Microstructural characterization of TFA-MOD processed Y(₁-x)Gd(x)Ba₂Cu₃O(₇-y) with BaZrO₃.
Y(₁-x)Gd(x)Ba₂Cu₃O(₇-y) with BaZrO₃ film was fabricated on CeO₂ buffered LaMnO₃/ion beam assisted deposition-MgO/Gd₂Zr₂O₇/Hastelloy C276TM substrates by the metal organic deposition process using trifluoroacetates. Both microstructural and analytical characterizations were performed by transmission electron microscopy with selected area electron diffraction method and energy dispersive X-ray spectroscopy. The thickness of Y(₁-x)Gd(x)Ba₂Cu₃O(₇-y) with BaZrO₃ film was found approximately 700 nm and the film was composed of c-axis oriented Y(₁-x)Gd(x)Ba₂Cu₃O(₇-y) grains. Several types of particles, (Y,Gd)₂Cu₂O₅, CuO and BaZrO₃, were formed within the Y(₁-x)Gd(x)Ba₂Cu₃O(₇-y) film, whose sizes were about 100-200 nm for (Y,Gd)₂Cu₂O₅ and CuO particles, and about 10-20 nm for BaZrO₃ particles, respectively. In the Y(₁-x)Gd(x)Ba₂Cu₃O(₇-y) film, (Y,Gd)₂Cu₂O₅ and CuO particles were dispersed heterogeneously, whereas BaZrO₃ nanoparticles were found dispersed homogeneously with random orientation. In addition, electron tomographic observation was carried out to attain the three-dimensional information of polyhedral BaZrO₃ nanoparticles.


The antiepileptogenic effect of low-frequency stimulation on perforant path kindling involves changes in regulators of G-protein signaling in rat.
G-protein coupled receptors may have a role in mediating the antiepileptogenic effect of low-frequency stimulation (LFS) on kindling acquisition. This effect is accompanied by changes at the intracellular level of cAMP. In the present study, the effect of rolipram as a phosphodiesterase inhibitor on the antiepileptogenic effect of LFS was investigated. Meanwhile, the expression of αs- and αi-subunit of G proteins and regulators of G-protein signaling (RGS) proteins following LFS application was measured. Male Wistar rats were kindled by perforant path stimulation in a semi-rapid kindling manner (12 stimulations per day) during a period of 6days. Application of LFS (0.1ms pulse duration at 1Hz, 200 pulses, 50-150μA, 5min after termination of daily kindling stimulations) to the perforant path retarded the kindling development and prevented the kindling-induced potentiation and kindling-induced changes in paired pulse indices in the dentate gyrus. Intra-cerebroventricular microinjection of rolipram (0.25μM) partially prevented these LFS effects. Twenty-four hours after the last kindling stimulation, the dentate gyrus was removed and changes in protein expression were measured by Western blotting. There was no significant difference in the expression of α-subunit of Gs and Gi/o proteins in different experimental groups. However, application of LFS during the kindling procedure decreased the expression RGS4 and RGS10 proteins (that reduce the activity of Gi/o) and prevented the kindling-induced decrease of RGS2 protein (which reduces the Gs activity). Therefore, it can be postulated that the Gi/o protein signaling pathways may be involved in antiepileptogenetic effect of LFS, and this is why decreasing the cAMP metabolism by rolipram attenuates this effect of LFS.


Primary study authors of significant studies are more likely to believe that a strong association exists in a heterogeneous meta-analysis compared with methodologists.
To assess the interpretation of a highly heterogeneous meta-analysis by authors of primary studies and by methodologists. We surveyed the authors of studies on the association between insulin-like growth factor 1 (IGF-1) and prostate cancer, and 20 meta-analysis methodologists. Authors and methodologists presented with the respective meta-analysis results were queried about the effect size and potential causality of the association. We evaluated whether author responses correlated with the number of IGF-related articles they had published and their study results included in the meta-analysis. We also compared authors' and methodologists' responses. Authors who had published more IGF-related papers offered more generous effect size estimates for the association (ρ(s)=0.61, P=0.01) and higher likelihood that the odds ratio (OR) was greater than 1.20 (ρ(s)=0.63, P=0.01). Authors who had published themselves studies with statistically significant effects for a positive association were more likely to believe that the true OR is greater than 1.20 compared with methodologists (median likelihood 50% versus 2.5%, P=0.01). Researchers are influenced by their own investment in the field, when interpreting a meta-analysis that includes their own study. Authors who published significant results are more likely to believe that a strong association exists compared with methodologists.


The in vitro synthesis and degradation of prostaglandins during the development of bleomycin-induced pulmonary fibrosis in hamsters.
Subsequent to optimization of conditions for enzyme assay, we examined the in vitro synthesis and degradation of prostaglandins by the lung during the development of bleomycin-induced pulmonary fibrosis in hamsters. It was found that the microsomal protein content on a per lung basis was significantly increased to 144, 129, 134, and 121% of control (2.3 mg protein/lung) at 4, 7, 14 and 21 days post-treatment, respectively. The synthesis of PGD2 was significantly elevated to 10.2, 10.8, and 12.5 nmoles/lung at 7, 21 and 28 days, respectively, as compared to the control value of 5.6 nmoles/lung. Significant increases in PGF2 alpha synthesis from the control value of 3.3 nmoles/lung to 5.2, 8.2 and 5.5 nmoles/lung were found at 4, 7 and 21 days post-treatment, respectively. The synthesis of PGE2 also showed significant increases above the control value of 6.1 nmoles/lung to 10.5, 12.2 and 11.0 nmoles/lung at 7, 21 and 28 days post-treatment, respectively. Similarly, the synthesis of 6-keto-PGF1 alpha was significantly increased to 7.4, 7.5 and 8.6 nmoles/lung at 7, 21 and 28 days post-treatment, respectively, as compared to the control value of 4.4 nmoles/lung. The synthesis of TxB2 was also significantly increased from the control value of 3.9 nmoles/lung to 7.5 and 6.4 nmoles/lung at 7 and 21 days post-treatment, respectively. Accompanying the increased synthesis of prostaglandins in general, the in vitro degradation of PGF2 alpha was significantly increased from the control value of 71.1 nmoles/lung to 173.5, 131.7 and 143.3 nmoles/lung at 2, 4 and 7 days after bleomycin treatment, respectively. We conclude that bleomycin-induced pulmonary fibrosis leads to changes in prostaglandin synthesis and degradation possibly as a result of an accompanying inflammatory response and resident cellular proliferation.


Frankenbacteriosis targeting interactions between pathogen and symbiont to control infection in the tick vector.
Tick microbiota can be targeted for the control of tick-borne diseases such as human granulocytic anaplasmosis (HGA) caused by model pathogen, Anaplasma phagocytophilum. Frankenbacteriosis is inspired by Frankenstein and defined here as paratransgenesis of tick symbiotic/commensal bacteria to mimic and compete with tick-borne pathogens. Interactions between A. phagocytophilum and symbiotic Sphingomonas identified by metaproteomics analysis in Ixodes scapularis midgut showed competition between both bacteria. Consequently, Sphingomonas was selected for frankenbacteriosis for the control of A. phagocytophilum infection and transmission. The results showed that Franken Sphingomonas producing A. phagocytophilum major surface protein 4 (MSP4) mimic pathogen and reduce infection in ticks by competition and interaction with cell receptor components of infection. Franken Sphingomonas-MSP4 transovarial and trans-stadial transmission suggests that tick larvae with genetically modified Franken Sphingomonas-MSP4 could be produced in the laboratory and released in the field to compete and replace the wildtype populations with associated reduction in pathogen infection/transmission and HGA disease risks.


[Scar sarcoidosis: a usually progressive disease (about a case)].
The sarcoidosis is a systemic granulomatous disease. It is usually characterized by skin manifestations which may be suggestive of progressive sarcoidosis with visceral involvement. We here report a case of pulmonary sarcoidosis revealed by the reactivation of an old cutaneous scar following a trauma occurred 20 years earlier. Radiological assessment showed mediastino-pulmonary sarcoidosis stage 2. The diagnosis of sarcoidosis should be suspected in patients with any recent scar modification in order to establish early management.


Using scores to identify patients at risk of short term mortality at arrival to the acute medical unit: A validation study of six existing scores.
"Early warning scores" (EWS) have been developed to quantify levels of vital sign abnormality. However, many scores have not been validated. The aim of this study was to validate six scores that all rely on vital signs: Rapid Acute Physiology Score (RAPS), Rapid Emergency Medicine Score (REMS) and the National Early Warning Score (NEWS) and the Goodacre, Groarke and Worthing physiological scores. A posthoc single-center observational cohort study of prospectively collected vital signs on acutely admitted medical patients to a Danish hospital. All adult patients arriving at an acute medical unit at a 450-bed regional teaching hospital were included. Upon arrival, we registered initial vital signs and only the first presentation in the study period was included. Patients were included from 1 June to 31 October 2012. All-cause 24-h mortality and overall in-hospital mortality were used as endpoints. A discriminatory power above 0.8 was considered acceptable. 5784 patients were included with a median age of 67 (49-78) years, 32 (0.6%) died within 24h and 161 (2.8%) while admitted. Discriminatory power for 24h mortality was above 0.8 for all scores (except the Groarke score (0.587)) and highest for the Worthing score (0.847). The discriminatory power for predicting overall in-hospital mortality was highest for the Goodacre and Worthing scores (0.810 and 0.800 respectively) but below 0.8 for the remaining scores. The Goodacre score and the Worthing physiological score have good discriminatory power at identifying patients at increased risk of 24-h and in-hospital mortality in our setting.


Cervical Alignment of Patients with Basilar Invagination: A Radiological Study.
To investigate the cervical alignment and the relative range of motion (ROM) in patients with basilar invagination (BI). A total of 40 BI cases (38.1 years old ± 17.9 years old, 19 male and 21 female) and 80 asymptomatic individuals (33.8 years old ± 10.8 years old, 40 male and 40 female) were included. The Skull-C2 /Skull-BV, Skull-C7 , C2 -C7 /BV-C7 wall angles, C0 -C2 /C0 -BV, C0 -C7 , C1 -C7 , and C2 -C7 /BV-C7 angles were measured in dynamic X-ray images (including neutral, extension, and flexion positions). Correlation between the upper and lower cervical curvatures were analyzed. The total, extension, and flexion ROMs of these angles were calculated, respectively. The BI patients had a smaller C0 -C2 /C0 -BV angle (18.2° ± 16.4° vs 30.9° ± 9.3°), but larger C2 -C7 /BV-C7 (32.2° ± 16.1° vs 19.4° ± 10.6°) and C2 -C7 /BV-C7 wall angles (37.8° ± 17.2° vs 23.6° ± 10.2°) than the control group in neutral position. The upper and lower curvatures correlated negatively in neutral (r = -0.371), extension (r = -0.429), and flexion (r = -0.648) positions among BI patients, as well as in extension position (r = -0.317) among control group. The BI patients presented smaller total ROMs in Skull-C2 /Skull-BV (12.3° ± 16.6° vs 19.7° ± 10.9°), C0 -C2 /C0 -BV (8.1° ± 11.1° vs 17.6° ± 10.5°), and C0 -C7 angles (57.8° ± 14.2° vs 78.3° ± 17.9°), but a larger total ROM in C2 -C7 /BV-C7 wall angle (52.8° ± 13.9° vs 27.0° ± 16.1°) than the control group. The BI patients also presented smaller extension ROMs in Skull-C2 /Skull-BV (6.9° ± 9.4° vs 12.5° ± 9.3°), Skull-C7 (24.5° ± 10.9° vs 30.7° ± 12.5°), and C0 -C2 /C0 -BV angles (4.4° ± 7.8° vs 9.9° ± 8.6°) than the control group. Moreover, the BI patients showed smaller absolute values of flexion ROMs in Skull-C2 /Skull-BV (-5.2° ± 9.4° vs -7.3° ± 8.0°), C0 -C2 /C0 -BV (-3.2° ± 8.8° vs -7.7° ± 8.7°), and C0 -C7 angles (-33.2° ± 13.0° vs -52.8° ± 19.2°), but a larger absolute value of flexion ROM in C2 -C7 /BV-C7 wall angle (-33.9° ± 14.8° vs -8.2° ± 15.1°). The cervical spine was stiffer in BI patients than the asymptomatic individuals, especially in the upper cervical curvature. The negative correlation between upper and lower cervical curvatures was more obvious in BI patients.


