Strategies for Behavioral Research in Neurology: Lessons Learned During the COVID-19 Pandemic and Applications for the Future.
Behavioral therapies are proven treatments for many neurologic conditions. However, the COVID-19 pandemic has posed significant challenges for conducting behavioral research. This article aims to (1) highlight the challenges of running behavioral clinical trials during the pandemic, (2) suggest approaches to maximize generalizability of pandemic-era studies, and (3) offer strategies for successful behavioral trials beyond the pandemic. Thousands of clinical trials have been impacted by the COVID-19 pandemic, from undergoing protocol revisions to suspension altogether. Furthermore, for ongoing trials, recruitment of diverse populations has suffered, thereby exacerbating existing inequities in clinical research. Patient adherence and retention have been affected by a myriad of pandemic-era restraints, and medical, psychiatric, and other complications from the pandemic have the potential to have long-term effects on pandemic-era study results. In the development of post-pandemic study protocols, attention should be given to designing studies that incorporate successful aspects of pre-pandemic and pandemic-era strategies to (1) broaden recruitment using new techniques, (2) improve access for diverse populations, (3) expand protocols to include virtual and in-person participation, and (4) increase patient adherence and retention.


High Rates of Damage to the Medial Patellofemoral Ligament, Lateral Trochlea, and Patellar Crest After Acute Patellar Dislocation: Magnetic Resonance Imaging Analysis.
The primary outcome of interest of this study was to determine the frequency, location, and extent of chondral injuries and medial patellofemoral ligament (MPFL) tears, along with the rate of loose bodies, in the knee after acute primary patellar dislocation. The secondary outcome of interest was to conduct a multivariate analysis to investigate whether the presence of pathoanatomic abnormalities, including structural differences in the knees of the patients, is associated with the features of the lesions. Patients who underwent magnetic resonance imaging after primary acute patellar dislocation were identified from our institutional databases. We analyzed a total of 175 magnetic resonance imaging scans of patients aged between 14 and 25 years who were eligible for inclusion. Chondral damage to the medial facet of the patella was present in 36 patients; patellar crest, 78 patients; and lateral patellar facet, 28 patients. One patient presented with chondral defects in the medial trochlear facet, whereas 118 patients showed chondral defects in the lateral trochlear facet. Loose bodies were present in 142 patients. A total of 161 patients (92%) showed MPFL damage. The patellar portion was affected in 119 patients. Of the patients, 28 showed a partially damaged MPFL (<50%), 42 showed MPFL damage greater than 50%, and 49 presented with a complete tear of the MPFL. MPFL lesions were observed on the femoral side in 42 patients. Fourteen patients presented with an avulsion fracture on the patellar side; 28 patients, on the femoral side. The MPFL was injured in 92% of 175 patients after a first-time acute patellar dislocation. Chondral damage was most frequent at the patellar crest, followed by the lateral femoral epicondyle. No association was found between patella alta, the sulcus angle, the Q angle, the tibial tubercle-trochlear groove distance, trochlear and patellar dysplasia, and soft-tissue damage. Level IV, retrospective cohort study.


Displacement of a dental implant into the maxillary sinus after internal sinus floor elevation: report of a case and review of literature.
Dental implant placement in the posterior maxilla may be complicated by implant migration into the maxillary sinus. To report the clinical and radiological characteristics of a patient who experienced dental implant displacement into the maxillary sinus following sinus floor elevation, and to compare our findings with those of other published reports of the displacement of dental implants. Implant placement and maxillary sinus elevation were performed simultaneously. The location of the displaced implant was monitored for 8 years, until the ectopic implant was surgically removed using the lateral window approach. The contributing factors, treatment modality, and clinical outcome for our patient were compared with those of patients reported in the literature. The clinical characteristics of our case were similar to those of patients with displaced implants who were also asymptomatic for long periods. The clinical outcome of our case was consistent with that of patients who underwent similar surgeries. Transnasal endoscopic removal of an ectopic implant may be suitable in cases in which the ectopic implant is accessible. Transoral direct approaches are adequate in most cases in which endoscopic approaches may be confounded. The bony-window transoral technique may allow the removal of large implants.


Multislice CT cholangiography without biliary contrast agent: technique and initial clinical results in the assessment of patients with biliary obstruction.
Our objective was to describe our technique for multislice CT cholangiography without cholangiographic contrast agent, and to present our preliminary clinical results. Thirty-seven patients with suspected biliary obstruction were studied. A multislice CT unit was used with the following technical parameters: 2.5-mm collimation; 7.5-mm/s table speed; pitch 6; 0.8-s rotation time; 300 mA; 120 kVp; 18- to 24-s scan time; scan volume ranging from the hepatic dome to below the pancreatic head; 70-s delay after injection of 150 ml of iodinated contrast agent at 4 ml/s. No biliary contrast material was given; oral iodinated contrast agent was administered to opacify bowel loops. Axial, multiplanar reformatted, and minimum intensity projection images were evaluated. The CT findings were compared with the gold standard techniques: endoscopic retrograde cholangiography (ERCP) in 30 patients, percutaneous transhepatic cholangiography in 5, and intraoperative cholangiography in 2. In 5 patients with ampullary lesions biopsy was made during ERCP, 9 underwent surgery, and 11 US-guided fine-needle aspiration. Bile ducts appeared hypodense within the surrounding enhanced structures. Regarding the site of obstruction, agreement between multislice CT and conventional cholangiography was observed in all cases. One patient presented negative findings on both CT and ERCP. In 31 of 36 (86%) patients, multislice CT cholangiography without cholangiographic contrast agent correctly assessed the cause of bile duct obstruction. Multislice CT cholangiography without cholangiographic contrast agent seems to be a promising diagnostic tool in the assessment of patients with bile duct obstruction.


Highly stereoselective synthesis of aryl/heteroaryl-C-nucleosides via the merger of photoredox and nickel catalysis.
A photoredox/nickel dual-catalyzed decarboxylative cross-coupling reaction of anomeric ribosyl/deoxyribosyl acids with aryl/heteroaryl bromides has been developed. The reaction proceeds smoothly under visible-light irradiation and features the using of cost-effective and easily handled catalysts and starting materials, which allows the highly stereoselective synthesis of diverse aryl/heteroaryl-C-nucleosides in moderate to high yields.


Specificity of Stress-Responsive Transcription Factors Nrf2, ATF4, and AP-1.
Cellular stress leads to an upregulation of gene transcription. We asked if there is a specificity in the activation of the stress-responsive transcription factors Nrf2, ATF4, and AP-1/c-Jun, or if activation of these proteins is a redundant cellular answer toward extracellular stressors. Here, we show that oxidative stress, induced by stimulation of the cells with the oxidant arsenite, strongly activated gene transcription via the stress-responsive element (StRE), while phorbol ester or tunicamycin, activators of AP-1/c-Jun or ATF4, respectively, activated AP-1 or nutrient-sensing response element-mediated transcription. Preincubation of the cells with N-acetyl-cysteine or overexpression of thioredoxin selectively attenuated arsenite-induced upregulation of StRE-regulated transcription. Expression of either dominant-negative or constitutively active mutants of Nrf2, ATF4, or c-Jun confirmed that distinct transcription units are regulated by these transcription factors. Physiological stimuli involving the activation of either Gαq-coupled designer receptors or the protein kinases c-Jun N-terminal protein kinase or p38 strongly stimulated transcription via AP-1/c-Jun, with minimal effects on Nrf2 or ATF4-responsive promoters. Thus, activation of transcription by extracellular signaling molecules shows specificity at the level of the chemical nature of the signaling molecule, at the level of the intracellular transduction process, and at the level of signal-responsive transcription factors. J. Cell. Biochem. 118: 127-140, 2017. © 2016 Wiley Periodicals, Inc.


SSRIs and cognitive performance in a working sample.
Studies of the impact of antidepressant use on cognitive performance have frequently been carried out among the elderly or on healthy volunteers. Comparatively little research has considered their impact on a relatively young, working population, particularly within the context of everyday life. To examine any association between SSRI use and cognitive performance, mood and human error at work. SSRI users and controls completed a battery of laboratory based computer tasks measuring mood and cognitive function pre- and post-work at the start and end of a working week. They also completed daily diaries reporting their work performance. SSRI use was associated with memory impairment: specifically poorer episodic, though not working or semantic memory. Effects of SSRI use on recognition memory seemed to vary according to the underlying psychopathology, while effects on delayed recall were most pronounced among those whose symptoms had not (yet) resolved. There were no detrimental effects on psychomotor speed, attention, mood or perceived human error at work. The findings lend support to the SSRIs comparative safety, even among workers, particularly as the symptoms of the underlying psychopathology are successfully addressed. Possible memory impairments may, however, be found in those taking SSRIs.


