PRELIMINARY MECHANICAL TEST OF PROXIMAL FEMUR REINFORCEMENT WITH CEMENTED X-SHAPED PMMA.
To evaluate the mechanical behavior of the proximal end of the femur submitted to the X-shaped polymethylmethacrylate (PMMA) reinforcement technique. Fifteen synthetic femurs, with a Nacional® density of 10 PCF, were divided into two groups: the DX group, with 5 units that were submitted to PMMA reinforcement, and the DP group, with 10 units, which were evaluated intact. The volume of PMMA required, the maximum load, and the absorbed energy to fracture were analyzed by means of a static mechanical bending test simulating a fall on the greater trochanter. A mean of 6 ml of PMMA was used to model the X-reinforcement; it was observed that the DX group presented significantly higher maximum load (median = 1553 N, p = 0.005) and absorbed energy to fracture (median = 9.7 J; p = 0.050) than the DP group (median = 905 N and 6.6 J). X-reinforcement of the proximal end of synthetic femurs showed a statistically significant increase in the maximum load and absorbed energy to fracture in the mechanical assay when compared to the control group. Level of Evidence III, Experimental study.


Unintended outcomes evaluation approach: A plausible way to evaluate unintended outcomes of social development programmes.
Social development programmes are deliberate attempts to bring about change and unintended outcomes can be considered as inherent to any such intervention. There is now a solid consensus among the international evaluation community regarding the need to consider unintended outcomes as a key aspect in any evaluative study. However, this concern often equates to nothing more than false piety. Exiting evaluation theory suffers from overlap of terminology, inadequate categorisation of unintended outcomes and lack of guidance on how to study them. To advance the knowledge of evaluation theory, methods and practice, the author has developed an evaluation approach to study unintended effects using a theory building, testing and refinement process. A comprehensive classification of unintended outcomes on the basis of knowability, value, distribution and temporality helped specify various type of unintended outcomes for programme evaluation. Corresponding to this classification, a three-step evaluation process was proposed including a) outlining programme intentions b) forecasting likely unintended effects c) mapping the anticipated and understanding unanticipated unintended outcomes. This unintended outcomes evaluation approach (UOEA) was then trialled by undertaking a multi-site and multi-method case study of a poverty alleviation programme in Pakistan and refinements were made to the approach.The case study revealed that this programme was producing a number of unintended effects, mostly negative, affecting those already disadvantaged such as the poorest, women and children. The trialling process demonstrated the effectiveness of the UOEA and suggests that this can serve as a useful guide for future evaluation practice. It also provides the discipline of evaluation with an empirically-based reference point for further theoretical developments in the study of unintended outcomes.


Prospectively ECG-triggered high-pitch spiral acquisition for cardiac CT angiography in routine clinical practice: initial results.
This study was conducted to evaluate the mode of application, image quality (IQ), and radiation exposure resulting from introduction of a prospectively electrocardiogram-triggered high-pitch cardiac computed tomography angiography (CTA) acquisition mode into routine clinical practice. A total of 42 prospectively triggered cardiac CTAs were conducted on 34 patients (11 female, 23 male; mean age 56 ± 15 y) using a high-pitch mode (pitch 3.4) on a dual-source CT. In 8 of these patients with higher heart rates or occasional premature ventricular contractions, 2 immediately subsequent CTAs were performed ("double flash protocol"). Subjective IQ was assessed for coronary arteries using a 4-point scale (1=unevaluable to 4=excellent). Contrast-to-noise ratio (CNR) was measured in 9 locations. CT Dose Index and dose-length product were obtained, and the patients' effective dose was calculated. Mean effective doses were 2.6 ± 1.4 mSv (range: 1.1 to 6.4) for the entire cardiac examination and 1.4 ± 0.7 mSv (0.4 to 3.1) for individual high-pitch cardiac CTA. z-coverage ranged from 9.9 cm in a native coronary CTA to 31.4 cm in a bypass graft case. The overall subjective IQ was good to excellent (mean score: 3.5), with 1.5% unevaluable coronary segments. The "double flash protocol" resulted in a fully diagnostic CT study in all cases just after taking both scans into consideration. The mean CNR of all locations was 19.7 ± 2.6. Prospectively electrocardiograph-triggered high-pitch-mode cardiac CTA is a feasible and promising technique in clinical routine, allowing for evaluation of coronaries at good-to-excellent IQ and providing high CNR and minimal radiation doses. The "double flash protocol" might become a more robust tool in patients with elevated heart rates or premature ventricular contractions.


Validation of a low-cost laser scanner device for the assessment of three-dimensional facial anatomy in living subjects.
The present study compared the reliability of a low-cost laser scanner device to an already-validated stereophotogrammetric instrument. Fifty volunteers underwent duplicate facial scans through laser scanner and stereophotogrammetry. Intra- and inter-instrument reproducibility of linear distances, angles, facial surface area and volume was verified through the Bland-Altman test and calculation of absolute (TEM) and relative (rTEM) technical errors of measurement; rTEM was then classified as follows: <1% excellent; 1-3.9% very good; 4-6.9% good; 7-9.9% moderate; >10% poor. The scans performed through different devices were registered and superimposed to calculate the root mean square (RMS) (point-to-point) distance between the two surfaces. The same protocol was applied to a mannequin head. In inter-instruments comparison, 12/26 measurements showed a "good" rTEM; 5 were "very good". In intra-instrument comparison, most performances worsened, with only 10 of 26 measurements classified as "good" and "very good". All the measurements made on mannequin scans were at least "good", and 14/26 were "very good". Surface area was "very good" only in intra-instrument comparison; conversely, volumes were poorly repeatable for all the comparisons. On average, RMS point-to-point distances were 0.65 mm (inter-devices comparison), 0.56 mm (mannequin scans), 0.42 mm (intra-device comparison). In conclusion, the low-cost laser scan device can be reliably applied to inanimate objects, but does not meet the standards for three-dimensional facial acquisition on living persons.


Rapid oxidative-elimination of the terminal base from model deoxynucleotide esters.
The 5'-isopropyl esters of 2'-deoxycytidylate, 2'-deoxyadenylate, 2'-deoxyguanylate and 2'-deoxythymidylate were synthesized and used as model substrates to demonstrate that the 3'-terminal deoxynucleoside can be rapidly removed by combined 3'-hydroxyl oxidation and beta-elimination. Trifluoroacetyloxy-dimethylsulfonium ion oxidation of the free 3'-hydroxyl group gave almost 80% yields of the free purine and pyrimidine bases in less than 5 minutes reaction at -80 degrees C.


The protective role of phosphodiesterase inhibitors in preventing colorectal cancer and advanced colorectal polyps: a systematic review and meta-analysis.
Inflammatory cells within the tumour microenvironment are the driving forces behind colorectal cancer (CRC) tumourigenesis. Understanding the different pathways involved in CRC carcinogenesis paves the way for effective repurposing of drugs for cancer prevention. Emerging data from preclinical and clinical studies suggest that, due to their antiproliferative and anti-inflammatory properties, phosphodiesterase-5 inhibitors (PDE5i) might have an anticancer effect. The aim of this study was to clarify through systematic review and meta-analysis of published peer-reviewed studies whether an association exists between PDE5i use and CRC risk. This study was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Prospective registration was performed on PROSPERO (CRD42022372925). A systematic review was performed for studies reporting CRC and advanced colorectal polyp incidence in PDE5i 'ever-users' and PDE5i 'never-users'. Meta-analysis was performed using RevMan version 5. Four observational cohort studies and two case-control studies, comprising 995 242 patients were included in the final analysis, of whom 347 126 were PDE5i ever-users. Patients who were PDE5i ever-users had a significantly lower incidence of CRC or advanced colorectal polyps than never-users (OR 0.88, CI 0.79-0.98, p = 0.02). To examine the primary preventative role of PDE5i, subgroup analysis of four studies including patients without a previous history of CRC found that use of PDE5i was associated with a lower incidence of CRC (OR 0.85, CI 0.75-0.95, p = 0.005, I2 = 64%). There was no significant temporal relationship found between PDE5i use and CRC risk as both current users and previous users had a significantly lower incidence of CRC than never-users. Our study found a significant anticancer effect of PDE5i, as shown by a reduced risk of CRC in the context of both primary and secondary CRC prevention.


Greater coronary lipid core plaque assessed by near-infrared spectroscopy intravascular ultrasound in patients with elevated xanthine oxidoreductase: a mechanistic insight.
Elevated serum uric acid level was reportedly associated with greater coronary lipid plaque. Xanthine oxidoreductase (XOR) is a rate-limiting enzyme in purine metabolism and believed to play an important role in coronary atherosclerosis. However, the relation of XOR to coronary lipid plaque and its mechanism are unclear. Patients with stable coronary artery disease undergoing elective percutaneous coronary intervention under near-infrared spectroscopy intravascular ultrasound (NIRS-IVUS) guidance were prospectively enrolled. They were divided into three groups according to serum XOR activities: low, normal, and high. Coronary lipid core plaques in non-target vessels were evaluated by NIRS-IVUS with lipid core burden index (LCBI) and a maximum LCBI in 4 mm (maxLCBI4mm). Systemic endothelial function and inflammation were assessed with reactive hyperemia index (RHI) and high-sensitivity C-reactive protein, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio. Of 68 patients, 26, 31, and 11 were classified as low, normal, and high XOR activity groups. LCBI (474.4 ± 171.6 vs. 347.4 ± 181.6 vs. 294.0 ± 155.9, p = 0.04) and maxLCBI4mm (102.1 ± 56.5 vs. 65.6 ± 48.5 vs. 55.6 ± 37.8, p = 0.04) were significantly higher in high XOR group than in normal and low XOR groups. Although RHI was significantly correlated with body mass index, diabetes, current smoking, and high-density lipoprotein cholesterol, no relation was found between XOR activity and RHI. There were also no relations between XOR activity and C-reactive protein, neutrophil-to-lymphocyte ratio, or platelet-to-lymphocyte ratio. In conclusion, elevated XOR activity was associated with greater coronary lipid core plaque in patients with stable coronary artery disease, without significant relations to systemic endothelial function and inflammation.