Fetal cardiac output in monochorionic twins.
To compare fetal cardiac output (CO) in donor and recipient twins of twin-twin transfusion syndrome (TTTS) pregnancies after laser therapy with that of monochorionic twins without TTTS and normal singletons. In a longitudinal, prospective study, we sonographically assessed fetal CO in donors (n = 10) and recipients (n = 10) with TTTS after fetoscopic laser therapy, in monochorionic twins without TTTS (n = 20) and in normal singleton pregnancies (n = 20). The fetal CO of TTTS twins was determined 1 day and 1 week after laser treatment, and from then on every 2-4 weeks until birth. Twins without TTTS were examined biweekly until birth. Singletons were examined twice, with an 8-week interval, at different gestational ages between 17 and 35 weeks. Absolute CO increased exponentially with advancing gestational age (P < 0.0001), and was significantly related to fetal weight in all groups (P < 0.0001). The median CO/kg in donors after laser therapy, recipients after laser therapy and non-TTTS monochorionic twins was significantly higher than that in singletons (all P < 0.001). Median CO/kg in donors after laser therapy, recipients after laser therapy, and non-TTTS monochorionic twins was not significantly different between groups. Monochorionic twins with TTTS have higher CO after laser therapy than normal singletons.


Mitogenic and protective activity associated with a lipopolysaccharide from Coxiella burnetii.
A purified lipopolysaccharide (LPS) isolated from the rickettsial agent of Q fever, Coxiella burnetii phase 1, possesses some of the in vivo and in vitro biological properties previously only associated with bacterial endotoxins. The Coxiella LPS is mitogenic for guinea pig leukocytes, induces non-specific resistance in mice to virulent Candida albicans, causes dermal Schwartzman reactions, and is positive by the limulus lysate assay.


Changes in muscarinic responsiveness, muscarinic receptor density and Ca2+ mobilization of the urinary bladder in streptozotocin-induced diabetic rats.
Functional changes in the urinary bladder obtained from diabetic rats were investigated by determining the responsiveness to acetylcholine (ACh). Maximal contraction of the detrusor strips in response to ACh was significantly enhanced in the diabetic rats. Ca(2+)-induced contracture of the detrusor strips, which had been incubated with 10(-3) M ACh in the presence of nicardipine in Ca(2+)-free medium, was significantly augmented in diabetic rats. Ca(2+)-contracture in Ca(2+)-free, isotonic high-K+ (60 mM) medium was not changed in diabetic state. The density of muscarinic receptors to 3H-QNB was significantly higher in the bladder from diabetic rats compared to age-matched control rats. These results suggest that tone of the autonomic nervous system in the bladder may be decreased in diabetes and, thus, compensatory increase in density of muscarinic receptors may occur. Furthermore, an increased contractile response of the detrusor strips of the urinary bladder to ACh in diabetic rats also may be due to an increased influx of extracellular Ca2+ through the receptor-operated Ca2+ channels but not the voltage-dependent Ca2+ channels.


Management of methylmalonic acidemia (MMA) with N-carbamylglutamate: A case report from Italy.
Methylmalonic acidemia (MMA) is an inborn error of metabolism whose optimal management, especially in the long-term remains to be established. We describe the case of a child with MMA mut0 who was in a cycle of episodes of decompensation and hospitalization when we started to use carglumic acid (CA), a well-known adjunctive therapy to standard care for the treatment of acute hyperammonemia due to MMA. Using the lowest effective therapeutic dose of CA and adjusting the patient's diet with caloric and protein intake adequate for her age and pathology, we managed to keep ammonium levels within the normal range, and to ensure a normal growth pattern. The present case adds further confirmation of the long-term management of MMA using CA, focusing on the long duration of follow up and on the use of a lower dose of CA in real life settings.


Left atrial volume measured by real-time 3-dimensional echocardiography predicts clinical outcomes in patients with severe left ventricular dysfunction and in sinus rhythm.
The clinical value of real-time 3-dimensional echocardiography assessments of left atrial volume in patients with left ventricular dysfunction has not been determined. Real-time 3-dimensional echocardiography and 2-dimensional Doppler echocardiography were performed on the same day in 108 patients with severe left ventricular dysfunction and in sinus rhythm. End-systolic left atrial volumes were measured using real-time 3-dimensional echocardiography images (LAV-3D) and end-systolic left atrial volumes were calculated by the biplane area-length formula using 2-dimensional echocardiography (LAV-2D). Patients were observed clinically over 10 +/- 7 months. LAV-2D showed excellent correlation with LAV-3D (r = 0.88, P < .001), but the former was significantly smaller than the latter (-12 +/- 21 mL, P < .001). During follow-up, 31 patients (29%) showed clinical events, including 3 cardiac deaths and 28 hospitalizations as a result of heart failure. Patients with clinical events had larger initial LAV-3D (P < .05) and LAV-2D (P = .05), higher transmitral E velocity, higher E/E' ratio, more severe mitral and tricuspid regurgitation, and higher maximal velocity of tricuspid regurgitation than the 77 patients without events. LAV-3D (P < .001) and age (P < .05) were independent predictors of cardiac events by Cox proportional hazard model, whereas LAV-2D was negatively involved. Patients with initial LAV-3D less than 100 mL had a significantly higher 1-year event-free survival than those with LAV-3D greater than or equal to 100 mL (80 +/- 7 vs 48 +/- 10%, P < .001). LAV-3D is a major predictor of clinical events in patients with severe left ventricular dysfunction and in sinus rhythm. The clinical value of LAV-3D seems to be superior to that of LAV-2D.


Effectiveness and Complications of Percutaneous Needle Tenotomy with a Large Needle for Muscle Contractures: A Cadaver Study.
Twenty-two percent of institutionalised elderly persons have muscle contractures. Contractures have important functional consequences, rendering hygiene and positioning in bed or in a chair difficult. Medical treatment (such as botulinum toxin injections, physiotherapy or positioning) is not very effective and surgery may be required. Surgery is carried out in the operating theatre, under local or general anaesthesia but is often not possible in fragile patients. Mini-invasive tenotomy could be a useful alternative as it can be carried out in ambulatory care, under local anaesthesia. To evaluate the effectiveness of percutaneous needle tenotomy and the risks of damage to adjacent structures in cadavers. Thirty two doctors who had never practiced the technique (physical medicine and rehabilitation specialists, geriatricians and orthopaedic surgeons) carried out 401 tenotomies on the upper and lower limbs of 8 fresh cadavers. A 16G needle was used percutaneous following location of the tendons. After each tenotomy, a neuro-orthopaedic surgeon and an anatomist dissected the area in order to evaluate the success of the tenotomy and any adjacent lesions which had occurred. Of the 401 tenotomies, 72% were complete, 24.9% partial and 2.7% failed. Eight adjacent lesions occurred (2%): 4 (1%) in tendons or muscles, 3 (0.7%) in nerves and 1 (0.2%) in a vessel. This percutaneous needle technique effectively ruptured the desired tendons, with few injuries to adjacent structures. Although this study was carried out on cadavers, the results suggest it is safe to carry out on patients.


Selenium incorporation into Saccharomyces cerevisiae cells: a study of different incorporation methods.
To study the effects of the selenium enrichment protocols in yeast at various points in the cell cycle, total selenium accumulation and the forms of selenium incorporated. The use of selenized yeast as enriched selenium supplements in human nutrition has become a topic of increasing interest over the last decade. Four enrichment procedures have been evaluated using sodium selenite as the selenium source: enrichment during the growth phase; enrichment at the non-growth phase, both of these at different selenium levels; enrichment by seeding in a fermentable carbon source (glucose); Se-enrichment with a non-fermentable carbon source (glycerol). A nitric acid digestion of the yeast samples prepared under different conditions has been performed in order to evaluate the total selenium incorporated into the yeast cells. Also, an enzymatic digestion of the yeast samples with pepsin has been carried out as an initial step to begin the process of determining which of the different possible selenium species are formed. The cell count evaluations of the selenium-enriched yeast showed that the growth phase, seeding and the use of YEPG media is influenced by the addition of Se, while the non-growth phase is not. Total selenium incorporation studies showed that seeding the yeast permits more accumulation of selenium. Speciation studies of the enriched yeast showed that the growth phase increases the formation of L-Se-methionine. When the aim of enriching yeast with selenium is the formation of L-Se-methionine, the best enrichment procedure is using the growth phase with small concentrations of sodium selenite. The use of selenium supplements is widespread and most of the supplements use selenium-enriched yeast in their formulation. Studies made on supplements do not have the appropriate Se-species for optimal absorption in the human body. This study presents and compares methods for the best selenium yeast enrichment that could ultimately be used in selenium supplement formulations.


Pre-operative testing and personal protective equipment in the operating room during a pandemic: A survey of Ontario general surgeons.
The coronavirus disease 2019 (COVID-19) pandemic has had major implications for general surgery practice. We sought to characterize general surgeons' perceptions of their surgical practice in Ontario, Canada, regarding operating room precautions to maximize safety during the pandemic. A web-administered cross-sectional survey was sent to general surgeons registered with the College of Physicians and Surgeons of Ontario on May 19, 2020. Surgeons were surveyed regarding their practices in pre-operative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing, use of intra-operative personal protective equipment (PPE) given a patient's COVID-19 status, and management of common general surgical emergencies with COVID-19 patients. Responses were compared between surgeons from high- and low-prevalence public health units (PHUs) in Ontario using chi-square tests. There were 81 respondents (rate: 81/271, 30%), 48 (59%) of whom were from a PHU in the top quartile of COVID-19 prevalence. Surgeons from low-prevalence PHUs reported pre-procedural COVID-19 testing rates similar to those reported in high-prevalence PHUs for elective (36% versus 55%), urgent (36% versus 54%), and emergent (20% versus 33%) surgeries. Seventy-eight percent of surgeons with COVID-19-negative patients limited trainees in the operating room compared with 96% of surgeons with COVID-19-positive patients. Use of N95 respirators was 17% for surgeons with COVID-19-negative patients, which dramatically increased to 62% for surgeons with patients whose COVID-19 status was unknown. These findings support a need for improved understanding of local disease prevalence and risk of COVID-19 transmission to conserve PPE and return surgical trainees to pre-pandemic standards.


