmacological effects of NPX. A logistic growth function accounting for natural paw growth and an indirect response model for paw edema and drug effects (inhibition of kin) was applied. Female rats showed a higher incidence of CIA, earlier disease onset, and more severe symptoms. NPX had stronger effects in males, owing to higher unbound ISF NPX concentrations and lower IC50 values. The model described the pharmacokinetics, unbound NPX in ISF, time course of anti-inflammatory effects, and sex differences in CIA rats.


Surface immobilizable chelator for label-free electrical detection of pyrophosphate.
A new pyrophosphate (PPi) chelator was designed for surface-sensitive electrical detection of biomolecular reactions. This article describes the synthesis of the PPi-selective receptor, its surface immobilization and application to label-free electrical detection on a silicon-based field-effect transistor (FET) sensor.


Estrogen Metabolism in African-American Women with and without Breast Cancer: A Pilot Study.
Studies in Caucasian women have shown that the formation of estrogen-DNA adducts is greater in women at high risk for breast cancer or already diagnosed with the disease. To begin investigating whether the role of estrogens in the etiology of breast cancer is similar in African-American (AA) women, a saliva sample and a spot urine sample were collected from 19 AA women with breast cancer and 23 AA women not diagnosed with breast cancer. In the urine samples, 20 estrogen metabolites, conjugates, and DNA adducts were analyzed by using ultraperformance liquid chromatography/tandem mass spectrometry, and then the ratio of adducts to metabolites and conjugates was calculated for each sample. The ratio of depurinating estrogen-DNA adducts to estrogen metabolites and estrogen conjugates was significantly greater in cases compared to controls (92.4 ± 46.4 vs 38.5 ± 18.9, p < 0.0001). From the saliva samples, genomic DNA was purified and analyzed for genetic polymorphisms in the genes for two estrogen-metabolizing enzymes, catechol- O-methyltransferase (rs4680) and cytochrome P450 1B1 (rs1056836). There was no association between rs4680 and rs1056836 genotypes and adduct ratios or breast cancer status. This pilot study found higher DNA adduct ratios in women with breast cancer, which suggests that estrogen metabolism is out of balance, and the formation of estrogen-DNA adducts may exert a critical role in breast cancer initiation in AA women.


Effects of Injectable platelet rich fibrin (i-PRF) on reduction of relapse after orthodontic tooth movement: Rabbits model study.
The objective of this study is to determine whether submucosal local injection of i-PRF may affect orthodontic relapse by increasing bone density, which further leads to reducing orthodontic relapse. Forty-five adult male albino rabbits were randomly divided into three groups: group I (control) with 15 rabbits injected with 200 μl of phosphate-buffered saline (PBS), group II with 15 rabbits injected with 200 μl of i-PRF, and group III of 15 rabbits inject with 400 μl of i-PRF. The lower incisors of rabbits moved distally by a modified orthodontic appliance for 2 weeks; then, the appliance was maintained in position to retain the gaining space for 2 weeks. During the retention period, each group was injected with the specific drug every 7 days. After the retention period, teeth were allowed to relapse by removal of the orthodontic appliance. The results were evaluated by measuring the amount of orthodontic relapse and bone density. The statistical analysis performed by ANOVA and Duncan (P < 0.05 was considered significant). I-PRF groups showed a significant reduction in the amount of relapse at 10, 13, 17, and 20 days compared to the control group, indicated by the highest percentage of relapse for the control group at the end of the study (20 days); it was (90.4%) in compared to lowest percentage of relapse for i-PRF groups-they were 61.2% and 59.9%, respectively. Results indicated that i-PRF has the potential to enhance the stability of teeth after orthodontic tooth movement and could have the ability to reduce relapse, probably by increasing the alveolar bone density.


Electrolytes induce long-range orientational order and free energy changes in the H-bond network of bulk water.
Electrolytes interact with water in many ways: changing dipole orientation, inducing charge transfer, and distorting the hydrogen-bond network in the bulk and at interfaces. Numerous experiments and computations have detected short-range perturbations that extend up to three hydration shells around individual ions. We report a multiscale investigation of the bulk and surface of aqueous electrolyte solutions that extends from the atomic scale (using atomistic modeling) to nanoscopic length scales (using bulk and interfacial femtosecond second harmonic measurements) to the macroscopic scale (using surface tension experiments). Electrolytes induce orientational order at concentrations starting at 10 μM that causes nonspecific changes in the surface tension of dilute electrolyte solutions. Aside from ion-dipole interactions, collective hydrogen-bond interactions are crucial and explain the observed difference of a factor of 6 between light water and heavy water.