A study on inhibition of the Aβ1-42-induced inflammatory response by the Huatuo Zaizao pill through the NF-κB signaling pathway.
The pathology of Alzheimer's disease (AD) includes β-amyloid (Aβ) (plaques) and neurofibrillary tangles (NFTs). This study aimed to explore the efficacy of Huatuo Zaizao pill (HTZP) in an AD mouse model induced by injecting Aβ1-42, and the neuroprotective mechanism of HTZP in AD. C57BL/6 (B6) mice were randomly divided into 4 groups (n = 10, per group): control group, AD model group, and 2 different doses of HTZP treated groups. The Morris water maze test was carried out on AD mice to assess the learning ability after treatment with HTZP for 15 day. The levels of inflammatory factors and the nuclear factor-κB (NF-κB) pathway were examined by western blot and real-time polymerase chain reaction (PCR). The content of microglia was investigated by immunofluorescence. This study revealed that a cognitive disorder could be mitigated when the AD mice were treated with HTZP, which might be associated with the decreased level of pro-inflammatory factors, and the inhibitory activities of microglia. Additionally, phosphorylation of IκB and NF-κB p65 could be reduced by prohibiting the neuroinflammation of NF-κB activation in the hippocampus of AD mice. These results showed that HTZP could mitigate a cognitive disorder, diminish the activation of microglia, and inhibit the content of inflammatory factors through the NF-κB pathway in Aβ1-42-induced AD mice. HTZP may be an appropriate agent for AD treatment in the future.


The role of secreted Hsp90α in HDM-induced asthmatic airway epithelial barrier dysfunction.
The dysfunction of airway epithelial barrier is closely related to the pathogenesis of asthma. Secreted Hsp90α participates in inflammation and Hsp90 inhibitor protects endothelial dysfunction. In the current study, we aimed to explore the role of secreted Hsp90α in asthmatic airway epithelial barrier function. Male BALB/c mice were sensitized and challenged with HDM to generate asthma model. The 16HBE and Hsp90α-knockdown cells were cultured and treated according to the experiment requirements. Transepithelial Electric Resistance (TEER) and permeability of epithelial layer in vitro, distribution and expression of junction proteins both in vivo and in vitro were used to evaluate the epithelial barrier function. Western Blot was used to evaluate the expression of junction proteins and phosphorylated AKT in cells and lung tissues while ELISA were used to evaluate the Hsp90α expression and cytokines release in the lung homogenate. HDM resulted in a dysfunction of airway epithelial barrier both in vivo and in vitro, paralleled with the increased expression and release of Hsp90α. All of which were rescued in Hsp90α-knockdown cells or co-administration of 1G6-D7. Furthermore, either 1G6-D7 or PI3K inhibitor LY294002 suppressed the significant phosphorylation of AKT, which caused by secreted and recombinant Hsp90α, resulting in the restoration of epithelial barrier function. Secreted Hsp90α medicates HDM-induced asthmatic airway epithelial barrier dysfunction via PI3K/AKT pathway, indicating that anti-secreted Hsp90α therapy might be a potential treatment to asthma in future.


[Derivatives of 1,3-bis-(methlendioxyphenoxy)propane with antispastic activity].
A number of amines derived from 1,3-bis(3,4-methylen-dioxyphenoxy)propane have been prepared from 1,3-bis-(3,4-methylendioxy-phenoxy)propan-2-one. The acute toxicity and the activity of these compounds on isolated guinea pig ileum have been studied. The majority of the compounds showed clear antagonist activity towards BaCl2, histamine and acetylcholine contracting responses, generally grater than that of papaverine; on the contrary, their antagonist activity towards 5-HT responses was slightly lower.


Cardiopulmonary resuscitation in prone position: a simplified method for outpatients.
The efficacy of cardiopulmonary resuscitation (CPR) is vital for saving lives of victims with sudden cardiac arrest. In 1960, Kuowenhoven and colleagues proposed the method that has become standard for CPR. Despite vast input of resources for public education and training of this procedure, its success rate outside hospitals remains poor to dismal. During CPR, restoration of respiration is as important as circulation. But opening the airway and giving effective mouth-to-mouth respiration is difficult for lay people to learn. Furthermore, most bystanders are reluctant to do mouth-to-mouth respiration because of the risk of infection. Therefore, the general population needs a more simplified CPR method for outpatients. The practice of CPR in the prone position, first proposed by McNeil in 1989, has not been adopted, despite the fact that it meets the desirable requirements of ideal resuscitation: simultaneous restoration of circulation and respiration with a very simple maneuver. Part 1 (circulation test): Eleven patients who expired in the intensive care unit (ICU), with arterial lines attached, received standard pre-cordial cardiac massage, and the generated blood pressure (BP) was recorded. They were then turned to the prone position, with the head turned to one side. We compressed the patient's thoracic spine with the same force used in standard CPR (rhythm of approximately 60 per minute each time when the back bounces back), and the BP was also recorded. Part 2 (ventilation test): Ten healthy volunteers (5 doctors and 5 nurses) were enlisted for respiratory assessment during compression on the back. With the nose clipped and spontaneous breathing held, the volunteer's exhaled tidal volume upon compression was measured with a spirometer. Standard external cardiac massage of the cadavers generated BPs of 55 +/- 20/13 +/- 7 mmHg; however, external compression on the back of the cadavers generated higher BP of 79 +/- 20/17 +/- 10 mmHg (p = 0.028, Wilcoxon signed-rank analysis). External compression on the back of the volunteers generated mean tidal volumes of 399 +/- 110 mL. Our study revealed that prone CPR provides good respiratory and circulatory support at the same time. It is easy to perform and it may be a good alternative way for bystanders to perform CPR in public surroundings. We recommend that more investigators do further studies on this topic.


Feline sporotrichosis: histopathological profile of cutaneous lesions and their correlation with clinical presentation.
Cutaneous lesions of feline sporotrichosis show high fungal load and are associated with severe disease and elevated zoonotic potential. The present study describes the histopathology and fungal load of the lesions in different clinical presentations of feline sporotrichosis. Cats with sporotrichosis were separated into groups L1, L2 and L3 (lesions in one, two and three or more locations, respectively) and subjected to skin biopsies for histopathology. Eighty-six cats were included in the study. Lesions were suppurative granulomatous in 84 cases and poorly formed granulomas were predominant. The well-formed granulomas were associated with group L1. The high fungal load was predominant in group L3 and in poorly formed granuloma cases and did not occur in well-formed granulomas cases. The good general condition was associated with low fungal load. These findings suggest that the fungal load control in animals with more localized lesions and well-organized response is linked with the improvement in the outcome of infected cats.


Primary disorders of the lymphatic vessels--a unified concept.
Congenital defects of lymphatics constitute a spectrum of disorders that may manifest with a variety of clinical presentations including lymphedema, chylous effusions, lymphangiomatous malformations with cystic masses and localized gigantism, and intestinal lymphangiectasia with malabsorption. These entities constitute a relatively rare group of disorders, the origin of which remains somewhat controversial, but in some it appears to be due to early lymphatic obstruction. Five cases are described, which demonstrate the anatomical pathology of these entities. A classification and description of the defects is also presented. An attempt is made to present a unified theory of origin for this seemingly diverse group of diseases. While these entities may be challenging from a diagnostic and therapeutic standpoint, a wide variety of imaging modalities, which includes lymphography, computed tomography scanning, and ultrasound, may be used to diagnose the extent and internal structural characteristics of the abnormalities.


Effect of combined teriparatide and monthly minodronic acid therapy on cancellous bone mass in ovariectomized rats: a bone histomorphometry study.
The purpose of the present study was to determine whether teriparatide and monthly minodronic acid would have an additive effect on cancellous bone mass in ovariectomized rats. Seven-week-old female Sprague-Dawley rats were randomized into five groups of 10 animals each, including a sham-operation+vehicle group, an ovariectomy (OVX)+vehicle group, an OVX+minodronic acid (6 μg/kgs.c., every 4 weeks) group, an OVX+teriparatide (20 μg/kgs.c., daily) group, and an OVX+minodronic acid+teriparatide group. After the 12-week experimental period, static and dynamic histomorphometric analyses were performed on the cancellous bone of the tibial proximal metaphysis. OVX decreased the bone volume per total volume (BV/TV) and the trabecular number (Tb.N) and increased the trabecular separation (Tb.Sp) as a result of increased bone remodeling. Minodronic acid prevented the OVX-induced decreases in BV/TV, while teriparatide increased the BV/TV and trabecular width (Tb.Wi) beyond the values of the sham controls. Minodronic acid prevented, but teriparatide only mitigated, the OVX-induced decrease in Tb.N, although both drugs similarly prevented the OVX-induced increase in Tb.Sp. A combination of teriparatide and minodronic acid further increased the BV/TV and Tb.N and decreased the Tb.Sp as a result of the suppression of bone remodeling, compared with teriparatide alone. These results suggest the differential effect of teriparatide and monthly minodronic acid on cancellous bone structure and the additive effect of the two drugs on cancellous bone mass in OVX rats.


Hindbrain orexin 1 receptors influence palatable food intake, operant responding for food, and food-conditioned place preference in rats.
Brain orexin 1 receptors (OX1Rs) are involved in food-motivated behavior. Most research has focused on forebrain OX1R populations, but hindbrain OX1Rs affect feeding. We hypothesized that hindbrain OX1Rs affect the reward value of food. We examined the effects of hindbrain OX1R stimulation or blockade on motivation for food, palatable high-fat (HF) food intake, and food-conditioned place preference. Rats trained to lever press for sucrose on a progressive ratio (PR) schedule received fourth intracerebroventricular (icv) injections of vehicle, orexin-A (0.1-1 nmol), or the OX1R antagonist SB334867 (10-20 nmol) before operant test sessions. Effects of these treatments on HF food intake during daily 1-h tests were assessed with fourth icv and nucleus of the solitary tract (NTS) injections. We conditioned a place preference by pairing HF food with one side of a two-sided chamber and then examined the effect of 20 nmol fourth icv SB334867 on the expression of that preference. In ad lib fed rats on the PR schedule, fourth icv orexin-A significantly increased responding and breakpoint relative to the vehicle. In 24-h food-deprived rats, fourth icv SB334867 significantly decreased responding and breakpoint. Orexin-A delivered to the fourth ventricle (0.1 nmol) or NTS (0.01 nmol) increased HF diet intake. Fourth icv SB334867 did not affect HF food intake, but SB334867 delivered either fourth icv (20 nmol) or intra-NTS (5-10 nmol) suppressed chow intake. Expression of HF food-conditioned place preference was inhibited by fourth icv SB334867. Hindbrain OX1R activity affects food-motivated operant behavior and may play a role in responding to cues that predict palatable food.


