[Massive delayed-action verapamil poisoning].
An 18-year old woman developed cardiogenic shock after ingestion of 16.8 g of a sustained release form of verapamil. Severe left ventricular diastolic dysfunction was demonstrated. For the first time muscular involvement was observed with myalgia and elevation of the MM isoenzyme of creatinine kinase. The efficacy isoproterenol and the need for prolonged treatment are emphasised.


Hepatitis C Virus RNA Real-Time Quantitative RT-PCR Method Based on a New Primer Design Strategy.
Viral nucleic acids are unstable when improperly collected, handled, and stored, resulting in decreased sensitivity of currently available commercial quantitative nucleic acid testing kits. Using known unstable hepatitis C virus RNA, we developed a quantitative RT-PCR method based on a new primer design strategy to reduce the impact of nucleic acid instability on nucleic acid testing. The performance of the method was evaluated for linearity, limit of detection, precision, specificity, and agreement with commercial hepatitis C virus assays. Its clinical application was compared to that of two commercial kits--Cobas AmpliPrep/Cobas TaqMan (CAP/CTM) and Kehua. The quantitative RT-PCR method delivered a good performance, with a linearity of R(2) = 0.99, a total limit of detection (genotypes 1 to 6) of 42.6 IU/mL (95% CI, 32.84 to 67.76 IU/mL), a CV of 1.06% to 3.34%, a specificity of 100%, and a high concordance with the CAP/CTM assay (R(2) = 0.97), with a means ± SD value of -0.06 ± 1.96 log IU/mL (range, -0.38 to 0.25 log IU/mL). The method was superior to commercial assays in detecting unstable hepatitis C virus RNA (P < 0.05). This quantitative RT-PCR method can effectively eliminate the influence of RNA instability on nucleic acid testing. The principle of primer design strategy may be applied to the detection of other RNA or DNA viruses.


Pharmacokinetics and hypotensive effect of diltiazem in rabbits: comparison of diltiazem with its major metabolites.
To assess the contribution of its metabolites to the antihypertensive effects of diltiazem, a previously established rabbit model has been used to compare the pharmacokinetics and haemodynamic effects of the drug with those of its major metabolites deacetyldiltiazem (M1) and deacetyl-N-monodemethyldiltiazem (M2). Diltiazem, M1 and M2 were administered separately to each animal (n = 5 or 6 per study group) as a single 5 mg kg(-1) intravenous dose. Blood samples, systolic and diastolic blood pressure (SBP and DBP) and heart rate were recorded for each rabbit up to 8 h, and urine samples were collected for 48 h post-dose. Plasma concentrations of diltiazem and its major metabolites were determined by HPLC. The results showed that systemic clearance (CL) and volume of distribution at steady state (Vdss) were smaller for diltiazem than for the metabolites. Diltiazem and the metabolites reduced both SBP and DBP, the effects of diltiazem being most potent. Their effects on heart rate were highly variable and not statistically different between treatment groups (P > 0.05). These results indicate that diltiazem is a more potent hypotensive agent than M1 or M2, possibly because of the higher plasma concentrations secondary to the smaller CL and Vdss of diltiazem compared with the metabolites. The effects of the metabolites might, however, be more sustained.


Trehalose induces B cell autophagy to alleviate myocardial injury via the AMPK/ULK1 signalling pathway in acute viral myocarditis induced by Coxsackie virus B3.
Viral myocarditis (VMC) is the main cause of sudden acute heart failure and cardiac death in adolescents; however, treatment for VMC is limited. Trehalose is a natural non-reductive disaccharide that protects against cardiovascular diseases by inducing autophagy. The protective effect of trehalose on VMC and the specific mechanism remains unclear. In this study, we established a VMC mouse model, treated with trehalose in vivo, and cultured B cells from VMC mice with trehalose in vitro to elucidate the effect of trehalose on B cells in acute VMC. Trehalose alleviated myocardial injury in VMC mice and increased the number of autophagosomes, LC3II/LC3I ratio, and expression level of LAMP2, whereas it decreased the expression of p62 in VMC-B cells. Bafilomycin A1 suppressed VMC-B cell autophagy induced by trehalose. At the mechanistic level, trehalose treatment significantly upregulated the phosphorylation of AMPK and ULK1 in VMC-B cells. Dorsomorphin and SBI-0206965 abolished the increased phosphorylation level and altered the expression levels of autophagy-related proteins. In conclusion, trehalose alleviates myocardial inflammatory damage of VMC by inducing B cell autophagy, mediated by the AMPK/ULK1 signalling pathway. Thus, trehalose may be a potentially useful molecule for alleviating myocardial injury in VMC.


Parents, Teachers, and Community: A Team Approach to Developing Physical Competence in Children.
Increasing children's physical activity engagement has short- and long-term health benefits. Developing physical competence is a key component of children's engagement in physical activity. The purpose of our study was to assess if a 12-week home, school, and community-based physical literacy intervention improved the physical competence of children in kindergarten and grade one. Four schools were either assigned to receive the intervention (n = 2 schools) or continue with their usual practice (control sites) (n = 2 schools). Physical competence was evaluated pre- and post-intervention in 103 intervention (41 female) and 83 usual practice (36 female) children using PLAY Fun. PLAY Parent and PLAY Coach tools measured parent and teacher perspectives of children's physical competence, respectively. The intervention effect was assessed with repeated measures MANOVA to evaluate change in physical competence, with alpha set at p < 0.05. Children in both groups improved their locomotor, object control, and overall physical competence (p < 0.05) over the 12-week intervention. There was a significant intervention effect for locomotor and overall physical competence (p < 0.05). Interestingly, parents did not perceive these changes in physical competence (p > 0.05). However, teachers perceived improved physical competence for children in the intervention. Our physical literacy intervention improved the physical competence of children in kindergarten and grade one.


Population-based incidence and time to classification of systemic lupus erythematosus by three different classification criteria: a Lupus Midwest Network (LUMEN) study.
To estimate the incidence and time-to-classification of SLE by the 1997 ACR (ACR97) criteria, the SLICC criteria, and the European Alliance of Associations for Rheumatology/ACR (EULAR/ACR) criteria. We identified all incident SLE cases from 2000-2018 in the well-defined Olmsted County population. Clinical data included in the ACR97, SLICC and EULAR/ACR criteria were manually abstracted from medical records. All incident cases met at least one of the three classification criteria. Time-to-classification was estimated from the first documented lupus-attributable disease manifestation to the time of criteria fulfilment by each of the three definitions. Annual incidence rates were age or age/sex adjusted to the 2000 US population. Of 139 incident cases there were 126 cases by the EULAR/ACR criteria, corresponding to an age/sex-adjusted incidence of 4.5 per 100 000 population (95% CI: 3.7, 5.2). The age/sex-incidence was higher than that of the SLICC criteria (113 cases; 4.0 per 100 000 [95% CI: 3.3, 4.7], P = 0.020) and the ACR97 (92 cases; 3.3 per 100 000 [95% CI: 2.6, 3.9], P < 0.001). The median time from first disease manifestation to criteria fulfilment was shorter for the EULAR/ACR criteria (29.4 months) than the ACR97 criteria (47.0 months, P < 0.001) and similar to the SLICC criteria (30.6 months, P = 0.83). The incidence of SLE was higher by the EULAR/ACR criteria compared with the ACR97 and the SLICC criteria, and the EULAR/ACR criteria classified patients earlier that the ACR97 criteria but similar to the SLICC criteria.


The effect of short-term training on repetition probability effects for non-face objects.
The magnitude of repetition suppression (RS) is modulated by the probability of stimulus repetitions when measured by fMRI. This repetition probability effect (P(rep)) is usually expressed in a stronger RS when the probability of repetition trials is higher when compared to blocks with less frequent repetitions. Previous studies have suggested that the P(rep) effect depends on the extensive long-term experience of participants with the stimuli. At the same time, the how short-term learning affects RS and its modulation by P(rep) remains largely unknown. To address this issue, we used fMRI and measured the RS and its modulation by P(rep) for non-face objects (cars) before and after a 10-day long perceptual learning (PL) period and for unfamiliar faces as control. The results showed a significant P(rep) effect for faces within the Fusiform Face Area (FFA) and for cars within the Lateral Occipital Complex (LO) in the pre-training fMRI measurement session. Following the PL period, participants exhibited strong improvements in the subordinate categorization of the trained stimuli. Surprisingly, the magnitude of RS did not change as a function of training, but the P(rep) effect was absent in the post-training fMRI sessions for both stimulus categories. These results suggest that the predictive processes, measured by P(rep) modulation of RS, may be modulated by the short-term perceptual learning experience.


Electrons for single molecule diffraction and imaging.
We demonstrate the potential of electrons for single molecule diffraction and imaging using C₆₀ molecules confined inside single-walled carbon nanotubes (C₆₀s@SWCNT or peapod) as a model system. A 25 nm diameter electron beam from a field emission gun source is used to record diffraction patterns from individual peapods using imaging plates. The electron beam illuminates about 25 C₆₀ molecules. Experimentally, we found that the molecules diffract inside ∼15% of the host nanotubes. With the help of simulations, we explore the limits of electron molecular diffraction and its sensitivity to the molecular configurations. We show that the combination of electron diffraction and electron direct imaging provides the best approach to single molecule imaging.


Thoracoscopic anatomy and approaches of the anterior thoracic spine: cadaver study.
[corrected] In spite of the extensive case studies considering thoracoscopic approaches to the anterior thoracic spine, the literature lacks studies of the thoracoscopic anatomic dissection and approaches. In this article, the authors present their study of thoracoscopic anatomy of the anterior spine with illustrated step-wise dissection and approaches for sympathectomy, discectomy and corpectomy. Four adult cadavers with no history of disease, local trauma or surgery were studied and bilateral thoracoscopic anterior spinal approaches were performed. Thoracoscopic dissections were done in the Department of Anatomy, using Karl Storz 30°, 5 mm and 30 cm rod lens rigid endoscope (Karl Storz and Co., Tuttlingen, Germany). As surgical instrumentation, Karl Storz Rosenthal endoscopic surgical set and 15 mm portals were used for all approaches. For sympathectomy, the cadaver is positioned supine and the port locations are in the third and fifth intercostal spaces in the anterior axillary line. The stellate ganglion is cephalad to the second rib, and the T2 and T3 ganglia are divided just superior to T2 ganglia and inferior to T3. For discectomy, the cadaver is positioned in the lateral decubitus position. The working portal is positioned directly over the affected disc in the posterior axillary line. The camera portal is positioned in the middle axillary line; 2-3 intercostal spaces caudal to the working portal. The rib head is removed and the lateral surface of the pedicle and neural foramen are exposed. The pedicle and the floor of the spinal canal are resected to decompress the ventral aspect of the spinal canal. For corpectomy, the position of the cadaver and ports are as same as for discectomy. The adjacent segmental vessels are divided first, and the discs above and below the targeted corpus are removed. The ipsilateral pedicle is then removed to decompress the anterior spinal cord, followed by median corpectomy. Thoracoscopic approaches are minimally invasive procedures and they can be used safely in patients who need anterior exposure to the thoracic spine for the treatment of a spectrum of diseases. Knowledge of the normal anatomy and thoracoscopic cadaver dissection are essential steps in improving the learning curve.


