Novel, simple and low-cost alternative method for fabrication of paper-based microfluidics by wax dipping.
Paper-based microfluidic devices are an alternative technology for fabricating simple, low-cost, portable and disposable platforms for clinical diagnosis. Hereby, a novel wax dipping method for fabricating paper-based microfluidic devices (μPADs) is reported. The iron mould for wax dipping was created by a laser cutting technique. The designed pattern was transferred onto paper by dipping an assembly mould into melted wax. The optimal melting temperature and dipping time were investigated. The optimal melting temperature was in the range of 120-130°C, and the optimal dipping time was 1s. The whole fabrication process could be finished within 1 min without the use of complicated instruments or organic solvents. The smallest hydrophilic channel that could be created by the wax dipping method was 639 ± 7 μm in size. The reproducibility of the μPAD fabrication for hydrophilic channel width of the test zone and sample zone was 1.48% and 6.30%, respectively. To verify the performance of the μPAD, multiple colorimetric assays for simultaneous detection of glucose and protein in real samples were performed. An enzymatic assay and the bromocresol green (BCG) method were conducted on the paper device to determine the presence of glucose and protein in a test solution. The results of the assays were not significantly different from those of the conventional methods (p>0.05, pair t-test and one-way ANOVA method). The wax dipping provides a new alternative method for fabricating lab-on-paper devices for multiple clinical diagnostics and will be very beneficial for developing countries.


The pharmacy workforce in public primary healthcare centers: promoting access and information on medicines.
Only few studies have analyzed the pharmaceutical workforce in primary healthcare centers, and a global recommendation calls for better understanding of the trends that shape workforce development and capacity. To analyze the distribution of the pharmaceutical workforce in primary healthcare centers in the national health system [Sistema Único de Saúde (SUS)] in Brazil. The study was conducted using data from the National Survey on Access, Use and Promotion of Rational Use of Medicines in Brazil. Secondary data referring to the socioeconomic indicators of each municipality were obtained from national public databases. Data stratification in geographic regions was considered, and data on workers in the management of the municipal pharmaceutical services and medicines dispensing centers were analyzed. Crude and adjusted prevalence ratios were calculated by Poisson regression in the study investigating the factors associated with low and high-density pharmacists per 10,000 inhabitants. The results showed that most Brazilian municipalities have a rate of 1 or more pharmacist per 10,000 inhabitants in primary healthcare public facilities, with a higher concentration of pharmacists in small municipalities. Even in Brazilian municipalities with lower economic capacity, the conditions of access to medicines and pertinent information on medicines were directly related to the number of pharmacists available in these centers. This study showed a high number of pharmacists in the public health system. The higher density of pharmacists in primary healthcare public facilities correlated to increased access to medicines information and better municipal social development.


Genetic polymorphism of N-acetyltransferase 2 in the susceptibility to laryngeal squamous cell carcinoma.
The purpose of this study was to investigate whether polymorphism of N-acetyltransferase 2 (NAT2) genotypes are associated with the risk of laryngeal squamous cell carcinoma (SCC). The study group consisted of 45 white patients with laryngeal SCC (42 men, with a mean age of 54 years [range, 37-70 years] and three women, with a mean age of 47 years [range, 32-55 years]) and 104 control subjects (68 men and 36 women; mean age, 50 years; range, 28-73 years). All of the patients were primarily treated with surgical intervention. Blood samples (5 mL) were obtained before surgery or from the patients under follow-up to 5 years after surgery (mean follow-up, 27 months; range, 6-48 months). DNA was extracted from the lymphocytes by high pure template preparation kit. NAT2*5A, NAT2*6A, NAT2*7A/B, and NAT2*14A were detected by use of LightCycler-NAT2 mutation detection kit by real-time polymerase chain reaction with Light Cycler instruments. The association between NAT2 polymorphisms and laryngeal SCC was prospectively modeled through multivariate logistic regression analysis. We found that the risk of laryngeal SCC was 7.3-fold higher in individuals with NAT2*5 mutant allele, 3.8-fold higher in subjects with NAT2*6 heterozygote allele, and 38.3-fold higher in NAT2*6 mutant allele. We also found that individuals with NAT2*7 heterozygote allele had a 0.2-fold less risk for the development of laryngeal SCC (p = .018). In this population, patients with NAT2*5 mutant and *6 heterozygous and mutant genotypes had a significantly higher risk for development of laryngeal SCC.


A case study comparing static and spatially explicit ecological exposure analysis methods.
Exposure to chemical contaminants must be estimated when performing ecological risk assessments. A previous article proposed a habitat area and quality conditioned population exposure estimator, E[HQ]P, and described an individual-based, random walk, Monte Carlo model (SE3M) to facilitate calculation of E[HQ]P. In this article, E[HQ]P was compared with exposure estimates from a baseline risk assessment that evaluated mink and great blue heron exposure to fluoride at a federal Superfund site. Calculation of E[HQ]P took into consideration a receptor's forage area, movement behavior, population size, and the areal extent and quality of suitable habitat. The baseline assessment used four methods that did (total and unit Tier 2) and did not (total and unit Tier 1) consider habitat area or quality; where "total" included all exposure units on site and "unit" only a given exposure unit. Total Tier 1 estimates were consistently higher than E[HQ]P (e.g., 169.1 mg/kg x d versus 21.6 mg/kg x d). Risk managers using total Tier 1 results for decision making would be unlikely to underestimate exposure; however, implementability of correspondingly lower remedial objectives could be challenging. Unit Tier 1 estimates were higher (e.g., 96.5 mg/kg x d versus 61.6 mg/kg x d) or lower (e.g., 3.5 mg/kg x d versus 51.1 mg/kg x d) than E[HQ]P depending on variations in landscape features. Total Tier 2 and E[HQ]P estimates were similar (e.g., 20.7 mg/kg x d versus 21.6 mg/kg x d) when an ecologically questionable average exposure was assumed. Unit Tier 2 estimates were consistently well below E[HQ]P (e.g., 17.8 mg/kg x d versus 61.6 mg/kg x d) when an average exposure was not assumed. Risk managers using unit Tier 1 or 2 results could be basing their decisions on potentially large underestimates of exposure. By forgoing average exposure assumptions, and explicitly addressing landscape heterogeneity, SE3M appears capable of yielding exposure estimates that are not as potentially misleading to risk managers as those produced with traditional averaging methods.


The diffusion of federal Title IX complaints throughout U.S. colleges and universities, 1994-2014.
This article uses an original dataset of federal Title IX complaints to assess whether and how mobilization of the law to confront sexual harassment has diffused throughout four-year (and above) nonprofit colleges and universities. Event history analyses show that complaints spread more rapidly among schools of similar selectivity as well as among institutions linked by a new indicator for social proximity-school Twitter ties-that encompasses multiple forms of social proximity simultaneously. The same diffusion patterns do not emerge for other types of sex discrimination complaints filed under Title IX, indicating that networks channel the capacity to mobilize law differently across different types of claims. The findings illuminate a dramatic transformation in the deployment of Title IX that has reshaped how colleges and universities govern gender relations.


Photopic sensitivities to ultraviolet and visible wavelengths and the effects of the macular pigments in human aphakic observers.
Psychophysical spectral sensitivities were obtained from aphakic human subjects in the photopic range. The foveal spectrum has a primary peak near 550 nm and a secondary peak about 0.7 log units lower around 380 nm. Off fovea, beyond most of the macular pigment, the curve is quite broad. While the peak is in the green, the gradual drop-off to 330 nm varies over only half a log unit. The two curves were compared in order to obtain an estimate of the macular pigments' spectrum. The macular pigments' curve has peaks at 460 and 490 nm as expected. It is broad and extends into the UV. These data suggest that the ocular media, including the macular pigments, have a profound effect on the spectral sensitivity.


Glial fibrillary acidic protein (GFAP) expression and nucleolar organizer regions (NORs) in human gliomas.
The frequency of nucleolar organizer regions (NORs) in each glioma tissue and the relation between the expression of glial fibrillary acidic protein (GFAP) and the frequency of NORs was investigated. The number of Ag-NORs per cell for glioblastoma multiforme was significantly higher than that for anaplastic astrocytoma (P less than 0.05) and that for astrocytoma (P less than 0.01). The number of Ag-NORs per cell for GFAP-positive cells was significantly lower than that for GFAP-negative cells in each histopathological grade (P less than 0.01). Moreover, the linear relationship was demonstrated between the Ag-NORs numbers of GFAP-negative cells and bromodeoxyuridine (BUdR) labeling indices. From these results, it is concluded that many GFAP-positive glioma cells may have low growth potential in glioma tissue and GFAP-negative cells may have a close relation to cell proliferation. The combination of immunohistochemical and silver colloid staining is a useful method for investigating the biological characteristics of brain tumors.


Stereotactic resection of intra-axial cerebral lesions in partial epilepsy.
We performed a retrospective study of stereotactic resections of intra-axial brain mass lesions in 30 patients with intractable partial epilepsy. The most common pathologic alterations observed were vascular malformations (11 lesions) and glial neoplasms (11 lesions). The locations of the lesions included the postcentral gyrus in five patients, the precentral gyrus in five, and the deep-seated left posterior temporal region in four, all of which were sites that may have precluded standard craniotomy and cortical resection. Of the 30 medically refractory patients, 26 had at least an 80% reduction in seizure activity at a mean duration of follow-up of 22 months postoperatively. Nineteen of 22 patients with at least 1 year (mean, 28 months) of follow-up and 13 of 15 patients with at least 2 years (mean, 34 months) of follow-up had favorable surgical outcomes. "Lesionectomy" may allow pathologic examination of intracranial lesions and may produce a worthwhile reduction in seizure activity in some patients with intractable partial epilepsy.


Vortex Counter-Current Chromatography: Performance of a New Preparative Column.
A New preparative column for the vortex counter-current chromatograph was fabricated by making many (966) cylindrical separation units to a high-dendity polyethylene disk and thenthreading them with 6-40 taps. The resulting column had a total capacity of 364 mL. The performance of this vortex column was examined with three different two-phase solvent systems each using a set of suitable test samples: hexane-ethyl acetate-methanol-0.1 M hydrochloric acid (1:1:1:1, v/v) for separation of DNP-amino acids; 1-butanol-acetic acid-water (4:1:5, v/v) for separation of dipeptides; and hexane-acetonitrile-water (20:15:2, v/v) for separation of Sudan dyes. Most of the separations show high partition efficiency of over a thousand theoretical plates, as expected based on the results previously obtained in preliminary separations with a small column. Overall, the results of the present study suggest that further improvement of the partition efficiency can be obtained by the modifying column configuration.