Growth inhibition and apoptosis-induced effect on human cancer cells of toosendanin, a triterpenoid derivative from chinese traditional medicine.
Toosendanin, a triterpenoid derivative isolated from the barks of Melia toosendan Sieb et Zucc, has been used as an anthelmintic vermifuge against ascaris for more than fifty years in China. In the present study, we investigated the growth inhibition and apoptosis-induced effect of toosendanin on human cancer cells. The result showed that toosendanin significantly suppressed the proliferation of tested human cancer cell lines. The IC(50) values were less than 1.7 x 10(-7) M and U937 was the most sensitive cell line with a IC(50) of 5.4 x 10(-9) M. Flow cytometric analysis revealed that treatment of U937 cells with toosendanin resulted in a dose- and time-dependent accumulation of cells in the S phase with a concomitant decrease in cells processing to G(0)/G(1) phase. The growth inhibition of U937 cells after exposure to toosendanin was subsequently associated with the induction of apoptosis, as evidence by the typical condensed and fragmented nuclei, DNA fragmentation, and exposure of phosphatidylserine on the outer leaflet of plasma membrane. All these results indicated that toosendanin could serve as a potential candidate for anticancer drug.


Myelolipoma of the adrenal gland. Review of diagnostic problems and surgical intervention.
Myelolipoma is a benign, rare, and hormone-inactive tumor of the adrenal gland. Its characteristic appearance on sonography and computed tomography enables preoperative diagnosis with a high degree of safety and accuracy. Symptomatic or large tumors have to be removed since there is a high risk of spontaneous hemorrhage. Common findings in patients with myelolipoma are reviewed, especially in those with surgically removed tumors.


Lectins and the radioallergosorbent test.
An investigation into the possible role of lectin binding of IgE in RAST of legume and wheat extracts is reported. Lectins from pea, broad bean, lentil, jack bean, soybean, peanut, and wheat germ were coupled to RAST discs. The discs were pretreated with lectin-specific sugars in an attempt to inhibit RAST with sera from 11 sensitive patients. In all cases, RAST was almost unaffected by the inhibitory sugars, indicating that nonimmune binding of IgE by lectins in legume or wheat RAST was not significant when RAST was carried out with allergens bound to the usual paper discs. IgE contains binding sites for all the lectins examined, and five of the sera had high total IgE greater than 300 IU/ml. It is suggested that competition by IgG and other serum glycoproteins may explain the lack of effect by the added sugars. All sera contained endogenous glucose at a level of about 3 mmol/L that may have accounted for some self-inhibition of the lectin binding by pea, broad bean, lentil, and jack bean lectins. There was, however, significant immune binding of some of the lectins by specific IgE, and it is concluded that these lectins may be important in expression of IgE-mediated allergic responses.


Comparison of allergic aspermatogenesis with that induced by vasectomy. II. In vitro studies of cell-mediated immunity to sperm after vasectomy in man and guinea-pig.
Transformation of peripheral blood leucocytes was shown to be a valid assay for cell-mediated immunity to sperm in male guinea-pigs immunized with homologous epididymal sperm (ES) in FCA. A heat-treated extract of ES (BES) was used for culture. Possible developement of cell-mediated immunity to sperm after vasectomy was investigated in patients and guinea-pigs, by culture of blood leucocytes before and at intervals after operation. Patients' leucocytes were cultured with a heat-treated extract of human seminal sperm (BHS); guinea-pigs' leucocytes were cultured with BES. These cultures showed no evidence of specific stimulation of leucocytes by sperm extract, up to 1 year after vasectomy in patients, or up to 6 months in guinea-pigs. Similarly, no evidence of delayed hypersensitivity could be demonstrated by skin tests with BES in animals vasectomized 1 year previously. We consider that this study establishes that cell-mediated immunity to sperm does not develop in either man or guinea-pigs, up to 1 year after conventional vasectomy.


Anonymous Audience Response Technology in Image-Based Quiz (IBQ) Neuropathology Lecture for Undergraduate Pre-clinical Medical Students: a Comparison with Traditional Lectures.
Pathology teaching, an intensively image loaded discipline, poses a significant challenge in its delivery. A lot of effort has been placed into sourcing teaching methods that could effectively enhance students' understanding and knowledge retention in this discipline. We describe for the first time in the literature the use of an image-based quiz (IBQ) to deliver a neuropathology lecture. The participating medical students were randomised into either the study group (IBQ) or the control group (traditional lecture, TL). The students were asked to complete the pre- and post-multiple choice question (MCQ) test before and after attending either of the allocated interventions. In the IBQ group, the students were presented with image-based quizzes, and answers to the quizzes were projected in real-time on screen. The students in the TL group were given the usual, traditional lecture. A total of 75 third-year medical students participated in this study. The participants were recruited from third-year medical students representing two different academic years. There was no significant difference in the pre- and post-MCQ scores between the IBQ and TL groups. However, a significant improvement in the mean scores for the pre- and post-MCQ results in both the study (p = 0.001; 95% CI 0.572-1.954) and control (p < 0.001; 95% CI 0.561-1.763) groups was observed. We found that the IBQ was a simple, personalised, and cost-effective digitalised tool which our study suggests it to be as effective as the traditional lecture in the delivery of pathology knowledge in undergraduate medical students.


Development and application of a fast ultra-high performance liquid chromatography-trapped ion mobility mass spectrometry method for untargeted lipidomics.
The alteration of lipid profile in biological specimens, such as plasma, mirrors abnormalities in their homeostasis and offers pivotal information for disease comprehension. Fast analytical methods are needed to highlight changes in plasma lipid profile and deliver rapid results. In this study we developed a fast reversed phase ultra high performance liquid chromatography-trapped ion mobility mass spectrometry (RP-UHPLC-TIMS-MS) method for untargeted lipidomics. A short, narrow-bore fully porous particle CSH column (50 mm × 2.1 mm, 1.7 µm) was used, and by selecting appropriate flow rate, temperature and gradient conditions, the total analysis time was reduced from 20 to 4 min. TIMS was operated in parallel accumulation serial fragmentation mode (PASEF) which allowed to select multiple precursors for MS/MS and separate co-eluting lipids based on their different mobility. Lipid annotation was performed by rule-based approach, comparison with LipidBlast spectral library and manual data curation, by taking into account class-specific fragmentation pattern, accurate mass, adduct form, retention behavior in RP and comparison of their collision cross-section (CCS) values for increased confidence. 306 unique lipids from 21 subclasses were annotated from 20 µL of plasma, while their concentration was estimated by class-specific deuterated internal standards. The analytical method was validated and finally applied to elucidate the alteration of plasma lipid profiles in a small cohort of amyotrophic lateral sclerosis (ALS) patients. Univariate and multivariate statistics evidenced significant differences with respect to control patients, particularly in the levels of ether linked lipids (PC-O, PE-O, PE-P and LPC-O), sphingolipids (Ceramides), and triacylglycerols, showing the usefulness of this fast approach in providing accurate and rapid results with respect to longer (≥15 min) untargeted UHPLC-HRMS methods.


Nucleosomes determine their own patch size in base excision repair.
Base excision repair (BER) processes non-helix distorting lesions (e.g., uracils and gaps) and is composed of two subpathways that differ in the number of nucleotides (nts) incorporated during the DNA synthesis step: short patch (SP) repair incorporates 1 nt and long patch (LP) repair incorporates 2-12 nts. This choice for either LP or SP repair has not been analyzed in the context of nucleosomes. Initial studies with uracil located in nucleosome core DNA showed a distinct DNA polymerase extension profile in cell-free extracts that specifically limits extension to 1 nt, suggesting a preference for SP BER. Therefore, we developed an assay to differentiate long and short repair patches in 'designed' nucleosomes containing a single-nucleotide gap at specific locations relative to the dyad center. Using cell-free extracts or purified enzymes, we found that DNA lesions in the nucleosome core are preferentially repaired by DNA polymerase β and there is a significant reduction in BER polymerase extension beyond 1 nt, creating a striking bias for incorporation of short patches into nucleosomal DNA. These results show that nucleosomes control the patch size used by BER.


The effect of environmental tobacco smoke on the dose requirements of rocuronium in children.
Smoking affects the pharmacodynamic and pharmacokinetic behaviour of several drugs. The aim of this study was to evaluate the effects of environmental tobacco smoke on onset and recovery time after single dose rocuronium in children. Forty children between 4 and 10 years were enrolled into the study. Children who have no familial smoking history were included in the first group whereas passive smokers included in the second group. Sevoflurane in 50% O2 and 50% N2O was used for induction of anaesthesia. Evoked adductor pollicis electromyography was used to monitor neuromuscular block. The T95 and T25 values were recorded. The T95 values (+/-sd) for rocuronium were 110.1 +/- 39.3 s and 79.3 +/- 35.6 s for group 1 and group 2, respectively (P < 0.05). The T25 value of group 2 was 40.1 +/- 10.6 min and compared with group 1 values (30.85 +/- 7.02 min) it was significantly longer (P < 0.01). This study shows that passive smoking children consume less rocuronium than nonsmokers during similar anaesthesia. We think that a history of passive smoking must also be taken into consideration during preoperative evaluation of paediatric patients.


A vagabond pleural pebble.
This article concerns a case of an extremely mobile pulmonary opacity. This opacity was attributed to a free calcified mass in the pleural space. It is probably a small benign neoplasm whose peduncle underwent necrosis.


Quantile regression provides a fuller analysis of speed data.
Considerable interest already exists in terms of assessing percentiles of speed distributions, for example monitoring the 85th percentile speed is a common feature of the investigation of many road safety interventions. However, unlike the mean, where t-tests and ANOVA can be used to provide evidence of a statistically significant change, inference on these percentiles is much less common. This paper examines the potential role of quantile regression for modelling the 85th percentile, or any other quantile. Given that crash risk may increase disproportionately with increasing relative speed, it may be argued these quantiles are of more interest than the conditional mean. In common with the more usual linear regression, quantile regression admits a simple test as to whether the 85th percentile speed has changed following an intervention in an analogous way to using the t-test to determine if the mean speed has changed by considering the significance of parameters fitted to a design matrix. Having briefly outlined the technique and briefly examined an application with a widely published dataset concerning speed measurements taken around the introduction of signs in Cambridgeshire, this paper will demonstrate the potential for quantile regression modelling by examining recent data from Northamptonshire collected in conjunction with a "community speed watch" programme. Freely available software is used to fit these models and it is hoped that the potential benefits of using quantile regression methods when examining and analysing speed data are demonstrated.