Diagnostic yield of repeat sampling with immunoassay, real-time PCR, and toxigenic culture for the detection of toxigenic Clostridium difficile in an epidemic and a non-epidemic setting.
Current international guidelines lack definite conclusions regarding repeat stool sampling for the detection of toxigenic Clostridium difficile. We assessed the value of repeat sampling and compared the diagnostic yield in an epidemic to a non-epidemic setting. Consecutive fecal samples obtained during two time frames were analyzed using direct stool immunoassay toxin testing (enzyme immunoassay [EIA]), direct stool real-time PCR toxin gene testing, and toxigenic culture. Samples collected within 7 days of the initial sample were considered repeat tests. In the epidemic setting 989 patients were analyzed, and in the non-epidemic setting 1,015. In the epidemic setting 204 patients had two or more specimens included for analysis and in the non-epidemic setting 287 patients. In the epidemic setting 136 samples yielded a positive results, either by EIA or toxigenic culture; of these, 108 were positive according to EIA and 123 according to toxigenic culture. In the first test round 98 (90.7%, 95% CI 85.3 to 96.2), 114 (92.7%, 88.1 to 97.3), and 126 (92.6%, 88.3 to 97.0) positives were detected. Subsequent test rounds yielded 10 (9.3%, 3.8 to 14.7), 9 (7.3%, 2.7 to 11.9), and 10 (7.4%, 3.0 to 11.7) extra positives. In the non-epidemic setting EIA, toxigenic culture and PCR detected 33, 66, and 83 positives. The three tests combined 93 detected positives. In the first test round 30 (90.9%, 81.1 to 100.7), 63 (95.5%, 90.4 to 110.5), 76 (91.6%, 85.6 to 97.5), and 87 (93.5%, 88.6 to 98.5) positives were detected. Subsequent test rounds yielded 3 (9.1%, -0.7 to 18.9), 3 (4.5%, -0.5 to 9.6), 7 (8.4%, 2.5 to 14.4), and 6 (6.5%, 1.5 to 11.4) extra positives. In conclusion, repeat testing resulted in 4.5% to 9.3% extra positives. No significant difference between the settings studied could be demonstrated. Repeat sampling and multimodality testing may be chosen in an outbreak situation to detect all cases, effectively controlling nosocomial spread.


Serum pentraxin 3 as a biomarker of hepatocellular carcinoma in chronic hepatitis B virus infection.
Biomarkers for early diagnosis of hepatocellular carcinoma (HCC) are needed in chronic hepatitis B virus (HBV) infection, a leading cause of HCC. We evaluated whether measurement of serum pentraxin 3 (PTX3) could improve diagnosis of HCC in chronic HBV infection. Data from patients with HBV-related chronic hepatitis (n = 159), cirrhosis (n = 99) and HCC (n = 107), and healthy controls (n = 151) were analyzed. Serum PTX3 concentration was measured by immunoassay. Area under the receiver operating characteristic curve (AUC) was applied to assess diagnostic accuracy. PTX3 levels were significantly higher in HBV patients than in healthy controls (P < 0.001) and in HCC than in chronic hepatitis (P < 0.001) or cirrhosis patients (P < 0.001). PTX3 was an independent risk factor of HCC [odds ratio (OR) 1.617, P < 0.001] and could distinguish HCC in chronic HBV infection [cutoff 9.231 ng/mL, AUC 0.929 with 95% confidence interval (CI) of 0.898-0.953], including α-fetoprotein (AFP) negative [cutoff 8.985 ng/mL, AUC (95%CI) 0.947 (0.908-0.973)] and early-stage HCC [cutoff 9.359 ng/mL, AUC (95%CI) 0.920 (0.885-0.947)]. Combination of PTX3 with AFP improved the discrimination of early HCC from chronic HBV infection [AUC (95%CI) 0.948 (0.918-0.970)]. In short, PTX3 measurement could identify HCC, including AFP-negative and early-stage HCC, in chronic HBV infection.


Effect of the heme/heme oxygenase pathway on the relationship between salt consumption and blood pressure.
Some studies have shown that heme oxygenase inhibition increases blood pressure in rats. This effect may be due to the consequent lower levels of the heme degradation products (carbon monoxide, biliverdin, and Fe3+) or due to heme accumulation. However, it is not yet known if the variable effect of NaCl on blood pressure levels is influenced by the heme/heme oxygenase pathway activity. This enzymatic system may be studied by blocking its activity with zinc protoporphyrin IX (ZnPP IX), a heme oxygenase inhibitor. Male Wistar rats were fed from weaning with low (LSD--0.15% NaCl), normal (NSD--1.3% NaCl), or high (HSD--8% NaCl) salt diet On the 12th week of age, assessment of the tail-cuff blood pressure (tc-BP) response to acute inhibition of heme oxygenase with ZnPP IX or after vehicle (Na2CO3) was performed. A higher tc-BP was observed on HSD both before ZnPP IX (P< 0.001) and vehicle (P = 0.003). After ZnPP IX, tc-BP decreased on HSD (P < 0.001) and increased on NSD (P = 0.003) and on LSD (P < 0.001). The area under the curve (AUC) of the percentage change in the blood pressure response was calculated. On putting all the rats from the three dietary groups together, an inverse correlation was observed between individual AUC after ZnPP IX and control tc-BP (r = -0.71; P< 0.001) but not after vehicle (r = 0.34; P < 0.05). Chronic salt overload increases blood pressure in Wistar rats and the pressure response to heme oxygenase is modulated by the effect of NaCl consumption on blood pressure levels.


Simultaneous transmission of Borrelia burgdorferi and Babesia microti by individual nymphal Ixodes dammini ticks.
Nymphal Ixodes dammini ticks, selected from a group of ticks in which 22 of 31 (71%) contained dual Borrelia burgdorferi and Babesia microti infections, simultaneously transmitted B. burgdorferi and B. microti to 4 of 7 (57%) hamsters exposed to individual ticks.


Particles as carriers of matter in the aquatic environment: Challenges and ways ahead for transdisciplinary research.
A diverse array of natural and anthropogenic particles found in the aquatic environment, can act as carriers of co-transported matter (CTM), such as nutrients, genetic material and contaminants. Thus, understanding carrier particle transport will increase our understanding of local and global fluxes of exogenous CTM (affiliated with the particle) and endogenous CTM (an inherent part of the particle). In the present contribution, researchers from multiple disciplines collaborated to provide perspectives on the interactions between carrier particles and CTM, and the fundamentals of transport of particles found in the aquatic environment and the generic spherical smooth particles, often used to make predictions about particle behavior in suspension. Evidently, the particles in the aquatic environment show a great variety of characteristics and vary greatly from each other as well as from the generic particle. However, in spite of these differences, many fundamental concepts apply to particles in general. We emphasize the importance of understanding the basic concepts of transport of particle-associated CTM, and the main assumptions in the generic-founded models, which are challenged by the diverging characteristics of particles found in the aquatic environment, as paramount moving forward. Additionally, we identified the need for a conceptual and semantic link between different scientific fields of particle research and initiated the formation of a consistent terminology. Disciplinary and organizational (academic and funding) barriers need to be overcome to enable individual researchers to move beyond their knowledge sphere, to stimulate future interdisciplinary collaborations and to avoid research silos. Hereby, we can foster faster and better progress of evolving research fields on new and emerging anthropogenic carrier particles, and stimulate the development of solutions to the technological and environmental challenges.


Rising high-acuity emergency care services independently billed by advanced practice providers, 2013 to 2019.
Advanced practice providers (APPs) comprise an increasing proportion of the emergency medicine (EM) workforce, particularly in rural geographies. With little known regarding potential expanding practice patterns, we sought to evaluate trends in independent emergency care services billed by APPs from 2013 to 2019. We performed a repeated cross-sectional analysis of emergency clinicians independently reimbursed for at least 50 evaluation and management (E/M) services (99281-99285, 99291) from Medicare Part B, with high-acuity services including Codes 99285 and 99291. We describe the outcome proportion of E/M services by acuity level and report at (1) the encounter level and (2) at the clinician level. We stratified analyses by clinician type and geography. A total of 47,323 EM physicians, 10,555 non-EM physicians, and 26,599 APPs were included in analyses. APPs billed emergency care services independently for 5.1% (rural 7.3%, urban 4.8%) of all high-acuity encounters in 2013, increasing to 9.7% (rural 16.4%, urban 8.8%) by 2019. At the clinician level, in 2013, the average rural-practicing APP independently billed 22.8% of services as high acuity, 72.6% as moderate acuity, and 4.5% as low acuity. By 2019, the average rural-practicing APP independently billed 36.2% of services as high acuity, representing a +58.8% relative increase from 2013. Relative increases in high-acuity visits independently billed by APPs were substantially greater when compared to EM physicians across both rural and urban geographies. In 2019, APPs billed independent services for approximately one in six high-acuity ED encounters in rural geographies and one in 11 high-acuity ED encounters in urban geographies, and well over one-third of the average APPs' encounters were for high-acuity E/M services. Given differences in training and reimbursement between clinician types, these estimates suggest further work is needed evaluating emergency care staffing decision making.


Sonographic evaluation of the rotator cuff: correlation with arthroscopy.
High-resolution real-time sonography has been reported as a non-invasive means of evaluating the integrity of the rotator cuff. Fifty-two patients underwent both sonographic and arthroscopic evaluation of the rotator cuff. There were 42 men and 10 women with an average age of 47 years (range 28-71 years). The duration of shoulder pain averaged 24 months (range 3 months to 9 years). Thirty-five rotator cuff tears were noted arthroscopically. Twenty-seven of the tears were diagnosed by sonography for a sensitivity rate of 77%. Eleven of the 17 intact rotator cuffs were normal by sonography for a specificity rate 65%. The overall accuracy of sonography was 73% and the predictive value of a positive sonogram was 82%. Sonography appears to be a good initial screening examination in evaluating the integrity of the rotator cuff. It is noninvasive and relatively inexpensive. Technical limitations of this technique as well as the experience of the radiologist in performing and interpreting the examination play a major role in the accuracy of this test. As instrumentation improves and as experience in using this technique increases, we expect the accuracy of sonography in detecting tears of the rotator cuff to continue to improve.