Increasing secular trends in height and obesity in children with type 1 diabetes: JSGIT cohort.
Recently, anthropometric indices in children with type 1 diabetes mellitus (T1DM) have begun to change. To examine secular trends in patients' anthropometric indices. Japanese children with T1DM from the 1995, 2000, 2008 and 2013 cohorts of The Japanese Study Group of Insulin Therapy for Childhood and Adolescent Diabetes. We analysed serum haemoglobin A1c (HbA1c) levels, the incidence of severe hypoglycaemic events, the types and doses of insulin, height standard deviation scores (SDS), body mass index (BMI) percentiles compared with healthy Japanese children and obesity prevalence over time. We also stratified the patients according to glycaemic control levels of <58 mmol/mol (optimal), 58-75 mmol/mol (suboptimal) and ≥75 mmol/mol (high-risk). Data for 513-978 patients from each of the cohorts were analysed. The incidence of severe hypoglycaemic events decreased over time (from 21 to 4.8/100 patient-years), while the proportion of insulin analogue doses increased (14.6% to 98.6%). In addition, patient height SDS (-0.22 to +0.17), BMI percentile (52.1 to 58.7) and obesity prevalence (2.1% to 5.1%) increased. Height SDS increased in all of the glycaemic control subgroups, while BMI percentile and obesity prevalence increased in the suboptimal and high-risk groups. Since 1995, the average height of children with T1DM has increased in parallel with increasing insulin doses. Clinicians should be aware of increased BMI in these patients and the associated risk of developing cardiovascular disease in the future.


Primary Outcomes for Adults Receiving the Unified Protocol after Hurricane Harvey in an Integrated Healthcare Setting.
The Unified Protocol for Transdiagnostic Treatment of Emotional Disorders (UP) has demonstrated efficacy for treating anxiety and depression. However, there are limited effectiveness data when conducted in real-world settings with diverse populations, including those with trauma. We evaluated treatment outcomes in a naturalistic, community setting among 279 adults who received UP following Hurricane Harvey. We examined change in overall clinical severity, depression and anxiety symptoms, functional impairment, and baseline outcome predictors (i.e., demographic characteristics, impact from Hurricane Harvey, co-occurrence of depression and anxiety symptoms). Global clinical severity, depression and anxiety symptoms, and functional impairment decreased by end-of-treatment. Participants experienced global symptom improvement to a lesser degree than demonstrated in efficacy trials. Participants who experienced greater storm impact reported larger reductions in anxiety symptoms than those less impacted by Harvey. Further studies evaluating the effectiveness of the UP post-disaster and with diverse samples are needed.


Effect of Mixed Reality on Delivery of Emergency Medical Care in a Simulated Environment: A Pilot Randomized Crossover Trial.
Mixed-reality (MR) technology has the potential to enhance care delivery, but there remains a paucity of evidence for its efficacy and feasibility. To assess the efficacy and feasibility of MR technology to enhance emergency care delivery in a simulated environment. This pilot randomized crossover trial was conducted from September to November 2021 at a single center in a high-fidelity simulated environment with participants block randomized to standard care (SC) or MR-supported care (MR-SC) groups. Participants were 22 resident-grade physicians working in acute medical and surgical specialties prospectively recruited from a single UK Academic Health Sciences Centre. Data were analyzed from September to December 2022. Participants resuscitated a simulated patient who was acutely unwell, including undertaking invasive procedures. Participants completed 2 scenarios and were randomly assigned to SC or MR-SC for the first scenario prior to crossover. The HoloLens 2 MR device provided interactive holographic content and bidirectional audiovisual communication with senior physicians in the MR-SC group. The primary outcome was error rate assessed via the Imperial College Error Capture (ICECAP) multidimensional error-capture tool. Secondary outcomes included teamwork (Observational Teamwork Assessment for Surgery [OTAS]; range, 0-6 and Teamwork Skills Assessment for Ward Care [T-SAW-C]; range, 1-5), scenario completion, stress and cognitive load (NASA Task Load Index [NASA-TLX; range 0-100]), and MR device user acceptability. A total of 22 physicians (15 males [68.2%]; median [range] age, 28 [25-34] years) were recruited. MR technology significantly reduced the mean (SD) number of errors per scenario compared with SC (5.16 [3.34] vs 8.30 [3.09] errors; P = .003), with substantial reductions in procedural (0.79 [0.75] vs 1.52 [1.20] errors; P = .02), technical (1.95 [1.40] vs 3.65 [2.03] errors; P = .01), and safety (0.37 [0.96] vs 0.96 [0.85] errors; P = .04) domains. MR resulted in significantly greater scenario completion rates vs SC (22 scenarios [100%] vs 14 scenarios [63.6%]; P = .003). It also led to significant improvements in the overall quality of teamwork and interactions vs SC as measured by mean (SD) OTAS (25.41 [6.30] vs 16.33 [5.49]; P < .001) and T-SAW-C (27.35 [6.89] vs 18.37 [6.09]; P < .001) scores. As reported via mean (range) NASA-TLX score, there were significant reductions for MR-SC vs SC in participant temporal demands (38 [20-50] vs 46 [30-70]; P = .03) and significant improvements in self-reported task performance (50 [30-60] vs 39 [10-70]; P = .01). Overall, 19 participants (86.4%) reported that they were more confident in making clinical decisions and undertaking clinical procedures with MR support. This study found that the use of MR technology reduced error, improved teamwork, and enhanced practitioner confidence when used to support the delivery of simulated emergency medical care. ClinicalTrials.gov Identifier: NCT05870137.


The benefits and limitations of cell-free DNA screening for 47, XXY (Klinefelter syndrome).
The purpose of this paper is to provide an overview of the 47, XXY syndrome, which is the most commonly occurring X and Y chromosomal variation. This paper seeks to review what is currently known of noninvasive prenatal testing (NIPT) and 47, XXY and investigate potential risks and benefits of prenatal identification. A literature review of NIPT and 47, XXY was performed to identify limitations of current NIPT techniques. As NIPT becomes an increasingly more routine procedure, prenatal findings of 47, XXY may increase. Awareness of this disorder and appropriate genetic counseling is necessary. X and Y chromosomal variations will be identified through this screening, and the benefits and limitations to this finding need to be thoughtfully considered. © 2017 John Wiley & Sons, Ltd.


Inhibition of cancer procoagulant by peptidyl diazomethyl ketones and peptidyl sulfonium salts.
Cancer procoagulant (CP) is a cysteine proteinase from cancer cells that initiates blood coagulation. Members of two classes of unique and highly specific cysteine proteinase inhibitors, peptidyl diazomethyl ketones (PDK) and peptidyl sulfonium salts (PSS), were studied to determine whether or not they inhibited CP. The inhibitors did not impair the activity of the coagulation system. There was a differential inhibitory effect of the 6 PDK and 2 PSS inhibitors, influenced by the amino acid composition or sequence of the peptide moiety, that suggests differences in structural features of the active site of CP and papain. CP was inhibited by both classes of inhibitors.


Batrachotoxin blocks slow and retrograde axonal transport in vivo.
The accumulation of choline acetyltransferase (CAT) proximal to and nerve growth factor (NGF) distal to the intraneural site of tetrodotoxin (TTX) or batrachotoxin (BTX) injection in vivo was used to monitor orthograde and retrograde axonal transport. Orthograde axonal transport was blocked by BTX for up to 7-10 days while TTX had no effect. Similarly, retrograde transport of [125I]NGF was blocked by BTX and not by TTX.


Sonographically guided intrasheath percutaneous release of the first annular pulley for trigger digits, part 2: randomized comparative study of the economic impact of 3 surgical models.
Trigger digit surgery can be performed by an open approach using classic open surgery, by a wide-awake approach, or by sonographically guided first annular pulley release in day surgery and office-based ambulatory settings. Our goal was to perform a turnover and economic analysis of 3 surgical models. Two studies were conducted. The first was a turnover analysis of 57 patients allocated 4:4:1 into the surgical models: sonographically guided-office-based, classic open-day surgery, and wide-awake-office-based. Regression analysis for the turnover time was monitored for assessing stability (R(2) < .26). Second, on the basis of turnover times and hospital tariff revenues, we calculated the total costs, income to cost ratio, opportunity cost, true cost, true net income (primary variable), break-even points for sonographically guided fixed costs, and 1-way analysis for identifying thresholds among alternatives. Thirteen sonographically guided-office-based patients were withdrawn because of a learning curve influence. The wide-awake (n = 6) and classic (n = 26) models were compared to the last 25% of the sonographically guided group (n = 12), which showed significantly less mean turnover times, income to cost ratios 2.52 and 10.9 times larger, and true costs 75.48 and 20.92 times lower, respectively. A true net income break-even point happened after 19.78 sonographically guided-office-based procedures. Sensitivity analysis showed a threshold between wide-awake and last 25% sonographically guided true costs if the last 25% sonographically guided turnover times reached 65.23 and 27.81 minutes, respectively. However, this trial was underpowered. This trial comparing surgical models was underpowered and is inconclusive on turnover times; however, the sonographically guided-office-based approach showed shorter turnover times and better economic results with a quick recoup of the costs of sonographically assisted surgery.


Mandibular reconstruction using a poly(L-lactide) mesh combined with autogenous particulate cancellous bone and marrow: a prospective clinical study.
The purpose of this study was to evaluate the stability and viability of mandibular bone regeneration using a poly(L-lactide) (PLLA) mesh and autogenous particulate cancellous bone and marrow (PCBM). Sixty-two procedures were undertaken at eight hospitals (22 malignant tumours, 30 benign tumours, five cysts, two osteomyelitis, two trauma, and one atrophy of the alveolar ridge); the success rate was 84%. The follow-up period was between 9 and 200 months (mean 88.2 months). Consequently, bone regeneration at 6 months postoperation was excellent in 35 cases (57%), good in 17 cases (27%), and poor in 10 cases (16%). In six of the 'poor' cases, the PLLA mesh was removed due to local infection early after surgery. Bone resorption>20% was observed in only one of 46 cases with a follow-up term of >1 year. There were no signs of any other adverse effects except in one case where a section of the tray broke off late in the follow-up period. It is concluded that this method is stable and effective due to favourable morphological and functional recovery and low invasiveness. It may thus be a useful alternative procedure for mandibular reconstruction.


Dispersion stability and rheological properties of silica suspensions in aqueous solutions.
This historical perspective overviews the dispersion stability and rheological properties of fumed and colloidal silica suspensions in aqueous solutions as a function of the volume fraction of silica (ϕ) (where ϕ is ≤0.1). The silica suspensions exist in a gel state at lower ϕ in acidic conditions than at alkaline pH. The steady-state shear viscosities of silica suspensions at acid conditions exhibit shear thinning behavior at lower ϕ than in alkaline conditions; the magnitudes of the dynamic moduli of the silica suspensions at acidic pH are larger than those at alkaline pH. Changes in the dispersion stability and rheological behavior of the silica suspensions may be attributable to the addition of salt, which decreases electrostatic repulsion. Furthermore, the effects of polymer adsorption on the dispersion stability and rheological behavior of hydrophilic or hydrophobic silica suspensions are discussed.