Binocular 3D otolith-ocular reflexes: responses of chinchillas to prosthetic electrical stimulation targeting the utricle and saccule.
From animal experiments by Cohen and Suzuki et al. in the 1960s to the first-in-human clinical trials now in progress, prosthetic electrical stimulation targeting semicircular canal branches of the vestibular nerve has proven effective at driving directionally appropriate vestibulo-ocular reflex eye movements, postural responses, and perception. That work was considerably facilitated by the fact that all hair cells and primary afferent neurons in each canal have the same directional sensitivity to head rotation, the three canals' ampullary nerves are geometrically distinct from one another, and electrically evoked three-dimensional (3D) canal-ocular reflex responses approximate a simple vector sum of linearly independent components representing relative excitation of each of the three canals. In contrast, selective prosthetic stimulation of the utricle and saccule has been difficult to achieve, because hair cells and afferents with many different directional sensitivities are densely packed in those endorgans and the relationship between 3D otolith-ocular reflex responses and the natural and/or prosthetic stimuli that elicit them is more complex. As a result, controversy exists regarding whether selective, controllable stimulation of electrically evoked otolith-ocular reflexes (eeOOR) is possible. Using micromachined, planar arrays of electrodes implanted in the labyrinth, we quantified 3D, binocular eeOOR responses to prosthetic electrical stimulation targeting the utricle, saccule, and semicircular canals of alert chinchillas. Stimuli delivered via near-bipolar electrode pairs near the maculae elicited sustained ocular countertilt responses that grew reliably with pulse rate and pulse amplitude, varied in direction according to which stimulating electrode was employed, and exhibited temporal dynamics consistent with responses expected for isolated macular stimulation.NEW & NOTEWORTHY As the second in a pair of papers on Binocular 3D Otolith-Ocular Reflexes, this paper describes new planar electrode arrays and vestibular prosthesis architecture designed to target the three semicircular canals and the utricle and saccule. With this technological advancement, electrically evoked otolith-ocular reflexes due to stimulation via utricle- and saccule-targeted electrodes were recorded in chinchillas. Results demonstrate advances toward achieving selective stimulation of the utricle and saccule.


Biomaterial-assisted biotherapy: A brief review of biomaterials used in drug delivery, vaccine development, gene therapy, and stem cell therapy.
Biotherapy has recently become a hotspot research topic with encouraging prospects in various fields due to a wide range of treatments applications, as demonstrated in preclinical and clinical studies. However, the broad applications of biotherapy have been limited by critical challenges, including the lack of safe and efficient delivery systems and serious side effects. Due to the unique potentials of biomaterials, such as good biocompatibility and bioactive properties, biomaterial-assisted biotherapy has been demonstrated to be an attractive strategy. The biomaterial-based delivery systems possess sufficient packaging capacity and versatile functions, enabling a sustained and localized release of drugs at the target sites. Furthermore, the biomaterials can provide a niche with specific extracellular conditions for the proliferation, differentiation, attachment, and migration of stem cells, leading to tissue regeneration. In this review, the state-of-the-art studies on the applications of biomaterials in biotherapy, including drug delivery, vaccine development, gene therapy, and stem cell therapy, have been summarized. The challenges and an outlook of biomaterial-assisted biotherapies have also been discussed.


A simple method for the measurement of blood cholinesterase activities under field conditions.
A new separation method using a hand-driven discoidal micro-centrifuge was developed. It is suitable for separating red cells from plasma in field conditions. The amounts of plasma produced are sufficient to be used for the dip-stick estimation of pseudocholinesterase activity. The strip estimations of plasma pseudochoninesterase activity correlated well with the spectrophotometric method of plasma cholinesterase. The test paper methods seem to be reliable under field conditions in acute organophosphate poisonings. To verify the results of the paper strip methods the blood method absorbed on paper can be used. This method is applicable for the measuring of blood cholinesterase activities and thus monitoring humans exposed to organophosphates under field conditions.


The use of two in-situ simultaneously-perfused placentas to investigate the effect of carrier proteins on linoleic and palmitic acid transfer in the guinea pig.
By perfusing two placentas concurrently in five animals we have found that linoleic acid is transferred across the guinea-pig placenta more readily than palmitic acid. In the in-situ perfusion this transfer is modulated by the type of albumin used in the perfusate. Removing the associated lipid from the perfusate albumin reduced the amount of non-esterified fatty acid (NEFA) transfer rather than enhanced it. Many researchers use fat free albumin as a protein carrier in in vivo and in-vitro systems, our results indicate that this may not be the most appropriate substance to use.


Control of resistance against bacteriophage killing by a metabolic regulator in meningitis-associated Escherichia coli.
Ecologically beneficial traits in bacteria are encoded by intrinsic and horizontally acquired genes. However, such traits are not universal, and the highly mosaic nature of bacterial genomes requires control at the transcriptional level to drive these processes. It has emerged that regulatory flexibility is widespread in the Escherichia coli species, whereby preexisting transcription factors can acquire new and unrelated roles in regulating beneficial traits. DsdC is the regulator of D-serine tolerance in E. coli, is essential for D-serine catabolism, and is often encoded by two copies in neonatal meningitis-associated E. coli (NMEC). Here, we reveal that DsdC is a global regulator of transcription in NMEC and does not require D-serine for the control of novel beneficial traits. We show that DsdC binds the chromosome in an unusual manner, with many binding sites arranged in clusters spanning entire operons and within gene coding sequences, such as neuO. Importantly, we identify neuO as the most significantly down-regulated gene in a strain deleted for both dsdC copies, in both the presence and absence of D-serine. NeuO is prophage encoded in several NMEC K1 isolates and mediates capsule O-acetylation but has no effect on attachment to or invasion of human brain endothelial cells. Instead, we demonstrate that NeuO provides resistance against K1 bacteriophage attack and that this critical function is regulated by DsdC. This work highlights how a horizontally acquired enzyme that functions in cell-surface modulation can be controlled by an intrinsic regulator to provide a key ecological benefit to an E. coli pathotype.


Electron microscopy of tRNA crystals. I. Thin crystals negatively stained with uranyl acetate.
The first attempt to study crystal structures of tRNA by electron microscopy is described. Sufficiently thin crystals were prepared from yeast tRNAphe. The thickness of the thinnest was estimated at 130 A corresponding to a bilayer of the molecules. The L-shaped structure seemed to be maintained even after the negative staining with uranyl acetate. Optically filtered images from electron micrographs were compared with those simulated from the drawing of the molecular model by optical transform. The results suggest that the observed images reflect the real molecular arrangements within the crystal lattice although the shape of tRNA molecules seems to be somewhat modified by the uneven staining.


Endotracheal metastases from colon adenocarcinoma.
Endotracheal metastases (ETM) from non-lung cancer are seldom seen. Their main clinical symptoms are cough, haemoptysis and dyspnoea, although occasionally an incidental finding is made during a bronchoscopy. Breast, colon and kidney adenocarcinoma might be associated with ETM, lung cancer being the most frequent cause. Its finding is associated with advanced disease but survival will depend on the primary origin, patient status and comorbidity. Therefore, treatment should be individual for each patient. In our centre we recommend pre-surgery bronchoscopy to exclude metastatic endotracheal lesions in patients with metastatic colon adenocarcinoma disease, as this might affect the final outcome and therefore management of the disease.


Occurrence, congener patterns, and potential ecological risk of chlorinated paraffins in sediments of Yangtze River Estuary and adjacent East China Sea.
Chlorinated paraffins (CPs) are high production volume chemicals with immense scientific research interest due to their wide distribution, persistence, toxicity, and bioaccumulation potential. In this study, 87 surface sediments were collected from the Yangtze River Estuary (YRE) and the adjacent East China Sea (ECS). We investigated the concentrations, spatial distribution, and composition profiles of short-chain chlorinated paraffins (SCCPs) and medium-chain chlorinated paraffins (MCCPs) using ultra-high-performance liquid chromatography coupled with Orbitrap Fusion Tribrid mass spectrometry. The sedimentary concentrations of SCCPs and MCCPs ranged from 2.85 to 94.7 ng·g-1 (median 13.7 ng·g-1) and 3.33 to 77.8 ng·g-1 (median 13.3 ng·g-1), respectively. Higher CP concentrations were found in YRE sediments. The values decreased away from the location, implying a direct influence of the Yangtze River. The SCCP concentrations were higher than those of MCCPs in most sediment samples. Overall, the predominant homologs were C13Cl5-7 and C14Cl6-8 for MCCPs and SCCPs, respectively. Overall, the sediment-dwelling organisms in the region are susceptible to low ecological risks.


Positive and negative selection of mutant forms of prokaryotic (cyanobacterial) ribulose-1,5-bisphosphate carboxylase/oxygenase.
A system for biological selection of randomly mutagenized ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco) genes from the cyanobacterium Synechococcus PCC6301 was designed in which a Rubisco deletion mutant of the photosynthetic bacterium Rhodobacter capsulatus served as a host. Trans-complementation with the Synechococcus PCC6301 rbcLS genes enabled anaerobic photoautotrophic growth of the R.capsulatus deletion strain with 5% CO(2), but not with 1.5% CO(2) in the atmosphere, and this strain could not grow under aerobic chemoautotrophic conditions. Phenotypic differences between the R.capsulatus host strain complemented with the wild-type rbcLS genes and transconjugates carrying mutated genes were used to identify mutants that were able to complement to photoautotrophic growth with 1.5% CO(2). These "positive" mutant proteins were unaffected for any measured kinetic properties, with a single exception. A mutant with a valine substitution at phenylalanine 342 had an increased affinity for ribulose-1,5-bisphosphate. Mutants with changes in the affinity for CO(2) were isolated through negative selection, in which mutants incapable of complementing R.capsulatus to photoautotrophic growth with 5% CO(2) were identified. Mutations at aspartate 103 resulted in enzymes that were greatly affected for different kinetic parameters, including an increased K(m) for CO(2). This study demonstrated that random mutagenesis and bioselection procedures could be used to identify mutations that influence important properties of bacterial Rubisco; these residues would not have been identified by other methods.


[Transrectal prostatic biopsy management policy for patients older than 50 years in relation to PSA values elaborated by a mathematical decision tree].
To decide the action politics (to perform or not transrectal prostatic biopsy) for a PSA cut point of 4 and 10 ng/ml through the construction of a mathematical decision tree. We calculate the usefulness of the biopsy through a subjective score, from 0 to 10, established after a survey of the 20 staff members of the health-care area, applying an global analysis with creation of total profile cards through an orthogonal design. The main usefulness of prostate cancer screening would be not to perform transrectal prostatic biopsies when PSA is lower than 4 ng/ml.


Long-term cultures of testicular biopsies from boys with cryptorchidism: effect of FSH and LH on the number of germ cells.
A long-term culture system of testicular biopsies from boys with undescended testes was established to evaluate the effect of gonadotrophins on germ cell survival and growth. Biopsies from 25 boys with cryptorchidism, aged 1.1-9.9 years, were obtained at the time of surgery. Each biopsy was subdivided into fragments and cultured for 1 or 3 weeks in a testis culture medium without gonadotrophins or supplemented with FSH (50 IU/l) or LH (5 IU/l), or a combination of FSH (50 IU/l) plus LH (5 IU/l). The survival of the germ cells was evaluated by calculating the ratio of spermatogonia and gonocytes per cross-sectioned testicular tubule, the S/T ratio. All cultured fragments maintained their overall morphology. A significantly reduced S/T ratio was observed in the fragments cultured in the presence of LH (P = 0.006), independently of the culture period. The mean tubular diameter in fragments cultured for 1 week with hormones was significantly larger than that of the controls (P < 0.0002). All cultured fragments had a larger tubular diameter than the uncultured fragments (P = 0.0002). This culture system supports survival of spermatogonia for at least 3 weeks. LH either alone or in combination with FSH results in a significantly reduced S/T ratio.