Endothelium-dependent relaxation in estrogen-treated spontaneously hypertensive rats.
Female spontaneously hypertensive rats (SHR) were injected subcutaneously with mestranol twice a week for 12 weeks. Isolated segments of thoracic aorta were then used to generate relaxation response curves to acetylcholine or ATP after precontraction with phenylephrine. Estrogen treatment attenuated the development of hypertension. Further, augmented endothelium-dependent relaxation to acetylcholine was seen in the estrogen-treated SHR. There was no difference, however, in the relaxation produced by ATP. Since the relaxation of both acetylcholine and ATP is endothelium-dependent, these findings suggest that different mechanisms may be involved in the relaxation produced by acetylcholine and ATP.


Spinal subdural hematoma following craniotomy: case report.
Spinal subdural hematomas (SSH) are a rare cause of spinal cord compression. SSH following clipping of an aneurysm has only been reported once. We now report such a case and discuss the mechanism of SSH development after aneurysmal neck clipping. A 32-year-old man complained of lumbago 7 days after craniotomy for the clipping of an aneurysm. Neurologic examination revealed no abnormality, but magnetic resonance imaging (MRI) demonstrated a lumbosacral spinal subdural hematoma. He received conservative management and his lumbago showed improvement. An MRI taken 19 days after surgery revealed a residual hematoma. The downward movement of blood from the cranial subdural compartment under the influence of gravity is the most appropriate explanation for SSH following craniotomy.


Propionate-induced relaxation in rat mesenteric arteries: a role for endothelium-derived hyperpolarising factor.
Short chain fatty acids, including propionate, are generated in the caecum and large intestine, and when absorbed may elicit localised increases in intestinal blood flow. We sought to assess the mechanism by which propionate caused vasorelaxation. Propionate-mediated relaxation of noradrenaline-preconstricted rat mesenteric small arteries (RMSAs, i.d. 200-300 microm) was studied using small vessel myography. Propionate (1-30 mM) produced a concentration-dependent relaxation. Relaxation induced by 10 mM propionate (the approximate EC50) was almost abolished by endothelial denudation, although a marked relaxation to a very high concentration of propionate (50 mM) persisted in the absence of the endothelium. In endothelium-intact RMSAs, relaxation to 10 mM propionate was almost abolished by elevating [K+]o to 25 mM, but was unaffected by 100 microM N(omega)-nitro-L-arginine methyl ester (L-NAME) (68 +/- 4 vs. 66 +/- 3% in controls, n = 35), or by 1 microM indomethacin (60 +/- 4 vs. 61 +/- 7 % in controls, n = 15). In the presence of L-NAME, relaxation to 10 mM propionate was significantly and markedly (i.e. > 50 %) inhibited by 50 microM Ba2+ and by the combination of 100 nM charybdotoxin and 100 nM apamin. A similar effect on propionate-mediated relaxation was also exerted by 100 microM ouabain, and by the combination of 50 microM barium with ouabain. Relaxation was also significantly and markedly inhibited by pre-treatment of RMSAs with 100 nM thapsigargin or 10 microM cyclopiazonic acid (CPA). The results demonstrate that 10 mM propionate relaxes RMSAs via endothelium-derived hyperpolarising factor (EDHF). The observation that relaxation by propionate is inhibited by thapsigargin and CPA suggests that this action of propionate involves the release of endothelial cell Ca2+ stores.


Corrigendum: Case report: Primary aldosteronism and subclinical cushing syndrome in a 49-year-old woman with hypertension plus hypokalaemia.
[This corrects the article DOI: 10.3389/fcvm.2022.911333.].


Neurochemistry of the sympathetic innervation to the uterus.
1. The uterus is supplied by numerous noradrenergic sympathetic nerve fibres, which supply the intramural vasculature and also, in some species at least, the myometrium. 2. Pregnancy is associated with progressive loss of catecholamine from these nerves. Although some direct mechanical damage due to stretching of the uterine wall contributes to this effect, it is primarily due to hormonal influences. 3. In animal experiments, the changes in uterine catecholamine occurring during pregnancy are mimicked by intra-uterine administration of progesterone. 4. The action of progesterone appears not to be selective for pelvic sympathetic neurons, or those in which transmitter turnover rate is particularly slow. The mechanism of depletion is probably through inhibition of tyrosine hydroxylase activity. 5. The functional role of this phenomenon during pregnancy, if one exists, seems likely to be related to protection of the fetoplacental blood supply against sympathetically mediated vasospasm. It is also possible that circulating progesterone may have a general inhibitory action on the female sympathetic nervous system.


Temporospatial expression of vascular endothelial growth factor and basic fibroblast growth factor during mandibular distraction osteogenesis.
Distraction osteogenesis is a vascular-dependent process. This study investigated expression patterns of two major angiogenic factors, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), in the distracted calluses following mandibular lengthening in a goat model. Bilateral mandibular osteotomies were performed in 15 young adult goats. After a latency of 7 days, the mandibles were elongated using custom-made distractors with a rate of 1 mm/day for 10 days. Three animals each were sacrificed at the end of the delay phase, at 0, 7, 14, and 28 days after completion of distraction, respectively. The lengthened mandibles were harvested and processed for histological and immunohistochemical examinations. Elevated cellular expression of VEGF and bFGF, with neovascularization in the distraction gap, was observed following mandibular lengthening. VEGF staining was noted in the endothelial cells and osteoblasts. bFGF staining was seen in the fibroblast-like cells, osteoblasts and immature osteocytes. Their strongest expression was found 0-7 days after the end of distraction, and declined with maturation of the newly formed bone. A temporal and spatial expression pattern of VEGF and bFGF was found during distraction osteogenesis in goat mandibles. It suggests that distraction forces can stimulate the production of VEGF and bFGF, which contribute to neovascularization and new bone formation during gradual distraction of the mandible. Application of angiogenic factors may be considered as a potential method to enhance angiogenesis and osteogenesis in osteodistraction, especially in sites without enough vascularization.


Genetic testing for renal diseases: medical and ethical considerations.
Advances in understanding the genetic basis of renal disorders will soon allow for the clinical use of genetic diagnostic testing. In this article, we review renal diseases with a known genetic basis and the current methods available for genetic testing. We then examine the potential medical indications for genetic testing, with special attention to autosomal dominant polycystic kidney disease (ADPKD). Because clinicians will be faced with patients considering genetic testing, we review the ethical considerations regarding genetic testing for renal diseases, recent genetic privacy legislation, and the special role genetic testing may have in transplantation. We conclude with a review of the necessary elements of informed consent, which provides the ethical foundation for patients deciding about genetic testing with the assistance of their physicians.


Nucleic Acid Isolation and Enrichment on a Microchip.
This paper presents a microchip that isolates and enriches target-binding single-stranded DNA (ssDNA) from a randomized DNA mixture using a combination of solid-phase extraction and electrophoresis. Strands of ssDNA in a randomized mixture are captured via specific binding onto target-functionalized microbeads in a microchamber. The strands are further separated from impurities and enriched on-chip via electrophoresis. The microchip consists of two microchambers that are connected by a channel filled with agarose gel. In the isolation chamber, beads functionalized with human immunoglobulin E (IgE) are retained by a weir structure. An integrated heater elevates the temperature in the chamber to elute desired ssDNA from the beads, and electrophoretic transport of the DNA through the gel to the second chamber is accomplished by applying an electric potential difference between the two chambers. Experimental results show that ssDNA expressing binding affinity to IgE was captured and enriched from a sample of ssDNA with random sequences, demonstrating the potential of the microchip to enhance the sensitivity of ssDNA detection methods in dilute and complex biological samples.


Antioxidant and hepatoprotective activity of Cordia macleodii leaves.
This investigation was undertaken to evaluate ethanolic extract of Cordia macleodii leaves for possible antioxidant and hepatoprotective potential. Antioxidant activity of the extracts was evaluated by four established, in vitro methods viz. 1,1-diphenyl-2-picryl hydrazyl (DPPH) radical scavenging method, nitric oxide (NO) radical scavenging method, iron chelation method and reducing power method. The extract demonstrated a significant dose dependent antioxidant activity comparable with ascorbic acid. The extract was also evaluated for hepatoprotective activity by carbon tetrachloride (CCl4) induced liver damage model in rats. CCl4 produced a significant increase in levels of serum glutamate pyruvate transaminase (GPT), serum glutamate oxaloacetate transaminase (GOT), Alkaline Phosphatase (ALP) and total bilirubin. Pretreatment of the rats with ethanolic extract of C. macleodii (100, 200 and 400 mg/kg po) inhibited the increase in levels of GPT, GOT, ALP and total bilirubin and the inhibition was comparable with Silymarin (100 mg/kg po). The present study revealed that C. macleodii leaves have significant radical scavenging and hepatoprotective activities.


Active Surveillance of Atypical Ductal Hyperplasia of the Breast.
When needle core biopsy (NCB) of the breast yields atypical ductal hyperplasia (ADH), excision is typically recommended. The natural history of ADH undergoing active surveillance (AS) is not well described. We investigate the rates of upgrade to malignancy of excised ADH and the rates of radiographic progression under AS. We retrospectively reviewed records of 220 cases of ADH on NCB. Of patients who had surgery within 6 months of NCB, we examined the malignancy upgrade rate. In the AS cohort, we examined rates of radiographic progression on interval imaging. The malignancy upgrade rate among patients who underwent immediate excision (n = 185) was 15.7%: 14.1% (n = 26) ductal carcinoma in situ (DCIS) and 1.6% (n = 3) invasive ductal carcinoma (IDC). Upgrade to malignancy was less common in lesions <4 mm in size (0%) or with focal ADH (5%), and more common among lesions presenting with a radiographic mass (26%). Among the 35 patients who underwent AS, median follow-up was 20 months. Two lesions progressed on imaging (incidence 3.8% at 2 years). One patient without radiographic progression was found to have IDC at delayed surgery. The remaining lesions remained stable (46%), decreased in size (11%), or resolved (37%). Our findings suggest that AS is a safe approach to managing ADH on NCB for most patients. This could spare many patients with ADH from unnecessary surgery. Given that AS is being investigated for low-risk DCIS in multiple international prospective trials, these results suggest that AS should also be investigated for ADH.