Evaluation of cardiometabolic risk markers linked to reduced left ventricular ejection fraction (LVEF) in patients with ST-elevation myocardial infarction (STEMI).
It is well established that left ventricular systolic dysfunction (LVSD), as marked by reduced left ventricular ejection fraction (LVEF), notably worsens the prognosis of ST-elevation myocardial infarction (STEMI). However, the link between cardiometabolic risk markers and LVSD seems unclear. This study aimed to investigate the differences in variables affecting reduced LVEF in STEMI patients. In the current retrospective study, 200 consecutive STEMI patients were enrolled between April 2016 to January 2017. Analysis of serum parameters, anthropometric evaluation, and echocardiography was performed after admission. The participants were categorized according to LVEF levels as follows: group1 (normal: 50-70%, n = 35), group2 (mildly reduced: 40-49%, n = 48); group3 (moderately reduced: 30-39%, n = 94) and group4 (severely reduced: < 30%, n = 23). Between-group comparisons were made using the Kruskal-Wallis test. Overall, of 200 STEMI patients with a mean age of 62 years, 27%(n = 54) were females. The median of BMI of patients in group4 (31.07 kg/m2) was significantly higher than group3 (26.35 kg/m2), group2 (25.91 kg/m2), and group1 (24.98 kg/m2; P value < 0.0001). Group4 patients showed significantly increased fasting blood sugar (FBS) than groups 1 (212.00, vs. 139.00 mg/dl; P value = 0.040). Patients in groups 1 and 2 exerted significantly elevated triglyceride levels than those in group4 (142.00, 142.50, and 95.00 mg/dl; P value = 0.001). WBC count, neutrophil%, and neutrophil to lymphocyte ratio among those in group1 (10,200/m3, 70.00%, and 2.92, respectively) were significantly lower than group4 (12,900/m3, 83.00%, and 5.47, respectively; P value < 0.05). These findings highlight higher BMI, FBS, and leucocyte count linked to LVSD, probably through increasing the inflammation and reducing LVEF levels. More extensive studies are needed to clarify the clinical relevance of these results.


The Effect of Evaluator Training on Inter- and Intrarater Reliability in High-Stakes Assessment in Simulation.
The aim of this study was to evaluate the effectiveness of a training intervention in achieving inter- and intrarater reliability among faculty raters conducting high-stakes assessment of clinical performance in simulation. High-stakes assessment of simulation performance is being adopted in nursing education. However, limited research exists to guide best practices in training raters, which is essential to ensure fair and defensible assessment. A nationwide sample of 75 prelicensure RN program faculty participated in an experimental, randomized, controlled study. Participants completing a training intervention achieved higher inter- and intrarater reliability than control group participants when using a checklist evaluation tool. Mixed results were achieved by participants when completing a global competency assessment. The training intervention was effective in helping participants to achieve a shared mental model for use of a checklist, but more time may be necessary to achieve consistent global competence decisions.


Characterization of the copper-sensing transcriptional regulator CopR from the hyperthermophilic archeaon Thermococcus onnurineus NA1.
A putative copper ion-sensing transcriptional regulator CopR (TON_0836) from Thermococcus onnurineus NA1 was characterized. The CopR protein consists of a winged helix-turn-helix DNA-binding domain in the amino-terminal region and a TRASH domain that is assumed to be involved in metal ion-sensing in the carboxyl-terminal region. The CopR protein was most strongly bound to a region between its own gene promoter and a counter directional promoter region for copper efflux system CopA. When the divalent metals such as nickel, cobalt, copper, and iron were present, the CopR protein was dissociated from the target promoters on electrophoretic mobility shift assay (EMSA). The highest sensible ion is copper which affected protein releasing under 10 µM concentrations. CopR recognizes a significant upstream region of TATA box on CopR own promoter and acts as a transcriptional repressor in an in vitro transcription assay. Through site-directed mutagenesis of the DNA-binding domain, R34M mutant protein completely lost the DNA-binding activity on target promoter. When the conserved cysteine residues in C144XXC147 motif 1 of the TRASH domain were mutated into glycine, the double cysteine residue mutant protein alone lost the copper-binding activity. Therefore, CopR is a copper-sensing transcriptional regulator and acts as a repressor for autoregulation and for a putative copper efflux system CopA of T. onnurineus NA1.


Early recognition and treatment of postintubation dysphonia.
The most common complication of prolonged endotracheal intubation is vocal change. This dysphonia is a result of the laryngeal pathology produced by the recurrent frictional irritation of the endotracheal tube with each respiratory exchange. The purpose of this paper is to present three representative cases, stress early recognition, and outline a course of vigorous early treatment which has proved to be successful in alleviating and reducing the prolonged symptoms of this iatrogenic dysphonia.


Restoration of analgesic response of C57BL/6J-bgJ (beige-J) mice to morphine by carbachol.
C57BL/6J-bgJ (beige-J) mice respond poorly to the analgesic effects of centrally administered (intracerebroventricular; i.c.v.) morphine in the tail-flick test. In the present study C57BL/6J-bgJ mice, their littermate (heterozygous) controls, and normal Swiss mice were given carbachol (200 micrograms/ml) in their drinking water for three weeks. Carbachol had no effect on control animals. However, the carbachol-treated beige-J mice responded to i.c.v.-administered morphine (1 microgram) significantly better than untreated beige-J mice and nearly as well as the normal mice.


Circadian rhythm in the retinal pigment epithelium related to vitamin B12.
The wake-sleep rhythm is a typical circadian rhythm. It has been reported that severely disturbed wake-sleep rhythms are improved by the administration of vitamin B12. This study was designed to clarify whether vitamin B12 is universally related to the circadian rhythm. Three-week-old male Wistar Kyoto rats were fed a vitamin B12 deficient diet for 3 months. Then some of them were given intraperitoneal injections of vitamin B12. We counted phagocytized lamellar structures in the retinal pigment epithelium after the start of exposure to light in negative electron microscopic films. In vitamin B12 deficient rats, the maximum number of phagocytized lamellar structures in the retinal pigment epithelium appeared 3 hours after the start of light exposure, while in the control and vitamin B12 injected groups the peak occurred at 2 hours. This difference suggests that the retinal circadian rhythm is closely related to the level of vitamin B12.


Gram-negative bacteremia. Two cases in adults with chronic otitis media.
Chronic otitis media was the cause of septicemia in two hospitalized men. The organisms involved, K pneumoniae and B fragilis, are not usually associated with primary infections of the middle ear and would not have been traced to this site had proper cultures not been performed. In adults, the true incidence of bacteremia arising from the middle ear may be higher than suspected.


Correlation between the linearized Frank-Starling relationship and myocardial energetics in the ejecting heart. Effect of unprotected and protected global ischemia.
Previous studies noted augmented postischemic myocardial oxygen consumption as a subtle indicator of ischemic injury in the isovolumically contracting left ventricle. The present study was done to determine if the linear relationship between oxygen utilization and stroke work present in the ejecting heart would facilitate compartmentalization of this increased oxygen consumption into resting and working metabolic demands. Therefore, 18 canine hearts instructed for computerized acquisition of instantaneous pressure-volume data and quantitation of myocardial oxygen consumption were studied during incremental volume infusion while undergoing right heart bypass. Data acquisition before and after either 20 minutes of 37 degrees C global ischemia or 2 hours of 20 degrees C cardioplegic arrest allowed construction of stroke work versus end-diastolic volume and myocardial oxygen consumption versus stroke work relationships by least squares regression analysis. Although contractility was depressed 48% (p less than 0.01) after unprotected ischemia and was unchanged after cardioplegic arrest, neither group demonstrated a change in the efficiency of converting consumed oxygen to external mechanical work. In contrast, in both groups the oxygen utilization for unloaded contraction was comparably augmented by 21% and 16% (p less than 0.05), despite the varying ischemic conditions and disparate preservation of contractile function. These data suggest a highly linear correlation between oxygen consumption and external mechanical work that persists after ischemia and discriminates the components of postischemic energetic derangements. This model may be useful in the development and assessment of specific myoprotective strategies.


On the use of machine learning methods for mPSD calibration in HDR brachytherapy.
We sought to evaluate the feasibility of using machine learning (ML) algorithms for multipoint plastic scintillator detector (mPSD) calibration in high-dose-rate (HDR) brachytherapy. Dose measurements were conducted under HDR brachytherapy conditions. The dosimetry system consisted of an optimized 1-mm-core mPSD and a compact assembly of photomultiplier tubes coupled with dichroic mirrors and filters. An 192Ir source was remotely controlled and sent to various positions in a homemade PMMA holder, ensuring 0.1-mm positional accuracy. Dose measurements covering a range of 0.5 to 12 cm of source displacement were carried out according to TG-43 U1 recommendations. Individual scintillator doses were decoupled using a linear regression model, a random forest estimator, and artificial neural network algorithms. The dose predicted by the TG-43U1 formalism was used as the reference for system calibration and ML algorithm training. The performance of the different algorithms was evaluated using different sample sizes and distances to the source for the mPSD system calibration. We found that the calibration conditions influenced the accuracy in predicting the measured dose. The decoupling methods' deviations from the expected TG-43 U1 dose generally remained below 20%. However, the dose prediction with the three algorithms was accurate to within 7% relative to the dose predicted by the TG-43 U1 formalism when measurements were performed in the same range of distances used for calibration. In such cases, the predictions with random forest exhibited minimal deviations (<2%). However, the performance random forest was compromised when the predictions were done beyond the range of distances used for calibration. Because the linear regression algorithm can extrapolate the data, the dose prediction by the linear regression was less influenced by the calibration conditions than random forest. The linear regression algorithm's behavior along the distances to the source was smoother than those for the random forest and neural network algorithms, but the observed deviations were more significant than those for the neural network and random forest algorithms. The number of available measurements for training purposes influenced the random forest and neural network models the most. Their accuracy tended to converge toward deviation values close to 1% from a number of dwell positions greater than 100. In performing HDR brachytherapy dose measurements with an optimized mPSD system, ML algorithms are good alternatives for precise dose reporting and treatment assessment during this kind of cancer treatment.


Sport Participation and Ageing: Evidence from Marathon Events.
The purpose of this research is to study expectations regarding ageing (ERA) among individuals who participate in running events as well as to explore personality and demographic features as potential variables that influence ERA values. A quantitative questionnaire was selected as the predominant means of collecting the data and 196 successfully completed questionnaires were analyzed by means of the SPSS. Results indicate a positive correlation between ERA values and Change Seeker Index in our sample. Moreover gender and frequency of exercise found to have no significant effect on ERA score. Finally, ERA was examined among three generational cohorts and differences were noticed to physical subscale.