Glial cell-derived neurotrophic factor decrease may mediate learning, memory and behavior impairments in rats after neonatal surgery.
Patients who have surgery during the first few years of their lives may have an increased risk of behavioral abnormality. Our previous study has shown a role of glial cell-derived neurotrophic factor (GDNF) in neonatal surgery-induced learning and memory impairment in rats. This study was designed to determine whether neonatal surgery induced hyperactive behavior in addition to learning and memory impairment and whether GDNF played a role in these changes. Postnatal day 7 male and female Sprague-Dawley rats were subjected to right common carotid arterial exposure under sevoflurane anesthesia. Their learning, memory and behavior were tested from 23 days after the surgery. GDNF was injected intracerebroventricularly at the end of surgery. Surgery reduced GDNF expression in the hippocampus. Surgery impaired learning and memory and induced a hyperactive behavior as assessed by Barnes maze, fear conditioning and open field tests. In addition, surgery reduced dendritic arborization and spine density. The effects were attenuated by GDNF injection. These results suggest that surgery induces a hyperactive behavior pattern, impairment of learning and memory, and neuronal microstructural damage later in the lives in rats. GDNF reduction may mediate these surgical effects.


Purification of Clostridium botulinum type G progenitor toxin.
Clostridium botulinum type G cultured for 6 days at 30 degrees C in proteose peptone-yeast extract-glucose medium produced toxin of 1.3 x 10(4) LD50/ml. The toxin was precipitated at pH 4.0, extracted with 0.2 M phosphate buffer, pH 6.0, and activated with trypsin. Sonic treatment and trypsinization of the residual precipitate released additional toxin, the toxicity of which corresponded to that detected in whole culture. Activated toxin obtained from the first extract and that from the residual precipitate were combined and purified by salting out, acid precipitation, gel filtration on Sephadex G-200, chromatography on SP-Sephadex, and a second gel filtration on Sephadex G-200. The yield of purified toxin from 10 liters of culture was 22.9 mg an 1.1 X 10(8) mouse ip LD50 with a specific toxicity of 3.0 X 10(7) mouse ip LD50/mg nitrogen. The molecular weight of the toxin was about 500,000, corresponding to that of L toxin of the other types. No M nor LL toxin was detected.


Accelerated metallic artifact reduction imaging using spectral bin modulation of multiacquisition variable-resonance image combination selective imaging.
To assess the clinical utility of a prototype sequence for metal artifact reduction, the multiacquisition variable-resonance image combination selective (MAVRIC-SL) at 3 T. This sequence allows a surgical prosthesis-dependent reduction in the number of spectral bins. We compared the prototype MAVRIC SL to the conventional two-dimensional fast spin-echo (FSE) sequences and MAVRIC SL images acquired with all spectral bins to those acquired with the optimized number of spectral bins. MAVRIC SL images were acquired in 25 image sets from August 2017 to April 2018. For each subject, the optimized number of spectral bins was determined using a short spectral calibration scan. The image sets obtained with magnetic resonance imaging that were used for the analysis consisted of MAVRIC-SL proton density (PD)-weighted or short inversion time inversion recovery (STIR) images acquired with all 24 spectral bins, the corresponding images with the optimized number of spectral bins, and the conventional two-dimensional FSE or STIR PD-weighted images. A musculoskeletal radiologist reviewed and scored the images using a five-point scale for artifact reduction around the prosthesis and visualization of the prosthesis and peri-prosthetic tissues. Quantitative evaluation of the peri-prosthetic tissues was also performed. The Wilcoxon rank-sum test was used to test for significance. The MAVRIC SL images enabled a significantly improved reduction in metallic artifacts compared to the conventional two-dimensional FSE sequences. The optimized number of spectral bins ranged from 6 to 20, depending on the prosthesis susceptibility difference, size, and orientation to the B0 field. The scan times significantly decreased with a reduced number of spectral bins (354.0 ± 139.1 versus 283.0 ± 89.6 s; 20% reduced scan time; p < .05). Compared to the MAVRIC SL images acquired with all 24 bins, the artifact reduction and visualization of the prosthesis and peri-prosthetic tissues on the MAVRIC SL images acquired with calibrated bins were not significantly different. Compared to the MAVRIC SL images acquired with all 24 spectral bins, those acquired with an optimized number of spectral bins can reduce metallic artifacts with no significant image quality degradation while providing reduced scan time.


Rationale for treating unruptured intracranial aneurysms: actuarial analysis of natural history risk versus treatment risk for coiling or clipping based on 14,050 patients in the Nationwide Inpatient Sample database.
The treatment of small unruptured intracranial aneurysms has been questioned based on the results of the International Study of Unruptured Intracranial Aneurysms. Our objective was to compare natural history rupture risk versus treatment risk for coiling and clipping small unruptured aneurysms using data in the Nationwide Inpatient Sample database. Data for clipping and coiling of unruptured aneurysms was collected from the Nationwide Inpatient Sample from 2002-2008. Treatment risks were adjusted for age, gender, and medical comorbidities. Logistic regression models were used to create curves depicting the estimated probability of poor outcome as a function of patient age for clipping and coiling. These treatment risk curves were compared against natural history actuarial risk curves calculated from four prominent studies. There were 14,050 hospitalizations: 7439(53%) coiling; 6611(47%) clipping. For patients who underwent coiling or clipping, the mortality rate was 2.17% and 2.66%, and the morbidity rate was 2.16% and 4.75%, respectively. The adjusted risk of poor outcome from clipping and coiling, when modeled against most natural history studies, demonstrates a treatment benefit for clipping for patients <70 years and for coiling patients <81 years. Models using the International Study of Unruptured Intracranial Aneurysms data demonstrate a treatment benefit for clipping for patients <61 years and for coiling for patients <70 years. Both clipping and coiling of unruptured intracranial aneurysms are safe. This analysis demonstrates rationale for clipping small unruptured aneurysms in patients <61-70 years and coiling small unruptured aneurysms in patients <70-80 years. Treatment beyond these age ranges is associated with increased risk of poor outcome.


Intra-corporeal anastomosis in laparoscopic surgery for benign colorectal disease.
Recent studies have described the benefits of performing bowel resections for benign and malignant diseases as a total laparoscopic procedure with intra-corporeal anastomosis. We describe our preliminary experience with total laparoscopic surgery for benign lower gastrointestinal diseases. All patients (n = 32) who had received elective bowel surgery with intra-corporeal anastomosis for benign diseases between November 2013 and August 2015 were included in this retrospective study. A total of 15 patients (47%) had a primary anastomosis, 17 patients (53%) had a stoma reversal. The median length of stay was five days (range: 3-16). Surgical complications requiring re-operation were present in five patients (Clavien-Dindo grade IIIb) of whom two presented with anastomotic leaks (6%; 95% confidence interval: 2-20%). No post-operative medical complications according to the Clavien-Dindo Classification were seen. The median duration of surgery was 127 min. (range: 61-211 min.). No deaths occurred. A total laparoscopic approach to benign lower gastrointestinal diseases with intra-corporeal ana-stomosis was feasible. none. The trial is registered with the Danish Data Protection Agency.


The influence of alkyl pyridinium sponge toxins on membrane properties, cytotoxicity, transfection and protein expression in mammalian cells.
The ability of two alkyl pyridinium sponge toxin preparations (poly-APS and halitoxin) to form transient pores/lesions in cell membranes and allow transfection of plasmid cDNA have been investigated using HEK 293 cells. Poly-APS and halitoxin preparations caused a collapse in membrane potential, reductions in input resistance and increased Ca2+ permeability. At least partial recovery was observed after poly-APS application but recovery was more rarely seen with halitoxin. The transfection with plasmid cDNAs for an enhanced green fluorescent protein (EGFP) and human tumour necrosis factor receptor 2 (TNFR2) was assessed for both toxin preparations and compared with lipofectamine. Stable transfection was achieved with poly-APS although it was less efficient than lipofectamine. These results show that viable cells transfected with alien cDNA can be obtained using novel transient pore-forming alkyl pyridinium sponge toxins and a simple pre-incubation protocol. This provides the first proof of principle that pore-forming alkyl pyridinium compounds can be used to deliver cDNA to the intracellular environment without permanently compromising the plasma membrane.


Assessment of Healthcare Professionals' Knowledge and Awareness on Aspects Related to Ionizing Radiation Examinations in Athens, Greece.
Healthcare professionals involved with ionizing radiation must have sufficient knowledge of its effects on the human body in order to avoid potential risks for both patients and themselves. The aim of this study was to estimate the knowledge and awareness of healthcare professionals about the hazards of radiological examinations on their health and on their patients. This is a cross-sectional study, and the data collection was carried out with a self-administered questionnaire. The study group included a total of 210 individuals from different professional groups: nurses, doctors, medical technicians, radiologists, and other staff working in different clinics that use radiation in their work. The study was carried out in a large hospital in Athens, Greece. The study population consisted of 210 subjects aged 44.7 ± 9.1 years. In a total of 23 questions, participants answered correctly to 6.4 ± 2.6 questions. The factors for predicting the correct responses were male gender (β = -1.034, p = 0.004), frequency of contact with imaging examinations of patients requiring ionizing radiation (β = 0.496, p = 0.007), participation in any educational process (β = -0.918, p = 0.014), the number of published articles on radiation protection (β = 0.720, p = 0.001), and knowledge of the principle of ALARA (β = -0.391, p = 0.001). It is proposed to include a radiation protection course in the total healthcare professionals' undergraduate curricula in order to address the current knowledge gap in clinical practice.


Preconditioning the 2023 Kahramanmaraş (Türkiye) earthquake disaster.
The 2023 Kahramanmaraş earthquakes occurred on active faults that were known to be a high seismic hazard, yet the devastating impacts of these earthquakes show that the risk was not adequately considered. Vulnerabilities arising from exposure, corruption and poverty led to a lack of seismic preparedness which amplified the earthquake risk into a tragic disaster.