Differential growth and transmission in cats of feline leukaemia viruses of subgroups A and B.
The outcome of infecting cats with FeLV of sub-groups A (FeLV-A) or B (FeLV-B) was different. After FeLV-A infection, virus was quickly recovered from the blood and oropharynx of most animals. Following infection with FeLV-B, only a small proportion of cats developed a viraemia, and this after a long interval. There was no evidence that FeLV-B was transmitted by contact. The result of infecting cats with mixtures of FeLV-A and B (FeLV-AB) was that to a large extent each virus operated independently. FeLV-A was recovered from the plasma first, in a high proportion of the cats, and FeLV-B appeared later but not in all cats. There was evidence of interaction, however, in that the proportion of cats which were viraemic with FeLV-B was greater following FeLV-AB infection than after infection with FeLV-B alone; also FeLV-B was transmitted by contact from cats excreting FeLV-AB. These results help to explain the apparent dependence of FeLV-B on FeLV-A under natural conditions and the frequency of occurrence of sugroups A and B in FeLV isolates.


Evolving the Behavior of Machines: From Micro to Macroevolution.
Evolution gave rise to creatures that are arguably more sophisticated than the greatest human-designed systems. This feat has inspired computer scientists since the advent of computing and led to optimization tools that can evolve complex neural networks for machines-an approach known as "neuroevolution." After a few successes in designing evolvable representations for high-dimensional artifacts, the field has been recently revitalized by going beyond optimization: to many, the wonder of evolution is less in the perfect optimization of each species than in the creativity of such a simple iterative process, that is, in the diversity of species. This modern view of artificial evolution is moving the field away from microevolution, following a fitness gradient in a niche, to macroevolution, filling many niches with highly different species. It already opened promising applications, like evolving gait repertoires, video game levels for different tastes, and diverse designs for aerodynamic bikes.


Surgeon estimation of retropubic trocar position in blind 3D space.
Retropubic midurethral sling surgery involves the blind passage of trocars near vital organs. We quantified the proximity of surgeons' mental representation of trocar position relative to actual position using a pelvis simulation platform. We hypothesized that novice surgeons, compared with experts, would estimate the trocar's location to be further from the actual location. Novice and expert surgeons performed bilateral retropubic trocar passes of a Gynecare TVT trocar (#810041B-#810,051) on the simulation platform. We measured the trocar tip's position using a motion capture system, and recorded vocalizations when they perceived contacting the bone and crossing three landmark-oriented planes. We calculated differences (∆Bone, ∆Turn, ∆Top, ∆Pop) between vocalization times and when the trocar crossed the corresponding plane. We performed Mann-Whitney and Chi-squared tests to investigate differences between novices and experts and Levene's test to assess equality of variances for subject-level variation. A total of 34 trials, including 22 expert and 12 novice trials, were performed by six participants. ∆Bone was significantly smaller among novice surgeons (1.27 vs 2.81 s, p=0.013). There were no significant differences in the remaining three deltas or in vocalizing early versus late. Levene's test revealed no significant differences in within-subject variability for any of the four deltas. Novices passed the trocar anterior to the pubic bone on three passes. Novices were similar to expert surgeons in their estimation of the trocar's location and may have relied more heavily on anticipatory mechanisms to compensate for lack of experience. Teaching surgeons should make sure the novice surgeon trocar pass starts posterior to the bone.


Effects of cypermethrin and methyl parathion mixtures on hormone levels and immune functions in Wistar rats.
To study interaction and dose-related effects of mixed cypermethrin and methyl parathion on endocrine and immune functions, 120 Wistar rats were divided randomly into six groups of ten male and ten female rats, respectively, at the age of 2 months. All groups were force-fed every 2 days for 30 days with cypermethrin 0.0, 8.0, 0.0, 8.0, 1.8, 0.4 mg/kg bw and methyl parathion 0.0, 0.0, 0.23, 0.23, 0.0518, 0.0115 mg/kg bw. Controls received vehicle solvent only. Body weight gain and organ weights were measured. Serum or blood were used to test luteinizing hormone, follicle stimulating hormone, estradiol (E(2)), testosterone, thyroid hormones (T(3), T(4), TSH), IgG, IgA, rate of neutrophil phagocytosis and of lymphocyte transformation. The effects on relative weights of ovaries and adrenals, IgA and rate of lymphocyte transformation were antagonistic interaction; the effect on estradiol was synergistic in female, whereas addictive in male rats; and the other indices indicated addictive interaction. Organ weights were similar in exposed and control animals except for adrenal (heavier in exposed rats, P<0.01). Serum levels of FSH and estradiol were higher in exposed groups than in controls (P<0.01). IgG levels were lower in exposed rats than in controls (P<0.01), and IgA levels were higher in exposed females than in controls (P<0.01). Lymphocyte transformation rates were lower (P<0.01) and neutrophil phagocytosis rates were higher (P<0.01) in exposed rats than in controls. Our results showed that exposure to low-dose mixtures of cypermethrin and methyl parathion may affect hormone levels (especially estradiol) and immune function in rats, and the NOAELs of combined compounds were located at 1/600 LD(50).


Reproductive endocrinology: maternal cholestasis and offspring metabolic abnormalities.
Papacleovoulou and colleagues demonstrate that maternal cholestasis during pregnancy is associated with offspring adiposity and metabolic abnormalities, both in humans and in mice. This study reinforces the overwhelming evidence of the critical role of the in utero environment as a major determinant of adult health and disease.


Japanese postmarketing surveillance of clopidogrel in patients with non-ST-segment elevation acute coronary syndrome, stable angina, old myocardial infarction, and ST-segment elevation myocardial infarction after percutaneous coronary intervention in a real-life setting: the final report (J-PLACE Final).
The present postmarketing surveillance investigated the safety and efficacy of clopidogrel for prevention of cardiovascular events following percutaneous coronary intervention (PCI) in a real-life setting with a large patient population. This study included patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) who had unstable angina, and patients with non-ST-segment elevation myocardial infarction, stable angina, and old myocardial infarction (SA/OMI), or ST-segment elevation myocardial infarction (STEMI). For safety assessment in 4049 patients, the incidence of adverse drug reactions (ADR) and bleeding adverse events (AE), and for efficacy assessment in 3900 patients, that of major adverse cardiovascular events (MACE) and MACE and cerebrovascular events (MACCE), was calculated in the primary diagnosis groups (NSTE-ACS, SA/OMI, or STEMI). ADR incidence did not significantly differ by group (10.1, 11.6, and 12.2 % in the NSTE-ACS, SA/OMI, and STEMI groups, respectively). Cumulative ADR incidence was highest in the STEMI for 52 weeks. Both total and cumulative bleeding AE incidences were higher in the SA/OMI group (5.9 and 6.8 %, respectively) than in the other groups (3.5 and 3.8 % in the NSTE-ACS, 3.6 and 4.5 % in the STEMI). The MACCE and MACE incidence rates were higher in the STEMI groups than in the other groups. In conclusion, we did not find additional concerns regarding safety and efficacy of clopidogrel in patients who have undergone PCI, regardless of their diagnoses.


Anatomic evaluation of the carotid artery bifurcation in cadavers: implications for open and endovascular therapy.
Knowledge of carotid bifurcation (CB), common carotid artery (CCA) and its branches and their recognition during diagnostic imaging are also important for vascular surgical procedures in the region, such as carotid endarterectomy or radical neck dissection, catheterization and aneurysms. The surgical anatomy of the carotid arteries was studied in 20 cadavers. Micrometric values of the CB and its relation with surrounding structures, measurements belonging to the external carotid artery (ECA) and internal carotid artery (ICA), and metric data, such as lower face including the greater horn, laryngeal prominence have been evaluated by making linear measures. The diameter of the CCA at the CB under 2 cm and CB diameter was measured as 8.1 +/- 2.24 mm and 12.79 +/- 2.87 mm, respectively. Evaluating data related to the ICA and the ECA in samples, the aspect was measured the ICA and the ECA in the CB discrimination point as 21.52 +/- 20.53 degrees . In the most location of the ECA origin according to the ICA has been determined as medial position in 35 specimens. The origin of the superior thyroid artery (STA) was found to be at the same level with the CB in 40% and below it in 25% specimens. This study has provided measured objective criteria for the arterial features of the neck region, which are crucial during surgery. The origins of the branches of the CCA act as key landmarks for adequate and appropriate placement of the cross-clamp on the carotid arteries.


Solid state fermentation of broiler litter for production of biocontrol agents.
Several varieties of heat-sterilized broiler litter with 60% (wet basis, wb) moisture content were substrate in solid-state fermentations to produce biocontrol agents. Litter varieties included litter produced by one flock of broilers from medicated and non-medicated controlled rations, and litter produced by two flocks and four flocks on a single application of bedding material from medicated commercial sources. Litter preparations were inoculated with monocultures of Bacillus thuringiensis serovar japonensis strain Buibui, a pathogen of Japanese beetle larvae (Popillia japonica), or Pseudomonas fluorescens 2-79. B. thuringiensis did not grow in unextracted 1-flock litter nor in water extracted litter, but grew in methanol extracted litter to 5 x 10(10) cell forming units (CFU)/g litter (dry weight, dw) and a spore count of 1 x 10(10) CFU/g litter (dw). B. thuringiensis also grew in unprocessed 2-flock and 4-flock litter, achieving cell counts of 3 x 10(9) and 1 x 10(9) CFU/g litter (dw), respectively, and spore counts of 1 x 10(9) CFU/g litter (dw). P. fluorescens grew in medicated 1-flock litter with no extraction to a cell density greater than 4 x 10(11) CFU/g litter (dw). Bioassays in soil containing over 0.5% (db) litter fermented with B. thuringiensis resulted in over 90% mortality in 21 days for first instars of Japanese beetle when compared to a control treatment using compost without fermented litter. The investigations demonstrate that bacterial biocontrol agents produced via solid substrate fermentations using broiler poultry litter have potential in biocontrol applications in the soil environment.


The multifaceted care-seeking practices among caregivers of children with cerebral palsy: Perspectives from mothers and providers in Ghana.
Research on cerebral palsy (CP) has lacked emphasis on knowledge and treatment practices among caregivers, particularly in low- and middle-income countries where socio-cultural contexts encourage a variety of treatment alternatives. In this study, we explored the beliefs and experiences that motivate care-seeking practices among caregivers of children with CP in Ghana. Semi-structured interviews were conducted with 25 caregivers, 10 medical providers, and 5 alternative providers in the Greater Accra Region. Participant interviews were analyzed using principles adapted from grounded theory. A conceptual model was constructed to illustrate salient patterns and motivational factors influencing care-seeking practices. Participants' experiences showed that caregivers initially sought physiotherapy and prescription medications from medical providers. Many of them then transitioned to alternative methods to search for a cure or address specific CP symptoms. Over time, most caregivers discontinued both medical and alternative care in favor of at-home treatment. A few withdrew completely from all forms of care. Cost of treatment, caregiver burden, and stigma strongly inhibited care-seeking outside the home. Although caregivers were open to exploring a variety of treatment options, at-home treatment was preferred by long-time caregivers for its convenience, low cost, and adaptability to patient and caregiver needs.