Ischemia induces cell proliferation and neurogenesis in the gerbil hippocampus in response to neuronal death.
We studied hippocampal cellular proliferation and neurogenesis processes in a model of transient global cerebral ischemia in gerbils by labelling dividing cells with 5'-Bromo-2'-deoxyuridine (BrdU). Surrounding the region of selective neuronal death (CA1 pyramidal layer of the hippocampus), an important increase in reactive astrocytes and BrdU-labelled cells was detected 5 days after ischemia. A similar result was found in the dentate gyrus (DG) 12 days after ischemia. The differentiation of the BrdU+ cells was investigated 28 days after BrdU administration by analyzing the morphology, anatomic localization and cell phenotype by triple fluorescent labelling (BrdU, adult neural marker NeuN and DNA marker TOPRO-3) using confocal laser-scanning microscopy. This analysis showed increased neurogenesis in the DG in case of ischemia and triple positive labelling in some newborn cells in CA1. Seven brain hemispheres from gerbils subjected to ischemia did not develop CA1 neuronal death; hippocampus from these hemispheres did not show any of the above mentioned findings. Our results indicate that ischemia triggers proliferation in CA1 and neurogenesis in the DG in response to CA1 pyramidal neuronal death, independently of the reduced cerebral blood flow or the cell migration from subventricular zone (SVZ).


Pharmacy students' attitudes toward patient safety in Saudi Arabia: a cross-sectional study.
There is a growing recognition of the importance of teaching patient safety to medical students to improve healthcare and minimize patients' harm; however, few studies evaluated the attitudes of pharmacy students toward patient safety. The purpose of this study was to explore the attitudes toward patient safety among pharmacy students in Saudi Arabia. A cross-sectional study was conducted among pharmacy students from four different universities using a self-administered questionnaire. The Attitudes to Patient Safety Questionnaire III (APSQ-III) was used to measure the attitude toward patient safety. The data were presented using descriptive statistics, such as percentages and means, and compared across gender using Student's t-test. All of the students who agreed to participate and signed the consent form have completed the questionnaire. Of the 347 pharmacy students who participated in the study; 63% were enrolled in the Doctor of Pharmacy Program and 37% were enrolled in the Bachelor of Pharmaceutical Sciences program. Only 46% of the participants received courses for patient safety mainly in the fourth year of their pharmacy program, and around 93% were interested to learn more about patient safety. A more positive attitude toward patient safety was reported in the domain of 'confidence to report errors', 'working hours as error cause', 'patient involvement in reducing error', and 'team functioning'. However, most negative attitudes were reported in the domains of 'Error inevitability' and 'Disclosure responsibility'. Gender differences were noticed in the attitude toward patient safety; female students had more positive attitudes in most domains of patient safety. Around one-half of the surveyed pharmacy students did not receive any courses on patient safety. Our findings emphasize the need for including patient safety courses in the curricula of the different pharmacy programs given the patient safety training importance in improving the quality of patient care.


Declining incidence trends for hip fractures have not been accompanied by improvements in lifetime risk or post-fracture survival--A nationwide study of the Swedish population 60 years and older.
Hip fracture is a common cause of disability and mortality among the elderly. Declining incidence trends have been observed in Sweden. Still, this condition remains a significant public health problem since Sweden has one of the highest incidences worldwide. Yet, no Swedish lifetime risk or survival trends have been presented. By examining how hip fracture incidence, post-fracture survival, as well as lifetime risk have developed between 1995 and 2010 in Sweden, this study aims to establish how the burden hip fractures pose on the elderly changed over time, in order to inform initiatives for improvements of their health. The entire Swedish population 60 years-old and above was followed between 1987 and 2010 in the National Patient Register and the Cause of Death Register. Annual age-specific hip fracture cumulative incidence was estimated using hospital admissions for hip fractures. Three-month and one-year survival after the first hip fracture were also estimated. Period life table was used to assess lifetime risk of hip fractures occurring from age 60 and above, and the expected mean age of the first hip fracture. The age-specific hip fracture incidence decreased between 1995 and 2010 in all ages up to 94 years, on average by 1% per year. The lifetime risk remained almost stable, between 9% and 11% for men, and between 18% and 20% for women. The expected mean age of a first hip fracture increased by 2.5 years for men and by 2.2 years for women. No improvements over time were observed for the 3-month survival for men, while for women a 1% decrease per year was observed. The 1-year survival slightly increased over time for men (0.4% per year) while no improvement was observed for women. The age-specific hip fracture incidence has decreased over time. Yet the lifetime risk of a hip fracture has not decreased because life expectancy in the population has increased in parallel. Overall, survival after hip fracture has not improved.


C-cadherin ectodomain structure and implications for cell adhesion mechanisms.
Cadherins are transmembrane proteins that mediate adhesion between cells in the solid tissues of animals. Here we present the 3.1 angstrom resolution crystal structure of the whole, functional extracellular domain from C-cadherin, a representative "classical" cadherin. The structure suggests a molecular mechanism for adhesion between cells by classical cadherins, and it provides a new framework for understanding both cis (same cell) and trans (juxtaposed cell) cadherin interactions. The trans adhesive interface is a twofold symmetric interaction defined by a conserved tryptophan side chain at the membrane-distal end of a cadherin molecule from one cell, which inserts into a hydrophobic pocket at the membrane-distal end of a cadherin molecule from the opposing cell.


Lithium distribution in mania: single-dose pharmacokinetics and sympathoadrenal function.
We examined lithium distribution after a single dose of 25 mEq in 14 drug-free manic patients. Lithium concentrations were measured in plasma, red blood cells, and urine. Maximum concentrations of lithium, times at which they were attained, and influx and efflux rate constants for extracellular fluid, red blood cell, and muscle-like compartments were estimated using a three-compartment pharmacokinetic model. Tissue lithium concentrations may continue to increase for hours after plasma lithium concentrations have peaked. Rate constants for absorption, excretion, and influx and efflux for the tissue compartments were similar to those previously reported for normal subjects. Rate constants for transport into and out of the tissue compartments correlated negatively with norepinephrine or epinephrine excretion and positively with the plasma/red cell Na+ gradient. Rate constants for efflux from red blood cell and muscle compartments correlated with measures of adrenocortical function and were higher in dexamethasone nonsuppressors than in suppressors. These data show that distribution of lithium may be related to sympathodrenal activity and Na+ distribution in manic patients.


Foliar particulate matter retention and toxic trace element accumulation of six roadside plant species in a subtropical city.
As a major source of air pollution, particulate matter (PM) and associated toxic trace elements pose potentially serious threats to human health and environmental safety. As is known that plants can reduce air PM pollution. However, the relationship between PM of different sizes and toxic trace elements in foliar PM is still unclear. This study was performed to explore the association between PM of different sizes (PM2.5, PM10, PM>10) and toxic trace elements (As, Al, Cu, Zn, Cd, Fe, Pb) as well as the correlation among toxic trace elements of six roadside plant species (Cinnamomum camphora, Osmanthus fragrans, Magnolia grandiflora, Podocarpus macrophyllus, Loropetalum chinense var. rubrum and Pittosporum tobira) in Changsha, Hunan Province, China. Results showed that P. macrophyllus had the highest ability to retain PM, and C. camphora excelled in retaining PM2.5. The combination of P. macrophyllus and C. camphora was highly recommended to be planted in the subtropical city to effectively reduce PM. The toxic trace elements accumulated in foliar PM varied with plant species and PM size. Two-way ANOVA showed that most of the toxic trace elements were significantly influenced by plant species, PM size, and their interactions (P < 0.05). Additionally, linear regression and correlation analyses further demonstrated the homology of most toxic trace elements in foliar PM, i.e., confirming plants as predictors of PM sources as well as environmental monitoring. These findings contribute to urban air pollution control and landscape configuration optimization.


Helix-coil stability constants for the naturally occurring amino acids in water. IX. Glutamic acid parameters from random poly(hydroxybutylglutamine-co-L-glutamic acid).
The synthesis and characterization of water-soluble random copolymers containing L-glutamic acid with N5-(4-hydroxybutyl)-L-glutamine and the thermally induced helix-coil transitions of these copolymers in water and in 0.1 N KCl are described. The incorporation of L-glutamic acid was found to increase the helix content of the polymer at low pH and to decrease it at high pH even though the presence of 0.1 N KCl effectively eliminated the difference between the electrostatic free energies of the helix and the coil. The Zimm-Bragg parameters sigma and s for the helix-coil transition in poly(L-glutamic acid) in water and in 0.1 N KCl were deduced from an analysis of the melting curves of the copolymers in the manner described in earlier papers. The synthesis of N-acetyl-N'-methylglutamic acid amide and its titration, as well as that of the copolymers and poly(L-glutamic acid), in 0.1 N KCl are described.


Neighborhood Resources Associated With Active Travel in Older Adults-A Cohort Study in Six European Countries.
To study associations between perceived neighborhood resources and time spent by older adults in active travel. Respondents in six European countries, aged 65-85 years, reported on the perceived presence of neighborhood resources (parks, places to sit, public transportation, and facilities) with response options "a lot," "some," and "not at all." Daily active travel time (total minutes of transport-related walking and cycling) was self-reported at the baseline (n = 2,695) and 12-18 months later (n = 2,189). Reporting a lot of any of the separate resources (range B's = 0.19-0.29) and some or a lot for all four resources (B = 0.22, 95% confidence interval [0.09, 0.35]) was associated with longer active travel time than reporting none or fewer resources. Associations remained over the follow-up, but the changes in travel time were similar, regardless of the neighborhood resources. Perceiving multiple neighborhood resources may support older adults' active travel. Potential interventions, for example, the provision of new resources or increasing awareness of existing resources, require further study.