Purification of dolabellanin-C an antineoplastic glycoprotein in the body fluid of a sea hare, Dolabella auricularia.
An antineoplastic factor, dolabellanin C, inducing tumor lysis was purified to apparent homogeneity from the body fluid of the sea hare Dollabella auricularia. Purified dolabellanin C is a glyco-protein of 215 K daltons containing 3 subunits of 70 K daltons. The amino acid sequence of the amino terminal region was also determined. This factor was active even at 0.38 ng protein/ml, but did not lyse normal white or red blood cells.


Evaluation of the distribution of activation inside a compact medical cyclotron.
The distribution of activation inside a compact medical cyclotron was evaluated by measuring 1cm dose equivalent rates and γ-ray spectra. Analysis of the distribution of activation showed high activation at the deflector and the magnetic channel. Radionuclides 60Co, 57Co, 65Zn, and 54Mn were detected. Different radionuclides were generated from different components of the cyclotron, and low-activity radionuclides could be detected under low-background-radiation conditions.


Outcomes of Cardiac Resynchronization Therapy with Image-Guided Left Ventricular Lead Placement at the Site of Latest Mechanical Activation: A Systematic Review and Meta-Analysis.
To assess evidence for an image-guided approach for cardiac resynchronization therapy (CRT) that targets left ventricular (LV) lead placement at the segment of latest mechanical activation. A systematic review of EMBASE and PubMed was performed for randomized controlled trials (RCTs) and prospective observational studies from October 2008 through October 2020 that compared an image-guided CRT approach with a non-image-guided approach for LV lead placement. Meta-analyses were performed to assess the association between the image-guided approach and NYHA class improvement or changes in end-systolic volume (LVESV), end-diastolic volume (LVEDV), and ejection fraction (LVEF). From 5897 citations, 5 RCTs including 818 patients (426 image-guided and 392 non-image-guided) were identified. The mean age ranged from 66 to 71 years, 76% were male, and 53% had ischemic cardiomyopathy. Speckle tracking echocardiography was the primary image-guided method in all studies. LV lead placement within the segment of the latest mechanical activation (concordant) was achieved in the image-guided arm in 45% of the evaluable patients. There was a statistically significant improvement in the NYHA class at 6 months (odds ratio 1.66; 95% confidence interval (CI) [1.02, 2.69]) with the image-guided approach, but no statistically significant change in LVESV (MD -7.1%; 95% CI [-16.0, 1.8]), LVEDV (MD -5.2%; 95% CI [-15.8, 5.4]), or LVEF (MD 0.68; 95% CI [-4.36, 5.73]) versus the non-image-guided approach. The image-guided CRT approach was associated with improvement in the NYHA class but not echocardiographic measures, possibly due to the small sample size and a low rate of concordant LV lead placement despite using the image-guided approach. Therefore, our meta-analysis was not able to identify consistent improvement in CRT outcomes with an image-guided approach.


Modulatory effect of liraglutide on doxorubicin-induced testicular toxicity and behavioral abnormalities in rats: role of testicular-brain axis.
Doxorubicin (DOX) is a powerful chemotherapeutic agent used in many types of malignancies. However, its use results in testicular damage. DOX-induced testicular damage results in low level of serum testosterone which may affect cognitive function. The current study investigated the protective effect of liraglutide (50, 100 μg/kg/day) in testicular toxicity and the consequent cognitive impairment induced by DOX. DOX treatment reduced sperm count (62%) and sperm motility (53%) and increased sperm abnormalities (786%), as compared to control group. DOX also reduced serum testosterone level (85%) and the gene expression of testicular 3β-HSD (68%) and 17β-HSD (82%). Moreover, it increased testicular oxidative stress (MDA and GSH) by 103% and 59%, respectively, apoptotic (caspase-3 and P53) by 996% and 480%, respectively. In addition, DOX resulted in increasing autophagic markers including PAKT, mTOR, and LC3 by 48%, 56%, and 640%, respectively. Additionally, rats' behavior in Y-maze (60%) and passive avoidance task (85%) was disrupted. The histopathological results of testis and brain supported the biochemical findings. Treatment with liraglutide (100 μg/kg/day) significantly abrogated DOX-induced testicular damage by restoring testicular architecture, increasing sperm count (136%) and sperm motility (106%), and decreasing sperm abnormalities (84%) as compared to DOX group. Furthermore, liraglutide increased serum testosterone (500%) and steroidogenesis enzymes 3β-HSD (105%) and 17β-HSD (181%) along with suppressing oxidative stress (MDA and GSH) by 23% and 85%, respectively; apoptotic (caspase-3 and P53) by 59% and55%, respectively; and autophagic markers including PAKT, mTOR, and LC3 by 48%, 97%, and 60%, respectively. Moreover, it enhanced the memory functions in passive avoidance and Y-maze tests (132%). In conclusion, liraglutide is a putative agent for protection against DOX-induced testicular toxicity and cognitive impairment through its antioxidant, antiapoptotic, and antiautophagic effects.


Putting on a clinic in Va. Carilion, a not-for-profit hospital system based in Roanoke, is taking a $100 million risk to become a physician-run venture.
Carilion Health System needs to change or die, according to its leaders, so the Roanoke, Va., organization is converting from a typical not-for-profit system into a physician-run clinic. The switch is an extreme version of an industrywide push to employ doctors. James Thweatt Jr., left, of rival Lewis-Gale, says his hospital joined the trend when it hired 80 specialists from a failing local clinic.


Quantification and distribution of mast cells in oral periapical inflammatory lesions.
Periapical granuloma and periapical cysts develop as a sequela of inflammation of dental pulp, usually a consequence of an infected root canal. Mast cells (MCs) have most frequently been implicated in the pathophysiology of periapical lesions such as periapical granulomas and cysts. The present study was undertaken to emphasize the presence and quantification of MCs in periapical lesions (granulomas and cysts) using toluidine blue stain, with an aim to elucidate their role in the pathogenesis of these lesions. The study comprised a total of 55 previously diagnosed cases (30 cases of radicular cyst and 25 cases of periapical granuloma) selected from the departmental archives. The MCs were quantified in all the sections in the three zones, namely the epithelial, subepithelial, and deeper connective tissue zones. The results were sent for statistical analysis. Wilcoxon paired t-test and Mann-Whitney U test were applied for intra- and intergroup comparison MCs in different zones of periapical granulomas and radicular cyst, respectively. A statistically significant difference was observed between the two lesions in all the three zones, i.e., epithelial, subepithelial, and in deeper connective tissue zone with P = 0.001. Although MCs were present in all the three zones of both periapical cysts and granuloma, they were predominantly observed in radicular cysts than in periapical granuloma. This suggests a significant role of MC in initiation, development, and progression of these periapical lesions.


Patient's perceptions of buprenorphine use receiving treatment for cancer.
To assess knowledge and attitudes toward opioids and buprenorphine (BUP) of patients with cancer. Single-site, single-intervention telephone survey of patients under palliative care at the cancer center. Forty percent of the participants recognized the word "buprenorphine," and 28 percent recognized BUP indication for addiction treatment. Four percent addressed potential BUP misuse. None recognized BUP indication for pain. Seventy-one percent were not worried about addiction or dependency while using opioids to treat their cancer-related-pain, and 73 percent were not worried about being stigmatized in the healthcare setting about their pain regimens. Patients on opioids for less than 3 months were most strongly correlated with the fear of addiction and stigma. This study identifies patients' knowledge gap regarding BUP products for pain, which gives professionals the opportunity to provide education. This study identified that patients are most worried early on about addiction and stigma when using opioids.


Reliability and Validity of the Sensory Component of the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI): A Systematic Review.
Since 1982, the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) has been used to classify sensation of spinal cord injury (SCI) through pinprick and light touch scores. The absence of proprioception, pain, and temperature within this scale creates questions about its validity and accuracy. To assess whether the sensory component of the ISNCSCI represents a reliable and valid measure of classification of SCI. A systematic review of studies examining the reliability and validity of the sensory component of the ISNCSCI published between 1982 and February 2013 was conducted. The electronic databases MEDLINE via Ovid, CINAHL, PEDro, and Scopus were searched for relevant articles. A secondary search of reference lists was also completed. Chosen articles were assessed according to the Oxford Centre for Evidence-Based Medicine hierarchy of evidence and critically appraised using the McMasters Critical Review Form. A statistical analysis was conducted to investigate the variability of the results given by reliability studies. Twelve studies were identified: 9 reviewed reliability and 3 reviewed validity. All studies demonstrated low levels of evidence and moderate critical appraisal scores. The majority of the articles (~67%; 6/9) assessing the reliability suggested that training was positively associated with better posttest results. The results of the 3 studies that assessed the validity of the ISNCSCI scale were confounding. Due to the low to moderate quality of the current literature, the sensory component of the ISNCSCI requires further revision and investigation if it is to be a useful tool in clinical trials.


Molecular characterization of oncostatin M-induced growth arrest of MCF-7 cells expressing a temperature-sensitive mutant of p53.
Our previous studies have shown that treatment of MCF-7 breast cancer cells with cytokine oncostatin M (OM) results in a growth arrest and a concurrent decrease in p53 expression. It remains to be determined whether these two important events are directly connected, as changes in p53 protein levels can lead to variable biological outcomes. In this study we have generated stable cell lines (MCF7-ptsp53) that express p53Val135 a p53 temperature-sensitive mutant. We demonstrate that overexpression of the wildtype (wt) p53 at permissive temperature in MCF7-ptsp53 cells leads to growth arrest at the G2-M phase of the cell cycle. Inhibition of endogenous p53 function with the expression of mutant p53 protein at non-permissive temperature did not affect the OM-induced G1 cell cycle arrest. Microarray studies were further carried out to identify p53- and OM-regulated genes that mediate the G2/M or G1 cell cycle arrest. We show that the expression of p21 was upregulated and expressions of cdc2, cyclin B2 and protein regulator of cytokinesis 1 (PRC1) were suppressed by overexpression of the wt p53 in MCF7-ptsp53 cells at the permissive temperature. In contrast, OM treatment caused coordinate changes of mRNA expression of several cell cycle components including c/EBPdelta, cdc20, and thymidine kinase 1 (TK1) that mainly affect G1-S phase transition. All together, our results suggest that the downregulation of p53 transcription may be involved in some other cellular changes induced by OM but it is not directly connected to the antiproliferative activity of OM per se.