[Electron microscopic studies on phagocytosis of iron particles by smooth muscle cells in experimental vascular injury induced by intravascular application of direct current (author's transl)].
In experimentally induced arterial thrombosis of minipigs caused by intravascular application of direct current iron deposits deriving from the steel wire electrode are found. Intimal proliferation can be observed 6 weeks after induction of thrombosis. Iron deposits are phagocytized by modified smooth muscle cells participating in intimal proliferation. These findings indicate that smooth muscle cells under certain conditions can realize functions of macrophages.


Diabetes, prediabetes, and long-term sickness absence due to mental disorders: Japan Epidemiology Collaboration on Occupational Health Study.
To investigate the association of diabetes and prediabetes with long-term sickness absence (LTSA) due to mental disorders or specific mental disorders. A prospective cohort study was conducted using data from the Japan Epidemiology Collaboration on Occupational Health Study. A total of 62,065 workers who received health check-ups in 2011 (nine companies) or 2014 (two companies) and were followed up to March 31, 2020 were included in this study. Diabetes status was defined based on the American Diabetes Association criteria, and diabetes was differentiated into diabetes with/without anti-diabetic treatment for additional analysis. A Cox proportional hazards regression model was used to investigate these associations. During maximum 8-year follow-up period, 1024 participants underwent LTSA due to mental disorders. The adjusted hazard ratio (aHR) and corresponding 95% confidence interval (CI) of LTSA due to all mental disorders were 1.10 (0.88-1.38) and 1.45 (1.07-1.98) for prediabetes and diabetes, respectively. Diabetic individuals with/without treatment were both at a high risk of LTSA due to mental disorders. For specific mental disorders, diabetes was associated with a higher risk of LTSA due to reaction to severe stress and adjustment disorders (aHR = 3.02, 95% CI = 2.01-4.52) while it was marginally associated with LTSA due to depressive episode (aHR = 1.25, 95% CI = 0.98-1.60). Prediabetes was also associated with LTSA due to reaction to severe stress and adjustment disorders (aHR = 1.41, 95% CI = 1.08-1.84). The present study suggests the importance of screening diabetes status and providing psychological support for decreasing the risk of LTSA due to mental disorders within working populations.


Assessing the health risks associated with the usage of water-atomization shower systems in buildings.
In the context of climate change policies, buildings must implement solutions to reduce energy and water consumption. One such solution is showering with water atomization showerheads, which can significantly reduce water and energy usage. However, the lack of risk assessment for users' health has hindered the widespread adoption of this technology. To address this gap, we assess the risk of spreading bacteria, in particular the pathogenic bacterium Legionella pneumophila, from shower hose biofilms of different ages grown under controlled or uncontrolled conditions considering different levels of water hardness, during showering using water atomization showerheads (ECO) or continuous flow showerheads (STA). We compared the aerosol and bioaerosol emission - total, viable and cultivable - during a 10 min shower event between the two shower systems. We showed that the water-atomization showerhead emitted slightly more nanoparticles smaller than 0.45 µm and slightly fewer particles larger than 0.5 µm than the continuous flow showerhead. Additionally, ECO showerheads emitted fewer cultivable bacteria than STA, regardless of the biofilm's age or growth conditions. When Legionella pneumophila was detected in biofilms, ECO showerheads released slightly less cultivable Legionella in the first flush of shower water compared to the STA, ranging from 6.0 × 102 to 1.6 × 104 CFU·L-1. However, cultivable L. pneumophila was not detected in the aerosols emitted during showering with either showerhead. These findings suggest that emerging water-drop emission technologies might affect human exposure to aerosols differently than traditional systems, emphasizing the importance of assessing the health risks associated with any new shower system. Additionally, these findings provide valuable insights for achieving a balance between water and energy conservation.


Genome Sequences of Microbacterium foliorum Bacteriophages StrawberryJamm, Quammi, Teehee, and Casend.
Four microbacteriophages infecting the host Microbacterium foliorum were isolated at Gonzaga University as part of the SEA-PHAGES program. Phages Teehee, StrawberryJamm, Quammi, and Casend are in the EG cluster, with average genome sizes of 62,263 bp and GC contents of 67.2%, with other interesting characteristics.


Effects of endocrine disrupting chemicals on in vitro global DNA methylation and adipocyte differentiation.
Recent studies suggest that endocrine disrupting chemicals (EDCs) may form a risk factor for obesity by altering energy metabolism through epigenetic gene regulation. The goal of this study is to investigate the effects of a range of EDCs with putative obesogenic properties on global DNA methylation and adipocyte differentiation in vitro. Murine N2A and human SK-N-AS neuroblastoma cells and murine preadipocyte fibroblasts (3T3-L1) were exposed to tributyltin (TBT), diethylstilbestrol (DES), bisphenol A (BPA), 2,3,7,8-tetrachlorodibenzo-[p]-dioxin (TCDD), 2,2',4,4',5,5'-hexachlorobiphenyl (PCB-153), hexachlorobenzene (HCB), hexabromocyclododecane (HBCD), 2,2',4,4'-tetrabrominated diphenyl ether (BDE-47) , perfluorinated octyl acid (PFOA) and perfluorinated octyl sulfonate (PFOS). A modest decrease in global DNA methylation was observed in N2A cells exposed to 10 μM DES, BPA, TCDD, BDE-47, PCB-153 and 1 μM HCB, but no changes were found in the human SK-N-AS cells. We reveal for the first time that BDE-47 increases adipocyte differentiation in a dose-dependent manner (2.5-25 μM). Adipocyte differentiation was also enhanced by TBT (≥ 10 nM) and BPA (>10 μM) and inhibited by TCDD (≥ 0.1 nM). The other chemicals showed either modest or no effects on adipocyte differentiation at the concentrations tested (PFOA, PFOS and HBCD at 10 μM; PCB-153, 3.4 μM and HCB, 1 μM). This study demonstrates that selected EDCs can induce functional changes in murine adipocyte differentiation in vitro which are accompanied by decreased global DNA methylation.


Manipulating the QT interval of the ECG by cognitive effort.
Abnormal prolongation of the QT interval of the ECG has been reported to indicate a hazard of sudden arrhythmic death. Therefore, with the aid of biofeedback from a newly devised instrument capable of measuring and recording the QT interval of the ECG in real time, ten healthy subjects, aided by biofeedback, attempted to shorten and also to lengthen QT. Although the changes achieved were relatively small, the ten subjects as a group were successful in both shortening and lengthening QT at the 0.01 level of significance. The degree of success varied, however, from person to person and from time to time in the same individual. If the findings reported here can be applied more generally to patients at risk for sudden death, and if biofeedback effects can be made to persist without reinforcement, it or other cognitive techniques may prove clinically useful for shortening QT.


Previous nonhepatectomy abdominal surgery did not increase the difficulty in laparoscopic hepatectomy for hepatocellular carcinoma: A case-control study in 100 consecutive patients.
Laparoscopic hepatectomy (LH) is still technically challenging for patients with previous nonhepatectomy abdominal surgery (AS). Therefore, this study aimed to assess the difficulty of performing LH for patients with hepatocellular carcinoma (HCC) and a history of nonhepatectomy AS during the initial developing period of LH. The retrospective study enrolled patients who were newly diagnosed with HCC receiving LH from January 2013 to June 2021. Demographic characteristics, perioperative variables, and surgical complications were prospectively collected. One hundred patients were reviewed consecutively, comprising 23 in the AS group and 77 in the non-AS group. No significant differences were observed in median IWATE score (5 vs. 5, P = 0.194), operative time (219 vs. 200 min, P = 0.609), blood loss (100.0 vs. 200.0 mL, P = 0.734), transfusion rate (4.3% vs. 10.4%, P = 0.374), duration of parenchyma transection (90.0 vs. 72.4 min, P = 0.673), and mean nonparenchymal transection time (191.0 vs. 125.0 min, P = 0.228), without increasing the conversion rate (0.0% vs. 3.9%, P = 0.336), postoperative complications (30.3% vs. 33.8%, P = 0.488), and postoperative hospital stay (6 vs. 7 days, P = 0.060) in AS group and non-AS groups. History of previous nonhepatectomy AS can lead to longer nonparenchymal transection time instead of conversion and did not increase the difficulty. Prolonged nonparenchymal transection time did not increase the surgical complications, prolong the postoperative hospital stay, and compromise the survival outcomes.


Insight into the characteristics and sorption behaviors of aged polystyrene microplastics through three type of accelerated oxidation processes.
Ageing process can significantly alter the structural properties, environmental behaviors and potential ecotoxicity of microplastics (MPs) in water. In this study, the structural properties of aged polystyrene (PS) MPs being exposed to UV/H2O, UV/H2O2 and UV/Cl2 artificially accelerated oxidation processes and related sorption behaviors of bisphenol A (BPA) on those virgin/aged PS were investigated. The surface oxidation and hydrophilicity of aged PS were significantly increased according to infrared spectroscopy (IR) and water contact angle (CA) measurements. The differential scanning calorimetric (DSC) and gel permeation chromatography (GPC) revealed apparent degradation of aged PS especially in their amorphous domain. Obviously deteriorative BPA sorption capacity on aged PS was observed compared with that of virgin PS. The sorption rates of BPA on aged PS were accelerated and sorption of BPA shifted from partition dominant mechanism on virgin PS to the adsorption dominant mechanism through being fitted with the dual-mode sorption model. Besides, ageing in UV/Cl2 system introduces C-Cl groups on the surface of PS which strengthen the combination with BPA through halogen bonding interaction. Salt and dissolved organic matters (DOM) in marine water may increase the BPA sorption on aged MPs due to enhanced polar interaction.


Genes for human U4 small nuclear RNA.
A study of human genes coding for U4 small nuclear RNA is presented. It is known from previous studies that mammalian cells contain three major U4 RNA species, designated U4A, U4B, and U4C (Krol and Branlant, 1981). A clone was isolated from a human DNA library which contained two transcriptionally active genes for U4 RNA. U4 transcription was sensitive to low concentrations of alpha-amanitin, inferring that U4 RNA is a product of RNA polymerase II or RNA polymerase II-like activity. One of the two genes contains a coding region which matches the sequence of U4C RNA perfectly. The coding region of the second gene resembles U4B RNA although there are two differences between the sequence of this gene and the U4B RNA sequence, suggesting that it may encode a minor, hitherto undetected U4 RNA species. The 5'-flanking regions of the two U4 genes contain several almost perfectly conserved sequence motifs. One is located between positions -50 and -60. This motif is present in equivalent positions in the two U4 genes as well as in human U1 and U2 genes. A second motif, which is 19 nucleotides (nt) long and centered around nt position -140, is present in the two U4 genes but absent from U2 RNA genes. A third highly conserved region, located between nt positions -210 and -250, is a putative enhancer element. It includes one copy of the so-called octanucleotide motif, previously identified as adjacent to the early SV40 promoter and immunoglobulin promoters. Another highly conserved sequence motif, CTCTGTGA, is located approximately one helical turn upstream from the octanucleotide motif in both U2 and U4 genes. The human genome appears to contain a family of U4 RNA genes comprising at least 100 copies.