Domain structure of Salmonella FlhB, a flagellar export component responsible for substrate specificity switching.
We have investigated the properties of the cytoplasmic domain (FlhB(C)) of the 383-amino-acid Salmonella membrane protein FlhB, a component of the type III flagellar export apparatus. FlhB, along with the hook-length control protein FliK, mediates the switching of export specificity from rod- and hook-type substrates to filament-type substrates during flagellar morphogenesis. Wild-type FlhB(C) was unstable (half-life, ca. 5 min), being specifically cleaved at Pro-270 into two polypeptides, FlhB(CN) and FlhB(CC), which retained the ability to interact with each other after cleavage. Full-length wild-type FlhB was also subject to cleavage. Coproduction of the cleavage products, FlhB(delta CC) (i.e., the N-terminal transmembrane domain FlhB(TM) plus FlhB(CN)) and FlhB(CC), resulted in restoration of both motility and flagellar protein export to an flhB mutant host, indicating that the two polypeptides were capable of productive association. Mutant FlhB proteins that can undergo switching of substrate specificity even in the absence of FliK were much more resistant to cleavage (half-lives, 20 to 60 min). The cleavage products of wild-type FlhB(C), existing as a FlhB(CN)-FlhB(CC) complex on an affinity blot membrane, bound the rod- and hook-type substrate FlgD more strongly than the filament-type substrate FliC. In contrast, the intact form of FlhB(C) (mutant or wild type) or the FlhB(CC) polypeptide alone bound FlgD and FliC to about the same extent. FlhB(CN) by itself did not bind substrates appreciably. We propose that FlhB(C) has two substrate specificity states and that a conformational change, mediated by the interaction between FlhB(CN) and FlhB(CC), is responsible for the specificity switching process. FliK itself is an export substrate; its binding properties for FlhB(C) resemble those of FlgD and do not provide any evidence for a physical interaction beyond that of the export process.


[Isolated neoplastic foci in the central nervous system in generalized non-Hodgkin-lymphomas. A prospective pathomorphological study (author's transl)].
A comprehensive post-mortem investigation of the central nervous system (CNS) in 103 patients with malignant non-Hodgkin-lymphomas was performed. Neoplastic foci were revealed in the CNS in 21 cases. Five of them were visible at gross examination. Strong evidence exists that the incidence of the CNS-involvement is correlated with the lymphoma-type. Our cases were classified according to the Kiel-classification (Lennert 1975). The findings suggest that CNS-infiltrations are rather common in lymphoblastomas and immunocytomas whereas they seldom occur in plasmocytomas.


Comparative study of SARS-CoV-2 antibody titers between male and female COVID-19 patients living in Kurdistan region of Iraq.
Recently, there is increasing evidence that coronavirus disease 2019 (COVID-19) causes men to experience more serious symptoms and have a higher mortality rate than women, but the association between sex and immune response stays unknown till now, and weather patient's prognosis associated with sex or not is another vague in COVID-19. In this study, the SARS-CoV-2-specific antibody titer test was performed for 727 patients who were a positive RT-PCR result for COVID-19 and we determined the difference in immune response in both genders. Patients were divided into two groups based on their genders, which were 383 males and 344 females. Plasma was collected from the patients after 17 days of diagnosis with COVID-19, and the concentrations of specific antibodies (IgG and IgM) was measured by multiparametric immunoassay system (VIDAS). Results demonstrated that there was no significant difference in both IgM and IgG production in male participants compared to women. Moreover, despite there was a weak significant positive association between age and IgM in male patients, while there was no significant correlation between IgG and age for the same gender. On the other hand, a slight positive correlation between IgM and IgG with age was observed in female participants. Finally, it concluded that there was no sex biases in patients with COVID-19 in Erbil, Iraq. So, these findings are crucial to treat and care male and female's patients infected with COVID-19 at hospitals.


Effects of COVID-19 pandemic on pediatric tuberculosis: decrease in notification rates and increase in clinical severity.
The outbreak of COVID-19 resulted in a decrease in tuberculosis notification rates globally. We compared tuberculosis incidence rates and disease severity in children seen in our centre prior and during COVID-19 pandemic.We performed a cohort study enrolling children aged under 18 years who received a diagnosis of tuberculosis (January 1st, 2010-December 31st, 2021) at our Pediatric Infectious Diseases Unit. Disease severity was evaluated based on: the classification proposed by Wiseman et al., smear positivity, presence of symptoms at presentation, lung cavitation, extrapulmonary disease, respiratory failure and need for intensive care support. Overall, 168 children (50.6% female, median age 69 months, IQR 95.4) received a diagnosis of tuberculosis, 156 (92.8%) between 2010-2019, before COVID-19 outbreak, and 12 (7.2%) between 2020-2021, during the pandemic. The annual tuberculosis notification rate dropped by 73% in 2021 (0.38/100000, 95%CI 0.1-0.96) compared with 2019 (1.46/100000, 95%CI 0.84-2.37). Compared to the pre-pandemic period, the proportion of children classified as severe was higher in 2020-2021 (5, 41.6% vs 23, 15.7%, p = 0.006) with a higher rate of respiratory failure (2, 16.7%, vs 4, 2.6%, p = 0.01) and an increased need for intensive care support (1, 8.3% vs 1, 0.6%, p = 0.01). Conclusion: During COVID-19 pandemic we observed a reduction in tuberculosis notification rate in pediatric population and a significant increase in disease severity. This scenario may be the consequence of a delay in diagnosis and an underreporting of cases, rather than the effect of a reduced transmission of tuberculosis. Children reached health-care services only in the need of urgent medical attention. What is Known: • COVID-19 pandemic had a huge impact on national health care systems, resulting in a reduction of access to medical care. What is New: • In Campania Region, Italy, a low tuberculosis incidence country, we witnessed a 75% reduction in tuberculosis notification rate during pandemic. In parallel we demonstrated a significant increase in disease severity, suggesting that the reduction in notification rate may be attributed to an underreporting of cases and consequential diagnostic delay, rather than a reduced transmission of infection.


[Practical experience with overviews of reviews--valuable decision aid or academic exercise?].
The "overview of reviews" has evolved as a method to aggregate information from systematic reviews. Based on research projects conducted by two Austrian institutions, this article aims to point out methods and perceived strengths and limitations of overviews of reviews and to discuss their application and constraints for different healthcare settings. The six analysed projects differed in their objectives as well as in the corresponding methodology. We identified the following strengths of the overviews of reviews performed: the overview of the evidence base on an issue, the rapid detection of the results of numerous reviews, the demonstration of evidence gaps and potential savings in time and resources. At the same time, the methodology could lead to a loss of information, limited relevance and to uncertainties regarding the robustness of the overall results. However, the heterogeneity of the methods used shows that the development of methods for overviews of reviews is still ongoing. Whether overviews of reviews provide valuable decision support depends on the research question and realistic expectations towards the method.


Association between polypharmacy and dementia in older people: a population-based case-control study in Taiwan.
The aim of the present study was to investigate whether polypharmacy correlates with the risk of dementia in older people. From representative claims data established from the National Health Insurance with a population coverage rate of 99% in Taiwan, we identified 7135 newly diagnosed patients with dementia in 2000-2008 and 2,8540 randomly selected controls without dementia, both aged ≥ 65 years. The daily use of prescribed drugs in the past 2 years was compared between cases and controls, controlling for demographic characters and comorbidities. The incidence of dementia increased with the number of medications used and age. Cases were older than controls, predominant with women and more likely to use five or more drugs daily (44.0% vs 32.0%, P < 0.0001). Multivariate logistic regression analysis showed that, compared with participants using zero to one drug, the odds ratios (OR) of dementia were 1.28 (95% confidence interval [CI] 1.18-1.38) for those using two to four drugs, 1.34 (95% CI 1.23-1.46) for those using five to nine drugs and 1.56 (95% CI 1.38-1.76) for those using 10 or more drugs. Cerebrovascular disease (OR 3.19), diabetes mellitus (OR 1.23), chronic kidney disease (OR 1.21) and hypertension (OR 1.08) were significant comorbidities predicting the risk of dementia. There was significant interaction between cerebrovascular disease and the number of medications used in the dementia risk. The risk of dementia increases steadily with the number of medications used and age in older people in Taiwan. Cerebrovascular disease, diabetes mellitus, chronic kidney disease and hypertension might also correlate with the risk of dementia.


Biochemical studies of the matrix of craniovertebral chordoma and a metastasis.
Glycosaminoglycans of human chordoma and a metastasis were studied. The glycosaminoglycans were derived from the extracellular matrix and consisted of chondroitin 4- and 6-sulphate, keratan sulphate and hyaluronate. The ratio of chondroitin sulphate to keratan sulphate was much lower in the metastasis than in the primary. Proteoglycan extracted with 4M guanidinium chloride and purified by associative density-gradient centrifugation was assessed on Sepharose 2B before and after reduction and alkylation. The result of this experiment suggested that only a small proportion of the proteoglycans were aggregated.


Fumarase deficiency presenting with periventricular cysts.
A fumarase-deficient patient expressed a novel phenotype of congenital cerebral ventricular dilatation and periventricular cysts. The patient was a compound heterozygote for two mutations that are the only ones among the 12 published mutations that have been found in multiple, unrelated, fumarase-deficient patients.