High-dose Propofol Anesthesia Reduces the Occurrence of Postoperative Cognitive Dysfunction via Maintaining Cytoskeleton.
Postoperative cognitive dysfunction (POCD) is a common postoperative complication observed in patients following. Here we tested the molecular mechanisms of memory loss in hippocampus of rat POCD model. We found that high-dose propofol anesthesia significantly alleviated spatial memory loss. The proteomes and transcriptomes in hippocampus showed that hippocampal cytoskeleton related pathways were abnormal in low group while not in high group. The protein assays confirmed that hippocampal actin cytoskeleton was depolymerized in low group while maintained in high group. This study confirms that high-dose propofol anesthesia could mitigate the development of POCD and provides evidences for actin cytoskeleton associated with this syndrome.


Association analysis of IL20RA and IL20RB genes in psoriasis.
The interleukin-20-receptor I complex (IL-20-RI) is composed of two chains, IL20RA and IL20RB. Its ligands are the three members of the IL19 subfamily of cytokines, IL-19, IL-20 and IL-24. These cytokines are important in the manifestation of psoriatic lesions and, recently, an association of polymorphisms of IL20 with psoriasis has been described. In the present study we tested the hypotheses that genetic variations of the IL-20-RI influence susceptibility to psoriasis and investigated single nucleotide polymorphisms (SNPs) in the IL20RA and IL20RB genes in psoriasis patients (n=254) and healthy controls (n=224). We found no association of any of the investigated SNPs with the disease. Analysis of pairwise linkage disequilibrium (LD) across studied markers revealed a strong level of LD between SNPs within the IL20RA gene and SNPs within the IL20RB gene, and, for both genes six common haplotypes were identified with an estimated frequency >or=1%. Haplotype analyses suggested that the IL20RA haplotype CCG (rs1184860, rs1167846, rs1167849) is significantly associated with psoriasis (OR 3.14, 95% CI 1.61-6.14), whereas the TTG haplotype had a protective effect (OR 0.20, 95% CI 0.07-0.55). The risk haplotype defining SNPs 1167846 and 1184860 were found to modify paired box 5 and homeobox A9 sites, respectively, two transcription factors related to the differentiation of immune cells. Further studies are needed to confirm the genetic association and to investigate the functional relevance of IL20RA haplotypes in psoriasis.


Small Fiber Neuropathy Incidence, Prevalence, Longitudinal Impairments, and Disability.
There are limited population-based data on small fiber neuropathy (SFN). We wished to determine SFN incidence, prevalence, comorbid conditions, longitudinal impairments, and disabilities. Test-confirmed patients with SFN in Olmsted, Minnesota, and adjacent counties were compared 3:1 to matched controls (January 1, 1998-December 31, 2017). Ninety-four patients with SFN were identified, with an incidence of 1.3/100,000/y that increased over the study period and a prevalence of 13.3 per 100,000. Average follow-up was 6.1 years (0.7-43 years), and mean onset age was 54 years (range 14-83 years). Female sex (67%), obesity (body mass index mean 30.4 vs 28.5 kg/m2), insomnia (86% vs 54%), analgesic-opioid prescriptions (72% vs 46%), hypertriglyceridemia (180 mg/dL mean vs 147 mg/dL), and diabetes (51% vs 22%, p < 0.001) were more common (odds ratio 3.8-9.0, all p < 0.03). Patients with SFN did not self-identify as disabled with a median modified Rankin Scale score of 1.0 (range 0-6) vs 0.0 (0-6) for controls (p = 0.04). Higher Charlson comorbid conditions (median 6, range 3-9) occurred vs controls (median 3, range 1-9, p < 0.001). Myocardial infarctions occurred in 46% vs 27% of controls (p < 0.0001). Classifications included idiopathic (70%); diabetes (15%); Sjögren disease (2%); AL-amyloid (1%); transthyretin-amyloid (1%); Fabry disease (1%); lupus (1%); postviral (1%); Lewy body (1%), and multifactorial (5%). Foot ulcers occurred in 17, with 71% having diabetes. Large fiber neuropathy developed in 36%, on average 5.3 years (range 0.2-14.3 years) from SFN onset. Median onset Composite Autonomic Severity Score (CASS) was 3 (change per year 0.08, range 0-2.0). Median Neuropathy Impairment Scale (NIS) score was 2 at onset (range 0-8, change per year 1.0, range -7.9 to +23.3). NIS score and CASS change >1 point per year occurred in only AL-amyloid, hereditary transthyretin-amyloid, Fabry, uncontrolled diabetes, and Lewy body. Death after symptom onset was higher in patients with SFN (19%) vs controls (12%, p < 0.001), 50% secondary to diabetes complications. Isolated SFN is uncommon but increasing in incidence. Most patients do not develop major neurologic impairments and disability but have multiple comorbid conditions, including cardiovascular ischemic events, and increased mortality from SFN onsets. Development of large fiber involvements and diabetes are common over time. Targeted testing facilitates interventional therapies for diabetes but also rheumatologic and rare genetic forms.


Risk of nodal metastases from malignant salivary gland tumors related to tumor size and grade of malignancy.
Indications for elective treatment of the neck are not well defined in salivary gland tumors. We retrospectively reviewed 153 cases of malignant salivary gland tumors treated from 1965 to 1985 at the Hospital de Oncología, Mexico City. There were 106 parotid cancers, 26 in the submandibular gland and 21 in minor salivary glands. Median follow-up was 48 months. In T1-2 tumors there was a 12% incidence of nodal metastases as compared with 27% in T3-4 cancers (P = 0.01). Thirty-six elective neck dissections were performed. Patients with high-grade tumors had an increased risk (50%) of occult node metastases, while no cases were found in low-grade carcinomas (P < 0.05). The risk of neck recurrence was higher in N+ (23.5%) than in N0 patients (3.2%). The 5-year actuarial survival was significantly better in low-grade tumors (78%), T1-2 tumors (85%) and negative nodes (63%) than in high-grade neoplasms (49%), T3-4 tumors (35%) and positive nodes (P = 0.001, P = 0.001 and P = 0.04, respectively).


A technique for salvaging a critical internal mammary artery bypass graft damaged during resternotomy.
Resternotomy in the presence of a patent internal mammary artery graft poses an addition hazard to the reoperation. We describe a situation in which the patent mammary artery graft to the left anterior descending artery was severed and retracted during sternal reentry for an aortic valve replacement. We illustrate a simple technique for restoring the blood supply using a coronary artery shunt.


Effects of sleep disruption and high fat intake on glucose metabolism in mice.
Poor sleep quality or quantity impairs glycemic control and increases risk of disease under chronic conditions. Recovery sleep may offset adverse metabolic outcomes of accumulated sleep debt, but the extent to which this occurs is unclear. We examined whether recovery sleep improves glucose metabolism in mice subjected to prolonged sleep disruption, and whether high fat intake during sleep disruption exacerbates glycemic control. Adult male C57BL/6J mice were subjected to 18-h sleep fragmentation daily for 9 days, followed by 1 day of recovery. During sleep disruption, one group of mice was fed a high-fat diet (HFD) while another group was fed standard laboratory chow. Insulin sensitivity and glucose tolerance were assessed by insulin and glucose tolerance testing at baseline, after 3 and 7 days of sleep disruption, and at the end of the protocol after 24h of undisturbed sleep opportunity (recovery). To characterize changes in sleep architecture that are associated with sleep debt and recovery, we quantified electroencephalogram (EEG) recordings during sleep fragmentation and recovery periods from an additional group of mice. We now report that 9 days of 18-h daily sleep fragmentation significantly reduces rapid eye movement sleep (REMS) and non-rapid eye movement sleep (NREMS). Mice respond with increases in REMS, but not NREMS, during the daily 6-h undisturbed sleep opportunity. However, both REMS and NREMS increase significantly during the 24-h recovery period. Although sleep disruption alone has no effect in this protocol, high fat feeding in combination with sleep disruption impairs glucose tolerance, effects that are reversed by recovery sleep. Insulin sensitivity modestly improves after 3 days of sleep fragmentation and after 24h of recovery, with significantly greater improvements in mice exposed to HFD during sleep disruption. Improvements in both glucose tolerance and insulin sensitivity are associated with NREMS rebound, raising the possibility that this sleep phase contributes to restorative effects of recovery sleep on glycemic control.


Distribution of occlusal contacts in maximum intercuspation.
This study describes the use of the T-Scan system to record and analyze tooth contact data by calculating time moment statistics in the sagittal and transverse axes of the occlusal plane and reports the results of this method to analyze the occlusion of 93 normal subjects. Results confirm the findings of previous investigators and indicate that in a normal dentition there is a tendency for bilateral equality of the tooth contacts about the sagittal axis and that the center of effort for tooth contacts anteroposteriorly is located in the region of the first molar and is symmetrical bilaterally. Because of the rapid and accurate ability of the T-Scan system to identify the distribution of the tooth contacts, it shows great promise as a clinical diagnostic screening device for occlusion.


Cirrhotic cardiomyopathy and hepatopulmonary syndrome: prevalence and prognosis in a series of patients.
Hepatopulmonary syndrome (HPS) is of prognostic value in patients awaiting for orthotopic liver transplantation (OLT), but little is known about the effect of cirrhotic cardiomyopathy (CCM). The aim of the present study was to estimate the prevalence and possible relation between respiratory and cardiac abnormalities in a same series of patients awaiting OLT. Special attention was paid to the prognostic value of CCM in comparison to HPS. Eighty-three patients were included (19 females, 64 males; 52.1 ± 10.0 yrs). All had lung function testing with arterial blood gases and echocardiographic evaluation at rest with a contrast echocardiography in case of arterial oxygenation defect. To estimate the presence of CCM, patients underwent a complete left and right echocardiography and Doppler examination. Complete echocardiographic assessment could be obtained in 64 of the 83 patients of the study. HPS was observed in 16.9% (14/83) and CCM in 23.4% (15/64) of patients. There was a tendency of more serious adverse events before and after OLT in patients with HPS in comparison to others but CCM was not of prognostic value. HPS and CCM were frequent in these patients awaiting OLT but both abnormalities were not found in the same patients. CCM was neither related to death before OLT nor to death or serious adverse events after OLT.