Silencing of spinal Trpv1 attenuates neuropathic pain in rats by inhibiting CAMKII expression and ERK2 phosphorylation.
Accumulating evidence suggests a potential role of transient receptor potential vanilloid 1 (TRPV1) channels in inflammatory and cancer-related pain. However, the role of TRPV1 in the maintenance of neuropathic pain remains elusive. The current study investigated the effects of transient Trpv1 gene silencing using a small interference RNA (siRNA) on neuropathic pain induced by chronic constriction injury (CCI) of the sciatic nerve in rats. Seven days after CCI, the TRPV1 siRNA was intrathecally administered (5 µg/15 µl, once daily for 2 days). TRPV1 and Ca2+/calmodulin-dependent protein kinase II (CAMKII) expression and extracellular signal-regulated kinase (ERK) phosphorylation in the spinal cord were detected using western blotting. The thresholds to mechanical and thermal stimuli were determined before and after intrathecal TRPV1 siRNA administration. TRPV1 and CAMKII expression and ERK2 phosphorylation in the spinal cord were upregulated after CCI. Intrathecal administration of the TRPV1 siRNA not only attenuated behavioural hyperalgesia but also reduced the expression of TRPV1 and CAMKII, as well as ERK2 phosphorylation. Based on these results, silencing of the TRPV1 gene in the spinal cord attenuates the maintenance of neuropathic pain by inhibiting CAMKII/ERK2 activation and suggests that TRPV1 represents a potential target in pain therapy.


Optimizing medication adherence with home-monitoring - A feasibility study using capillary microsampling and mHealth in solid organ-transplanted adolescents.
Reliable methods to detect and reduce medication nonadherence in solid organ-transplanted (SOT) adolescents are warranted. We aimed to evaluate the feasibility of combining a medication-manager application (TusenTac®-app) with home-sampling of tacrolimus (Tac) in young SOT recipients. Kidney and combined SOT recipients between 14 and 25 years were included. During an 8-week intervention period, the participants were instructed to use the transplant-specific, age-adapted TusenTac®-app daily and to perform weekly at-home Tac trough finger-prick microsampling. Microsample Tac concentrations were controlled against timed venous samples twice. Medication implementation and persistence adherence were measured with BAASIS© questionnaires, TusenTac®-registrations, Tac trough concentration coefficient of variation (CV%) and self-reporting by interview. For comparison, venous Tac trough CV% were obtained from the year before and after the short-term intervention. Twenty-two recipients were included, two withdrawals, leaving 20; median age 17.9 (14.5-24.8) years, 12 females (60%). The participants registered their dosage intake 88% (1502/1703) of the expected times, and 90% (106/118) of the microsamples were obtained correctly. At inclusion, 11 recipients (55%) were nonadherent assessed with BAASIS© questionnaire, four of these (36%) turned adherent during the intervention period. At the end, 70% reported improved timing-adherence at the interview. There was no significant change in TacCV% from the year before to the year after the short-term intervention. Home-sampling was reliable and measured Tac concentrations accurately. Home-monitoring, combining Tac finger-prick microsampling and a medication-manager app, is feasible in adolescent SOT recipients with 70% perceived improvement in medication timing-adherence. There were no significant long-term changes in TacCV% confirming the need for continuous use and individualized interventions.


[Determination of cinnamic acid in rat plasma after oral administration of subing orally disintegrating tablets and study of its pharmacokinetics behavior].
To develop a RP-HPLC method for determination of cinnamic acid in rat plasma. The plasma samples were acidified with acetic acid and extracted with chloroform. Cinnamic acid was separated on a Kromasil C18 column (250 mm x 4.6 mm, 5 microm) eluted with a mobile phase of methanol-acetonitrile-water-glacial acetic acid (25:20:55:0.3) at a flow rate of 1.0 mL x min(-1) and room temperature with UV detection at 278 nm, carbamazepine as internal standard. The standard curve was linear over the range of 4.0 to approximately 400 ng x mL (-1) r = 0..99 9. The LOQ was 4.0 ng x mL(-1), the mean extraction recovery of the spiked samples at low, middle and high levels was 86.4%, while the mean method recovery was 100.3%. The RSD of intra-day and inter-day were both less than 6.0%. The method was sensitive, specific, accurate and precise, which was used to study the pharmacokinetic profile of cinnamic acid in rat plasma after oral administration of the Subing orally disintegrating tablets.


Erratum: Cooccurrence patterns of plants and soil bacteria in the high-alpine subnival zone track environmental harshness.
[This corrects the article on p. 347 in vol. 3, PMID: 23087675.].


The effect of a putative anti-atherosclerotic agent (S 1204) on lipid metabolism in rabbit aorta.
The effects of the novel fenfluramine derivative, S 1204 (meta-trifluoromethyl phenyl-1 [beta(sulfamyl-3'-chloro-4'-benzoyloxyethyl)]amino-2-propane) were studied on lipid metabolism in rabbit aorta and other tissues. Pretreatment of rabbits with S 1204 (50 mg/kg orally) for 10 days strongly inhibited the aortic incorporation of an intravenous 20 muCi tracer-dose of [4-(14)C]-cholesterol given 24 h earlier. However, incorporation of such cholesterol radioactivity into the liver, intestine, lung or plasma was not affected, in comparison with control animals. One hour after i.v. injection of a 100 muCi tracer-dose of [2-(14)C]acetate, S 1204 significantly reduced the radioactivity of total lipids in the aorta and liver. Such inhibition of acetate incorporation into arterial lipids was observed with all lipid fractions (that is, free fatty acids, esterified cholesterol, especially phospholipids, glycerides and free cholesterol). Incorporation of acetate into intestinal triglyceride fractions was also significantly decreased. The results indicate that S 1204 may have anti-atherogenic properties, which could be valuable in the clinical treatment of atherosclerosis.


Multiparametric Magnetic Resonance Imaging in the Diagnosis of Prostate Cancer: A Systematic Review.
A systematic review was conducted to investigate the use of multiparametric magnetic resonance imaging (MPMRI) followed by targeted biopsy in the diagnosis of clinically significant prostate cancer (CSPC) and to compare it with transrectal ultrasound-guided (TRUS-guided) systematic biopsy in patients with an elevated risk of prostate cancer who are either biopsy-naive or who have a previous negative TRUS-guided biopsy. MEDLINE, PubMed and EMBASE (1997 to April 2014), the Cochrane Library and six relevant conferences were searched to find eligible studies. Search terms indicative of 'prostate cancer' and 'magnetic resonance imaging' with their alternatives were used. Twelve systematic reviews, 52 full texts and 28 abstracts met the preplanned study selection criteria; data from 15 articles were extracted. In patients with an elevated risk of prostate cancer who were biopsy-naive, MPMRI followed by targeted biopsy could detect 2-13% of CSPC patients whom TRUS-guided systematic biopsy missed; TRUS-guided systematic biopsy could detect 0-7% of CSPC patients whom MPMRI followed by targeted biopsy missed. In patients with an elevated risk of prostate cancer who had a previous negative TRUS-guided biopsy, MPMRI followed by targeted biopsy detected more CSPC patients than repeated TRUS-guided systematic biopsy in all four studies, with a total of 516 patients, but only one study reached a statistically significant difference. In patients with an elevated risk of prostate cancer who are biopsy-naive, there is insufficient evidence for MPMRI followed by targeted biopsy to be considered the standard of care. In patients who had a prior negative TRUS-guided systematic biopsy and show a growing risk of having CSPC, MPMRI followed by targeted biopsy may be helpful to detect more CSPC cases as opposed to a repeat TRUS-guided systematic biopsy.


Sex differences in clinical characteristics and outcomes in patients undergoing heart transplantation.
Whether sex affects selection for and outcomes after heart transplantation (HTx) remains unclear. We aimed to show sex differences in pre-transplant characteristics and outcomes after HTx. From 1995 to 2019, 49 200 HTx recipients were prospectively enrolled in the Organ Procurement and Transplantation Network. Logistic regression models were used to evaluate clinical characteristics by sex. Multivariable Cox regression models were fitted to assess sex differences in all-cause mortality, cardiovascular mortality, graft failure, cardiac allograft vasculopathy (CAV), and malignancy. In 49 200 patients (median age 55 years, interquartile range 46-62; 24.6% women), 49 732 events occurred during a median follow-up of 8.1 years. Men were older than women, had more often ischaemic cardiomyopathy (odds ratio [OR] 3.26, 95% confidence interval [CI] 3.11-3.42; P < 0.001), and a higher burden of cardiovascular risk factors, whereas women had less malignancies (OR 0.47, CI 0.44-0.51; P < 0.001). Men were more often treated in intensive care unit (OR 1.24, CI 1.12-1.37; P < 0.001) with a higher need for ventilatory (OR 1.24, CI 1.17-1.32; P < 0.001) or VAD (OR 1.53, CI 1.45-1.63; P < 0.001) support. After multivariable adjustment, men had a higher risk for CAV (hazard ratio [HR] 1.21, CI 1.13-1.29; P < 0.001) and malignancy (HR 1.80, CI 1.62-2.00; P < 0.001). There were no differences in all-cause mortality, cardiovascular mortality, and graft failure between sexes. In this US transplant registry, men and women differed in pre-transplant characteristics. Male sex was independently associated with incident CAV and malignancy even after multivariable adjustment. Our results underline the need for better personalized post-HTx management and care.


Adjuvant Postoperative Radiotherapy with or without Chemotherapy for Locally Advanced Squamous Cell Carcinoma of the Head and Neck: The Importance of Patient Selection for the Postoperative Chemoradiotherapy.
We wanted to evaluate the role of postoperative chemoradiotherapy (CRT) for patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). From March 1993 to July 2008, 101 patients with advanced SCCHN and who had undergone macroscopically complete resection were enrolled. Survival and the cumulative incidence of local or regional relapse, metastasis, and acute toxicity were analyzed. There was a marginally significant difference of disease-free survival at five years in favor of the CRT arm (51.3% vs. 41.8%, respectively; p=0.10). However, there was no significant difference in overall survival between the two treatment arms (p=0.20). The rate of locoregional failure only for the radiotherapy arm was significantly higher than that for the CRT arm (23.2% vs. 4.4%, respectively; p=0.01). The incidence of grade 3 or 4 hematologic toxicity was significantly higher in the CRT arm than that in the radiotherapy arm (37.7% vs. 1.7%, respectively; p=0.01). In CRT arm, early mortality group within 1 year had low performance status and old age over sixty compared with those of the others. After curative-intent surgery, adjuvant CRT is more effective in locoregional tumor control than radiotherapy alone for patients with advanced SCCHN. However, compared with radiotherapy alone, this combined modality treatment had no survival benefit, and was significantly associated with increased toxicity. Thus, patients with low performance status and old age must be cautious in selection of toxic trimodality treatment.