Defining the physiologic and pathophysiologic roles of renin: the role of specific inhibitors.
Although renin was identified as playing a role in cardiovascular homeostasis by the experiments of Goldblatt in the 1930's, neither its physiologic role in organs other than the kidney nor its contribution to the genesis of essential hypertension has been defined as yet. It is difficult to interpret studies with converting enzyme inhibitors because of their multiple pharmacologic effects. Specific inhibitors of renin appropriate for clinical investigation would help resolve many questions. Four classes of compounds have been demonstrated to be renin inhibitors of high potency: specific antibody, general peptide inhibitors of acid proteases, analogs of angiotensinogens, and peptides that are related to the amino-terminal sequence of prorenin. Of these, it is likely that angiotensinogen analogs will be the first applied in human studies. The minimal substrate for renin has the sequence: His-Pro-Phe-His-Leu-Leu-Val-Tyr. Variants of this sequence have yielded competitive inhibitors. Recently, remarkably active compounds have been synthesized by reducing the peptide bond that is cleaved by renin, or by incorporating the amino acid statine, found in pepstatin. These compounds have been shown now to be effective in dogs, rats, and monkeys, and most recently, preliminary studies have reported their efficacy in humans. Recent studies with one of these inhibitors, RIP, raise questions concerning both its specificity and site of action.


Saxagliptin ameliorated the depressive-like behavior induced by chronic unpredictable mild stress in rats: Impact on incretins and AKT/PI3K pathway.
Depression is a widespread, withering illness, resulting in a massive personal suffering and economic loss. The chronic exposure to stress may be involved in the etiology of human psychiatric disorders; such as depression. In the current study, the animals were subjected to chronic unpredictable mild stress (CUMS) for 14 days. Saxagliptin (SAXA) is a member of dipeptidyl peptidase-4 (DPP-4) inhibitors class. The current study was the first one to examine the anti-depressive effect of SAXA in an experimental model of CUMS-induced depression in rats and the possible underlying mechanisms. Animals were orally treated with SAXA (0.5, 1 and 2 mg/kg) for 14 days. SAXA treatment reversed the CUMS-induced alterations in the behavioral, biochemical as well as histopathological parameters. Moreover, it hindered the CUMS-induced increase in the oxidative stress, inflammatory, and apoptotic markers. On the other hand, it increased the monoamines levels and the neurogenic brain derived neurotrophic factor (BDNF). In addition, SAXA treatment increased the incretin hormones, glucagon like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), which are linked to the activation of protein kinase B (AKT)/phosphatidylinositol3-kinase (PI3K) pathway. In conclusion, the current study revealed that the modulation of the interplay between the key events involved in depression, including oxidative stress, inflammation, and GLP-1/PI3K/AKT signaling pathway, can explain the anti-depressant activity of SAXA.


Xiao Tan He Wei Decoction reverses MNNG-induced precancerous lesions of gastric carcinoma in vivo and vitro: Regulation of apoptosis through NF-κB pathway.
In recent years, Chinese medicine has played an important role in the prognosis of gastric cancer. Precancerous lesions of gastric carcinoma (PLGC) is a class of gastric cancer which is closely related to the gastric mucosal pathology changes in the role of carcinogenic incentives, and plays key role in the progression of normal gastric mucosal cells into gastric cancerous cells. In current experiment, we explore the relationship between Chinese traditional medicine (Xiao Tan He Wei Decoction) and gastric cancer in the PLGC rat animal models and epithelial-mesenchymal transitioned GES-1 cells which were induced useing 1- Methyl-3-nitro-1-nitrosoguanidine (MNNG). PLGC rat model showed significant deterioration in the gastric mucosa with terrible growth rate in body weight and more atypical hyperplasia in gastric mucosa. MC cells, MNNG induced GES-1 cells which epithelial- mesenchymal-transition (EMT)-related proteins have a great change compare with normal GES-1 cells. The cells had characteristics of malignant cells including proliferation, invasion and metastasis ability. Our research founds that Xiao Tan He Wei Decoction could inhibit cell proliferation and increased apoptosis by increase the level of pro-apoptotic proteins like Bax and caspase-3 and decreased the level of anti-apoptotic protein Bcl-2, block the cells in G0/G1 phase simultaneously. Furthermore, Xiao Tan He Wei Decoction could inhibit nuclear factor kappa-light-chain-enhancer (NF-kB) activity and inhibit its transfer from the cytoplasm to the nucleus. However, when we incubated with NF-κB activator PMA, the effect of Xiao Tan He Wei Decoction was reversed. These results suggested that Xiao Tan He Wei Decoction could be used as a method for the treatment of gastric precancerous lesions, and possibly provide a theoretical basis for the clinical treatment of gastric cancer and gastric precancerous lesions.


Visual dreams in the congenitally blind?
An EEG study of sleep in congenitally blind persons revealed a significant correlation between the visual activity reported during dreaming and the decrease of alpha strength recorded from the central and occipital regions of the scalp. This provides the first objective evidence that subjects who have never had visual experiences can have dreams with virtual images that are probably mediated by the activation of the cortical areas responsible for visual representations.


High-performance liquid chromatographic method for quantitation of pentamidine in blood serum.
A high-performance liquid chromatographic procedure has been developed for the determination of pentamidine concentrations in serum samples. A microbore, reversed-phase column was used with a mobile phase consisting of methanol and water with sodium heptanesulfonate and triethylamine as modifiers. Pentamidine could be extracted from serum only by the addition of an ion-pairing agent, di(2-ethylhexyl) phosphoric acid, to the chloroform used for extraction. The method can be used to reliably detect levels as low as 5 ng/ml. The pentamidine concentration in the serum of eleven patients 24 h after their tenth daily dose of pentamidine averaged 60 +/- 34 ng/ml.


Ifosfamide.
The alkylating agent ifosfamide, an analog of cyclophosphamide, has demonstrated significant activity in soft tissue sarcoma and testicular carcinoma. Understanding and control of the urinary toxicity of ifosfamide therapy has allowed greater use and inclusion of ifosfamide in combinations in the treatment of malignant diseases. While preliminary results with ifosfamide in a number of diseases are encouraging, final determination of its efficacy awaits further study. A comprehensive review of preclinical data and clinical trials with ifosfamide is presented.


Functional characterization of pathogenic human MSH2 missense mutations in Saccharomyces cerevisiae.
Hereditary nonpolyposis colorectal cancer (HNPCC) is associated with defects in DNA mismatch repair. Mutations in either hMSH2 or hMLH1 underlie the majority of HNPCC cases. Approximately 25% of annotated hMSH2 disease alleles are missense mutations, resulting in a single change out of 934 amino acids. We engineered 54 missense mutations in the cognate positions in yeast MSH2 and tested for function. Of the human alleles, 55% conferred strong defects, 8% displayed intermediate defects, and 38% showed no defects in mismatch repair assays. Fifty percent of the defective alleles resulted in decreased steady-state levels of the variant Msh2 protein, and 49% of the Msh2 variants lost crucial protein-protein interactions. Finally, nine positions are predicted to influence the mismatch recognition complex ATPase activity. In summary, the missense mutations leading to loss of mismatch repair defined important structure-function relationships and the molecular analysis revealed the nature of the deficiency for Msh2 variants expressed in the tumors. Of medical relevance are 15 human alleles annotated as pathogenic in public databases that conferred no obvious defects in mismatch repair assays. This analysis underscores the importance of functional characterization of missense alleles to ensure that they are the causative factor for disease.


Electroencephalograms in basilar artery migraine.
Nine cases of 'basilar artery migraine' (BAM) have been recorded. In 8 cases, excess of beta activity was observed during the attacks and disappeared in less than 3 days. The inter-ictal EEGs were normal. Drug ingestion was excluded each time. These EEG patterns are different from those which have been reported in the literature, i.e., transitory posterior abnormal slow waves. However, case no.1 is in agreement with the literature. The expression 'BAM' probably covers different syndromes which are further discussed.


Self-injection: Inescapable DIY and real danger? A case study and literature review.
Aesthetic medicine is booming, and expanding Internet delivery is not controlled by health authorities. More than ever, conditions are thus favorable for patient self-injection. We present the case of a 45-year-old woman self-injected in breast with hyaluronic acid purchased on the Internet. She developed a bilateral breast infection treated with antibiotic treatment. Despite the ban on the use of filler in the breast by our health authorities since 2011, we will talk about the management of this type of patient. In light of this complication, we will discuss the public health issue raised by the development of the injectable products market. We wish to emphasize in France the emergency of establishing a strict legal framework for the use of fillers.


Syphilis serology among transvestite prostitutes attending an HIV unit in Rome, Italy.
Sixty-seven transvestite prostitutes from Latin America (49 from Brazil and 18 from Colombia) who attended an HIV unit located in the inner city of Rome between January 1991 and June 1992 were studied for syphilis markers by means of both the Treponema pallidum haemoagglutination test (TPHA) and a solid phase haemadsorption test for detection of specific IgM (SPHA-IgM) which are typically present in recent infections. All participants reported more than 500 sexual partners in the past year, and 67.1% of them more than 1500 partners (between 5 and 10 partners per working day). The overall prevalence of anti-HIV antibodies in this population was 65.7%. The prevalence of positive TPHA tests in the population studied was 73.1%, while that of positive SPHA-IgM tests was 10.4%. The prevalence of positive TPHA and SPHA-IgM tests was higher among Columbians than among Brazilians (83.3% vs 69.4% and 22.2% vs 6.1%, respectively) and also showed a positive correlation with the duration of their permanence in Italy. The TPHA and SPHA-IgM positivities were significantly higher among subjects older than 29 years. Positive TPHA was also significantly higher in subjects who reported a history of heroin and/or cocaine abuse while positive SPHA-IgM was higher in subjects who did not use condoms or reported irregular use of them than in subjects who regularly used condoms. No overall correlation was evident between TPHA positivity and anti-HIV positivity, while SPHA-IgM positivity was found to be higher among anti-HIV-negative subjects.(ABSTRACT TRUNCATED AT 250 WORDS)


The necessity for improving lipid testing reagents: A real world study.
We investigated the interference of vitamin C (VitC), glycerol fructose, lipoprotein X (LpX) and lipemia on the analysis of serum lipids. Serum were collected from 44 patients with VitC infusion, serum lipid concentrations before and after VitC auto-oxidation were compared. Serum of 31 patients with glycerol fructose infusion were collected, triglycerides (TG) measured by glycerol blanking and non-blanking reagents were compared. Forty-four serum samples suspected to contain LpX were collected, LDL-C measured by reagents from five manufacturers were compared. Lipemia samples were collected, LDL-C measured using five different reagents were compared. The interference rate was considered unacceptable if it was greater than 1/2 total allowable error (TEa). In patients with VitC infusion, the interference rates of TG and total cholesterol (TC) were -59% (-123%, -28%) and -15% (-21%, -11%), respectively. In patients with glycerol fructose infusion, the interference rate of TG was 13% (4%, 113%). LpX interference led to increased LDL-C results for most reagents. Lipemia caused great interference with LDL-C analysis. VitC, glycerol fructose, LpX and lipemia significantly interfered with lipid assays. The reagent formulation should be improved to get reliable results.