Nanopore Dwell Time Analysis Permits Sequencing and Conformational Assignment of Pseudouridine in SARS-CoV-2.
Direct RNA sequencing for the epitranscriptomic modification pseudouridine (Ψ), an isomer of uridine (U), was conducted with a protein nanopore sensor using a helicase brake to slowly feed the RNA into the sensor. Synthetic RNAs with 100% Ψ or U in 20 different known human sequence contexts identified differences during sequencing in the base-calling, ionic current, and dwell time in the nanopore sensor; however, the signals were found to have a dependency on the context that would result in biases when sequencing unknown samples. A solution to the challenge was the identification that the passage of Ψ through the helicase brake produced a long-range dwell time impact with less context bias that was used for modification identification. The data analysis approach was employed to analyze publicly available direct RNA sequencing data for SARS-CoV-2 RNA taken from cell culture to locate five conserved Ψ sites in the genome. Two sites were found to be substrates for pseudouridine synthase 1 and 7 in an in vitro assay, providing validation of the analysis. Utilization of the helicase as an additional sensor in direct RNA nanopore sequencing provides greater confidence in calling RNA modifications.


Pulse pressure as a prognostic marker in patients receiving extracorporeal life support.
It is not easy to predict the prognosis of patients receiving extracorporeal life support (ECLS) because of the highly variable situation around its implementation. We evaluated the role of pulse pressure (PP), which is available on real-time basis, as a hemodynamic prognostic marker during ECLS. From January 2009 to August 2011, data from 69 patients who were treated with ECLS for at least 6h in a single center for any cause was collected. We calculated the mean PP over the first 6h after ECLS implantation and examined if there was any correlation between mean PP and the study endpoints, in-hospital death and ECLS weaning failure. The causes of ECLS were of cardiac origin in 36 patients (52%). 27 patients (39.1%) weaned off ELCS and 13 patients (18.8%) survived to discharge. In Cox regression analysis (with age, Killip class ≥3, ECLS implementation during cardiopulmonary resuscitation (CPR), CPR duration, out-of-hospital arrest, initial laboratory results including blood gas analysis, initial systolic blood pressure (SBP), mean SBP over the first 6h after ECLS implantation, mean PP over the first 6h after ECLS implantation as independent variables), mean PP over the first 6h after ECLS implantation (hazard ratio [95% confidence interval]=0.96[0.94-0.98], P<0.001) and out-of-hospital arrest (HR[95%CI]=2.04[1.14-3.62], P=0.02) were independent predictors of in-hospital mortality and mean PP over the first 6h after ECLS implantation (HR[95% CI]=0.95[0.93-0.98], P<0.001) was the sole independent predictor of weaning failure. Higher mean PP over the initial 6h after ECLS implementation independently predicted successful weaning and survival. Our findings may help better predict and analyze prognosis in patients receiving ECLS.


[From morbid obesity to complex obesity: somato-psychic issues].
Complex obesity is a chronic, multifactorial pathology. These repercussions (respiratory insufficiency, hypoventilation syndrome, cardiac insufficiency, loss of functional autonomy and mobility with a tendency to grabatization, depression, behavioral disorders) directly sustain the disease. Access to care is virtually impossible for them outside specialized obesity centers (CSO) and specialized medical and rehabilitation care (SMR). We need to support healthcare teams by analyzing their practices, including those of expert patients, to ensure that complex obesity is treated with the humanity it requires.


Energy efficiency in residential buildings amid COVID-19: A holistic comparative analysis between old and new normal occupancies.
Stringent lockdowns have been one of the defining features of the COVID-19 pandemic. Lockdowns have brought about drastic changes in living styles, including increased residential occupancy and telework practices predicted to last long. The variation in occupancy pattern and energy use needs to be assessed at the household level. Consequently, the new occupancy times will impact the performance of energy efficiency measures. To address these gaps, this work uses a real case study, a two-story residential building in the Okanagan Valley (British Columbia, Canada). Further, steady-state building energy simulations are performed on the HOT2000 tool to evaluate the resiliency of energy efficiency measures under a full lockdown. Three-year monitored energy data is analyzed to study the implications of COVID-19 lockdowns on HVAC and non-HVAC loads at a monthly temporal scale. The results show a marked change in energy use patterns and a higher increase in May 2020 compared to the previous two years. Calibrated energy models built on HOT2000 are then used to study the impacts of pre-COVID-19 (old normal occupancy) and post-COVID-19 (new normal occupancy) on energy upgrades performance. The simulations show that under higher occupancy times, the annual electricity use increased by 16.4%, while natural gas use decreased by 7.6%. The results indicate that overall residential buildings following pre-COVID-19 occupancy schedules had higher energy-saving potential than those with new normal occupancy. In addition, the variation in occupancy and stakeholder preferences directly impact the ranking of energy efficiency measures. Furthermore, this study identifies energy efficiency measures that provide flexibility for the decision-makers by identifying low-cost options feasible under a range of occupancy schedules.


[Diagnosis and therapy of masseter hypertrophy].
The history, clinical signs and radiographic features of masseteric muscle hypertrophy are illustrated. Functional treatment is described based on the cause and pathogeny of the gnathic disorder. Malocclusion appears to be the most important aetiological factor.


Homogentisate phytyltransferase from the unicellular green alga Chlamydomonas reinhardtii.
Homogentisate phytyltransferase (HPT) (EC 2.5.1.-) catalyzes the first committed step of tocopherol biosynthesis in all photosynthetic organisms. This paper presents the molecular characterization and expression analysis of HPT1 gene, and a study on the accumulation of tocopherols under different environmental conditions in the unicellular green alga Chlamydomonas reinhardtii. The Chlamydomonas HPT1 protein conserves all the prenylphosphate- and divalent cation-binding sites that are found in polyprenyltransferases and all the amino acids that are essential for its catalytic activity. Its hydrophobicity profile confirms that HPT is a membrane-bound protein. Chlamydomonas genomic DNA analysis suggests that HPT is encoded by a single gene, HPT1, whose promoter region contains multiple motifs related to regulation by jasmonate, abscisic acid, low temperature and light, and an ATCTA motif presents in genes involved in tocopherol biosynthesis and some photosynthesis-related genes. Expression analysis revealed that HPT1 is strongly regulated by dark and low-temperature. Under the same treatments, α-tocopherol increased in cultures exposed to darkness or heat, whereas γ-tocopherol did it in low temperature. The regulatory expression pattern of HPT1 and the changes of tocopherol abundance support the idea that different tocopherols play specific functions, and suggest a role for γ-tocopherol in the adaptation to growth under low-temperature.


Exhaled aerosols among PCR-confirmed SARS-CoV-2-infected children.
Available data on aerosol emissions among children and adolescents during spontaneous breathing are limited. Our aim was to gain insight into the role of children in the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and whether aerosol measurements among children can be used to help detect so-called superspreaders-infected individuals with extremely high numbers of exhaled aerosol particles. In this prospective study, the aerosol concentrations of SARS-CoV-2 PCR-positive and SARS-CoV-2 PCR-negative children and adolescents (2-17 years) were investigated. All subjects were asked about their current health status and medical history. The exhaled aerosol particle counts of PCR-negative and PCR-positive subjects were measured using the Resp-Aer-Meter (Palas GmbH, Karlsruhe, Germany) and compared using linear regression. A total of 250 children and adolescents were included in this study, 105 of whom were SARS-CoV-2 positive and 145 of whom were SARS-CoV-2 negative. The median age in both groups was 9 years (IQR 7-11 years). A total of 124 (49.6%) participants were female, and 126 (50.4%) participants were male. A total of 81.9% of the SARS-CoV-2-positive group had symptoms of viral infection. The median particle count of all individuals was 79.55 particles/liter (IQR 44.55-141.15). There was a tendency for older children to exhale more particles (1-5 years: 79.54 p/L; 6-11 years: 77.96 p/L; 12-17 years: 98.63 p/L). SARS-CoV-2 PCR status was not a bivariate predictor (t = 0.82, p = 0.415) of exhaled aerosol particle count; however, SARS-CoV-2 status was shown to be a significant predictor in a multiple regression model together with age, body mass index (BMI), COVID-19 vaccination, and past SARS-CoV-2 infection (t = 2.81, p = 0.005). COVID-19 vaccination status was a highly significant predictor of exhaled aerosol particles (p < .001). During SARS-CoV-2 infection, children and adolescents did not have elevated aerosol levels. In addition, no superspreaders were found.


Germ Line Versus Soma in the Transition from Egg to Embryo.
With few exceptions, all animals acquire the ability to produce eggs or sperm at some point in their life cycle. Despite this near-universal requirement for sexual reproduction, there exists an incredible diversity in germ line development. For example, animals exhibit a vast range of differences in the timing at which the germ line, which retains reproductive potential, separates from the soma, or terminally differentiated, nonreproductive cells. This separation may occur during embryonic development, after gastrulation, or even in adults, depending on the organism. The molecular mechanisms of germ line segregation are also highly diverse, and intimately intertwined with the overall transition from a fertilized egg to an embryo. The earliest embryonic stages of many species are largely controlled by maternally supplied factors. Later in development, patterning control shifts to the embryonic genome and, concomitantly with this transition, the maternally supplied factors are broadly degraded. This chapter attempts to integrate these processes--germ line segregation, and how the divergence of germ line and soma may utilize the egg to embryo transitions differently. In some embryos, this difference is subtle or maybe lacking altogether, whereas in other embryos, this difference in utilization may be a key step in the divergence of the two lineages. Here, we will focus our discussion on the echinoderms, and in particular the sea urchins, in which recent studies have provided mechanistic understanding in germ line determination. We propose that the germ line in sea urchins requires an acquisition of maternal factors from the egg and, when compared to other members of the taxon, this appears to be a derived mechanism. The acquisition is early--at the 32-cell stage--and involves active protection of maternal mRNAs, which are instead degraded in somatic cells with the maternal-to-embryonic transition. We collectively refer to this model as the Time Capsule method for germ line determination.


Surgical management of perineal lacerations and rectovestibular fistulae in the mare: a retrospective study of 47 cases.
The case records of 47 mares with third-degree perineal lacerations or rectovestibular fistulae were examined to evaluate their fertility following surgical repair. Of 32 mares bred, 24 became pregnant, suggesting that surgical repair is indicated in any mare with sufficient genetic potential. Perineal trauma after surgical repair was recorded in 3 of 20 mares at subsequent parturition.


Influence of temperature and reducing conditions on the sorption of sulfate on magnetite.
The reactivity of aqueous sulfate toward magnetite was studied between 50 and 275 °C as a function of pH and the redox conditions. Under oxidizing conditions, we did not observe redox reactions and the sorption of aqueous sulfate is promoted under acidic conditions when the magnetite surface is positively charged. The effect of temperature on this retention is moderate but complex. From 50 to 125 °C the sorption edge is shifted toward low pH values, according to the variation of the point of zero charge. Above 125 °C, the effect of temperature is inverted, leading to a shift to basic pH values and an increase of the sorbed quantity. This inversion of the temperature effect is interpreted as related to changes in the nature of the complexes formed, correlated to the evolution of speciation of dissolved S(VI) species. Under reducing conditions (2bar hydrogen), sulfate is involved in redox reactions, likely as a consequence of the catalytic effect of the sorption that enhances the H(2)-sulfate reaction, producing sulfides in the gaseous, liquid, and solid phases. However, this effect is better evidenced at 125 °C than at 275 °C, illustrating the importance of surface speciation, assumed to change with temperature.