Roles of the indole ring of Trp396 covalently bound with the imidazole ring of His398 coordinated to type I copper in bilirubin oxidase.
Bilirubin oxidase has a post-translationally formed covalent-bond between the imidazole ring of His398 coordinated to type I copper and the indole ring of Trp396 located in the outer-coordination sphere. We performed point mutations at Trp396 with Ala, Thr, Phe, and Tyr with the aim of elucidating the role of the imidazole-indole moiety found only in bilirubin oxidase. The result showed shifts in the redox potential of type I copper towards negative direction by > 100 mV and decreases in cathodic current in electrochemistry, whereas optical and magnetic properties of type I copper were not affected or sparingly affected. Along with the conspicuous changes in redox properties enzymatic activities of the Trp396 mutants were prominently decreased. Further, chemical modification of the Trp residues with N-bromosuccinimide and photo-induced formylations of bilirubin oxidase exerted more pronounced effects on both redox properties and enzymatic activities compared to the Trp396 mutants. All these results unequivocally indicate that the covalent-bond formed between Trp396 and His398 plays a crucial role to enhance enzymatic activities of bilirubin oxidase by shifting the redox potential of type I Cu towards positive direction and also by functioning as the effective pathway of electron transport.


TGFalpha and AVP in the mouse suprachiasmatic nucleus: anatomical relationship and daily profiles.
Daily rhythms in behavior and physiology are under control of the suprachiasmatic nucleus (SCN), the main mammalian circadian pacemaker located in the hypothalamus. The SCN communicates with the rest of the brain via various output systems. The aim of the present study was to determine the neuroanatomical and temporal relationship between two output systems, arginine-vasopressin (AVP) and transforming growth factor alpha (TGFalpha), in the mouse SCN. TGFalpha-positive cells were found throughout the SCN, but more abundantly in the core than the shell area, while AVP was predominantly found in the shell. Fluorescent double labeling revealed a total lack of co-expression for the two proteins in SCN cells. The circadian profile, studied by way of optical density in immunostaining at 3 h intervals, showed peak values for AVP shortly after the LD transitions. Immunoreactivity for TGFalpha was highly variable, especially at time points before the LD transitions. In addition, strong lateralization in TGFalpha immunostaining in the SCN was found in some individuals. Daily fluctuations in the paraventricular nucleus were absent for TGFalpha, and only weakly present for AVP. The main conclusion derived from this study is that these two output systems of the biological clock are anatomically separated with different daily profiles in expression.


E-clonal antibodies: selection of full-length IgG antibodies using bacterial periplasmic display.
Here we describe a protocol for the selection of full-length IgG antibodies from repertoires displayed on Escherichia coli. In the method described here, full-length heavy and light chains are assembled in the periplasm into aglycosylated IgGs that are fully functional for antigen binding. Expression of an inner membrane-tethered Fc-binding protein is used to capture the IgG molecules and anchor them to the cell. Following outer-membrane permeabilization, fluorescently labeled ligand-binding library clones are selected by multiple rounds of fluorescence-activated cell sorting. Selection of a comprehensive set of IgG clones can typically be obtained within 3-4 weeks, a timescale that is comparable with most prevalent antibody display technologies. The isolated antibodies are well expressed in bacteria and exhibit affinities per binding site in the nanomolar range.


Effect of high-pressure processing and thermal treatments on color and in vitro bioaccessibility of anthocyanin and antioxidants in cloudy pomegranate juice.
In this study, the effect of high-pressure processing (HPP) and thermal treatments, including pasteurization (PT) and high-temperature short-time sterilization (HTST) on pomegranate juice (PJ) color attributes, anthocyanin (ACNs), vitamin C, and in vitro bioaccessibility of ACNs and antioxidants were investigated. Compared to HPP, thermal treatments significantly changed the CIE color, decreased the total monomeric ACNs and total vitamin C contents, and increased the percent polymeric color (PPC) and browning index (BI). Correlation analysis showed that the generation of polymeric ACNs played a significant role in color change during thermal treatments. The recovery of 7 ACNs in the control sample after in vitro gastrointestinal digestion was ranged from 0.43% to 5.0% and total individual ACNs after digestion showed no significant changes among different treatments. These results contributed to promoting the color quality and health benefits of pomegranate juice rich in ACNs by optimizing the processing conditions in the food industry.


[Cervicomanubrial route for the ventral upper thoracic spine: technical note about six cases].
Ventrolateral cervicotomy provides a narrowed working space for surgical management of upper thoracic spine. We report our experience about ventral upper thoracic spinal cord decompression with reconstruction and plating via the cervicomanubrial route. Six patients (24 to 75 years old) were operated on by the same operator (LN) by cervicomanubriotomy from 2002 to 2007 for upper thoracic spinal cord compression (one case of Pott's disease, three cases of metastases, one fracture, one invasive hemangio-epithelioma), with a good outcome in five patients. Lesions were located from the cervicothoracic junction down to the fourth thoracic vertebra (T4). In all cases, anterior spinal cord decompression, strut graft reconstruction (iliac bone in two cases, cement in four cases) and osteosynthesis were performed. In two cases, a second stage posterior decompression with fixation was performed. The approach begins by a left sided anterior cervicotomy, medial to the sternocleidomastoid muscle and lateral to the trachea and esophagus, associated with division of the infrahyoid muscles close to their insertion at the upper thoracic outlet followed by osteotomy of the manubrium sterni. Then, division of the thyropericardic fascia and thymus, control of the brachiocephalic vein, control of the thoracic lymphatic duct and the horizontal thoracic aorta are performed. The ventral part of fifth cervical vertebra body down to T4 is then exposed between the left primitive carotid artery laterally, the esophagus medially and the thoracic aorta caudally. Compared to total sternotomy without or with clavicle resection, cervicomanubriotomy seems to be a less aggressive, safe and reliable procedure.


Comparative Analysis of the APOL1 Variants in the Genetic Landscape of Renal Carcinoma Cells.
Although the relative risk of renal cell carcinoma associated with chronic kidney injury is particularly high among sub-Saharan African ancestry populations, it is unclear yet whether the APOL1 gene risk variants (RV) for kidney disease additionally elevate this risk. APOL1 G1 and G2 RV contribute to increased risk for kidney disease in black populations, although the disease mechanism has still not been fully deciphered. While high expression levels of all three APOL1 allelic variants, G0 (the wild type allele), G1, and G2 are injurious to normal human cells, renal carcinoma cells (RCC) naturally tolerate inherent high expression levels of APOL1. We utilized CRISPR/Cas9 gene editing to generate isogenic RCC clones expressing APOL1 G1 or G2 risk variants on a similar genetic background, thus enabling a reliable comparison between the phenotypes elicited in RCC by each of the APOL1 variants. Here, we demonstrate that knocking in the G1 or G2 APOL1 alleles, or complete elimination of APOL1 expression, has major effects on proliferation capacity, mitochondrial morphology, cell metabolism, autophagy levels, and the tumorigenic potential of RCC cells. The most striking effect of the APOL1 RV effect was demonstrated in vivo by the complete abolishment of tumor growth in immunodeficient mice. Our findings suggest that, in contrast to the WT APOL1 variant, APOL1 RV are toxic for RCC cells and may act to suppress cancer cell growth. We conclude that the inherent expression of non-risk APOL1 G0 is required for RCC tumorigenicity. RCC cancer cells can hardly tolerate increased APOL1 risk variants expression levels as opposed to APOL1 G0.


The Role of Decreased Levels of Neuronal Autophagy in Increased Susceptibility to Post-traumatic Epilepsy.
Post-traumatic epilepsy (PTE) caused by mild TBI (mild traumatic brain injury, mTBI) has a high incidence and poor prognosis, but its mechanisms are unclear. Herein, we investigated the role of reduced levels of neuronal autophagy during the latency period in the increased susceptibility to PTE. In the study, a gentle whole-body mechanical trauma rat model was prepared using Noble-Collip drums, and the extent of injury was observed by cranial CT and HE staining of hippocampal tissue. The incidence of epilepsy and its seizure form were observed 7-90 days after mTBI, and electroencephalography (EEG) was recorded during seizures in rats. Subcortical injection of non-epileptogenic dose of ferrous chloride (FeCl2) was used to observe the changes of PTE incidence after mTBI. Western blot and Real-time PCR were used to detect the level of autophagy in hippocampal cells at different time points during the latency period of PTE, and its incidence was observed after up-regulation of autophagy after administration of autophagy agonist-rapamycin. The results showed that mTBI was prepared by Noble-Collip drum, which could better simulate the clinical mTBI process. There was no intracerebral hemorrhage and necrosis in rats, no early-onset seizures, and the incidence of PTE after mTBI was 26.7%. The incidence of PTE was 56.7% in rats injected cortically with FeCl2 at a dose lower than the epileptogenic dose 48 h after mTBI, and the difference was significant compared with no FeCl2 injection, suggesting an increased susceptibility to PTE after mTBI. Further study of neuronal autophagy during PTE latency revealed that autophagy levels were reduced, and the incidence of PTE was significantly reduced after administration of rapamycin to upregulate autophagy. Taken together, the decreased level of neuronal autophagy during the latency period may be a possible mechanism for the increased susceptibility to PTE after mTBI.


Cytokeratins as targets for bile acid-induced toxicity.
Cholestasis is associated with retention of potentially toxic bile acids and profound cytoskeletal alterations of hepatocytes. Given the well-established cytoprotective role of hepatocyte keratins this study aimed to determine the effects of cholestasis on the cytokeratin (CK) intermediate filament network in mouse liver. Mice were subjected to common bile duct ligation or sham operation. Mice were also fed a cholic acid or ursodeoxycholic acid (UDCA)-supplemented diet (0.1%, 0.5%, and 1%) or control diet for 7 days. CK 8 and CK 18 expression was studied by competitive reverse transcriptase-polymerase chain reaction, in situ hybridization, Western blot analysis, and immunofluorescence microscopy. Common bile duct ligation and cholic acid feeding significantly stimulated CK 8 and CK 18 mRNA and protein levels compared to controls, whereas UDCA had no effect. CK overexpression was accompanied by pronounced phosphorylation. Our results show that potentially toxic bile acids induce hepatocytic CK 8 and CK 18 expression and phosphorylation whereas nontoxic UDCA has no effect on CKs. Thus, increased hepatocellular CK expression and phosphorylation in cholestasis may be caused by retention of toxic bile acids and reflect a hepatocellular stress response with potential beneficial effects.