Determination of interchain crosslinkages in insulin B-chain dimers by fast atom bombardment mass spectrometry.
New methodology for identifying and locating crosslinkages in peptides is described. Pepsin is used to cleave insulin and B-chain dimers of insulin into fragments under conditions which retain the original peptide crosslinkages. After partial separation by HPLC, the peptides are analyzed by fast atom bombardment mass spectrometry (FABMS) to determine their molecular weights. The molecular weights of peptide fragments expected from the pepsin digests of human insulin and related model compounds are calculated from the amino acid sequence of the intact peptide. Digestion products are identified by matching their molecular weights, as determined by FABMS, with calculated molecular weights. Locations of interchain crosslinkages are deduced after the peptide fragments have been assigned to specific segments of the parent peptide. The validity of the method has been established by correctly identifying structurally important products in the pepsin digests of model compounds such as human, bovine, and porcine insulins. Procedures developed with the model compounds were used to identify crosslinkages in peptides of unknown structure isolated from an insulin A-chain/B-chain combination reaction mixture. Evidence is presented for formation of three different types of crosslinkages, disulfide, lanthionine, and sulfoxide.


Genetic characterization of non-5q proximal spinal muscular atrophy in a French cohort: the place of whole exome sequencing.
Proximal spinal muscular atrophy (SMA) is defined by a degeneration of the anterior horn cells resulting in muscle weakness predominantly in the proximal lower limbs. While most patients carry a biallelic deletion in the SMN1 gene (localized in chromosome 5q), little is known regarding patients without SMN1-mutation, and a genetic diagnosis is not always possible. Here, we report a cohort of 24 French patients with non-5q proximal SMA from five neuromuscular centers who all, except two, had next-generation sequencing (NGS) gene panel, followed by whole exome sequencing (WES) if gene panel showed a negative result. The two remaining patients benefited directly from WES or whole genome sequencing (WGS). A total of ten patients with causative variants were identified, nine of whom were index cases (9/23 families = 39%). Eight variants were identified by gene panel: five variants in DYNC1H1, and three in BICD2. Compound heterozygous causative variants in ASAH1 were identified directly by WES, and one variant in DYNC1H1 was identified directly by WGS. No causative variant was found using WES in patients with a previous panel with negative results (14 cases). We thus recommend using primarily NGS panels in patients with non-5q-SMA and using WES, especially when several members of the same family are affected and/or when trio analyses are possible, or WGS as second-line testing if available.


Acute sodium arsenite treatment induces Cyp2a5 but not Cyp1a1 in the C57Bl/6 mouse in a tissue (kidney) selective manner.
Modulation of hepatic and extrahepatic detoxication enzymes Cyp1a1, Cyp2a5, glutathione S-transferse Ya (GSTYa) and NAD(P)H:quinone oxidoreductase (QOR) dependent catalytic activity and mRNA levels were investigated at 1, 2, or 4 days in liver, lung, or kidney of male, adult CD57 Bl/6 mice treated sc with a single dose (85 micromol/kg) of sodium arsenite (As3+). Maximum decreases of total hepatic cytochrome P450 (CYP) monooxygenase content and catalytic activities, occurring at 24 h, corresponded with maximum increases of heme oxygenase (HO-1) in all tissues, as well as maximum plasma total bilirubin. Extrahepatic increases in CYP were observed only in non-AHR dependent isozymes in the kidney, where both Cyp2a5 mRNA and catalytic activity increased maximally 24 h after treatment. In contrast, no significant changes in Cyp2b1/2-dependent PROD or mRNA activity and decreases in Cyp1a1-dependent-EROD activity were noted 1, 2, or 4 days after treatment. Increases in QOR catalytic activities were observed in all tissues examined with increased mRNA in kidney. On the other hand, GSTYa catalytic activity and mRNA increases were only detected in kidney. This study demonstrates the differential modulation of CYP, QOR, and GST-Ya, important drug metabolizing enzymes after acute As3+ administration. The induction of Cyp2a5, QOR, and GSTYa catalytic activity and gene expression occurred primarily in kidney during or shortly after conditions of oxidant stress.


Effect of high ovarian response on the expression of endocrine gland-derived vascular endothelial growth factor (EG-VEGF) in peri-implantation endometrium in IVF women.
To investigate the effect of ovarian stimulation on the expression of EG-VEGF mRNA and protein in peri-implantation endometrium in women undergoing IVF and its relation with endometrial receptivity (ER). Prospective laboratory study. University hospital. Eighteen women in stimulated cycles (SC) as study subjects and 18 women in natural cycles (NC) as controls. Women in SC group were classified with two subgroups, high ovarian response (SC1, n=9) with peak serum E2>5,000 pg/mL and moderate ovarian response (SC2, n=9) with peak serum E2 1,000-5,000 pg/mL. Endometrial biopsies were collected 6 days after ovulation in NC or after oocyte retrieval in SC. Endometrium histological dating was observed with HE staining. EG-VEGF mRNA expression levels determined by real-time polymerase chain reaction analysis, and protein levels by immunohistochemistry. All endometrial samples were in the secretory phase. The endometrial development in SC1 was 1 to 2 days advanced to NC, and with dyssynchrony between glandular and stromal tissue. Immunohistochemistry analysis showed that EG-VEGF protein was predominantly expressed in the glandular epithelial cells and endothelial cells of vessels, and also presented in the stroma. The image analysis confirmed that both the gland and stroma of endometrium in SC1 had a significantly lower EG-VEGF protein expression than that in SC2 and NC endometrium. Moreover, EG-VEGF mRNA levels were significantly lower in SC1 than in NC. Both EG-VEGF protein and mRNA levels had no significant difference between SC2 and NC. Decreased expression of EG-VEGF in the peri-implantation is associated with high ovarian response, which may account for the impaired ER and lower implantation rate in IVF cycles.


Compliance with the north American Society of Pacing and Electrophysiology guidelines on amiodarone monitoring in Riyadh, Saudi Arabia: a retrospective charts review study.
Amiodarone is known for its efficacy as an antiarrhythmic agent; however, its extensive side-effect profile requires careful selection of patients and frequent monitoring. The purpose of this study was to evaluate the performance of the baseline tests before initiating amiodarone therapy and the on-going monitoring based on the North American Society of Pacing and Electrophysiology guidelines recommendations. A retrospective descriptive charts review study included all patients who are 18 years of age and older and were started on oral amiodarone with a primary diagnosis of any type of cardiac arrhythmia from January 2016 to December 2018 in King Abdualziz Medical City, Riyadh, Saudi Arabia. The medical charts were reviewed and evaluated based on the performance of the recommended baseline and follow-up of chest X-ray (CXR), liver function test (LFT), thyroid function test (TFT) and electrocardiogram (ECG). The continuous variables were analyzed and presented as mean ± SD and the categorical variables were presented as percentages. Over the study period, 143 eligible participants on amiodarone therapy were included, with an average of 165 ± 207 days on amiodarone. Of patients, 36.4% had the entire recommended baseline assessments before initiating amiodarone. Our results indicated optimal compliance rates to the baseline tests of CXR (79.7%), LFT (79.7%) and ECG (86.7%). However, there was a lower compliance rate to TFT recommendations (40.6%). The compliance rate to the guideline recommendations related to the follow-up tests was minimal. On-going monitoring performance rates were 47.6% of CXR, 49% of LFT, 54.5% of ECG and 22.4% of TFT. The compliance with the guideline recommendations related to amiodarone baseline assessments was optimal for all the baseline tests, except for TFT. However, the proportion of patients who received all the recommended baseline assessments was minimal. In addition, the performance of on-going monitoring was suboptimal for all the follow-up tests. Improvements could be made by establishing a local protocol for amiodarone monitoring and pharmacists participating in amiodarone therapy assessments.


J. G. Hierzel: a lip-switch flap in 1756.
After reviewing the historical aspects of the various lip-switch flaps, the authors draw attention to the existence of a report of a lip-switch flap performed in Sweden in 1756 by J.G.Hierzel.


Commercial head-mounted display virtual reality for upper extremity rehabilitation in chronic stroke: a single-case design study.
Rehabilitation is crucial for maximizing recovery after stroke. Rehabilitation activities that are fun and rewarding by themselves can be more effective than those who are not. Gamification with virtual reality (VR) exploits this principle. This single-case design study probes the potential for using commercial off-the-shelf, room-scale head-mounted virtual reality for upper extremity rehabilitation in individuals with chronic stroke, the insights of which can inform further research. A heterogeneous volunteer sample of seven participants living with stroke were recruited through advertisement. A single-case design was employed with a 5-week baseline (A), followed by a 10-week intervention (B) and a 6-month follow-up. Upper extremity motor function was assessed with validated kinematic analysis of drinking task. Activity capacity was assessed with Action Research Arm Test, Box and Block Test and ABILHAND questionnaire. Assessments were done weekly and at follow-up. Playing games on a VR-system with head-mounted display (HTC Vive) was used as rehabilitation intervention. Approximately 300 games were screened and 6 tested. Visual analysis and Tau-U statistics were used to interpret the results. Visual analysis of trend, level shift and overlap as well as Tau-U statistics indicated improvement of Action Research Arm Test in six participants. Four of these had at least a moderate Tau-U score (0.50-0.92), in at least half of the assessed outcomes. These four participants trained a total of 361 to 935 min. Two out of four participants who were able to perform the drinking task, had the highest training dose (> 900 min) and showed also improvements in kinematics. The predominant game played was Beat Saber. No serious adverse effects related to the study were observed, one participant interrupted the intervention phase due to a fall at home. This first study of combining commercial games, a commercial head-mounted VR, and commercial haptic hand controls, showed promising results for upper extremity rehabilitation in individuals with chronic stroke. By being affordable yet having high production values, as well as being an easily accessible off-the-shelf product, this variant of VR technology might facilitate widespread adaption. Insights garnered in this study can facilitate the execution of future studies. Trial registration The study was registered at researchweb.org (project number 262331, registered 2019-01-30, https://www.researchweb.org/is/vgr/project/262331 ) prior to participant enrolment.


Mild course of fetal RhD haemolytic disease due to maternal alloimmunisation to paternal HLA class I and II antigens.
The patient is a pregnant women of African origin with a prior history of spontaneous abortion and newborn dystrophy. The investigation showed an anti-Rh D antibody (IgG isotypes 1 and 3) with an indirect antiglobulin tube test (IAT) titre of 1:512. The monocyte monolayer assay (MMA) proved clearly the interaction of Fc receptors with the maternal anti-D, and so a clinical significance was expected. In spite of this, no signs of severe haemolysis in the Rh-D-positive and direct antiglobulin test-positive fetus could be observed. Furthermore, two HLA class I and II alloantibodies (anti-A10, anti-DR13) directed against paternal and fetal antigens were detected in the serum of the gravida. Both antibodies showed an inhibitory effect on the in vitro phagocytosis capacity of mononuclear cells expressing at least one of the corresponding HLA antigens (immunophagocytosis inhibition (IPI) test). Thus, the mild course of haemolytic disease may be explained by an effective inhibition of the fetal mononuclear phagocyte system by maternal HLA class I and/or class II antibodies resulting in a diminished destruction of anti-D-coated fetal red blood cells.