Risperidone-induced priapism in an autistic child: a case report.
Priapism is a prolonged stimulation with painful, persistent penile erection unaccompanied by sexual desire. It is a rare but serious urological emergency. Risperidone is an atypical antipsychotic widely prescribed for the treatment of behavior problems in children with autism spectrum disorder. It seems associated with priapism in children. We present a case of a 12-year-old Moroccan boy diagnosed with autism spectrum disorder who developed priapism while on an existing regimen of risperidone, and we report the treatment decisions that followed. Clinicians who prescribe risperidone should be aware of the possibility of this rare complication in their patients. Information about this possible side effect and instructions regarding appropriate response should be made available to caregivers of those in the at-risk group of young patients.


Plasma zinc, copper and serum ceruloplasmin levels of autism spectrum disorder children in Bangladesh.
Neural and cognitive processes require zinc and copper homeostasis and a normal zinc/copper ratio. Ceruloplasmin, an intrinsic antioxidant protein, maintains copper homeostasis, which might also influence autism spectrum disorder (ASD). ASD children are frequently reported with altered levels of these elements with wide geographical variations. This study evaluated any alteration in plasma zinc, copper, zinc/copper ratio and serum ceruloplasmin levels in Bangladeshi ASD children with respect to healthy controls. A cross-sectional study was conducted on 67 children aged 2 to 9 years of both sexes. Among them, 35 had ASD, while 32 were age, sex and body mass index (BMI) matched apparently healthy children. Plasma zinc and copper levels were estimated by the flame atomic absorption spectrophotometry method. Serum ceruloplasmin levels were estimated by the immunoturbidimetric method. Zinc and zinc/copper ratio in the 2-9 years old ASD children group were significantly lower (p=0.032 and p=0.002 respectively). On the other hand, copper (p=0.020) and ceruloplasmin (p = 0.045) levels were significantly higher than those of apparently healthy children. ASD was significantly associated with zinc deficiency (p=0.000) and copper toxicity (p=0.05). All children were again divided into 2-5 and 6-9 years age groups according to laboratory reference values for zinc and copper. Copper toxicity was significantly associated with ASD in the 2-5 years old age group (p=0.011), with a significant difference in plasma copper levels (p=0.009) and zinc/copper ratio (p=0.001) but not serum ceruloplasmin levels (p=0.110) compared to healthy controls. Serum ceruloplasmin was positively associated with plasma copper in ASD children of all age groups. This study shows that ASD in Bangladesh can be associated with low plasma zinc and high plasma copper and serum ceruloplasmin levels.


The participation of enteric inhibitory nerves in accommodation of the intestine to distension.
1. The amounts by which various weights distended isolated segments from the distal colons of guinea-pigs were measured. 2. Tetrodotoxin substantially reduced the distensibility of the intestine, but bretylium, guanethidine, hyoscine and methysergide had no significant effect. 3. It is concluded that a local reflex involving enteric inhibitory nerves causes an accomodation of the intestine to stretch.


No changes in the distribution of organisms responsible for septic arthritis over a 20 year period.
To assess changes in the distribution and resistance of the pathogens responsible for septic arthritis over a 20 year period in patients admitted to the same hospital unit. Retrospective study of the hospital records of patients admitted between 1979 and 1998 for septic arthritis with positive microbiological diagnosis after blood or joint cultures, or both. 303 cases of septic arthritis were studied, 141 in the period 1979-88 and 162 in the period 1989-98. The incidence between the first and second period did not vary significantly for the staphylococci (67% v. 63%), streptococci (16% v. 20%), and Gram negative bacilli (7% v. 10%). Tuberculous infections decreased from 9% to 4% (p<0.04). No gonococci were isolated in the second 10 year period. Among the staphylococcal species, there was an increase in the number of coagulase negative staphylococci (10 cases v. 21, p<0.05) between the two periods. There was no significant difference in the frequency of occurrence of methicillin resistant pathogens (12.6% v. 16.6%). The number of streptococcal B infections increased (2 v. 10 cases), and beta-lactamine resistant pneumococci emerged. In the second 10 year period, patients were older and were more likely to have co-existing disease, particularly tumoral growth, and less commonly were receiving dialysis. Localisation of joint infection was comparable except for an increase in prosthetic knee infections. The distribution and sensitivity of pathogens causing septic arthritis changed little over a 20 year period.


In vivo effect of dopamine antagonists on melanocyte-stimulating hormone cells of the goldfish (Carassius auratus L.) pituitary.
Young goldfish were injected with three dopaminergic antagonists, pimozide, sulpiride, and domperidone, for 5 (low dose) and 7 days (higher dose). Cytological and immunocytochemical techniques using anti-alpha-melanocyte-stimulating hormone (MSH) serum were applied to the pituitary. MSH cells in the three treated groups showed a decrease in immunoreactive cytoplasmic granules, a significant nuclear hypertrophy, and, after 7 days, a cellular enlargement. The nucleolus and the lamellar endoplasmic reticulum were more developed and some mitotic figures occurred. Erythrophores and occasional melanophores were in a stage of maximal dispersion. These changes were not apparent in the solvent-injected controls. The responses to the three blockers of dopaminergic receptors were similar. These data suggest that MSH release seems to be under a dopaminergic inhibitory control in the goldfish. The other cell type of the pars intermedia (PAS-positive and calcium-sensitive in the goldfish) was not clearly affected by the three drugs.


The role of degradation of fetal haemoglobin in the energy supply of very low body weight pre-term babies.
Low body weight premature babies born before the 32nd gestational week were studied to analyse the postnatal fall in plasma haemoglobin and in quantitative changes in amino acid levels. Red blood cells of premature low body weight infants were found to disintegrate more rapidly than those of mature newborns. Thin-layer ion-exchange chromatographic studies showed that amino acids originating from the degrading haemoglobin-F lead to rise in plasma amino acids. These amino acids might play a role as substrates for gluconeogenesis in the energy supply of low body weight premature babies during the special fasting state just after birth.


Retracted: Monitoring Mycoplasma pneumoniae-Specific Antibody, C-Reactive Protein, and Procalcitonin Levels in Children with Mycoplasma Pneumonia Is Important.
[This retracts the article DOI: 10.1155/2022/7976858.].


Efficacy potential of Goal Management Training to improve cognitive function in older people living with HIV.
Goal Management Training® (GMT) teaches strategies to reduce cognitive load and improve focus in everyday tasks. The aim of this study was to ascertain feasibility, acceptability, and efficacy potential of GMT for people (≥50 years) with stable HIV infection scoring low on tests of cognitive ability. A two-sample, parallel, controlled trial was carried out. Feasibility was demonstrated, as 21/30 participants in the GMT group attended ≥8 of the 9 sessions and completed at least half of the homework. There was no change on the primary performance-based cognitive outcomes in the GMT group or in the control group (n = 23). There was a meaningful improvement in self-reported cognition in those adherent to the intervention. GMT is a promising intervention for people aging with HIV who are dealing with cognitive difficulties affecting their everyday life and should be further investigated.


Microsatellite markers reveal a strong geographical structure in European populations of Castanea sativa (Fagaceae): evidence for multiple glacial refugia.
Large-scale studies on the genetic diversity of forest trees are relevant for the inventory, conservation, and management of genetic resources and provide an insight into the geographical origins of the species. This approach is appropriate to use with Castanea sativa, a tree of great economic importance and the only species from the genus Castanea in Europe. The history of C. sativa was deduced from fossil pollen data, but the large-scale genetic structure of this species needs to be elucidated. We evaluated the genetic diversity of C. sativa to define previously unclarified genetic relationships among the populations from Turkey and those from Greece and western Europe. The influence of natural events such as glaciations and human impact in terms of species distribution are discussed. • Wild chestnut trees (779) were sampled in 31 European sites. Six polymorphic microsatellites were used for the analysis. A set of measures of intra- and interpopulation genetic statistics were calculated. The population structure was inferred by using a Bayesian approach. • The population structure showed a genetic divergence between the eastern (Greek and Turkish) and western (Italian and Spanish) populations. Two gene pools and a zone of gene introgression in Turkey were revealed. • The inferred population structure shows a strong geographical correspondence with the hypothesized glacial refugia and rules out the migration of the chestnut from Turkey and Greece to Italy. The homogeneous gene pool observed in Italy and Spain could have been originated from common refugia along with human-mediated colonization.


Harnessing Diesel-Degrading Potential of an Antarctic Microalga from Greenwich Island and Its Physiological Adaptation.
Microalgae are well known for their metal sorption capacities, but their potential in the remediation of hydrophobic organic compounds has received little attention in polar regions. We evaluated in the laboratory the ability of an Antarctic microalga to remediate diesel hydrocarbons and also investigated physiological changes consequent upon diesel exposure. Using a polyphasic taxonomic approach, the microalgal isolate, WCY_AQ5_1, originally sampled from Greenwich Island (South Shetland Islands, maritime Antarctica) was identified as Tritostichococcus sp. (OQ225631), a recently erected lineage within the redefined Stichococcus clade. Over a nine-day experimental incubation, 57.6% of diesel (~3.47 g/L) was removed via biosorption and biodegradation, demonstrating the strain's potential for phytoremediation. Fourier transform infrared spectroscopy confirmed the adsorption of oil in accordance with its hydrophobic characteristics. Overall, degradation predominated over sorption of diesel. Chromatographic analysis confirmed that the strain efficiently metabolised medium-chain length n-alkanes (C-7 to C-21), particularly n-heneicosane. Mixotrophic cultivation using diesel as the organic carbon source under a constant light regime altered the car/chl-a ratio and triggered vacuolar activities. A small number of intracellular lipid droplets were observed on the seventh day of cultivation in transmission electron microscopic imaging. This is the first confirmation of diesel remediation ability in an Antarctic green microalga.


Kinetic energy deposited into a nanodroplet, cluster, or molecule in a sticking collision with background gas.
In processes when particles such as nanodroplets, clusters, or molecules move through a dilute background gas and undergo capture collisions, it is often important to know how much translational kinetic energy is deposited into the particles by these pick-up events. For sticking collisions with a Maxwell-Boltzmann gas, an exact expression is derived, which is valid for arbitrary relative magnitudes of the particle and thermal gas speeds.