Effects of amrinone on atrioventricular conduction in the intact canine heart.
The effects of amrinone on conduction in the intact canine heart were studied. Intracardiac His-electrode catheter recordings were used to measure the functional refractory period (FRP) of the AV node and conduction time through the AV node (A2H2 interval) and in the His-Purkinje system (H2V2 interval). Amrinone (2.5 to 10 mg/kg) shortened the FRP and A2H2 in a dose-dependent manner but had no significant effect on H2V2. In hearts where AV conduction was depressed by treatment with verapamil, propranolol, or ouabain, amrinone partially reversed this depression. Amrinone also shortened the recovery time of spontaneous sinoatrial (SA) node activity following a train of rapid atrial stimulation. This effect was also observed after depression of SA nodal recovery with verapamil, propranolol, or ouabain. These results indicate that amrinone enhances AV conduction and SA nodal activity in the normal heart and may favorably influence depressed AV conduction and SA nodal activity induced by a variety of cardioactive agents.


Analytical dataset on the molecular compositional changes of dissolved organic matter during hyperthermophilic composting.
The aim of this research work was to determine the molecular compositional changes of dissolved organic matter (DOM) taken from different phases of the hyperthermophilic composting (HTC) process. The DOM samples were extracted by the standard protocol of C18 extraction methodology, and then analyzed by electrospray ionization coupled with Fourier transform ion cyclotron resonance mass spectrometry (ESI FT-ICR MS). The profiles of negative ion mass spectrum and DOM molecular formulas of four compost samples were reported. Data related to the molecular compositional changes of DOM during HTC were also presented. Further interpretation and discussion on these datasets can be found in the related article entitled "Molecular insights into the transformation of dissolved organic matter during hyperthermophilic composting using ESI FT-ICR MS" [1].


HbA1c levels and circulating inflammatory proteins at onset of type 1 diabetes in children and adolescents.
Type 1 diabetes is an autoimmune disease that often develops during childhood. Complications such as retinopathy often occur during the course of the disease. Studies to identify possible predictors of complications in type 1 diabetes are needed; in particular markers able to identify risk of complications long before they occur. The first aim of this study was to investigate plasma levels of sCD163, sST2 and Gal-3 at diagnosis of type 1 diabetes in children and adolescents. The second aim was to study their correlation to HbA1c in this study cohort. Patients (n = 242, 0-18 years) with type 1 diabetes, at Helsingborg's Hospital were included in this study and circulating levels of sCD163, sST2 and Gal-3 were investigated in plasma using commercially available DuoSet ELISA and supplementary ancillary kit. Circulating sCD163 was significantly higher at diagnosis compared to after diagnosis (666 ± 318ng/ml and 505 ± 223ng/ml respectively; p < 0.001). Also sST2 was significantly higher (18.2 [12.7-25.6] ng/ml respectively 9.1 [6.3-13.5] ng/ml (p < 0.001), but Gal-3 levels did not differ from onset of diabetes to after diagnosis. HbA1c was shown to correlate to sCD163 (rs=0.36; p < 0.001), sST2 (rs=0.22; p = 0.016) and Gal-3 (rs=0.2; p = 0.020) in patients with a diabetes duration < 5 years. sCD163 levels increased in patients with recent-onset type 1 diabetes and the levels increased with higher HbA1c. Patients included in this study will be followed annually until the eventual development of diabetic complications, while continuously studying circulating levels of inflammatory proteins such as sCD163.


Compound heterozygous mutations in SNAP29 is associated with Pelizaeus-Merzbacher-like disorder (PMLD).
Pelizaeus-Merzbacher-like disease (PMLD) is an autosomal recessive hypomyelinating leukodystrophy, which is clinically and radiologically similar to X-linked Pelizaeus-Merzbacher disease (PMD). PMLD is characterized by early-onset nystagmus, delayed development (motor delay, speech delay and dysarthria), dystonia, hypotonia typically evolving into spasticity, ataxia, seizures, optic atrophy, and diffuse leukodystrophy on magnetic resonance imaging (MRI). We identified a 12-year-old Caucasian/Hispanic male with the classical clinical characteristics of PMLD with lack of myelination of the subcortical white matter, and absence of the splenium of corpus callosum. Exome sequencing in the trio revealed novel compound heterozygous pathogenic mutations in SNAP29 (p.Leu119AlafsX15, c.354DupG and p.0?, c.2T > C). Quantitative analysis of the patient's blood cells through RNA sequencing identified a significant decrease in SNAP29 mRNA expression, while western blot analysis on fibroblast cells revealed a lack of protein expression compared to parental and control cells. Mutations in SNAP29 have previously been associated with cerebral dysgenesis, neuropathy, ichthyosis, and keratoderma (CEDNIK) syndrome. Typical skin features described in CEDNIK syndrome, such as generalized ichthyosis and keratoderma, were absent in our patient. Moreover, the early onset nystagmus and leukodystrophy were consistent with a PMLD diagnosis. These findings suggest that loss of SNAP29 function, which was previously associated with CEDNIK syndrome, is also associated with PMLD. Overall, our study expands the genetic spectrum of PMLD.


Characteristics, therapy and outcome in an unselected and prospectively registered cohort of patients with gastro-oesophageal cancer.
The purpose was to examine characteristics, treatment and outcome in an unselected, prospectively registered complete population of patients with gastro-oesophageal adenocarcinoma cancer (GEA). All cases diagnosed with GEA between 2008 and 2009 in the Region of Southern Denmark (pop: 1,200,000) were registered. Patient characteristics, including performance status, stage and therapy, were retrieved from patient charts and used to compare sub-groups of patients. Three hundred and thirty patients were registered as having GEA. Patients were divided into three clinical subgroups based on initial treatment option: group 1: patients with resectable GEA (n = 113); group 2: patients receiving first-line therapy (n = 107); group 3: patients receiving no tumour-directed therapy (n = 110). Median overall survival (95% CI) in the three groups was 36 months (25-not reached), 7.1 months (7-9) and 2.4 months (2-3), respectively. Seven percent of patients participated in clinical trials. Among patients not amendable to resection, around 30% are candidates for three-drug combination chemotherapy. Age > 65 years was found not to be a poor prognostic factor for survival, giving the possibility of treating elderly patients in the future. Many patients (approx. 30%), however, never received cancer-directed therapy. In order to improve survival in the entire population, it is important that future trials also focus on this group of patients.


Is there an association between fetal scalp electrode application and early-onset neonatal sepsis in term and late preterm pregnancies? A case-control study.
Early-onset neonatal sepsis (EONS), defined as neonatal sepsis occurring within the first week after birth, is a major cause of morbidity and mortality. Fetal scalp electrode application, used for fetal heart rate monitoring during labour, could potentially increase the risk of EONS. The objective of this study was to determine whether this practice is associated with a significant risk for EONS in term and late preterm pregnancies. This case-control study enrolled subjects from three maternity hospitals in Edmonton. Cases were neonates with EONS who were born at ≥ 34 weeks between January 1, 2000, and March 1, 2011. Two control subjects were enrolled for each case identified. Control subjects were neonates of similar gestation (≥ 34 weeks), born at the same hospital site, who did not develop EONS. Maternal charts were accessed for information about fetal scalp electrode application and potential confounding variables. Forty cases and 80 control subjects were identified. There was no difference in the rate of exposure to fetal scalp electrode in cases (6/40) and control subjects (10/80) (OR 1.24; 95% CI 0.42 to 3.68, P = 0.92). The association between fetal scalp electrode application and EONS remained non-significant despite adjustment for confounders. We did not detect an association between the use of fetal scalp electrode and EONS, but our study was powered to detect only a strong association between the exposure of interest and the disease outcome. We cannot rule out a weakly positive association that may still exist.


Slice-selective adiabatic magnetization T2 -preparation (SAMPA) for efficient T2 -weighted imaging at ultrahigh field strengths.
At high field, T2 -weighted (T2 w) imaging is limited by transmit field inhomogeneity and increased radiofrequency power deposition. In this work, we introduce SAMPA (Slice-selective Adiabatic Magnetization T2 PrepAration) and demonstrate its use for efficient brain T2 w imaging at 7 Tesla (T). SAMPA was designed by subsampling an optimized B1 insensitive rotation (BIR4) waveform with small tip angle linear subpulses. To perform T2 w imaging, SAMPA was inserted before a fast gradient echo acquisition. The off-resonance behavior, B1 robustness, and slice selectivity of the novel T2 preparation module were analyzed using Bloch simulations. The performance of SAMPA for T2 w imaging was demonstrated in phantom experiments as well as in the brains of healthy volunteers at 7T. Based on simulations, the proposed design operates at peak B1 of 15 μT and higher, within a 400 Hz bandwidth. T2 values were in strong agreement with spin echo-based T2 mapping in phantom experiments. Whole brain, interleaved multislab three-dimensional imaging could be acquired with 0.8 mm3 isotropic resolution in 5:36 min per T2 weighting. Compared with previous adiabatic T2 preparation techniques, SAMPA allows for slice-selectivity, which can lead to efficient and robust acquisitions for T2 w imaging at high field. Magn Reson Med 76:1741-1749, 2016. © 2015 International Society for Magnetic Resonance in Medicine.


Internet based patient pathway as an educational tool for breast cancer patients.
The aim of this paper was to describe the process of developing an Internet-based empowering patient education program for breast cancer patients and to evaluate the quality of the program from the perspective of patients. In this program, the patient pathway was used as an educational tool. The Breast Cancer Patient Pathway (BCPP) was developed and tested at one Finnish university hospital in 2005-2007. Thirty-eight newly diagnosed breast cancer patients used the program during their treatment process until the end of all treatments (average 9 months) in 2008-2010. After the treatments the patients evaluated the content, language and structure, instructiveness, external appearance and technical characteristics of the web site as subcategories with the Evaluating Internet Pages of Patient Education instrument, which is a 37-item Likert scale (1-4) questionnaire. Comparison between the subcategories was done with Friedman's test. Dependencies between demographic variables and evaluation values were tested with Pearson correlation coefficients. The mean value of all evaluation criteria was 3.40. However, patients' evaluations between different subcategories varied, being the highest in language and structure (mean 3.48) and lowest in content (mean 3.13). Language and structure, external appearance and technical characteristics were significantly better than content, and language and structure better than instructiveness. Significant correlations were not found between demographic variables and evaluation values. Patients evaluated the quality of the BCPP to be best in language and structure and weakest in content. In terms of future development of the BCPP, the most improvement is needed in content and instructiveness. There is also a need for further development and study of Internet-based patient education.