Failure of glucose to affect 86rubidium efflux and 45calcium uptake of fetal rat pancreatic islets.
Ion movements and insulin secretion of pancreatic islets of adult and fetal rats have been studied at three glucose concentrations. In islets of adult rats, 86Rb efflux is maximally decreased by 5.6 mM-glucose. 16.7 mM-glucose caused a biphasic efflux pattern which may be due to glucose-stimulated Ca uptake. In islets of fetal rats elevation of the glucose concentration from 3 to 5.6 or 16.7 mM does not cause a change of 86Rb efflux, and the fractional efflux from fetal islets in the presence of 3 mM-glucose is similar to that from adult rat islets in the presence of 5.6 mM-glucose. Elevation of the glucose concentration from 3 to 16.7 mM is not associated with an increase in 45Ca uptake into fetal islets, although this change in glucose concentration doubles 45Ca uptake into adult islets. When challenged with 16.7 mM-glucose, fetal islets exhibit no insulin secretory response; however, they do respond to theophylline. It is concluded that the failure of fetal islets to exhibit an insulin-secretory response when challenged with glucose might be related to the inability of glucose to affect 86Rb efflux and Ca uptake. The present data are discussed in light of differences between pancreatic islets of fetal and adult rats with respect to the redox state of pyridine nucleotides, thiols and glucose metabolism.


Fluoroscopic Technique for Open Reduction and Internal Fixation of Proximal Humeral Fracture Using the Proximal Humeral Locking Plate: Proposal of "Plate" and "Screw" Views.
Proximal humeral fractures are common injuries with increasing incidence, particularly in the aging population. Nondisplaced or minimally displaced fractures can be treated conservatively whereas surgical fixation is usually indicated in the cases of displaced fractures. Various surgical options have been used for treatment of these fractures. Good outcomes have been reported with use of the Proximal Humeral Internal Locking System (PHILOS plate; Synthes, Zuchwil, Switzerland) as the implant of choice. However many complications have been reported, including varus malalignment, excessive retroversion of the articular part of the humerus, penetration of screws, and avascular necrosis of the humeral head. Therefore, we have hypothesized that an inadequate intraoperative fluoroscopic assessment may be an important factor contributing to these complications. We have described a step-by-step intraoperative fluoroscopic setup, including the proposal of a plate and screw view, focusing on the accuracy of reduction and proper placement of the PHILOS plate to prevent the complications previously described.


Posterior nasal septal abscess in a healthy adult patient.
We report an extremely rare case of bilateral posterior nasal septal abscess in an otherwise healthy adult patient. Case report and a review of the world literature concerning atraumatic nasal septal abscess and its management. The development of an atraumatic nasal septal abscess is rare, but it has been reported in association with acute sinusitis, in patients with poor immunity and in children. The presentation, clinical course and treatment are discussed in the presented patient. To our knowledge, this is the first report in the world literature of a bilateral posterior septal abscess associated with acute sinusitis in an otherwise healthy adult.


Studies on the assembly of a leucine zipper antibacterial peptide and its analogs onto mammalian cells and bacteria.
Membrane-interaction and assembly of a leucine zipper peptide (LZP), and its single (SASA) and double (DASA) alanine-substituted analog onto mammalian, hRBCs and 3T3 cells and bacteria, Escherichia coli and Staphylococcus aureus were studied as a model system to understand the plausible role of assembly on their contrasting cytotoxic but similar bactericidal activities. Peptides' ability to depolarize and damage the membrane organization of hRBC and 3T3 cells decreased from LZP to SASA and to DASA which may be related to their decrease in assembly onto these mammalian live cells and oligomerization states in the presence of these cell membranes or zwitterionic PC/Chol lipid vesicles. However, LZP and its analogs showed appreciable similarities in damaging or depolarizing the E. coli or S. aureus cells, which further matched with their comparable assembly and oligomerization either onto these live cells or the cell membranes or in the presence of negatively charged PC/PG lipid vesicles.


Changes in the concentration of cortisol in amniotic fluid after intra-amniotic prostaglandin for midtrimester abortion.
The effects of intra-amniotic prostaglandin E2 (PGE2) and PGF2alpha on the concentration of cortisol in amniotic fluid and in maternal peripheral plasma of patients undergoing abortion between 16 and 23 weeks gestation have been examined. There was a significant (P less than 0-01) increase in the concentration of cortisol in amniotic fluid for hours after PGE2, but not after PGF2alpha. The concentration of cortisol in the maternal peripheral plasma increased in both groups with the progression of abortion, but the levels were not significantly correlated with those in amniotic fluid. These results suggest that by mid-pregnancy fetal cortisol production can be stimulated by PGE2 but the mechanism of this action remains to be elucidated.


RIFM fragrance ingredient safety assessment, α-butylcinnamaldehyde, CAS Registry Number 7492-44-6.
The use of this material under current use conditions is supported by the existing information. This material was evaluated for genotoxicity, repeated dose toxicity, developmental toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity, skin sensitization potential, as well as, environmental safety. Repeated dose toxicity was determined to have the most conservative systemic exposure derived NO[A]EL of 29.9 mg/kg/day. A dietary 14-week subchronic toxicity study conducted in rats on a suitable read across analog resulted in a MOE of 3784810 while considering 9.54% absorption from skin contact and 100% from inhalation. A MOE of > 100 is deemed acceptable.


Color M-mode regurgitant flow propagation velocity: a new echocardiographic method for grading of mitral regurgitation.
The aim of this study was to evaluate the reliability of mitral regurgitation color M-mode regurgitant flow propagation velocity (RFPV) in grading mitral regurgitation (MR). We prospectively examined 52 consecutive patients with grades of MR mild in 10 patients, moderate in 19 patients, and severe in 23 patients with quantitative pulse Doppler echocardiography. MR was evaluated by vena contracta diameter (VCD), regurgitant jet area (RJA), and RFPV. These qualitative and quantitative methods were compared with the pulsed Doppler quantitative flow measurements and concordance of these three methods was determined. The mean RFPV for mild, moderate, and severe MR were 26.4 +/- 7 cm/sec, 43.3 +/- 7 cm/sec, and 60.3 +/- 7.3 respectively (P < 0.001). RFPV is highly sensitive and moderately specific in differentiating mild and severe MR from other subgroups. Sensitivity and specificity were 92.1%-64.3% for mild and 100%-68.5% for severe MR, respectively. Significant correlation was observed between pulse Doppler quantitative grades, RFPV, VC, and RJA (P < 0.0001, r = 0.87; P < 0.0001, r = -0.84; P < 0.0001, r = 0.76, respectively). This results show that RFPV is a reliable and simple semiquantitative new method that can be used for determining severity of MR.


Effects of clogging on ultrasonic transmission through saturated granular single and double porosity media.
The clogging caused by the deposition of suspended particles modifies in depth several mechanical parameters (permeability, porosity, bulk moduli, etc.) of porous media and influences the acoustic behaviour. Consequently, at a fixed position in the medium, changes in phase velocity and attenuation are observed in the amplitude of the temporal signal of the transmitted waves. In this work, ultrasonic techniques are presented both for detecting and measuring the clogging in a water saturated porous medium. The acoustic measurements from the clogged samples are compared with the deposition profiles obtained at the end of injection experiments. Moreover, links are established between on the one hand phase velocity and the total porosity, and on the other hand the transmitted signal energy and the variation of porosity as consequence of particle deposition.


Screening of CNVs using NGS data improves mutation detection yield and decreases costs in genetic testing for hereditary cancer.
Germline CNVs are important contributors to hereditary cancer. In genetic diagnostics, multiplex ligation-dependent probe amplification (MLPA) is commonly used to identify them. However, MLPA is time-consuming and expensive if applied to many genes, hence many routine laboratories test only a subset of genes of interest. We evaluated a next-generation sequencing (NGS)-based CNV detection tool (DECoN) as first-tier screening to decrease costs and turnaround time and expand CNV analysis to all genes of clinical interest in our diagnostics routine. We used DECoN in a retrospective cohort of 1860 patients where a limited number of genes were previously analysed by MLPA, and in a prospective cohort of 2041 patients, without MLPA analysis. In the retrospective cohort, 6 new CNVs were identified and confirmed by MLPA. In the prospective cohort, 19 CNVs were identified and confirmed by MLPA, 8 of these would have been lost in our previous MLPA-restricted detection strategy. Also, the number of genes tested by MLPA across all samples decreased by 93.0% in the prospective cohort. Including an in silico germline NGS CNV detection tool improved our genetic diagnostics strategy in hereditary cancer, both increasing the number of CNVs detected and reducing turnaround time and costs.


High prevalence of hepatitis B virus genotype C/C1 in the Minangkabau ethnic group in Indonesia.
The Minangkabau is one of the major ethnic groups in Indonesia. Previous studies with a limited number of samples have shown a different prevalence of HBV/C in the Minangkabau compared to the Indonesian population in general. The aim of this study was to assess the HBV genotype distribution pattern and the prevalence of pre-S, T1753V and A1762T/G1764A mutations among the Minangkabau HBV carriers. The samples were collected from Padang, West Sumatera and from western Java. Mixed primers for specific genotypes were used to determine the HBV genotype. Pre-S or S genes were amplified, sequenced and aligned with reference sequences from GenBank to derive a phylogenetic tree for subgenotyping. Pre-S genes were also analyzed for mutations. The basal core promoter (BCP) region was amplified and directly sequenced to analyze T1753V and A1762T/G1764A mutations. The predominant HBV genotype among the Minangkabau HBV carriers (n=117) was C (72.6%) followed by B (24.8%) and co-infection with B and C (2.6%). The prevalence of pre-S mutations, including both the pre-S deletion and pre-S2 start codon mutation, was 41.0%, and the T1753V and A1762T/G1764A mutations were found in 51.9% and 71.2% respectively. HBV/C1 was the predominant HBV subgenotype in the Minangkabau HBV carriers, and was found in 66.2%, followed by B3, B7, C8, B2, B9, C2, and C10 (18.3%, 7.0%, 2.8%, 1.4%, 1.4%, 1.4%, and 1.4% respectively). From samples that were found to be co-infected with HBV B and C, two samples were successfully cloned and subgenotyped, including one with mixed subgenotypes of B3 and C1, and another one with mixed subgenotypes of B7, C1, putative intergenotypic of B/A, and C/A. Furthermore, three samples from donors of non-Minangkabau ethnicity from Padang were found to be infected with an intragenotypic recombination form, including a putative recombinant of B8/B3 and B9/B7. HBV/C with subgenotype C1 was the predominant HBV genotype among HBV carriers of Minangkabau ethnicity. The prevalence of pre-S, A1762T/G1764A, and T1753V mutations was higher among the Minangkabau compared to Indonesian HBV carriers in general.