Transcriptomic analysis of intermuscular bone development in barbel steed (Hemibarbus labeo).
Intermuscular bones (IBs), which are little, bony spicules in muscle, are embedded in lower teleosts' myosepta. Despite the importance of studying IB development in freshwater aquaculture species, the genes associated with IB development need to be further explored. In the present study, we identified four stages of IB development in barbel steed (Hemibarbus labeo), namely stage 1: IBs have not emerged, stage 2: a few small IBs have emerged in the tail, stage 3: longer IBs gradually emerged in the tail and stage 4: all of the IBs in the tail are mature and long, via Alizarin red staining. Subsequently, we used the HiseqXTen platform to sequence and de novo assemble the transcriptome of epaxial muscle (between 35th and 40th myomere) of barbel steed at 29 days (stage 1) and 42 days (stage 3) after hatching. A total of 190,814 unigenes were obtained with an average length and N50 of 648 bp and 1027 bp, respectively. We found 2174 differentially expressed genes (DEGs) between stages 1 and 3, of which 378 and 1796 were up- and down-regulated, respectively. Functional enrichment analysis showed that several DEGs functioned in ossification, positive regulation of osteoblast differentiation, osteoblast differentiation, and BMP signaling pathway, and were further enriched in signal pathway, including osteoclast differentiation, TGF-β signaling pathway, cytokine-cytokine receptor interaction, Jak-STAT signaling pathway, and other KEEG pathways. In conclusion, we identified genes that may be related to IB development, such as kazal type serine peptidase inhibitor domain 1 (KAZALD1), extracellular matrix protein 1 (ECM1), tetranectin, bone morphogenetic protein 1 (bmp1), acid phosphatase 5 (ACP5), collagen type XI alpha 1 chain (COL11A1), matrix metallopeptidase 9 (MMP9), pannexin-3 (PANX3), sp7 transcription factor (Sp7), and c-x-c motif chemokine ligand 8 (CXCL8), by comparing the transcriptomes of epaxial muscle before and after IB ossification. This study provided a theoretical basis for identifying the molecular mechanisms underlying IB development in fish.


Nursing staff and euthanasia in the Netherlands. A nation-wide survey on attitudes and involvement in decision making and the performance of euthanasia.
To give insight into Dutch nursing staff's attitudes and involvement regarding euthanasia. The sample was recruited from a nation-wide existent research panel of registered nurses and certified nursing assistants. Descriptive analyses and multivariate logistic regression analyses were performed. 587 respondents (response of 65%) completed the questionnaire. The majority (83%) state that physicians have to discuss the decision about euthanasia with the nurses involved. Besides, 69% state that a physician should discuss a euthanasia request with nurses who have regular contact with a patient. Nursing staff who have religious or other beliefs that they consider important for their attitude towards end-of-life decisions, and staff working in a hospital or home care, are most likely to have this opinion. Being present during the euthanasia is quite unusual: only a small group (7%) report that this has ever been the case in their entire working life. Seven% (incorrectly) think they are allowed to administer the lethal drugs. The majority want to be involved in decision-making processes about euthanasia. Not all are aware that they are not legally allowed to administer the lethal drugs. Nursing staff should be informed of relevant existing legislation and professional guidelines.


An association of cocoa consumption with improved physical fitness and decreased muscle damage and oxidative stress in athletes.
Several studies have demonstrated the protective effects of cocoa consumption, due to its anti-inflammatory and antioxidant properties. Acute exercise induces oxidative stress and causes muscular damage during training. This study was designed to examine the effect of cocoa consumption on the markers of muscle damage, oxidative stress and physical fitness in professional soccer players. Fifteen players (15-18 years old) were included in the study. Biochemical parameters, markers of muscle damage and oxidative stress, and physical performance were evaluated before and after cocoa consumption. Biochemical parameters determined the healthy metabolic status of the study group; biomarkers of muscle and oxidative damage were measured in blood to establish muscle and redox status. However, high levels of biomarkers of muscle damage were detected. Interestingly, cocoa consumption decreased the muscle damage biomarkers of CK and LDH by 39.4% and 23.03%, respectively. The redox status was modified by a decrease in oxidative damage (carbonyl groups, 26.31%; thiol groups, 27.52%; MDA, 32.42%) and an increase in total antioxidant capacity (15.98%) and GSH-Px activity (26.37%). In addition, we observed an increase in physical performance by 4% in the Cooper Test. Our findings suggest that a short period of cocoa consumption could be useful in maintaining a good physical fitness, due to the favourable effects on muscle and redox status in athletes during exhaustive exercise.


Traditional birth home attendance and its implications for malaria control during pregnancy in Nigeria.
A longitudinal survey was carried out to assess prevalence of malaria infection among attendees of a traditional birth home (TBH) in the metropolis of Abeokuta, Nigeria. Malaria prevalence was 62.4%, and various degrees of anaemia were recorded in 80.3% of pregnant women. Patronage by pregnant teenagers was 10.8%, with all of them anaemic and 73.9% infected with malarial parasites. Knowledge of malaria transmission and prevention were generally poor, with the emphasis placed on exposure to direct rays and heat from the sun. Avoidance of the sun's heat was therefore considered to be an effective preventive measure; another was the consumption of specially prepared and packaged herbal tea, which the pregnant women were expected to drink daily. Only 36.3% of the women associated malaria infection with mosquito bites. The use of insecticide-treated nets (ITNs) was not recorded among the women, although a large proportion (91.3%) showed a willingness to buy ITNs. The cost of receiving antenatal care at the TBH was higher than that in public hospitals. Patronage of TBHs was observed to be linked more with cultural beliefs than poverty. This study suggests that there is a need to extend malaria control interventions to women attending TBHs.


Tumor grade may be used to select patients with multifocal hepatocellular carcinoma for resection.
While resection is a recommended treatment for patients with stage 1 hepatocellular carcinoma (HCC), it remains controversial for multifocal disease. We sought to identify patients with multifocal HCC with survival after resection similar to patients with clinical stage 1 HCC. The National Cancer Database was queried to identify patients that underwent resection for HCC. In this study, 2990 patients with a single tumor, and 1087 patients with multifocal disease confined to one lobe underwent resection. In the multifocal cohort, patients with clinical stage 3 (HR 1.54, CI 1.31-1.81, p < 0.0001) or 4 (HR 2.27, CI 1.57-3.29, p < 0.0001) disease, and those with moderately-differentiated (HR 1.32, CI 1.06-1.64, p = 0.012) or poorly differentiated/undifferentiated tumors (HR 1.53, CI 1.20-1.95, p = 0.0006) were associated with worse overall survival (OS). There was no difference in OS between patients with well-differentiated clinical stage 2 multifocal HCC and those with all grades of clinical stage 1 HCC (median of 84.8 (CI 66.3-107.2) vs 76.2 months (CI 71.2-81.3), respectively, p = 0.356). Patients with well-differentiated, clinical stage 2 multifocal HCC confined to one lobe experience similar OS following hepatic resection to patients with clinical stage 1 disease. These findings may impact the management of select patients with multifocal HCC.


Toward a better multi-model ensemble prediction of East Asian and Australasian precipitation during non-mature ENSO seasons.
An effective and reliable way for better predicting the seasonal Australasian and East Asian precipitation variability in a multi-model ensemble (MME) prediction system is newly designed, in relation to the performance of predicting El Niño-Southern Oscillation (ENSO) and its impact. While ENSO is a major predictability source of global and regional precipitation variation, the prediction skill of precipitation is not solely due to typical ENSO alone, of which variability and predictability exhibit strong seasonality. The first mode of ENSO variability has large variance with high prediction skill for boreal winter and small variance with low skill for spring and summer, while the second mode shows the opposite phase. The regional prediction skills for Australasian and East Asian precipitation also show such seasonal dependence, with low skill and large spread of individual models' skills during the boreal spring to summer and high skill and small spread during winter. Using the individual models' reproducibility of the association between ENSO and regional precipitation, the prediction skills of the MME with selected models can improve at regional levels, compared to those for all-inclusive MME, during boreal spring to summer. While typical ENSO as a predictability source may still dominate during boreal winter, consideration of complex ENSO structure and its diverse impact can lead to a better prediction of regional precipitation variability during non-mature phase of ENSO seasons.


Prenatal diagnosis of limb-girdle muscular dystrophy type 2C.
After studies which have mapped the gamma-sarcoglycan deficient limb-girdle muscular dystrophy (LGMD2C) to chromosome 13q12 and recent identification of mutations within this gene, prenatal diagnosis has become possible. The deletion of exon 5 in the gamma-sarcoglycan gene was found in a consanguineous family and prenatal diagnosis was successfully provided. This is the first prenatal diagnosis of LGMD2C.


Affective response to whole-body cryotherapy: Influence of sex, body mass index, age, time of day, and past experience.
Whole-Body Cryotherapy (WBC) has seen a recent surge in popularity with patients with inflammatory conditions, athletes, and even people seeking to improve general health and quality of life. WBC treatment usually requires participation in a dozen of 3-min long sessions. But compliance is considered difficult due to possible cold-induced unpleasant sensations. Based on hedonic psychology assumptions, ratings of pleasure-displeasure experienced during a taks or activity may be important to understand individual differences in attendance. Two hundred fifty nine customers from two French cryocenters took the Feeling Scale immediately after their first WBC session. End affect appeared to be negatively valenced (M = -1.85, SD = 1.38, 95 % confidence interval: -2.02 to -1.68). Additional statistical analyses revealed a moderating influence of past experience, in women only. Similarly, BMI was found to be negatively associated with displeasure in women, but not in men. These findings are discussed and further research directions are suggested.


Metabolic effects of some antibilharzial drugs. Studies on the inhibitory action of "bilharcid" on succinate oxidation in normal rat liver.
THE INHIBITION of succinate oxidation by Piperazine diantimonyl tartarate (Bilharcid) could be in part attributed to accumulation of oxaloacetate. This is discussed with reference to the effect of ATP, glutamate and cysteine on the reversal of the inhibitory action, of the drug on succinate oxidation.