Enhanced cycling performance of nanostructure LiFePO4/C composites with in situ 3D conductive networks for high power Li-ion batteries.
In this work, reduced nano-sized LiFePO4 precursor particles were fabricated via a green chemistry approach without the use of any organic solvent or surfactants by accelerating the feeding speed of ferrous sulfate. After carbon coating, a 4 nm thick high graphitic degree carbon layer was deposited uniformly on the surface of reduced nano-sized LiFePO4 particles and constructed in situ 3D conductive networks among the adjacent LiFePO4 particles, as a result of an elevated self-catalytic effect of the reduced nano-size LiFePO4 particles that promoted the formation of the conductive networks. The reduced nano-size LiFePO4/C particles with in situ 3D conductive networks were shown to have an excellent high rate discharge capacity and long cycle life, delivering a high initial reversible discharge capacity of 163 mA h g-1 at 0.2C and an even high rate discharge capacity of 104 mA h g-1 at 30C. Additionally, a capacity of 101.7 mA h g-1 with a capacity retention of 97% remained after 850 cycles at 30C. This work suggests that the enhanced electrochemical performance of the LiFePO4/C composite was improved via the combination of the reduced nano-sized and 3D conductive networks, facilitating the electron transfer efficiency and diffusion of lithium ions, especially over an extended cycling performance at a high rate.


Infectious disease consultation for Staphylococcus aureus bacteremia - A systematic review and meta-analysis.
Mortality and morbidity of Staphylococcus aureus bacteremia (SAB) still remains considerably high. We aimed to evaluate the impact of infectious disease consultation (IDC) on the management and outcomes of patients with SAB. We systematically searched 3 publication databases from inception to 31st May 2015 and reference lists of identified primary studies. Our search returned 2874 reports, of which 18 fulfilled the inclusion criteria, accounting for 5337 patients. Overall 30-day mortality was 19.95% [95% CI 14.37-27.02] with a significant difference in favour of the IDC group (12.39% vs 26.07%) with a relative risk (RR) of 0.53 [95% CI 0.43-0.65]. 90-day mortality and relapse risk for SAB were also reduced significantly with RRs of 0.77 [95% CI 0.64-0.92] and 0.62 [95% CI 0.39-0.99], respectively. Both, the appropriateness of antistaphylococcal agent and treatment duration was improved by IDC (RR 1.14 [95% CI 1.08-1.20] and 1.85 [95% CI 1.39-2.46], respectively). Follow-up blood cultures and echocardiography were performed more frequently following IDC (RR 1.35 [95% CI 1.25-1.46] and 1.98 [95% CI 1.66-2.37], respectively). Evidence-based clinical management enforced by IDC may improve outcome of patients with SAB. Well-designed cluster-randomized controlled trials are needed to confirm this finding from observational studies.


Aging tsunami coming: the main finding from China's seventh national population census.
China is undergoing great social changes, and its demographic makeup is shifting every year along with those changes. China released key indicators from the seventh national population census on 12 May 2021. The total population of China's mainland increased to 1.41178 billion in 2020 from 1.33972 billion in 2010 (sixth national population census) with an average annual growth rate of 0.53%. In the past 10 years, the share of the population aged above 60 and 65 years increased by 5.44% (from 13.26% in 2010 to 18.70% in 2020) and 4.6% (from 8.9 to 13.5%), respectively. The share of the population with a college education or above rose from 8.93% in 2010 to 15.47% in 2020, and the illiteracy rate dropped from 4.08% in 2010 to 2.67% in 2020. In the next decade, China is likely to face many changes, including the increasing proportion of older adults in the population, declining births, and economic transformation. In an effort to respond to the changed demographic landscape, the authorities should adopt new laws and strategies to improve government services for older adults and consider ways to support women and families and make childbearing more attractive to and feasible for women.


Mildly dysplastic oral lesions with optically-detectable abnormalities share genetic similarities with severely dysplastic lesions.
Optical imaging studies of oral premalignant lesions have shown that optical markers, including loss of autofluorescence and altered morphology of epithelial cell nuclei, are predictive of high-grade pathology. While these optical markers are consistently positive in lesions with moderate/severe dysplasia or cancer, they are positive only in a subset of lesions with mild dysplasia. This study compared the gene expression profiles of lesions with mild dysplasia (stratified by optical marker status) to lesions with severe dysplasia and without dysplasia. Forty oral lesions imaged in patients undergoing oral surgery were analyzed: nine without dysplasia, nine with severe dysplasia, and 22 with mild dysplasia. Samples were submitted for high throughput gene expression analysis. The analysis revealed 116 genes differentially expressed among sites without dysplasia and sites with severe dysplasia; 50 were correlated with an optical marker quantifying altered nuclear morphology. Ten of 11 sites with mild dysplasia and positive optical markers (91%) had gene expression similar to sites with severe dysplasia. Nine of 11 sites with mild dysplasia and negative optical markers (82%) had similar gene expression as sites without dysplasia. This study suggests that optical imaging may help identify patients with mild dysplasia who require more intensive clinical follow-up. If validated, this would represent a significant advance in patient care for patients with oral premalignant lesions.


The thyroid hormone analogue SKF L-94901: nuclear occupancy and serum binding studies.
1. We studied a brominated thyroid hormone analogue, SKF L-94901, which has the potential to lower serum cholesterol without adverse cardiovascular effects. This compound is about 50% as active as tri-iodothyronine (T3) in liver nuclear receptor binding in vivo but only 1% as active in vitro and has nearly 200 times more enzyme-inducing activity in liver than in heart. Our aim was to examine the interaction of SKF L-94901 with [125I]T3 binding to the intact nuclei in whole cells, isolated nuclei and nuclear extracts of human HeLa cells and to investigate the binding of this compound to human serum. 2. Relative to thyroxine (T4), the affinity of this compound for T4-binding globulin was 0.0035%, for transthyretin 1.66% and for albumin 1.26%. Low affinity for serum proteins, with a relatively high circulating free fraction, could explain why SKF L-94901 is more potent in vivo than in vitro. 3. Human HeLa cell nuclei, isolated after whole-cell incubations, bound [125I]T3 with high affinity (Kd = 78 +/- 8 pmol/l, mean +/- SEM), which was displaceable by T3 analogues in the order Triac [( 4-(4-hydroxy-3-iodophenoxy)-3,5-di-iodophenyl]acetic acid) greater than T3 greater than T4 much greater than reverse T3. Similar high-affinity (Kd = 58 +/- 6 pmol/l, mean +/- SEM) and identical specificity was observed in high-salt (0.4 mol/l KCl) nuclear extracts. In nuclei of whole cells incubated with [125I]T3 and SKF L-94901, the analogue was 0.8% as potent as T3, whereas in experiments with nuclear extract, the analogue was 7.7% as potent as T3.(ABSTRACT TRUNCATED AT 250 WORDS)


Structural and mutational studies of organophosphorus hydrolase reveal a cryptic and functional allosteric-binding site.
Organophosphorus hydrolase detoxifies a broad range of organophosphate pesticides and the chemical warfare agents (CWAs) sarin and VX. Previously, rational genetic engineering produced OPH variants with 30-fold enhancements in the hydrolysis of CWA and their analogs. One interesting variant (H254R) in which the histidine at position 254 was changed to an arginine showed a 4-fold increase in the hydrolysis of demetonS (VX analog), a 14-fold decrease with paraoxon (an insecticide), and a 183-fold decrease with DFP (sarin analog). The three-dimensional structure of this enzyme at 1.9A resolution with the inhibitor, diethyl 4-methylbenzylphosphonate (EBP), revealed that the inhibitor did not bind at the active site, but bound exclusively into a well-defined surface pocket 12 A away from the active site. This structural feature was accompanied by non-competitive inhibition of paraoxon hydrolysis by EBP with H254R, in contrast to the native enzyme, which showed competitive inhibition. These parallel structure-function characteristics identify a functional, allosteric site on the surface of this enzyme.


Effect of emicizumab on global coagulation assays for plasma supplemented with apixaban or argatroban.
Emicizumab is a bi-specific humanized monoclonal antibody mimicking the factor (F) VIII cofactor activity in mediating the activation of FX by FIXa. Recent observations showed that emicizumab when added to pooled normal plasma (PNP), hemophilic plasma or PNP added with unfractionated heparin is able to interfere with coagulation assays. To further explore the mechanisms of assay interference we investigated the effect of emicizumab on global coagulation assays for the PNP added with two direct oral anticoagulants, apixaban or argatroban. Aliquots of PNP were added with purified apixaban or argatroban at a concentration of 500 ng/mL and emicizumab at concentrations ranging from 0 to 100 µg/mL. Plasma samples were then tested for the activated partial thromboplastin time (APTT) and for thrombin generation (the latter for the apixaban plasma only). Emicizumab at a 25-50 µg/mL shortened the APTT of the PNP with or without apixaban or argatroban. The extent of correction was greater for the apixaban or argatroban plasma and amounted to 35% or 42%, respectively. The parameters of thrombin generation (lag-time and time-to-peak) for the PNP supplemented with apixaban were shortened by 30% or 25%, respectively and the endogenous thrombin potential and the peak-thrombin were marginally affected. Emicizumab attenuates in vitro the anticoagulant activity of the PNP induced by apixaban or argatroban as documented by the correction of prolonged APTT and velocity of thrombin generation (i.e., lag-time and time-to-peak). Whether the above effects have any relevance in vivo is unknown.


Absence of triradius d on the palms of normal people.
Absence of the digital triradius d is a very rare phenomenon, previously only reported in abnormal XXXXY males. During the past few years the anomaly has been found on the palms of three normal females, namely a young English woman and two sisters in the Nicobar Islands in the Indian Ocean. These cases are described and illustrations of the palmar dermatoglyphics presented. The occurrence of such a rare phenomenon in two sisters suggests that it is genetically determined.


The complement system, neuronal injury, and cognitive function in horizontally-acquired HIV-infected youth.
The complement system (C1q/C3) is a key mediator of synaptic pruning during normal development. HIV inappropriately induces C1q and C3 production in the brain, and reduces neuronal complement inhibition. HIV may thus alter neural connectivity in the developing brain by excessively targeting synapses for elimination. The resultant pattern of neuronal injury may fundamentally alter neurodevelopmental and cognitive processes differentially across ages. This study aimed to (1) measure the association between the cerebrospinal fluid (CSF) complement factors (C1q/C3) and a marker of neuronal injury (NFL) in HIV+ subjects; (2) quantify the differences in CSF C1q/C3 between HIV+ youth and older adults; and (3) define the relationship between CSF C1q/C3 and cognitive impairment in each age group. We performed a retrospective cross-sectional study of 20 HIV+ 18-24-year-old youth and 20 HIV+ 40-46-year-old adults with varying levels of cognitive impairment enrolled in the CNS Antiretroviral Therapy Effects Research study. We quantified C3, C1q, and NFL by ELISA in paired CSF/plasma specimens. We found that CSF C1q correlates with NFL in all subjects not receiving antiretroviral therapy (n = 16, rho = 0.53, p = 0.035) when extreme NFL outliers were eliminated (n = 1). There was no difference in plasma/CSF C1q or C3 between older adults and youth. In 18-24-year-old youth, a nearly significant (p = 0.052) elevation of CSF C1q expression was observed in cognitively impaired subjects compared to cognitively normal subjects. Further investigation into the role of the CNS complement system in the neuropathogenesis of HIV is warranted and should be considered in a developmentally specific context.