Feasibility analysis of bone density evaluation with Hounsfield unit value after fibula flap reconstruction of jaw defect.
Implant-supported dentures have become an essential means of restoring occlusal function after jaw reconstruction. Bone mineral density (BMD) may influence the success rate of implant denture restorations. This study aimed to explore whether the Hounsfield unit (HU) value can be used to monitor the changing trend of fibular BMD after jaw reconstruction. A total of 54 patients who underwent maxillar/mandibular reconstruction with a fibula flap were included in this study. There was a significant correlation between the HU value and BMD at 1 week, 3 months, and 6 months after surgery, and both were significantly correlated with follow-up time. The difference between each pair of absorption rates (DAR) was less than 10% in 66.7% and 75.9% of patients at 3 and 6 months; however, the DAR was more than 20% in 12% and 13.8% of patients at 3 and 6 months, respectively. There is a significant correlation between HU value and BMD. The HU value can be used to roughly reflect the fibular BMD changing trend in a group of patients as opposed to an individual, and the HU value is not equivalent to BMD. ChiCTR, ChiCTR2300069661, retrospectively registered on 22 March 2023. Retrospectively registered, https://www.chictr.org.cn/showproj.html?proj=188953 .


Sphingosine 1-phosphate differentially regulates proliferation of C2C12 reserve cells and myoblasts.
The effect of sphingosine 1-phosphate (S1P) on the proliferative response to low serum was examined in two closely related cell populations, such as C2C12 reserve cells and myoblasts. S1P reduced DNA synthesis promoted by serum in myoblasts, whereas it enhanced the mitogenic response to serum in reserve cells. By employing selective S1P receptor agonist and antagonists, the co-mitogenic action of S1P in reserve cells was shown to depend mainly on S1P(1). Real time PCR analysis revealed distinct S1P receptor pattern expression, which however could not account for the differential action of S1P in C2C12 reserve cells and myoblasts, thereby suggesting that the cell-specific responsiveness to S1P may depend on a different functional coupling of S1P(1). This study discloses a unique pleiotropic effect of S1P which stimulates proliferation of muscle resident stem cells, such as reserve cells, and favours the growth arrest of committed progenitors cells, such as myoblasts, required for their subsequent myogenic differentiation.


The 24-hour rhythm in alcohol craving and individual differences in sleep characteristics and alcohol use frequency.
Evidence implicates sleep/circadian factors in alcohol use, suggesting the existence of a 24-h rhythm in alcohol craving, which may vary by individual differences in sleep factors and alcohol use frequency. This study sought to (1) replicate prior findings of a 24-h rhythm in alcohol craving, and (2) examine whether individual differences in sleep timing, sleep duration, or alcohol use frequency are related to differences in the timing of the peak of the craving rhythm (i.e., the acrophase) or magnitude of fluctuation of the rhythm (i.e., amplitude). Finally, whether such associations varied by sex or racial identity was explored. Two-hundred fifteen adult drinkers (21 to 35 years of age, 72% male, 66% self-identified as White) completed a baseline assessment of alcohol use frequency and then smartphone reports of alcohol craving intensity six times a day across 10 days. Sleep timing was also recorded each morning of the 10-day period. Multilevel cosinor analysis was used to test the presence of a 24-h rhythm and to estimate acrophase and amplitude. Multilevel cosinor analysis revealed a 24-h rhythm in alcohol craving. Individual differences in sleep timing or sleep duration did not predict rhythm acrophase or amplitude. However, alcohol use frequency moderated this rhythm wherein individuals who used alcohol more frequently in the 30 days prior to beginning the study had higher mean levels of craving and greater rhythm amplitudes (i.e., greater rhythmic fluctuations). Associations did not vary by sex or racial identity. Results show that alcohol craving exhibits a systematic rhythm over the course of the 24 h and that the frequency of alcohol use may be relevant to the shape of this rhythm. Consideration of daily rhythms in alcohol craving may further our understanding of the mechanisms that drive alcohol use.


Species-specific neuronal localization of kynurenine aminotransferase-2 in the mouse cerebellum.
The immunohistochemical pattern of kynurenine aminotransferase-2 (KAT-2) - the key role enzyme in the production of neuroactive and neuroprotective kynurenic acid (KYNA) - was studied in the cerebellum of mice. It is known from literature that KAT-2 is localized mainly in astrocytes in different parts of the cerebrum. Kynurenine aminotransferase (KAT) activity in the cerebellum is relatively low and alternative production routes for KYNA have been described there. Therefore we examined the immunohistochemical pattern of KAT-2 in this part of the brain. Surprisingly, the cellular localization of KAT-2 in mice was proven to be unique; it localized characteristically in Purkinje cells and in some other types of neurons (not identified) but was not found in astrocytes nor microglia. The exclusive neuronal, but not glial localization of KAT-2 in the cerebellum is novel and may be related to its low activity and to the alternative pathways for KYNA production that have been described.


Targeting the Inside of Cells with Biologicals: Chemicals as a Delivery Strategy.
Delivering macromolecules into the cytosol or nucleus is possible in vitro for DNA, RNA and proteins, but translation for clinical use has been limited. Therapeutic delivery of macromolecules into cells requires overcoming substantially higher barriers compared to the use of small molecule drugs or proteins in the extracellular space. Breakthroughs like DNA delivery for approved gene therapies and RNA delivery for silencing of genes (patisiran, ONPATTRO®, Alnylam Pharmaceuticals, Cambridge, MA, USA) or for vaccination such as the RNA-based coronavirus disease 2019 (COVID-19) vaccines demonstrated the feasibility of using macromolecules inside cells for therapy. Chemical carriers are part of the reason why these novel RNA-based therapeutics possess sufficient efficacy for their clinical application. A clear advantage of synthetic chemicals as carriers for macromolecule delivery is their favourable properties with respect to production and storage compared to more bioinspired vehicles like viral vectors or more complex drugs like cellular therapies. If biologicals can be applied to intracellular targets, the druggable space is substantially broadened by circumventing the limited utility of small molecules for blocking protein-protein interactions and the limitation of protein-based drugs to the extracellular space. An in depth understanding of the macromolecular cargo types, carrier types and the cell biology of delivery is crucial for optimal application and further development of biologicals inside cells. Basic mechanistic principles of the molecular and cell biological aspects of cytosolic/nuclear delivery of macromolecules, with particular consideration of protein delivery, are reviewed here. The efficiency of macromolecule delivery and applications in research and therapy are highlighted.


Exercise-induced asthma and the generation of neutrophil chemotactic activity.
Heat-stable neutrophil chemotactic activity (HS NCA) has been demonstrated in serum of subjects with asthma after exercise and after allergen inhalation challenge. Heat-labile neutrophil chemotactic activity (HL NCA) has been investigated only after allergen inhalation challenge. In this study, we have measured HS NCA and HL NCA after exercise of 22 adult patients with asthma, 13 of whom had exercise-induced asthma (EIA). In the 13 patients, the effect of pharmacologic pretreatment on the generation of HS NCA and EIA was evaluated in a double-blind study with inhalation of either disodium cromoglycate, terbutaline, or budesonide 15 minutes before exercise. Additionally, the effect of 4 weeks of treatment with budesonide aerosol was evaluated in an open study. A significant increase (p less than 0.01) in HS NCA was found in the patients with EIA with peak activities 15 minutes after exercise. In patients without EIA, the activity of HS NCA was variable. No HL NCA was detectable after exercise. EIA was inhibited by disodium chromoglycate, terbutaline, and 4 weeks of treatment with budesonide. The generation of HS NCA was more or less inhibited by all three drugs with 4 weeks of treatment with budesonide as the most potent regimen. No late-phase asthmatic reactions to exercise were found. It is concluded that only HS NCA is generated after exercise of subjects with asthma and that this production is controlled by antiasthmatic drugs. However, the generation of HS NCA occurs irrespective of EIA.


Oviposition cycle in the oviparous fish Xenopoecilus sarasinorum.
To clarify the reproduction of the oviparous teleost Xenopoecilus sarasinorum, changes in oocyte composition and oviposition cycle were investigated. After release, a batch of spawned eggs hung from the urogenital pore by attaching filaments (36.3+/-0.8 in number, n=31; about 4.3-7.8 mm in length, 5-8 microm in diameter) on the chorion (egg envelope) in the vegetal pole region. Females accommodated a cluster of fertilized eggs in a belly concavity until the embryos hatched. Hatching of embryos took place from 18-19 days after oviposition (25 degrees C). Between 0-2 days following hatching, the attaching filaments disappeared from the urogenital pore. Between 3 and 4 days following hatching, most of the females spawned again. The growth of oocytes proceeded slowly throughout the period when the egg cluster was carried in the belly, and no ovulation occurred during this period. If the current brood was accidentally lost, the day of the next oviposition was sooner. This might imply that carrying embryos in the belly affects endocrine activity, as in viviparous reproduction.