Mercury distribution and speciation in different brain regions of beluga whales (Delphinapterus leucas).
The toxicokinetics of mercury (Hg) in key species of Arctic ecosystem are poorly understood. We sampled five brain regions (frontal lobe, temporal lobe, cerebellum, brain stem and spinal cord) from beluga whales (Delphinapterus leucas) harvested in 2006, 2008, and 2010 from the eastern Beaufort Sea, Canada, and measured total Hg (HgT) and total selenium (SeT) by inductively coupled plasma mass spectrometry (ICP-MS), mercury analyzer or cold vapor atomic absorption spectrometry, and the chemical forms using a high performance liquid chromatography ICP-MS. At least 14% of the beluga whales had HgT concentrations higher than the levels of observable adverse effect (6.0 mg kg(-1) wet weight (ww)) in primates. The concentrations of HgT differed between brain regions; median concentrations (mgkg(-1) ww) were 2.34 (0.06 to 22.6, 81) (range, n) in temporal lobe, 1.84 (0.12 to 21.9, 77) in frontal lobe, 1.84 (0.05 to 16.9, 83) in cerebellum, 1.25 (0.02 to 11.1, 77) in spinal cord and 1.32 (0.13 to 15.2, 39) in brain stem. Total Hg concentrations in the cerebellum increased with age (p<0.05). Between 35 and 45% of HgT was water-soluble, of which, 32 to 41% was methyl mercury (MeHg) and 59 to 68% was labile inorganic Hg. The concentration of MeHg (range: 0.03 to 1.05 mg kg(-1) ww) was positively associated with HgT concentration, and the percent MeHg (4 to 109%) decreased exponentially with increasing HgT concentration in the spinal cord, cerebellum, frontal lobe and temporal lobe. There was a positive association between SeT and HgT in all brain regions (p<0.05) suggesting that Se may play a role in the detoxification of Hg in the brain. The concentration of HgT in the cerebellum was significantly associated with HgT in other organs. Therefore, HgT concentrations in organs that are frequently sampled in bio-monitoring studies could be used to estimate HgT concentrations in the cerebellum, which is the target organ of MeHg toxicity.


Appropriate uses of fluorides for children: guidelines from the Canadian Workshop on the Evaluation of Current Recommendations Concerning Fluorides.
To prevent fluorosis caused by excessive fluoride ingestion by revising recommendations for fluoride intake by children. Limiting fluoride ingestion from fluoridated water, fluoride supplements and fluoride dentifrices. Reduction in the prevalence of dental fluorosis and continued prevention of dental caries. Before the workshop, experts prepared comprehensive literature reviews of fluoride therapies, fluoride ingestion and the prevalence and causes of dental fluorosis. The papers, which were peer-reviewed, revised and circulated to the workshop participants, formed the basis of the workshop discussions. Recommendations to limit fluoride intake were vigorously debated before being adopted as the consensus opinion of the workshop group. Decrease in the prevalence of dental fluorosis with continuing preventive effects of fluoride use. The only significant cost would be in preparing new, low-concentration fluoride products for distribution. Fluoride supplementation should be limited to children 3 years of age and older in areas where there is less than 0.3 ppm of fluoride in the water supply. Children in all areas should use only a "pea-sized" amount of fluoride dentifrice no more than twice daily under the supervision of an adult. These recommendations are almost identical to changes to recommendations for the use of fluoride supplements recently proposed by a group of European countries. The workshop was organized by Dr. D. Christopher Clark, of the University of British Columbia, and Drs. Hardy Limeback and Ralph C. Burgess, of the University of Toronto, and funded by Proctor and Gamble Inc., Toronto, the Medical Research Council of Canada and Health Canada (formerly the Department of National Health and Welfare). The recommendations were formally adopted by the Canadian Dental Association in April 1993.


Combining CT scanning with stereotactic surgery.
A procedure to allow calculation of coordinates from a CT scan taken with a GE 8800 or GE 9800 scanner is described. This permits introduction of a probe, such as a biopsy forceps or cannula, into any brain lesion identified on CT scanning. Thus, a neurosurgeon with access to a GE scanner can perform CT directed stereotactic surgery with any stereotactic apparatus.


Caught on the surface: Tustin on autistic experience.
According to Frances Tustin, the core of autism is found in sensory modifications-and tactile modifications in particular. Tustin argues that sensory experiences may become self-absorbed to such an extent that the sensory environment experientially flattens into a two-dimensional "feel," which complicates the individual's relations with the external environment and other people. Focusing on these fundamental modifications and their experiential consequences, the article introduces Tustin's main insight in terms of collapse of intentional depth, suggesting that this collapse concerns not only concrete spatial depth, but symbolic and intersubjective depth as well. By so doing, the article illustrates how Tustin's ideas render intelligible certain commonly recognized features of autism, such as "deficits in the ability to initiate and to sustain reciprocal social interaction and social communication" and "restricted, repetitive, and inflexible patterns of behavior, interests or activities" (ICD-11).


Use of procainamide in chronic ambulatory peritoneal dialysis: report of a case.
A patient on chronic ambulatory peritoneal dialysis (CAPD) was treated with procainamide for control of ventricular arrhythmias. A procainamide half-life of 11.5 hours was observed, with a dialysis clearance of 6.5 mL/min. The N-acetylprocainamide (NAPA) dialysis clearance was 5.3 mL/min. The CAPD clearance of procainamide and its active metabolite, NAPA, is much lower than that reported for hemodialysis. Procainamide therapy should be initiated with reduced dosages in patients with renal failure.


Prevalence of Salmonella spp in cloacal, fecal, and gastrointestinal mucosal samples from wild North American turtles.
To determine prevalence of Salmonella spp in samples collected from wild North American turtles. 94 wild North American turtles of 6 species in 2 genera. Prospective microbiologic study. A convenience sample of wild North Carolina turtles admitted to a veterinary college was evaluated for Salmonella spp by use of standard techniques via microbiologic culture of cloacal swab and fecal samples. Gastrointestinal mucosa samples were also collected at necropsy from turtles that died or were euthanized. Cloacal swab samples were also collected from wild pond turtles for bacteriologic culture. Controls were established by use of wild-type Salmonella Typhimurium LT2. 94 turtles were tested for Salmonella spp; Salmonella spp were not detected in any sample. By use of a pathogen-prevalence and sample-size table, the true prevalence of Salmonella spp was estimated as < 5%. Results suggested that wild turtles in central North Carolina may not be active shedders or carriers of Salmonella spp. Despite this 0% prevalence of infection, proper hygiene practices should be followed when handling wild turtles.


Child sexual abuse--Medical statement conclusions in criminal legal process.
To evaluate medical statement conclusions in the criminal-legal process in suspected cases of child sexual abuse (CSA). An observational study of a random sample of 130 medically examined, police reported CSA suspected cases during 2001-2009. Medical statements were evaluated and their conclusions were analyzed with an end-point in the legal process. The data consists of official investigation documents from the University Hospital records, the Police, crime laboratories, the State Prosecutor, and the Courts of Law. The median age of the children was 5.3 years (range 11 months-17.3 years) at the time of the suspected sexual abuse. In most cases (76.2%, 99/130) medical statement conclusions neither supported nor excluded the suspicion of CSA. Twenty-one (16.2%) medical statements supported and in 10 cases (7.7%) the conclusion did not support the suspected CSA. Of the suspected CSA cases a hundred (76.9%) proceeded to the Prosecutor. The charge filing rate was 41.5% (54/130). The final conviction rate was 30.8% (40/130) and 74% in the charged cases. Medical statements were mentioned as evidence in the Prosecutor's decision to file charges in 18 (33.3%) of suspected CSA cases and in 15 (36%) of verdicts. A child's clear disclosure of CSA (p<0.001) and medical statements (p=0.037) had a significant role in decision making on convictions. In medical statement conclusions, physical findings with proper documentation and interpretation are needed to avoid misunderstandings in the legal process. The present study supports a routine medical statement peer review to minimize the risk of neglect caused by lack of knowledge among authorities working with sexually abused children.


Ultrastructure of human endometrial epithelium in monolayer culture with and without steroid hormones.
Colonies of cells of epithelioid appearance were identified in monolayer cultures grown up to 50 days from normal human endometrial cell suspension obtained by a method designed to insure a maximum harvest of glandular cells. Groups of these cells were separated from stromal cells by means of cloning cylinders. Studies comparing the ultrastructure of cells of this type to fresh endometrial tissue revealed a number of similarities. The morphological characteristics common to both types of samples included junctional complexes, perinuclear microfilaments and microvilli with glycocalyx. Other common features were prominent nucleoli, well developed Golgi, rough endoplasmic reticulum and membrane-bound electron-dense bodies in the cytoplasm. A stripping technique applied to the fetal bovine serum used in the nutrient medium made it possible to initiate cultures in a steroid-free environment and to maintain them in the presence of the specified concentration of estradiol and/or progesterone. Isolation of epithelial cells of endometrium in monolayer culture may provide a useful model system in which to study the specific effects of steroid hormones on cellular function and differentiation.


Fear-like behavioral responses in mice in different odorant environments: Trigeminal versus olfactory mediation under low doses.
Odors can have repulsive effects on rodents based on two complementary adaptive behaviors: the avoidance of predator odors (potentially dangerous) and the avoidance of trigeminal stimulants (potentially noxious). The present study aimed to compare the behavioral effects on mice of odors according to their trigeminal properties and ecological significance. We used three different odors: 2,4,5-trimethylthiazoline (TMT: a fox feces odor frequently used to elicit fear-induced behaviors), toluene (a strong stimulant of the trigeminal system) and phenyl ethyl alcohol (PEA: a selective stimulant of the olfactory system). First, we checked preference and avoidance behaviors in mice with and without anosmia towards these odors to ensure their olfactory/trigeminal properties. Secondly, we used a standard test (open-field and elevated plus-maze) to assess the behaviors of mice when exposed to these odors. The results show that the anosmic and control mice both avoided TMT and toluene odors. In the open-field and the elevated plus-maze, mice exhibited "anxious" behaviors when exposed to TMT. Conversely, exposure to PEA induced "anxiolytic" effects confirmed by low blood corticosterone levels resulting from completion of the elevated plus-maze. Compared with TMT exposure, toluene exposure induced moderate "anxious" effects.


Responses of methanotrophic activity, community and EPS production to CH4 and O2 concentrations in waste biocover soils.
Biocover soils are known to be a good alternative material to mitigate CH4 emissions from landfills to the atmosphere. In this study, 16 treatments with four O2 concentrations (∼0%, 5%, 10% and 21%) and four CH4 concentrations (i.e. 1%, 10%, 20% and 50%) were conducted to estimate extracellular polymeric substances (EPS) production, methanotrophic activity and community in response to CH4 and O2 concentrations in waste biocover soil (WBS). When the CH4 concentration was saturated for CH4 oxidation in the WBS, the continuous exposure of CH4 above the saturated concentrations could not obviously enhance CH4 oxidation activity. In the WBS, extracellular protein (ECP) production was negatively related with the tested CH4 concentrations, while both ECP and extracellular polysaccharides (ECPS) productions were positively related with the tested O2 concentrations. Cloning and terminal restriction fragment length polymorphism analyses showed that type I methanotrophs (Methylocaldum, Methylococcaceae, Methylomicrobium and Methylobacter) and type II methanotrophs (Methylosinus) dominated in the WBS. Among them, Methylocaldum and/or Methylococcaceae were sensitive to low O2 concentrations of ∼0%. Methylobacter had propensity to grow at low O2 concentrations of ∼0% and 5%, while Methylosinus preferred environments with high concentrations of CH4 (⩾10%) and O2 (21%). In the tested five environmental variables of ECPS, O2, EPS, CH4 and ECP, only ECPS and O2 concentrations had significant effect on the methanotrophic communities. These results suggested that O2 concentration in landfill covers should be paid more attention to optimize and sustain CH4 oxidation for mitigating CH4 emission from landfills.