Creating a Community of Nurse Educator Scholars: The QSEN Academic Task Force Success.
Engaging in scholarship is a critical component of being an effective nurse educator and can have a significant impact on the nursing profession as a whole. Nurse educators are expected to teach and simultaneously engage in scholarship. Barriers include heavy workloads and lack of resources including faculty mentors. Evidence supports that organized work groups support success. Members of the Quality and Safety Education for Nurses (QSEN) Academic Task force were queried about scholarly activity as a result of engagement with fellow task force members. Scholarly outcomes included numerous peer-reviewed publications, teaching tips, presentations, and grants. Participating in national work groups can serve as a platform for fostering a community of scholars to make meaningful contributions to the profession.


Identification of the putative first cellular step of chemical hepatocarcinogenesis.
A first cellular step of chemical hepatocarcinogenesis is characterized by identifying hepatocytes with preneoplastic properties: positivity for glutathione transferase-P or GST-P+, cell proliferation marked by bromodeoxyuridine or BUDR+, resistance to hepatotoxins and persistence. Hepatocellular doublets, both GST-P+ and BUDR+, are located immunohistochemically 4 days after a single dose of diethylnitrosamine, 25 mg/kg, using antibodies bound to different chromogens. GST-P+ hepatocytes proliferate after selection for resistance to 2-acetylaminofluorene, and persist in the absence of selection for 6 weeks. The actual probability of the same cell being GST-P+ and BUDR+ is 200 times the expected value implying close links between cell proliferation and GST-P expression at initiation.


Dendritic cells and other innate determinants of T helper cell polarisation.
Adaptive immunity plays a crucial role in natural host defence against pathogens and tumours, and is central to the long-term protective effect of vaccines. It is mediated by T and B cells that are activated through antigen-specific receptors. By contrast, innate immunity responds immediately to infection and damage, and is activated through binding of conserved pathogen or damage-associated molecules to pattern recognition receptors (PRRs) on dendritic cells (DCs) and other innate immunity cell types. Recent studies have demonstrated that the innate immune system also functions to direct the adaptive immune response, not only through antigen presentation but also by providing the key signals for the differentiation of naive CD4+ T cells into functionally distinct T helper (Th) cell subtypes.


Isolation and identification of novel high strength phenol degrading bacterial strains from phenol-formaldehyde resin manufacturing industrial wastewater.
Phenols are toxic to all types of organisms. Two bacterial strains capable of utilizing phenol as a sole carbon source were isolated from the phenol bearing industrial wastewater. Based on the biochemical test results the organisms were identified as Pseudomonas cepacia and Bacillus brevis. The organisms were very efficient in phenol degradation, the lag phase increased with increase in phenol concentration. The well-acclimatized cultures of P. cepacia and B. brevis degraded 2500 and 1750 mg l(-1) of phenol in 144 h, respectively. The organisms degrade phenol even in the presence of toxicants like thiocyanate, sulphide and cyanide. The organisms can be effectively used for treating high strength phenol containing thiocyanate, sulphide and cyanide. The P. cepacia degrades phenol with a faster rate than B. brevis. P. cepacia can be used effectively for treating high strength phenolic wastewater.


User centered and ontology based information retrieval system for life sciences.
Because of the increasing number of electronic resources, designing efficient tools to retrieve and exploit them is a major challenge. Some improvements have been offered by semantic Web technologies and applications based on domain ontologies. In life science, for instance, the Gene Ontology is widely exploited in genomic applications and the Medical Subject Headings is the basis of biomedical publications indexation and information retrieval process proposed by PubMed. However current search engines suffer from two main drawbacks: there is limited user interaction with the list of retrieved resources and no explanation for their adequacy to the query is provided. Users may thus be confused by the selection and have no idea on how to adapt their queries so that the results match their expectations. This paper describes an information retrieval system that relies on domain ontology to widen the set of relevant documents that is retrieved and that uses a graphical rendering of query results to favor user interactions. Semantic proximities between ontology concepts and aggregating models are used to assess documents adequacy with respect to a query. The selection of documents is displayed in a semantic map to provide graphical indications that make explicit to what extent they match the user's query; this man/machine interface favors a more interactive and iterative exploration of data corpus, by facilitating query concepts weighting and visual explanation. We illustrate the benefit of using this information retrieval system on two case studies one of which aiming at collecting human genes related to transcription factors involved in hemopoiesis pathway. The ontology based information retrieval system described in this paper (OBIRS) is freely available at: http://www.ontotoolkit.mines-ales.fr/ObirsClient/. This environment is a first step towards a user centred application in which the system enlightens relevant information to provide decision help.


Large mobile versus small sedentary herbivores and their resistance to seaweed chemical defenses.
Small, relatively sedentary herbivores like amphipods and polychaetes (mesograzers) often live on the plants they consume and should therefore view plants as both foods and living sites. Large, relatively mobile herbivores like fishes commonly move among, and feed from, many plants; they should view plants primarily as foods and rarely as potential living sites. In marine communities, fishes that consume plants are also important predators on mesograzers. Since seaweeds avoided by fishes should represent safer living sites for small herbivores, mesograzers living on and consuming seaweeds that are not eaten by fishes should have higher fitness than mesograzers living on plants preferred by fishes. In previous work, we demonstrated that seaweed secondary metabolites that deterred feeding by a fish and sea urchin had no effect on feeding by a common amphipod (Hay et al. 1987a). We then hypothesized that mesograzers would, in general, be less affected by seaweed chemical defenses than larger, more mobile herbivores like fishes. In this investigation, we evaluate the generality of this hypothesis by comparing the feeding of an omnivorous fish (Lagodon rhomboides) with that of an omnivorous, tube-building polychaete (Platynereis dumerilii) to see if the mesograzer prefers seaweeds avoided by the fish and if it is less affected by seaweed chemical defense. Platynereis dumerilii fed almost exclusively on Dictyota dichotoma, the seaweed eaten least by Lagodon rhomboides. The diterpene alcohols (dictyol-E and pachydictyol-A) produced by Dictyota significantly deterred feeding by Lagodon but did not affect, or at one concentration stimulated, feeding by Platynereis. Our data support the hypothesis that small, relatively sedentary herbivores that live on plants are more resistant to chemical defenses than are large, relatively mobile herbivores that move among many plants.


[Connections between respiratory regulation and paradoxical sleep in a patient with Joubert's syndrome (author's transl)].
This study reports on eight patients whose cases have been described in literature, and two patients treated by the author, showing the typical signs of Joubert's syndrome. This disease pattern is characterised by episodic hyperpnoeas and apnoeas, retardation, muscular hypotension, opsoclonia, complete or partial agenesis of the vermiform process of cerebellum, as well as a dilated fourth ventricle. The clinical symptoms are compared with the characteristic signs of REM sleep and of cataplexy.


Comment on "Early Archaean microorganisms preferred elemental sulfur, not sulfate".
Philippot et al. (Reports, 14 September 2007, p. 1534) interpreted multiple-sulfur isotopic compositions of approximately 3.5-billion-year-old marine sulfide deposits as evidence that early Archaean microorganisms were not sulfate reducers but instead metabolized elemental sulfur. However, their data can be better explained by a scenario involving poor mixing of photochemical and surface sulfide sources.


Reliability of single- and paired-pulse transcranial magnetic stimulation for the assessment of knee extensor muscle function.
This study examined inter-session and intra-session transcranial magnetic stimulation (TMS) reliability at two test stimulus intensities in the knee extensors. Strong and weak TMS was delivered via single- and paired- (3-ms and 100-ms inter-stimulus interval) pulses on the same day and different days. All stimuli were delivered during isometric contractions of the knee extensors at 20% of maximal voluntary force. Motor-evoked potentials (MEP) were assessed in quadriceps femoris muscles. Relative (intra-class correlation coefficient, ICC) and absolute (standard error of measurement, SEM) reliability and variability (coefficient of variation) were assessed. MEPs elicited by strong and weak single-pulse TMS had excellent relative reliability in all muscles as did weak short-interval and strong long-interval paired-pulse TMS (all ICC>0.75). Conversely, relative reliability of strong short-interval and weak long-interval paired-pulse TMS was lower (ICC: 0.34-0.83 and 0.22-0.97, respectively). MEP size variability was lower (P<0.05) and SEM comparable or lower in strong compared to weak TMS conditions. These results suggest single- and paired-pulse TMS at both strong and weak intensities are generally reliable in the knee extensors. Strong (or both strong and weak) single-pulse TMS is recommended. The results indicate using weak test pulses for short-interval and strong test pulses for long-interval paired-pulse TMS are recommended.


Reduced audiovisual temporal sensitivity in Chinese children with dyslexia.
Temporal processing deficits regarding audiovisual cross-modal stimuli could affect children's speed and accuracy of decoding. To investigate the characteristics of audiovisual temporal sensitivity (ATS) in Chinese children, with and without developmental dyslexia and its impact on reading ability. The audiovisual simultaneity judgment and temporal order judgment tasks were performed to investigate the ATS of 106 Chinese children (53 with dyslexia) aged 8 to 12 and 37 adults without a history of dyslexia. The predictive effect of children's audiovisual time binding window on their reading ability and the effects of extra cognitive processing in the temporal order judgment task on participants' ATS were also investigated. With increasing inter-stimulus intervals, the percentage of synchronous responses in adults declined more rapidly than in children. Adults and typically developing children had significantly narrower time binding windows than children with dyslexia. The size of visual stimuli preceding auditory stimuli time binding window had a marginally significant predictive effect on children's reading fluency. Compared with the simultaneity judgment task, the extra cognitive processing of the temporal order judgment task affected children's ATS. The ATS of 8-12-year-old Chinese children is immature. Chinese children with dyslexia have lower ATS than their peers.


Cancer patients' perceptions of positive and negative illness-related changes.
We assessed perceived cancer-related change in 153 recently diagnosed patients. High levels of social support and optimism at the start of chemotherapy predicted higher numbers of perceived positive changes and lower numbers of negative changes nine months later. Higher numbers of perceived gains predicted an increase in positive affect, and higher numbers of negative changes predicted an increase in negative affect at follow-up. We conclude that finding positive consequences of cancer promotes psychological well-being, but patients with low levels of psychosocial resources are at risk for finding nothing beneficial in adversity.