A transient niche regulates the specification of Drosophila intestinal stem cells.
Stem cell niches are locations where stem cells reside and self-renew. Although studies have shown how niches maintain stem cell fate during tissue homeostasis, less is known about their roles in establishing stem cells. The adult Drosophila midgut is maintained by intestinal stem cells (ISCs); however, how they are established is unknown. Here, we show that an ISC progenitor generates a niche cell via Notch signaling. This niche uses the bone morphogenetic protein 2/4 homolog, decapentaplegic, to allow progenitors to divide in an undifferentiated state and subsequently breaks down and dies, resulting in the specification of ISCs in the adult midgut. Our results demonstrate a paradigm for stem cell-niche biology, where progenitors generate transient niches that determine stem cell fate and may give insights into stem cell specification in other tissues.


Real-time tracking, retrieval and gene expression analysis of migrating human T cells.
Dynamical analysis of single-cells allows assessment of the extent and role of cell-to-cell variability, however traditional dish-and-pipette techniques have hindered single-cell analysis in quantitative biology. We developed an automated microfluidic cell culture system that generates stable diffusion-based chemokine gradients, where cells can be placed in predetermined positions, monitored via single-cell time-lapse microscopy, and subsequently be retrieved based on their migration speed and directionality for further off-chip gene expression analysis, constituting a powerful platform for multiparameter quantitative studies of single-cell chemotaxis. Using this system we studied CXCL12-directed migration of individual human primary T cells. Spatiotemporally deterministic retrieval of T cell subsets in relation to their migration speed, and subsequent analysis with microfluidic droplet digital-PCR showed that the expression level of CXCR4 – the receptor of CXCL12 – underlies enhanced human T cell chemotaxis.


Hippocampal resection length and memory outcome in selective epilepsy surgery.
In temporal lobe epilepsy surgery, there is a trend towards becoming more selective in order to achieve seizure control with an optimal neuropsychological outcome. The present study evaluated whether mesial resection length matters for memory outcome after selective amygdalo-hippocampectomy (SAH). Therefore, a sub-analysis of the larger SFB/TR3/A1 multicentre randomised trial on seizure outcome and mesial resection length in temporal lobe surgery was performed. A homogeneous group of 67 selectively operated patients with hippocampal sclerosis as the sole pathology were allocated to a short (2.5 cm, n=34) or a long (3.5 cm, n=33) mesial resection. Repeated memory assessment and three-dimensional MRI data sets served as dependent within group variables, and intraoperatively determined resection lengths (short/long), resected hippocampal volumes (small/large) and side of surgery were independent between group variables. Resection length did not have a significant effect on seizure or on memory outcome. The resected hippocampal volume also did not affect seizure outcome but it did make a difference with regard to memory outcome. Outcome in verbal learning and memory was poorer after resection of larger left hippocampal volumes. Figural memory outcome was poorer with larger resected volumes on either side. The data indicate that in SAH, mesial resection length and resected volumes have no differential effect on seizure outcome. The findings on memory outcome are best explained by suggesting that hippocampal volumes take the degree of preoperative pathology into account whereas resection length does not. This suggests resection of non-pathological functional tissues as the basis for memory outcome after SAH.


IKBKAP mRNA in peripheral blood leukocytes: a molecular marker of gene expression and splicing in familial dysautonomia.
The common familial dysautonomia (FD) mutation results in tissue specific mis-splicing with reduced amount of wild-type (WT) IkappaB kinase associated protein gene (IKBKAP) mRNA and ELP1. ELP1 is a subunit of Elongator, formerly called the IkappaB kinase associated protein (IKAP) protein. We measured IKBKAP mRNA in peripheral blood leukocytes to determine whether FD subjects and carriers have characteristic levels. Estimated mean IKBKAP mRNA levels, measured by quantitative PCR and expressed as amount relative to the noncarrier average, were significantly different for the two groups when not adjusted for age and sex (p < 0.001): FD subjects 0.23, 95% confidence interval (CI) (0.19, 0.28); carriers 0.58, 95% CI (0.50, 0.68); or adjusted for age and sex (p < 0.001): FD subjects 0.21, 95% CI (0.16, 0.26); carriers 0.66, 95% CI (0.55, 0.79). Comparison of IKBKAP mRNA levels of the 22 FD subjects and their related carriers showed a strong correlation, providing evidence for genetic control of splicing efficiency. IKBKAP mRNA levels were not higher in those subjects using tocotrienols or epigallocatechin gallate. Levels of IKBKAP mRNA in peripheral blood leukocytes can be used to assess molecular response to therapies aimed at enhancing exon 20 inclusion and increasing cellular levels of ELP1/IKAP.