Comparing the outcome of two different procedures to handle complaints from a patient's perspective.
To assess differences in patient satisfaction between a complaints procedure designed towards the needs of complainants (referred to here as the 'Committee') and a procedure that primarily aims at improving the professional quality of health care (referred to here as the 'Board'). Patients' experiences and satisfaction were assessed through a questionnaire completed by 80 patients complaining to a Board and 335 to a complaints Committee. Only complainants with a complaint that was judged to be founded or partially founded were included. Only half of the complainants reported being satisfied with the procedure they underwent. After controlling for differences in respondent characteristics, satisfaction with the Board was higher than with the Committee. The level of variance explained, however, was low (3%). The majority of respondents reported favourably on procedural aspects, for example, the impartiality of the procedure, and empathy demonstrated for their situation. Only a minority of complainants in both procedures believed that changes would be made as a result of their complaint. The absence, in the eyes of most complainants, of tangible results of filing a complaint in both rather formal procedures may serve as an explanation for both the low level of overall satisfaction and the fact that the procedure which was developed specifically for patients did not perform better. To resolve the problem of low satisfaction with complaints handling, procedures should be developed that offer a basic degree of procedural safety. But this procedural safety should not stand in the way of what complainants really want: changes for the better.


Active site probes of flavoproteins. Determination of the solvent accessibility of the flavin position 8 for a series of flavoproteins.
The chemical reactivity of 8-chloroflavins and 8-mercaptoflavins has been exploited in order to examine the orientation of protein-bound flavins relative to solvent. The apoprotein form of a series of flavoproteins was prepared and the native flavin was replaced by either 8-Cl-flavin or 8-mercaptoflavin (FAD, FMN, or riboflavin form as was appropriate). The reconstituted proteins were exposed to reagents capable of reacting with the group at position 8. The 8-Cl-proteins were challenged with sodium sulfide and thiophenol, while the 8-mercaptoproteins were faced with iodoacetamide and iodoacetic acid. The kinetics of the ensuing reactions served as a measure of the solvent availability of position 8 for the protein-bound flavin. These studies indicated that position 8 of flavin bound to melilotate hydroxylase, D-amino acid oxidase, old yellow enzyme, p-OH-benzoate hydroxylase, and flavodoxin is accessible to solvent, while position 8 on L-lactate oxidase, glucose oxidase, putrescine oxidase, and riboflavin-binding protein appears to be inaccessible. For luciferase, D-lactate dehydrogenase, and xanthine oxidase, the data suggest that position 8 is exposed but the results are inconclusive. The effect of ligand binding on the accessibility of position 8 was also studied. NADPH binding to 8-mercapto old yellow enzyme and benzoate binding to 8-Cl-D-amino acid oxidase results in complete blockage of previously available position 8. On the other hand, p-OH-benzoate hydroxylase and melilotate hydroxylase bind their respective substrates (p-OH-benzoate and melilotate) without significantly altering the reactivity of position 8.


Preparation of a murine cell line which stably expresses human T lymphotropic virus type I (HTLV-I) env genome products.
We prepared the murine myeloma cell line NS-1, which stably expressed the human T lymphotropic virus type I (HTLV-I) env gene. The plasmid BCMGEnv was constructed from the episomal vector BCMGSNeo, which was primarily derived from bovine papilloma virus. Transfected env expression was detected by Northern blotting, as well as by flow cytometry using envelope protein-specific monoclonal antibodies (mAb). Expression was detectable for at least seven months. The env transfectants induced syncytium formation which is characteristic of HTLV-I-infected cells, in the human uterine cervical cancer line, HeLa, and the rat cell line, XC. The requirement of envelope proteins for syncytium formation was confirmed by an inhibition assay with envelope protein-specific mAb. Therefore, env transfectants are not only stable, but also have its specific biological function. This system may be useful to analyze the initial steps of viral attachment to the cell surface and to search for the HTLV-I receptor.


[Legislative and regulatory framework of medical products circulation].
An important task of modern public health is improvement of quality of rendering of medical aid to the population. Means for its support at all stages of the serve of a medical device (instruments, apparatus, materials, etc.), quality, safety and efficacy which play a key role to maintain and improve the quality of life of the population.


Cross-cultural adaptation and psychometric properties of the Chinese version of the Functional Remission of General Schizophrenia (FROGS) scale and the four-item version (mini-FROGS) among people with schizophrenia.
This study was designed to verify the cross-cultural psychometric properties of the Functional Remission of General Schizophrenia (FROGS) scale and the four-item version (mini-FROGS) in Chinese schizophrenic individuals. Item clustering analysis was used to show the clustering relationship among items. Confirmatory factor analysis (CFA) was used to test the structural validity of the scale. The Global Assessment of Functioning (GAF) was used as a criterion to test convergent validity. The receiver operating characteristic curve (ROC) and the area under the ROC curve (ROC-AUC) were calculated to test the sensitivity and specificity of FROGS and mini-FROGS for functional assessment. Fifty participants were randomly selected for retest at two-month intervals. A total of 228 schizophrenia individuals were enrolled in our study. The results of the item clustering analysis and CFA supported the 3-factor structure of the original scale, and all items, except for the item "absence of antisocial or violent", showed good psychometric characteristics. The correlated coefficients between FROGS and mini-FROGS with the GAF were excellent (FROGS: r = 0.74, p<0.01; mini-FROGS: r = 0.65, p<0.01). The retest showed that the scale had good stability and validity over time (ICC = 0.856; 95% CI = 0.701∼0.941). Both mini-FROGS and FROGS had good sensitivity and specificity for the measurement of social function (mini-FROGS: ROC-AUC = 84.3% (76.9%-91.6%), and FROGS: ROC-AUC = 89.2% (83.0%-95.4%)), and there was no difference between the two versions of ROC-AUC (P = 0.154). The results of our study showed that the Chinese version of FROGS and mini-FROGS had good psychometric properties for assessing the social function of people with schizophrenia in China. In particular, the mini-FROGS version was better used in the clinical setting because of its convenience and efficiency.


Dramatic regression of mesenteric abnormalities demonstrated on angiography following prednisolone and cyclophosphamide combination therapy in a patient with polyarteritis nodosa associated with Sjögren's syndrome.
A 63-year-old woman, who had been followed for Sjögren's syndrome, was admitted due to cryoglobulinemia, leukocytoclastic vasculitis, and mononeuritis multiplexa. In spite of the administration of 60 mg prednisolone, fecal occult blood was strongly positive. The colonoscopy showed multiple colonic ulcers, and a diagnosis of polyarteritis nodosa (PAN) was made because abdominal angiography revealed markedly serpentine and narrowed superior and inferior mesenteric arteries. After steroid pulse therapy and daily oral administration of cyclophosphamide were initiated, her symptoms improved and abdominal angiographic findings were finally normalized. Although there are only three case reports on improvements in abdominal angiographic findings of PAN in the literature, our case and previously reported cases suggest that improvements in angiographic findings may reflect a good prognosis of PAN.


Serum IgG2 levels are specifically associated with whole-body insulin-mediated glucose disposal in non-diabetic offspring of type 2 diabetic individuals: a cross-sectional study.
Preclinical studies suggested that IgG2c isotype may specifically impair skeletal muscle insulin sensitivity in mice. In this study we investigated the association between serum levels of the four IgG subclasses and insulin sensitivity in non-diabetic individuals. Total IgG, IgG1, IgG2, IgG3 and IgG4 levels were measured in 262 subjects. Whole-body insulin sensitivity was assessed by euglycemic hyperinsulinemic clamp. IgG2 levels were positively correlated with BMI, waist circumference, 2-h post-load glucose levels and complement C3. Serum IgG2, but not IgG1, IgG3 and IgG4 levels were negatively correlated with whole-body insulin sensitivity (r = -0.17; P = 0.003) and muscle insulin sensitivity index (r = -0.16; P = 0.03) after adjustment for age and gender. No significant correlation was found between IgG2 levels and hepatic insulin resistance assessed by HOMA-IR and liver IR index. In a multivariable regression analysis including variables known to affect insulin sensitivity such as age, gender, BMI, smoking, lipids, inflammatory markers, fasting and 2-h post-load glucose levels, IgG2 levels were independently associated with insulin-stimulated glucose disposal (β = -0.115, 95% CI: -0.541 to -0.024; P = 0.03). These data demonstrate the independent association between higher levels of IgG2 and decreased whole-body insulin sensitivity, thus confirming in humans the animal-based evidence indicating the pathogenic role of IgG2 in insulin resistance.


Genetic variation in ESR2 and estrogen receptor-beta expression in lung tumors.
To investigate the association between inherited variation in the estrogen receptor beta (ERβ) gene (ESR2) and ERβ lung tumor expression, a phenotype that possibly affects survival differently in men and women. We genotyped 135 lung cancer patients for 22 ESR2 single nucleotide polymorphisms (SNPs) and measured nuclear and cytoplasmic ERβ expression by immunohistochemistry (IHC) in their primary lung tumor. Distributing Allred ERβ IHC scores according to ESR2 genotype classified under a dominant genetic model, we used rank sum tests to identify ESR2 SNPs significantly associated (p<0.05) with ERβ expression. 35%, 35%, and 29% of lung tumors showed no/low (Allred<6), intermediate (Allred 6-7), and maximal (Allred 8) cytoplasmic ERβ expression, whereas 13%, 27%, and 60% showed no/low, intermediate, and maximal nuclear ERβ expression. For SNPs rs8021944, rs1256061 and rs10146204, ERβ expression was higher according to the rank sum test in lung tumors from patients with at least one minor allele. For each of these three SNPs, the odds of maximal (Allred 8) relative to no/low (Allred<6) ERβ expression was 3-fold higher in tumors from patients with at least one minor allele than in tumors from patients homozygous for the common allele. Inherited variability in ESR2 may determine ERβ lung tumor expression.


Introduction to value-based insurance design.
When all patients are required to pay the same out-of-pocket amount for imaging services, which have varying degrees of benefit dependent on patient characteristics, there is potential for overuse and underuse. Rising costs of health care have stimulated efforts to redesign health care packages. Cost sharing has emerged, whereby costs are the same for everybody. Unlike traditional health care plan designs, value-based insurance design tailors the cost of care delivery to the benefit that a patient or class of patients derives from that care. With value-based insurance design, cost sharing is still used, but a "clinically sensitive" approach is designed to mitigate the adverse health consequences of high out-of-pocket costs. The authors summarize the principles of value-based insurance design and review examples of its implementation in other areas of medicine.