Effects of prolonged selenium deficiency on open field behavior and Morris water maze performance in mice.
Neurobehavioral effects of prolonged Se deficiency were evaluated using ICR mice. Dams were fed Se-deficient or Se-adequate diet starting at 4 weeks before conception through the suckling period. After weaning, offspring of both groups were given the same diet as their dams were given. The behavior of these offspring was evaluated with open field apparatus (OPF) and Morris water maze. In OPF, Se-deficient females exhibited less locomotor activity, more defecation, and less entry to the center square areas than did the control females. No such difference was found in males. In the Morris maze, Se-deficient females showed slight but significant impairment during the initial phase of the trials. The behavioral changes in OPF and the maze might have been due to an altered reactivity to a novel environment, although this possibility needs further confirmation. The obtained data showed that the altered behavior was unlikely to be due to the changes in thyroid hormones. Mechanism of these behavioral effects is discussed in relation to possible neurochemical changes induced by Se deficiency.


Optiflex angle fixation lens.
The Optiflex anterior chamber lens was implanted in 153 eyes of 150 patients. This lens was selected because it was lathe cut, with a good surface finish as demonstrated by scanning electron microscopy, had an open haptic and required a simple implantation technique. The surgeon's standard intracapsular or extracapsular technique was used and adjunctive agents, such as Healon, were not required. Observations made over an 18-month period revealed no corneal decompensation, which was probably an advantage of the lens design and insertion technique. Corneal astigmatism was the principal disadvantage.


Heterogeneity of single molecule FRET signals reveals multiple active ribosome subpopulations.
Single molecule methods have revealed that heterogeneity is common in biological systems. However, interpretations of the complex signals are challenging. By tracking the fluorescence resonance energy transfer (FRET) signals between the A-site tRNA and L27 protein in single ribosomes, we attempt to develop a qualitative method to subtract the inherent patterns of the heterogeneous single molecule FRET data. Seven ribosome subpopulations are identified using this method and spontaneous exchanges among these subpopulations are observed. All of the pretranslocation subpopulations are competent in real-time translocation, but via distinguished pathways. These observations suggest that the ribosome may function through multiple reaction pathways.


Midterm results and complications rates in vancouver type B2 and B3 periprosthetic femoral fractures treated with modular fluted tapered stems.
Evaluate the mid-term success rate of these stems in periprosthetic femur fractures and to analyze the complications observed with the use of these stems. Thirty five patients that underwent hip revision surgery secondary to Vancouver type B2 and B3 periprosthetic femur fracture were evaluated. In all cases, modular fluted tapered stems were used. Average follow-up was 42 months. Average Postoperative Harris Hip Score (HHS) was 78.11. Fracture healing was obtained in a 100% of the patients. Average implant survival was 50 months. Modular fluted tapered stems demonstrated a high rate implant stability, proximal femoral bone reconstitution, and fracture healing.


Bufalin induced apoptosis in SCC‑4 human tongue cancer cells by decreasing Bcl‑2 and increasing Bax expression via the mitochondria‑dependent pathway.
The aim of the present study was to investigate the cytotoxic effects of bufalin on SCC‑4 human tongue cancer cells. Cell morphological changes and viability were examined using phase contrast microscopy and flow cytometry, respectively. The results indicated that bufalin induced morphological changes and reduced total viable cells. Apoptotic cell death was analyzed by DAPI staining and DNA gel electrophoresis; the results revealed that bufalin induced cell apoptosis. Levels of reactive oxygen species (ROS), Ca2+, nitric oxide (NO) and mitochondrial membrane potential (ΔΨm) were measured by flow cytometry, and bufalin was observed to increase Ca2+ and NO production, decrease the ΔΨm and reduce ROS production in SCC‑4 cells. In addition, western blotting was performed to detect apoptosis‑associated protein expression. The results demonstrated that bufalin reduced the expression of the anti‑apoptotic protein B‑cell lymphoma 2 (Bcl‑2) and increased the expression of the pro‑apoptotic protein, Bcl‑2‑associated X protein. However, bufalin treatment also increased the expression of other apoptosis‑associated proteins such as apoptosis‑inducing factor and endonuclease G in SCC‑4 cells. Based on these findings, bufalin may induce apoptotic cell death via mitochondria‑dependent pathways in human tongue cancer SCC‑4 cells.


Correlation of index finger length to vertical dimensions of occlusion for edentulous patients and their satisfaction: a randomized controlled trial.
The prevalence of edentulism is pandemic and people resort to complete dentures for the restoration of missing teeth and esthetics. However, the determination of the correct occlusal vertical dimensions (OVD) constitutes to play an important role in overall patient satisfaction. The objective of this study was to apply anthropometric methods to correlate the length of index finger (2D) to measure the OVD from base of the nose to the base of the chin (Sn-Me) and to assess satisfaction by comparing both the methods. A total of 80 edentulous patients were randomized and controlled for this trial into experimental and control groups. A correlation was found between Sn-Me and finger measurements, dentures' satisfaction was assessed after a 1-week follow-up and marked according to the Visual Analog Scale. Our findings established that finger measurements are greater among males, and in both genders, positive, and statistically significant correlations exist between the facial and finger length measurements. Moreover, 97.0% patients from experimental group were satisfied with the use of complete dentures through the new anthropometric method. Hence measuring the length of index finger can be an adjunct method for the restoration of OVD and is a relatively time-effective and simple method with a satisfactory follow-up.Trial registration: ID: NCT05153213 ( https://clinicaltrials.gov/ct2/show/NCT05153213 ).


MRI-based radiomics nomogram for distinguishing solitary fibrous tumor from schwannoma in the orbit: a two-center study.
To investigate the value of magnetic resonance imaging (MRI) radiomics for distinguishing solitary fibrous tumor (SFT) from schwannoma in the orbit. A total of 140 patients from two institutions were retrospectively included. All patients from institution 1 were randomized into a training cohort (n = 69) and a validation cohort (n = 35), and patients from institution 2 were used as an external testing cohort (n = 36). One hundred and six features were extracted from T2-weighted imaging (T2WI) and contrast-enhanced T1-weighted imaging (CET1WI). A radiomics model was built for each sequence using least absolute shrinkage and selection operator logistic regression, and radiomics scores were calculated. A combined model was constructed and displayed as a radiomics nomogram. Two radiologists jointly assessed tumor category based on MRI findings. The performances of the radiomics models and visual assessment were compared via area under the curve (AUC). The performances of the radiomics nomogram combining T2WI and CET1WI radiomics scores were superior to those of the pooled readers in the training (AUC 0.986 vs. 0.807, p < 0.001), validation (AUC 0.989 vs. 0.788, p = 0.009), and the testing (AUC 0.903 vs. 0.792, p = 0.093), although significant difference was not found in the testing cohort. Decision curve analysis demonstrated that the radiomics nomogram had better clinical utility than visual assessment. MRI radiomics nomogram can be used for distinguishing between orbital SFT and schwannoma, which may help tumor management by clinicians. It is of great importance and challenging for distinguishing solitary fibrous tumor from schwannoma in the orbit. In the present study, an MRI-based radiomics nomogram were developed and independently validated, which could help the discrimination of the two entities. • It is challenging to differentiate solitary fibrous tumor from schwannoma in the orbit due to similar clinical and image features. • A radiomics nomogram based on T2-weighted imaging and contrast-enhanced T1-weighted imaging has advantages over radiologists. • Radiomics can provide a non-invasive diagnostic tool for differentiating between the two entities.


Flow cytometric analysis of changes in cytoskeletal proteins during platelet destruction and activation using a monoclonal antibody against platelet myosin.
We developed a new monoclonal antibody directed against platelet myosin (NNKY6-19). Using this antibody, we analyzed platelet cytoskeletal changes related to stimulation with thrombin and to long-term storage. Immunoelectron microscopy showed increased binding of NNKY6-19 to pseudopods and the open canalicular system during treatment with thrombin (0.1 U/ml) and during storage for 7 days. Flow cytometry also showed increased binding to platelets by NNKY6-19 and an antiactin monoclonal antibody during storage. The binding of NNKY6-19 showed an increase greater than that with the antiactin antibody after storage of platelets for 7 days and after thrombin treatment. These findings indicated that the increased binding of NNKY6-19 had some relationship to changes in intracellular myosin and platelet morphology. Thus use of NNKY6-19 allowed analysis of subtle changes related to platelet activation, which differed from those detected by antibodies against platelet glycoproteins or by the antiactin antibody. This antibody appears to provide a simple method for studying changes in platelet cytoskeletal and surface proteins.


High expression of TAZ indicates a poor prognosis in retinoblastoma.
The transcriptional co-activator, TAZ, is an important effector of the Hippo pathway and is critical for the development of human cancers. However, the expression and prognostic significance of TAZ in retinoblastoma is currently unclear. TAZ expression was examined in 43 retinoblastoma samples by immunohistochemistry. The relationship between TAZ expression and the clinicopathological features of retinoblastoma was also analyzed. Cox regression and Kaplan-Meier survival analyses were used to identify the prognostic factors for retinoblastoma patients. Finally, the effects of TAZ on cell proliferation were explored through lentivirus-mediated downregulation of TAZ in retinoblastoma cells. TAZ was highly expressed in retinoblastoma tissues and was associated with regional lymph node classification (P = 0.013), largest tumor base (P = 0.045), and differentiation (P = 0.019). Moreover, patients with high TAZ expression had shorter overall survival (OS), progression-free survival (PFS), loco-regional relapse-free survival (LRRFS), and distant metastasis-free survival (DMFS) time than patients with low TAZ expression (P < 0.05). Multivariate analysis showed that high TAZ expression was an important prognostic factor for retinoblastoma patients. In addition, downregulation of TAZ expression significantly suppressed tumor cell proliferation by blocking the transition of the cell cycle from G1 to S phase. Our findings suggest that the high expression of TAZ plays a significant role in retinoblastoma's aggressiveness, and predicts poor prognosis for patients with retinoblastoma.