An investigation of movement dynamics and muscle activity during traditional and accentuated-eccentric squatting.
Accentuated-eccentric loading (AEL) takes advantage of the high force producing potential of eccentric muscle contractions, potentially maximising mechanical tension within the muscle. However, evidence is lacking on how AEL squatting may load the involved musculature, limiting scientifically justified programming recommendations. The purpose of this study was to investigate the effects of concentric and eccentric loads on joint loading and muscle activity of the lower limbs. Resistance trained males performed traditional squatting (20-100% of concentric one-repetition maximum [1RM]) and AEL squatting with eccentric loads (110-150% of 1RM) provided by a novel motorised isotonic resistance machine (Kineo). Kinetics and kinematics of the hip, knee, and ankle joints were collected, with electromyography from the gluteus maximus, vastus lateralis, biceps femoris, and gastrocnemius medialis. A secondary cohort underwent a kinematic and electromyography analysis of squatting technique to compare Kineo and back and front barbell squatting. Knee joint peak eccentric moments occurred at 120% 1RM (P = 0.045), with no further increase thereafter. As eccentric load increased, the time course of moment development occurred earlier in the eccentric phase. This resulted in a 37% increase in eccentric knee extensor work from the 80% 1RM trial to the 120% 1RM trial (P<0.001). Neither hip nor ankle joints displayed further change in kinetics as eccentric load increased above 100% 1RM. Electromyographic activity during traditional squatting was ~15-30% lower in all eccentric trials than in concentric trials for all muscles. EMG plateaued between a load of 80-100% 1RM during the eccentric trials and did not increase with AEL. No significant differences in kinematics were found between Kineo and barbell squatting. The knee extensors appear to be preferentially loaded during AEL squatting. The greater work performed during the eccentric phase of the squat as eccentric load increased suggests greater total mechanical tension could be the cause of adaptations from AEL. Our data suggest that AEL should be programmed with a load of 120% of 1RM. Further studies are needed to confirm the longer-term training effects of AEL.


Clinical Evaluation of the Medium-Term Efficacy of Laparoscopic Sleeve Gastrectomy against Obstructive Sleep Apnea-Hypopnea Syndrome in Obese Patients.
This study was designed to evaluate the efficacy of laparoscopic sleeve gastrectomy (LSG) for obstructive sleep apnea-hypopnea syndrome (OSAHS) in obese individuals and identify the related factors affecting its efficacy. The clinical and follow-up data of 37 obese patients with OSAHS who underwent LSG in the Laparoscopic Surgery Department of Zibo Central Hospital from January 2017 to July 2018 were analyzed retrospectively. The effect of this operation on patients' weight and OSAHS was studied, and the factors affecting weight and OSAHS were examined through univariate and multivariate logistic regression analysis. Over 12 months of regular postoperative follow-up with the 37 patients, their body mass index (BMI) decreased, and the percentage of excess weight loss (EWL%) reached 73.2%. Additionally, the rate of successful OSAHS treatment reached 91.89%, and the apnea-hypopnea index (AHI) and lowest arterial oxygen saturation (LSaO2) increased significantly. Univariate logistic regression analysis showed that gender, weight, EWL%, and smoking affected the efficacy of LSG against OSAHS (P < 0.05). EWL% and smoking were independent factors that helped determine the efficacy of LSG against morbid obesity (P < 0.05). LSG can effectively help obese patients lose weight and show medium-term efficacy against OSAHS in obese people. Smoking and EWL% were found to be the factors determining the efficacy of LSG.


Pharmacological Interventions versus Combined Treatment of Depression: A Prospective Study.
Depression is a common disease worldwide but still, the role of combined treatment (pharmacological and psychological interventions) needs to be clarified. The study aims to compare the effectiveness of integrated treatment versus exclusive pharmacological intervention of depression. The observational prospective study provided the collection of data relating to outpatients evaluated through the administration of the Hamilton Depression Rating Scale (HDRS), the Hamilton Anxiety Rating Scale (HARS), and the Clinical Global Impression Scale (CGI) both at T0 and at a 3-month follow up visit (T1). A statically significant association between sex (female) and psychotherapy utilization emerged. A statistically significant association between education (graduated patients) and psychotherapy use was observed. The other qualitative variables showed no statistically significance associations. No significant association between drop out and type of treatment emerged. Clinical research has not yet conclusively demonstrated the superiority of combined therapy over single treatments. As regards sex, the result is in line with the professional literature and provides support in describing how men have more stigmatizing beliefs about treatment of mental health. As regards education, graduated people present higher rates of adherence probably because they may have major introspective capacity and predisposition to communication. Limitations consist in small sample and short duration of the follow-up (3 months). The strengths, in the type of setting and the respect for routine clinical practice. Future perspective of the research could focus on application of rating instruments to highlight the variables involved in depressive disorder.


Biochemical mechanism of aminoglycoside-induced inhibition of phosphatidylcholine hydrolysis by lysosomal phospholipases.
Aminoglycosides such as gentamicin are hydrophilic, polycationic drugs which bind to negatively-charged phospholipid bilayers, inhibit the activities of the lysosomal enzymes involved in the degradation of the major phospholipids and cause, in kidney in vivo or in cultured cells, a lysosomal phospholipidosis. In the present study, we show that the hydrolysis of phosphatidylcholine induced in liposomes by lysosomal extracts at pH 5.4 in vitro is critically dependent on the negative charges carried by the bilayer. This hydrolysis, which is predominantly carried on by phospholipases A1 and A2, markedly increases when the phosphatidylinositol content is raised from 10 to 30% of the total phospholipids, i.e. in a range found in natural membranes. Addition of gentamicin decreases the activity of these enzymes in a non-competitive fashion, but the effect is inversely proportional to the amount of phosphatidylinositol present in the bilayer. Gentamicin and bis(beta-diethylaminoethylether)hexestrol (DEH), a cationic amphiphile which also binds to phospholipid bilayers, are equipotent inhibitors when added to negatively-charged liposomes at equinormal concentrations. Although direct aminoglycoside-enzyme interactions cannot be excluded, these results strongly suggest that gentamicin impairs the activities of the lysosomal phospholipases towards phosphatidylcholine by decreasing the available negative charges required for optimal activity.


Parental responsibility beliefs: associations with parental anxiety and behaviours in the context of childhood anxiety disorders.
High levels of parental anxiety are associated with poor treatment outcomes for children with anxiety disorders. Associated parental cognitions and behaviours have been implicated as impediments to successful treatment. We examined the association between parental responsibility beliefs, maternal anxiety and parenting behaviours in the context of childhood anxiety disorders. Anxious and non-anxious mothers of 7-12 year old children with a current anxiety disorder reported their parental responsibility beliefs using a questionnaire measure. Parental behaviours towards their child during a stressor task were measured. Parents with a current anxiety disorder reported a greater sense of responsibility for their child's actions and wellbeing than parents who scored within the normal range for anxiety. Furthermore, higher parental responsibility was associated with more intrusive and less warm behaviours in parent-child interactions and there was an indirect effect between maternal anxiety and maternal intrusive behaviours via parental responsibility beliefs. The sample was limited to a treatment-seeking, relatively high socio-economic population and only mothers were included so replication with more diverse groups is needed. The use of a range of stressor tasks may have allowed for a more comprehensive assessment of parental behaviours. The findings suggest that parental anxiety disorder is associated with an elevated sense of parental responsibility and may promote parental behaviours likely to inhibit optimum child treatment outcomes. Parental responsibility beliefs may therefore be important to target in child anxiety treatments in the context of parental anxiety disorders.


Potent HIV protease inhibitors incorporating high-affinity P2-ligands and (R)-(hydroxyethylamino)sulfonamide isostere.
Design and synthesis of a series of very potent nonpeptide HIV protease inhibitors are described. The inhibitors are derived from novel high affinity P2-ligands and (R)-(hydroxyethylamino)sulfonamide isostere.


Modified triple pelvic osteotomy for adult symptomatic acetabular dysplasia: clinical and radiographic results at midterm follow-up.
Acetabular dysplasia is the most common cause of secondary arthritis of the hip joint. Achieving maximum restoration of the acetabular coverage and medialization of the femoral head remains difficult with the original Steel triple pelvic osteotomy for acetabular dysplasia in children and adults. This study intended to answer the following questions: (1) Are the midterm functional results of our modified procedure favorable, particularly in relation to Harris scores? and (2) On the basis of the Tönnis grade, does this procedure has a different effect on radiographic parameters and functional results at midterm follow-up? This study included 26 consecutive adult patients with symptomatic acetabular dysplasia (28 hips) who underwent modified triple pelvic osteotomy through two incisions between July 2005 and June 2012. According to the preoperative Tönnis grade, the patients were divided into T0 (Tönnis grade 0), T1 (Tönnis grade 1), and T2 (Tönnis grade 2) groups. Wiberg center-edge (CE) angle, Sharp acetabular angle, lateralization, and Harris scores were analyzed to assess the radiographic and clinical outcomes. The mean CE angle (28.43° [± 3.58°], p < 0.05), Sharp acetabular angle (36.39° [± 3.26°], p < 0.05), lateralization (16.82 mm [± 3.10 mm], p < 0.05), and Harris scores (89.07 [± 4.97], p < 0.05) at the last follow-up significantly improved compared to those preoperatively. Multiple comparisons of radiographic outcomes among the three groups indicated no significant difference (p < 0.05). Harris scores in group T2 were significantly lower than those in groups T0 (p < 0.05) and T1 (p < 0.05). No major complication was observed. Our modified triple pelvic osteotomy for adult symptomatic acetabular dysplasia with early-stage osteoarthritis could lead to excellent radiographic outcomes, good clinical results, and lower complication rates.