Oxygen-Embedded Quinoidal Acene Based Semiconducting Chromophore Nanoprobe for Amplified Photoacoustic Imaging and Photothermal Therapy.
Photoacoustic (PA) imaging as a noninvasive biomedical imaging technology exhibits high spatial resolution and deep tissue penetration for in vivo imaging. In order to fully explore the potential of PA imaging in biomedical applications, new contrast agents with improved PA stability and efficiency are in high demand. Herein, we present a new PA agent based on an oxygen-embedded quinoidal nonacene chromophore that is self-assembled into nanoparticles (Nano(O-Nonacene)-PEG), assisted by polyethylene glycol (PEG). Notably, the photothermal conversion efficiency of Nano(O-Nonacene)-PEG is 1.5 fold that of semiconducting polymer nanoparticles (Nano(PCPDTBT)-PEG) and 2.8 fold that of Au nanorods, owing to the low quantum yield of Nano(O-Nonacene)-PEG. Thereby, Nano(O-Nonacene)-PEG possess a greatly elevated PA signal intensity, compared to Nano(PCPDTBT)-PEG and Au nanorods, which have been widely explored for PA imaging. Due to the high resistance to photo bleaching, Nano(O-Nonacene)-PEG exhibits higher PA signal stability, which may be employed for long-term PA imaging. Moreover, when magnetic Zn0.4Fe2.6O4 nanoparticles are incorporated into Nano(O-Nonacene)-PEG, not only are magnetic resonance signals generated but also the photoacoustic efficacy is greatly enhanced. Therefore, Nano(O-Nonacene)-PEG offers distinct properties: (i) the elevated photoacoustic effect allows for high-resolution photoacoustic imaging, (ii) small size (10 nm in diameter) results in efficient tumor-targeting, and (iii) the facile application of efficient photothermal therapy in vivo. The current work offers the possibility of oxygen-embedded quinoidal acene as a promising PA probe for precision phototheranostics.


Low-dose oral caffeine induces a specific form of behavioral sensitization in rats.
The present study assessed the effects of a low dose of orally administered caffeine on sensitization of open-field behavior in rats. Rats had free access to untreated water every day or water containing 0.2 mg/ml of caffeine every other day of the 14-day experiment. On alternate days discrete movements (horizontal and vertical) and ambulatory distance were measured in open-field activity monitors. Although caffeine intake significantly decreased across test sessions in caffeine-treated rats, the number of discrete horizontal movements significantly increased. These findings suggest that low doses of orally administered caffeine induce a specific form of behavioral sensitization in rats.


CBX7 deficiency plays a positive role in dentin and alveolar bone development.
To clarify the role of CBX7 deficiency in dentin and alveolar bone development, the dental and mandibular phenotypes of homozygous CBX7-knockout (CBX7(-/-)) mice were compared with their wild-type (WT) counterparts at 3 weeks age. In contrast to WT littermates, dental volume and dentin sialoprotein-positive area were significantly increased, whereas the area ratio of predentin to dentin was decreased markedly in CBX7(-/-) mice. Mineral density, cortical thickness, alveolar bone volume, type I collagen and osterix-immunopositive area, osteoblast number and activity, protein expression and mRNA level of Runt-related transcription factor 2 (Runx2), alkaline phosphatase, osteocalcin, osteopontin and bone morphogenetic protein 2 (BMP2) were all remarkably increased, while osteoclast number and activity, and mRNA expression ratio of NF-κB ligand (RANKL) to osteoprotegerin (opg) were all decreased significantly in the alveolar bone of CBX7(-/-) mice compared with their WT counterparts. Moreover, proliferating cell nuclear antigen (PCNA)-positive cells were found more in Hertwig' s epithelial root sheath of CBX7(-/-) mice, and their protein level of cyclin E1, cyclin-dependent kinase 2 (CDK2) were correspondingly increased in contrast to WT mice. Taken together, these results of this study suggest that CBX7 deficiency plays a positive role in dentin and alveolar bone formation.


Sulfatases are determinants of alveolar formation.
Alveolar formation or alveolarization is orchestrated by a finely regulated and complex interaction between growth factors and extracellular matrix proteins. The lung parenchyma contains various extracellular matrix proteins including proteoglycans, which are composed of glycosaminoglycans (GAGs) linked to a protein core. Although GAGs are known to regulate growth factor distribution and activity according to their degree of sulfation the role of sulfated GAG in the respiratory system is not well understood. The degree of sulfation of GAGs is regulated in part, by sulfatases that remove sulfate groups. In vertebrates, the enzyme Sulfatase-Modifying Factor 1 (Sumf1) activates all sulfatases. Here we utilized mice lacking Sumf1(-/-) to study the importance of proteoglycan desulfation in lung development. The Sumf1(-/-) mice have normal lungs up until the onset of alveolarization at post-natal day 5 (P5). We detected increased deposition of sulfated GAG throughout the lung parenchyma and a decrease in alveolar septa formation. Moreover, stereological analysis showed that the alveolar volume is 20% larger in Sumf1(-/-) as compared to wild type (WT) mice at P10 and P30. Additionally, pulmonary function test was consistent with increased alveolar volume. Genetic experiments demonstrate that in Sumf1(-/-) mice arrest of alveolarization is independent of fibroblast growth factor signaling. In turn, the Sumf1(-/-) mice have increased transforming growth factor β (TGFβ) signaling and in vivo injection of TGFβ neutralizing antibody leads to normalization of alveolarization. Thus, absence of sulfatase activity increases sulfated GAG deposition in the lungs causing deregulation of TGFβ signaling and arrest of alveolarization.


Reduced cerebral blood flow but intact reactivity to hypercarbia and hypoxia following subarachnoid hemorrhage in rabbits.
Subarachnoid hemorrhage (SAH) was produced in rabbits by four subarachnoid injections of blood (n = 7) or saline (n = 6); a control group (n = 6) had no injections. Basilar artery vasospasm was assessed by serial angiograms. Resting CBF (microspheres) and CBF reactivity to hypercapnia (65 and 85 mm Hg) and hypoxia (fractions of inspired oxygen of 0.15 and 0.10) were determined. Basilar artery vasospasm was seen with SAH. Resting CBF was reduced by 31% (SAH 43 +/- 12, saline 65 +/- 17, control 60 +/- 21 ml 100 g-1 min-1), and resting cerebrovascular resistance was increased (SAH 1.84 +/- 0.30, saline 1.31 +/- 0.49, control 1.39 +/- 0.25 mm Hg ml-1 100 g-1 min-1) after SAH. CBF rose to a similar degree in all three groups in response to hypercarbia and hypoxia. We conclude that resting CBF is reduced in this model of SAH, but vascular reactivity remains intact.


CT and MR imaging of laryngeal metastasis from renal cell carcinoma: A case report.
Laryngeal metastasis is an extremely rare condition. To the best of our knowledge, there has been no previous report on a laryngeal metastasis from renal cell carcinoma, which describes on details of the CT and MR imaging findings. A male patient in his 80s. Laryngoscopy revealed reddish-colored masses in the right false vocal cord and in the subglottic larynx. CT and MR imaging of this case showed multiple hypervascularized lesions with a wash-out effect in the supra and subglottis of the larynx and in the right intervertebral foramen of the cervical spine. Angiography revealed a hypervascular tumor consistent with the subglottic lesion. The histopathology and immunohistochemistry findings were compatible with laryngeal metastasis from renal clear cell carcinoma. A history of postoperative renal clear cell carcinoma about 7 years ago was later confirmed, which was not stated at the time of the initial imaging evaluation. It is a possible differential diagnosis in cases of multiple hypervascular masses in the head and neck region with a history of renal carcinoma. In particular, if the contrast-enhancement pattern of the lesion on the dynamic CT is similar to that of renal cell carcinoma. It is also important to reconfirm the patient's medical history, including postoperative status.


Near-infrared fluorophore IR-61 delays postovulatory aging of mouse oocytes through suppressing oxidative stress mediated by mitochondrial protection.
Postovulatory aging can trigger deterioration of oocyte quality and subsequent embryonic development, and thus reduce the success rates of assisted reproductive technology (ART). The molecular mechanisms underlying postovulatory aging, and preventative strategies, remain to be explored. The near-infrared fluorophore IR-61, a novel heptamethine cyanine dye, has the potential for mitochondrial targeting and cell protection. In this study, we found that IR-61 accumulated in oocyte mitochondria and reduced the postovulatory aging-induced decline in mitochondrial function, including mitochondrial distribution, membrane potential, mtDNA number, ATP levels, and mitochondrial ultrastructure. In addition, IR-61 rescued postovulatory aging-caused oocyte fragmentation, defects in spindle structure, and embryonic developmental potential. RNA sequencing analysis indicated that the postovulatory aging-induced oxidative stress pathway might be inhibited by IR-61. We then confirmed that IR-61 decreased the levels of reactive oxygen species and MitoSOX, and increased GSH content in aged oocytes. Collectively, the results indicate that IR-61 may prevent postovulatory aging by rescuing oocyte quality, promoting successful rate in ART procedure.


Psychometric properties of the Spanish Human System Audit Short-Scale of transformational leadership.
The aim of this research is to examine the psychometric properties of a Spanish version of the Human System Audit transformational leadership short-scale (HSA-TFL-ES). It is based on the concept of Bass developed in 1985. The HSA-TFL is a part of the wider Human System Audit frame. We analyzed the HSA-TFL-ES in five different samples with a total number of 1,718 workers at five sectors. Exploratory Factor Analysis corroborated a single factor in all samples that accounted for 66% to 73% of variance. The internal consistency in all samples was good (alpha = .92 - .95). Evidence was found for the convergent validity of the HSA-TFL-ES and the Multifactor Leadership Questionnaire. These results suggested that the HSA-TFL short-scale is a psychometrically sound measure of this construct and can be used for a combined and first overall measurement.


Monospecific renaming within the cyanobacterial genus Limnospira (Spirulina) and consequences for food authorization.
The cyanobacterial genus, Limnospira (anc. Arthrospira Stizenberger ex Gomont 1892), commonly called "Spirulina", is widely used for commercial purposes because of its high protein content and beneficial probiotic metabolites. Thus, the taxonomy of this genus is important because of its consequences for food applications. We constructed a database with formation on all Limnospira strains plus new ones from 72 new French isolates. We used a polyphasic approach (phylogenetic, phylogenomic, presence or absence of coding DNA sequences, morphological, and ultrastructure analyses) to confirm that the species A. platensis belonged to the genus Limnospira (L. platensis Gomont comb. nov. Basionym. Arthrospira platensis Gomont 1892) and that the genus Limnospira was monospecific, only represented by L. platensis. This study highlighted the large intra-specific diversity of L. platensis, independent of the affiliations of the phylogenetic clades or geographical location of the habitats and the subsequent physiological and metabolic plasticity.


Surgery for gastric ulcer.
Despite the initial healing achieved by medical treatment with carbenoxolone, surgery is frequently needed in the management of gastric ulcer. We have studied 150 patients over the past 10 years in an attempt to define the place of conservative surgery compared with the standard partial gastrectomy of the Billroth I type. Functional results have not been significantly different and the individual surgeon's choice will depend on his philosophy with regard to the risk of cancer in the postoperative stomach, and his technical expertise with the newer kinds of vagotomy. To my mind it is perfectly justifiable to use highly selective vagotomy with excision of the ulcer to treat gastric ulcer alone, especially if the patient is one in whom postgastrectomy symptoms could be disabling. Further follow-up is needed to decide whether it should replace partial gastrectomy as the standard procedure.