Whole body movement strategies during sit-to-stand and stair ascent in individuals with a lower limb amputation: A systematic review.
Individuals with a lower limb amputation use compensatory strategies during essential tasks such as sit-to-stand and stair ascent leading to secondary physical conditions. The ensuing biomechanical parameters outlining the motion strategies they put in place need to be identified and described. We searched three databases (Embase, IEEE Xplore and PubMed) for articles on the spatiotemporal, the kinematics and the kinetics that compared the amputated, the intact lower limbs, or the trunk of individuals with a unilateral transtibial or transfemoral amputation with the limbs of a control group. We found twenty articles. During sit-to-stand, individuals with a lower limb amputation increased the trunk inclination angle toward the intact lower limb, explaining higher ground reaction forces and peak knee sagittal power generation. During stair ascent, individuals with a lower limb amputation increased the stance phase duration on the intact lower limb. Moreover, individuals with a lower limb amputation increased both lower limbs hip extension moment and power, and the amputated lower limb knee extension moment. In both tasks, the individuals with a transfemoral amputation presented larger differences than those with transtibial compared to the control group. Both lower limbs intact joint moment and power were increased to compensate for the prosthesis passive joint and to ensure stability. Stair gait studies mainly focused on the lower limbs' biomechanical changes in the sagittal plane, while sit-to-stand studies focused on asymmetries without comparing the lower limbs independently. Better methodological descriptions are essential to enhance the external validity of previous results.


Reappraisal of the multicellular preparation for the in vitro physiopharmacological evaluation of myocardial performance.
In order to evaluate myocardial performance, single cardiomyocytes suffer from technical problems and from the fact that some basic functional properties vanish when one moves down the hierarchic scale from multicellularity to single cells. The isolated papillary muscle has at present proven to be superior to the isolated intact cardiomyocyte. A large number of major intra- and extracellular features required to describe myocardial performance can be derived from analyzing twitch contraction and relaxation in the multicellular isolated papillary muscle. In addition, the present paper illustrates the possibility to differentiate between effects of inotropic interventions on activating Ca2+ and Ca2+ sensitivity in multicellular preparations, from a grid analysis of isometric twitches in a coordinate system of peak rate of force development (+dF/dt; reflecting the time pattern of twitch contraction) versus time to half relaxation (tHR; reflecting the time pattern of twitch relaxation). The abundance of information about myocardial performance that can be derived from the easily accessible multicellular preparation reflects its physiological kinship with the intact ventricle.


Activation of the haemostatic system in children with juvenile rheumatoid arthritis correlates with disease activity.
Twenty-four children with juvenile rheumatoid arthritis (JRA) and 10 children with postinfectious arthropathies were investigated for markers of blood coagulation and fibrinolytic activity: Prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex (TAT), and D-Dimer were measured using solid phase enzyme linked immunosorbent assays (ELISA). Results were compared with clinical and conventional laboratory signs of disease activity. F1+2, TAT, D-Dimer, and fibrinogen were significantly elevated in children with JRA as compared with healthy children and children with postinfectious arthropathies. F1+2, TAT, and D-Dimer correlated significantly with disease activity, assessed by determination of the joint index score and C-reactive protein (CRP). The study demonstrates a subclinical activation of the haemostatic system in children with JRA correlating with disease activity, which might be caused by the action of several immunomediators on cells (monocytes, endothelial cells) playing a role in the regulation of blood coagulation activity.


Sexual selection versus alternative causes of sexual dimorphism in teiid lizards.
The presence and extent of sexual dimorphisms in body form (size and shape) of adult macroteiid lizards were investigated. Males were significantly larger than females in the temperate species, Cnemidophorus tigris, and in the tropical species, Ameiva ameiva and C. ocellifer. Young adult C. tigris males grew faster than young adult females within and between reproductive seasons. Adult males of all species had larger heads than adult females of the same body size; this difference increased with body size. Moreover, male C. tigris were heavier than females of the same snout-vent length. The causes and consequences of the sexual dimorphisms were also examined. The possible causes of body size are especially numerous, and distinguishing the relative influences of the various causal selection factors on body size is problematical. Nevertheless, observational field data were used to tentatively conclude that intrasexual selection was the cause of larger body size of C. tigris males relative to females because (1) larger males won in male aggressive interactions, (2) the winning males gained access to more females by repelling competitors and by female acceptance, (3) larger males consequently had higher reproductive success, and (4) other hypothetical causes of larger male size were unsupported.


Assessing the recovery in species, size and location diversities of a lowland tropical rainforest after shifting cultivation by multiple indices at stand and neighborhood scales.
Tropical forests are rapidly being converted for agricultural use, but abandoned agricultural lands can recover naturally through secondary succession. However, comprehensive knowledges of how species composition, size structure and spatial patterning (represented by species, size and location diversities) change during recovery at multiple scales are still lacking. Our aim was to explore these change patterns to understand the underlying mechanisms of forest recovery and propose corresponding solutions for restoring regrowing secondary forests. Here, twelve 1ha forest dynamics plots (4 plots each in young-secondary forests (YS), old-secondary forests (OS) and old-growth forests (OG) from a chronosequence of tropical lowland rainforest after shifting cultivation) were used to assessed the recovery in species, size and location diversity of trees at stand (plot) and neighborhood (focal tree and its neighbors) scale by using 8 indices. The relative recoveries of YS and OS were quantified by dividing each of the indices in YS and OS to those in OG. Results showed that species and size diversity increased while location diversity decreased with the recovery process. The relative recovery of location diversity was higher than those of species and size diversity in both YS and OS, while species diversity was only higher than size diversity in YS. The relative recovery of species diversity at neighborhood scale was higher than that at stand scale in OS, while there were no differences between scales in size and location diversity. Additionally, using only the Shannon index and Gini coefficient at two scales can provide consistent insights into the recovery patterns of diversity as indicated by the 8 indices. Our study demonstrated that recovery rates of secondary forests relative to old-growth counterparts could be comprehensively quantified using multiple diversity indices in three types at two scales. This quantitative assessment on the relative recovery of disturbed forests could be helpful in applying appropriate management activities and selecting rational approaches to speed up restoration process of degraded forest ecosystems.


Experimental acute pancreatitis: MR relaxation time studies using gadolinium-DTPA.
Spin-lattice (T1) and spin-spin (T2) relaxation times of normal and sodium taurocholate-induced pancreatitis (38 rats) were determined in vitro using a 10.7-MHz magnetic resonance (MR) spectrometer. The increase in pancreatic T1 time in acute hemorrhagic pancreatitis correlated well with the elevated water content of the organ. Gadolinium-DTPA did not affect significantly the relaxation times of normal pancreas in vitro during 1 t 20 min postinjection, but it decreased the elevated T1 times of inflamed pancreas almost to baseline values. MR imaging studies of rat pancreas in vivo (8 rats, 0.35-T resistive magnet) indicated that the swollen pancreas and associated edema were depicted using a T2-weighted SE sequence. Fifteen minutes postinjection of gadolinium-DTPA a homogeneous enhancement of inflamed pancreas was detected. The differentiation of pancreatic necrotic foci from surrounding viable tissue and edema could not be detected on Gd-DTPA-enhanced MR images after 15 min postinjection although microscopical workup indicated these different tissue constituents in the pancreas.


A survey study of resistance to discharge from speech-language therapy.
A survey was designed to investigate the previously unaddressed issue of resistance to discharge from speech therapy. One hundred and eighty-seven speech-language clinicians in clinical and hospital settings were sent a questionnaire based on research from the medical profession indicating that patients may become overly dependent on their physicians. Eighty-six percent of 159 usable respondents reported their clients resisted discharge. Many speech-language pathologists suggested techniques they have used to manage such clients.


Serum rapidly mobilizes calcium from an intracellular pool in quiescent fibroblastic cells.
Addition of dialysed fetal bovine serum to quiescent cultures of Swiss 3T3 cells loaded with 45Ca2+ causes a very rapid increase in the rate of 45Ca2+ efflux from an intracellular pool. Exposure to serum for 2 min leads to a fall of 0.59 nmol Ca2+/mg protein in the intracellular Ca2+ content of the cells. Inhibitors of mitochondrial function prevent the stimulation of 45Ca2+ efflux by serum. The stimulation of 45Ca2+ efflux by serum is also observed in quiescent cultures of Rat-1, Swiss 3T6 and BHK cells and in secondary cultures of whole mouse embryo fibroblasts.


Environmental enrichment and intranasal oxytocin administration reverse maternal separation-induced impairments of prosocial choice behavior.
Adverse early life experiences influence behavioral and physiological functions and increase vulnerability to neuropsychiatric disorders. Maternal separation (MS) is an established animal model that reproduces the features of chronic stress or adverse experiences during early life. Previous studies have been shown that MS may lead to impairments of social behaviors. Here, we investigated the effects of MS on mutual reward preferences in a double T-maze prosocial choice task. Since enriched environment (EE) and intranasal oxytocin (OT) administration have beneficial effects on cognition and social behaviors, in the present study we tested whether these treatments, alone or in combination, would affect prosocial behavior of rats which underwent MS during infancy. Rat pups underwent MS paradigm for 180 min/day from postnatal day (PND) 1-21. From PND 22-34, rats were exposed to an EE and/or received intranasal OT (2 μg/μl, 7 days). Hence, the 8 groups consisted of control (CTRL), MS, CTRL+EE, CTRL+OT and the saline groups. Assessment of prosocial choice behavior was started in adolescence. MS impaired prosocial choice behavior and reduced mutual reward preferences. Getting exposed to EE and intranasal OT administration could overcome MS-induced deficits and promoted mutual reward preferences of MS rats. Combination of short-term EE and OT strengthened prosocial behavior. Obtained results showed that EE and OT may be considered as profitable therapeutic approaches for promoting some aspects of social behavior.


Separation of cobalamin analogues in human sera binding to intrinsic factor and to R-type vitamin B12 binders.
Intrinsic factor (IF) and cobalamin-R-binding protein (R-binder) linked to polyacrylamide beads were used to absorb cobalamins from solutions and serum extracts. Both binding agents were equally effective in removing [57Co]B12 from aqueous solution. IF was more effective than R-binder in removing [57Co]B12 added to a serum extract. All endogenous cobalamins detectable in serum by saturation analysis assay were removed by absorption onto R-binder. Absorption with IF removed microbiologically-active cobalamins but left behind analogues assayable with an R-binder. However, when absorption with IF was continued the concentration of R-binding cobalamins steadily declined indicating that IF bound both types of cobalamins through the binding was less avid for the microbiologically-inactive analogues than for microbiologically-active cobalamins. Finally, the R-binding analogues in serum were carried on transcobalamin I and none was detectable on transcobalamin II. The absorption studies establish the presence of two types of cobalamins one binding preferentially to IF and the other preferentially to R-binder. Only the former is detected by microbiological assay.