Usefulness of EEG for the differential diagnosis of possible transient ischemic attack.
EEG value in possible transient ischemic attacks (TIA) is unknown. We aim to quantify focal slow wave activity (FSWA) and epileptiform activity (EA) frequency in possible TIA, and to analyse its contribution to the final diagnosis of seizures and/or definitive TIA. Prospective longitudinal study of possible TIA patients evaluated at a tertiary centre during 36 months and with 1-3 months follow-up. EEG was performed as soon as possible (early EEG) and one month later (late EEG). A stroke neurologist established final diagnosis after reassessing all clinical and diagnostic tests. 80 patients underwent an early EEG (45.8 h after possible TIA): 52 had FSWA and 6 of them also EA. Early FSWA was associated with epileptic seizure or definitive TIA final diagnosis (p = .041). Patients with these diagnoses had more frequently early FSWA (19/23; 82.6%) than EA (6/23; 26.1%). 6/13 (46.2%) patients with epileptic seizure final diagnosis had EA.In the late EEG, 43 (58.1%) patients demonstrated persistent FSWA and 3 of them also EA. Persistent FSWA in the late EEG was more frequent in seizures than in TIA patients (91.7% vs. 45.5%). FSWA disappearance was associated with acute vascular lesion on neuroimage. FSWA was the commonest EEG abnormality found in the early EEG of patients with possible TIA, but did not distinguish between TIA and seizure patients. In patients with seizures, FSWA was more common than EA and its presence in the late EEG was more likely in patients with epileptic seizures than with TIA. The majority of possible TIA patients with the final diagnosis of epileptic seizures do not have EA in the early or late EEG.


Safety assessment of foods from genetically modified crops in countries with developing economies.
Population growth particularly in countries with developing economies will result in a need to increase food production by 70% by the year 2050. Biotechnology has been utilized to produce genetically modified (GM) crops for insect and weed control with benefits including increased crop yield and will also be used in emerging countries. A multicomponent safety assessment paradigm has been applied to individual GM crops to determine whether they as safe as foods from non-GM crops. This paper reviews methods to assess the safety of foods from GM crops for safe consumption from the first generation of GM crops. The methods can readily be applied to new products developed within country and this paper will emphasize the concept of data portability; that safety data produced in one geographic location is suitable for safety assessment regardless of where it is utilized.


Potential shortcomings in current studies on the effect of intranasal oxytocin in Anorexia Nervosa and healthy controls - A systematic review and meta-analysis.
The psychopathology of anorexia nervosa (AN) includes altered social cognition and information processing of fear and anxiety. Oxytocin, a neuromodulating hormone, may influence these functions and could be valuable for the treatment of AN. The current study aimed at reviewing the effect of intranasal oxytocin (IN-OT) on attentional bias (AB) and emotion recognition (ER) in AN. A systematic literature review was done for free-text and the MeSH-terms: anorexia nervosa, feeding and eating disorders, and oxytocin. Six publications, reporting from 4 unique clinical trials, were included in this review. A meta-analysis was conducted to examine the effects of IN-OT on AB towards food images and ER on healthy controls (HC) and patients with AN. Overall, IN-OT did not influence AB towards food images (effect size = 0.20 [- 0.16, 0.57], p = 0.28) and had no effect on ER (effect size = - 0.01 [- 0.27, 0.26], p = 0.97) in patients with AN and healthy control (HC) subjects collectively. Assessing HC and AN separately in subgroup analyses did not show any significant effect on AB and ER in neither of the subgroups. All tests were done between 15 and 55 min post-administration of IN-OT, while peak concentration in the cerebrospinal fluid has been determined to be at 75 min. The current level of evidence is moderate showing no effect of IN-OT on AB or ER in AN. However, brain exposure may not have been sufficient which future studies with IN-OT need to ensure by considering dose and dose-to-task interval.


Stability in a multi-species assemblage of large herbivores in East Africa: an alternative interpretation.
Prins and Douglas-Hamilton (1990) analyzed data based on nine census counts of large herbivore species in Lake Manyara National Park, northern Tanzania, over the period 1959-1984. Their major conclusion was that even if individual species-showed large fluctuations in numbers, the different species compensated the fluctuations of the other species in a way resulting in a constancy of total herbivore biomass, constancy of plant biomass consumption, and "overall stability of the system under natural conditions". The authors believed that they had found a support for this view by calculating the "stability index" based on correlations between numbers of large herbivores. In this paper I show that Prins and Douglas-Hamilton's calculation of the stability index was not justified. Grazing and browsing pressure by large herbivores in Lake Manyara National Park seems to be remarkably constant. However, available information does not allow any rigorous conclusions about the stability of this community. We need more data from other systems dominated by large herbivores to be able to make comparisons and to be able to say which systems are more stable and in what sense.


Subtype-specific regulation of muscarinic receptor expression and function by heterologous receptor activation.
Incubation of cultured embryonic chicken heart cells with the beta-adrenergic agonist isoproterenol resulted in a dose-dependent increase in the number of mAChR on the surface of intact cells. The isoproterenol-mediated increase in mAChR number was time dependent and reached a maximum by 48 h. Chick heart cells treated with isoproterenol exhibited a greater than 6-fold increase in the sensitivity for carbachol-mediated inhibition of adenylyl cyclase activity as compared to control. Stimulation of cultured heart cells for 24 h with isoproterenol resulted in a 25-35% increase in cm2 mRNA levels as compared to control cm2 mRNA levels. In contrast, the level of cm4 mRNA was not significantly affected by isoproterenol treatment. cm2 mRNA levels were maximally elevated by 15 h following isoproterenol stimulation and remained elevated for up to 72 h. Incubation of cells with isoproterenol in the presence of Rp-cAMP, an inhibitor of cAMP-dependent protein kinase, blocked the increase in the level of cm2 mRNA. Thus, prolonged activation of beta-adrenergic receptors results in an increase in mAChR number and muscarinic responsiveness in chick heart cells due to a cAMP-dependent protein kinase mediated increase in cm2 mRNA levels.


Protein-protein complexation in bioluminescence.
In this review we summarize the progress made towards understanding the role of protein-protein interactions in the function of various bioluminescence systems of marine organisms, including bacteria, jellyfish and soft corals, with particular focus on methodology used to detect and characterize these interactions. In some bioluminescence systems, protein-protein interactions involve an "accessory protein" whereby a stored substrate is efficiently delivered to the bioluminescent enzyme luciferase. Other types of complexation mediate energy transfer to an "antenna protein" altering the color and quantum yield of a bioluminescence reaction. Spatial structures of the complexes reveal an important role of electrostatic forces in governing the corresponding weak interactions and define the nature of the interaction surfaces. The most reliable structural model is available for the protein-protein complex of the Ca(2+)-regulated photoprotein clytin and green-fluorescent protein (GFP) from the jellyfish Clytia gregaria, solved by means of Xray crystallography, NMR mapping and molecular docking. This provides an example of the potential strategies in studying the transient complexes involved in bioluminescence. It is emphasized that structural studies such as these can provide valuable insight into the detailed mechanism of bioluminescence.


Enhancement of biochemical transformation of mammalian cells by herpes simplex virus following nitrosomethylurea treatment.
A quantitative assay for the biochemical transformation of thymidine kinaseless mouse cells (N cIA cI10 cells) to an enzyme-positive phenotype by herpes simplex virus has been used to examine the effect of the carcinogen nitrosomethylurea on cell transformation. Exposure of cells to the chemical carcinogen, followed by virus infection, resulted in enhancement of transformation when compared to that seen with virus or chemical alone. Enhancement occurred after doses of nitrosomethylurea that were nontoxic to treated cells. A strong time dependence after treatment was demonstrated for enhancement which was correlated with the presence and excision-repair of alkylated DNA in treated cells.


Neuroendocrine and metabolic components of dopamine agonist amelioration of metabolic syndrome in SHR rats.
The hypertensive, pro-inflammatory, obese state is strongly coupled to peripheral and hepatic insulin resistance (in composite termed metabolic syndrome [MS]). Hepatic pro-inflammatory pathways have been demonstrated to initiate or exacerbate hepatic insulin resistance and contribute to fatty liver, a correlate of MS. Previous studies in seasonally obese animals have implicated an important role for circadian phase-dependent increases in hypothalamic dopaminergic tone in the maintenance of the lean, insulin sensitive condition. However, mechanisms driving this dopaminergic effect have not been fully delineated and the impact of such dopaminergic function upon the above mentioned parameters of MS, particularly upon key intra-hepatic regulators of liver inflammation and lipid and glucose metabolism have never been investigated. This study therefore investigated the effects of timed daily administration of bromocriptine, a potent dopamine D2 receptor agonist, on a) ventromedial hypothalamic catecholamine activity, b) MS and c) hepatic protein levels of key regulators of liver inflammation and glucose and lipid metabolism in a non-seasonal model of MS - the hypertensive, obese SHR rat. Sixteen week old SHR rats maintained on 14 hour daily photoperiods were treated daily for 16 days with bromocriptine (10 mg/kg, i.p.) or vehicle at 1 hour before light offset and, subsequent to blood pressure recordings on day 14, were then utilized for in vivo microdialysis of ventromedial hypothalamic catecholamine activity or sacrificed for the analyses of MS factors and regulators of hepatic metabolism. Normal Wistar rats served as wild-type controls for hypothalamic activity, body fat levels, and insulin sensitivity. Bromocriptine treatment significantly reduced ventromedial hypothalamic norepinephrine and serotonin levels to the normal range and systolic and diastolic blood pressures, retroperitoneal body fat level, plasma insulin and glucose levels and HOMA-IR relative to vehicle treated SHR controls. Such treatment also reduced plasma levels of C-reactive protein, leptin, and norepinephrine and increased that of plasma adiponectin significantly relative to SHR controls. Finally, bromocriptine treatment significantly reduced hepatic levels of several pro-inflammatory pathway proteins and of the master transcriptional activators of lipogenesis, gluconeogenesis, and free fatty acid oxidation versus control SHR rats. These findings indicate that in SHR rats, timed daily dopamine agonist treatment improves hypothalamic and neuroendocrine pathologies associated with MS and such neuroendocrine events are coupled to a transformation of liver metabolism potentiating a reduction of elevated lipogenic and gluconeogenic capacity. This liver effect may be driven in part by concurrent reductions in hyperinsulinemia and sympathetic tone as well as by reductions in intra-hepatic inflammation.


Patient-Based Long-Term Results of the Surgical Treatment of Congenital Talipes Equinovarus.
Long-term results of surgical treatment for congenital talipes equinovarus are documented in the literature but mainly in correlation with clinical and radiographic objective criteria. We present a retrospective study of 48 patients who underwent surgical correction (extended Cincinnati type "a la carte" approach) in our department with an average of 17 years' follow-up. Patients were interviewed and completed a validated disease specific instrument, which evaluates foot function as well as patients' satisfaction, the use of orthotics, shoe size, and the impact of this operation in their adult life. Parameters such as gender, age at first surgery, side affected, and the number of procedures were also studied. According to our findings, the greater the age at last surgery, the worse the outcome. Quality-of-life issues were expressed at a higher rate among women and by patients that underwent multiple surgeries. Unilateral correction has a correlation with the shoe size. Even if a "successful" surgical correction is achieved, residual symptoms may alter walking ability, self-image, and shoe wearing in adult life. It would be valuable to continue to follow these patients up over time. Therapeutic, Level IV: Case series.