Transgenic mice lacking FGF15/19-SHP phosphorylation display altered bile acids and gut bacteria, promoting nonalcoholic fatty liver disease.
Dysregulated bile acid (BA)/lipid metabolism and gut bacteria dysbiosis are tightly associated with the development of obesity and non-alcoholic fatty liver disease (NAFLD). The orphan nuclear receptor, Small Heterodimer Partner (SHP/NR0B2), is a key regulator of BA/lipid metabolism, and its gene-regulating function is markedly enhanced by phosphorylation at Thr-58 mediated by a gut hormone, fibroblast growth factor-15/19 (FGF15/19). To investigate the role of this phosphorylation in whole-body energy metabolism, we generated transgenic SHP-T58A knock-in mice. Compared with wild-type (WT) mice, the phosphorylation-defective SHP-T58A mice gained weight more rapidly with decreased energy expenditure and increased lipid/BA levels. This obesity-prone phenotype was associated with the upregulation of lipid/BA synthesis genes and downregulation of lipophagy/β-oxidation genes. Mechanistically, defective SHP phosphorylation selectively impaired its interaction with LRH-1, resulting in de-repression of SHP/LRH-1 target BA/lipid synthesis genes. Remarkably, BA composition and selective gut bacteria which are known to impact obesity, were also altered in these mice. Upon feeding a high-fat diet, fatty liver developed more severely in SHP-T58A mice compared to WT mice. Treatment with antibiotics substantially improved the fatty liver phenotypes in both groups but had greater effects in the T58A mice so that the difference between the groups was largely eliminated. These results demonstrate that defective phosphorylation at a single nuclear receptor residue can impact whole-body energy metabolism by altering BA/lipid metabolism and gut bacteria, promoting complex metabolic disorders like NAFLD. Since posttranslational modifications generally act in gene- and context-specific manners, the FGF15/19-SHP phosphorylation axis may allow more targeted therapy for NAFLD.


Gender related differences in the oxidative stress response to PCB exposure in an endangered goodeid fish (Girardinichthys viviparus).
Polychlorinated biphenyls (PCBs) are persistent xenobiotics within aquatic environments, which elicit diverse toxic effects such as induction of oxidative stress. Despite numerous earlier studies, no detailed information exists on the toxic response by different sexes in fish. The aim of this study was to determine sex-linked differences in oxidative stress response and antioxidant defenses in Girardinichthys viviparus, an endangered fish endemic to Mexico, when exposed to sub-lethal concentrations of waterborne PCBs. The biological markers evaluated were lipid peroxidation (LPOX), superoxide dismutase (SOD) and catalase (CAT) activity. Adult eight-month-old specimens born in the laboratory were exposed to (1/2) of the LC0 (0.92 mg PCBs/L) in semi-hard synthetic water and sacrificed on days 1, 2, 4, 8 and 16 for biomarker assays. Sex-linked differences were observed in the control fish with respect to all three factors assayed. PCBs elicited significant (p<0.01) time- and sex-dependent LPOX levels which were higher in the case of males. In PCB-treated G. viviparus, SOD activity was depressed in both sexes and appears to return to pre-exposure levels after 16 days in males only. In contrast, CAT was significantly induced (p<0.01) in both sexes. This enzyme may be responsible for balancing oxidative stress and antioxidant defenses under experimental conditions. PCBs at sub-lethal concentrations are hazardous to both sexes of G. viviparus since these compounds are able to induce liver LPOX and changes in the antioxidant defense activities. The relationship between these biomarkers and cytochrome P450 and CYP1A induction is also discussed.


Reliability of the spin-T cervical goniometer in measuring cervical range of motion in an asymptomatic Indian population.
To examine the intratester reliability of the Spin-T goniometer, a cervical range of motion device, in a normal Indian population. Subjects comprised 30 healthy adults with mean age of 34 years (range, 18-65 years). The subjects were stabilized in the sitting position and the Spin-T goniometer mounted on the head of the subject. The study design was a within-subject repeated intratester reliability trial conducted for cervical range of motion in 6 directions of movement. Three measurements were taken in each direction (flexion, extension lateral flexion, and lateral rotation) per participant. Reliability coefficients, intraclass correlation coefficients, and 95% confidence interval were derived from repeated-measures analysis of variance (ANOVA). Where differences in ANOVA were detected, a paired t test was conducted and the typical error values and coefficient of variance were calculated. All repeated measures showed high intraclass correlation coefficients (all >0.96, P < .01). The ANOVA detected no differences between trials for all movements except rotation. The typical error values for the rotation trials did not exceed 2.5 degrees and the coefficient of variance did not exceed 4%, which is clinically acceptable considering the normally variable cervical range of movement. In this study, the Spin-T goniometer proved to be a reliable measuring instrument for cervical range of movement in an Indian population. The use of a laser pointer fixed to the instrument ensured a consistent neutral start position.


[Effect of dietary arginine supplementation on wound healing and the relationship between dose and response in burn rats].
To examine the dose-effect of dietary L-arginine supplementation on burn wound healing. The effect of dietary L-arginine supplementation was studied in rats with deep thickness burn (10% TBSA). The time for epithelization of burn wound was determined. Photography of burn wound was taken for measuring percentage of burn wound healing area. Biopsies of burn wound were taken for measuring the content of hydroxyproline, the ratio between type I and type III collagen, and dermal cell cycle. Supplemental dietary L-arginine after burn in rats shortened the time for epithelization of burn wound, increased the content of hydroxyproline, decreased the ratio between type I and type III collagen, elevated the DNA content of dermis. Supplemental dietary L-arginine in the dose of 200 mg x kg(-1) x d(-1) was more effective than any other, 50 mg x kg(-1) x d(-1) and 800 mg kg(-1) x d(-1) showed no beneficial effect on the healing of burn wound. Suitable L-arginine supplementation can enhance burn wound healing in rats.


Neurological prognostication after cardiac arrest.
Prediction of neurological prognosis in patients who are comatose after successful resuscitation from cardiac arrest remains difficult. Previous guidelines recommended ocular reflexes, somatosensory evoked potentials and serum biomarkers for predicting poor outcome within 72 h from cardiac arrest. However, these guidelines were based on patients not treated with targeted temperature management and did not appropriately address important biases in literature. Recent evidence reviews detected important limitations in prognostication studies, such as low precision and, most importantly, lack of blinding, which may have caused a self-fulfilling prophecy and overestimated the specificity of index tests. Maintenance of targeted temperature using sedatives and muscle relaxants may interfere with clinical examination, making assessment of neurological status before 72 h or more after cardiac arrest unreliable. No index predicts poor neurological outcome after cardiac arrest with absolute certainty. Prognostic evaluation should start not earlier than 72 h after ROSC and only after major confounders have been excluded so that reliable clinical examination can be made. Multimodality appears to be the most reasonable approach for prognostication after cardiac arrest.


Analysis of childhood reactive arthritis and comparison with juvenile idiopathic arthritis.
There is currently no agreement on how to classify and diagnose reactive arthritis (ReA) and what kind of clinical and laboratory findings are specific for the diagnosis. This study retrospectively analyzed the initial clinical manifestations and laboratory findings in children diagnosed with ReA and juvenile idiopathic arthritis (JIA). A comparison was also made between these two groups to see if there were differences. A retrospective chart review was performed and 44 patients diagnosed with ReA and 80 patients with JIA were enrolled in this study. Their initial clinical manifestations and laboratory findings were also analyzed and compared. The initial clinical manifestations in ReA were analyzed including the demographic data, the preceding infection history, the duration of the infectious episode to the onset of arthritis, the duration of arthritic symptoms, and the involved joint pattern. Comparison of the initial laboratory findings between patients with ReA and JIA showed significant differences between erythrocyte sedimentation rates (ESR) in the first hour, platelet counts (p < 0.05), and ESR in the second hour (p = 0.052). Further, comparing ReA with the subtypes of JIA, significant differences were noted between ReA and the systemic type in terms of hemoglobin level, platelet counts, C-reactive protein, and first and second hour ESR (p < 0.05). However, if compared with the polyarticular or pauciarticular type, only the platelet counts showed any significant statistical difference (p < 0.05). This study summarizes clinical experiences in ReA. The differences in laboratory findings of ReA and JIA may provide a clue in making a differential diagnosis.


Cyclic haemodynamic and arterial blood gas changes during Cheyne-Stokes breathing.
A 74-year-old patient presented with congestive heart failure and continuous periodic breathing. Left ventricular ejection fraction was 20% and the lung-to-brain circulation time was prolonged to 35 s. We report on the phasic changes of the patient's arterial blood gas tensions and on the periodic fluctuations of pulmonary artery pressures and cardiac output that we observed during Swan-Ganz catheterisation.


SB-699551-A (3-cyclopentyl-N-[2-(dimethylamino)ethyl]-N-[(4'-{[(2-phenylethyl)amino]methyl}-4-biphenylyl)methyl]propanamide dihydrochloride), a novel 5-ht5A receptor-selective antagonist, enhances 5-HT neuronal function: Evidence for an autoreceptor role for the 5-ht5A receptor in guinea pig brain.
This study utilised the selective 5-ht(5A) receptor antagonist, SB-699551-A (3-cyclopentyl-N-[2-(dimethylamino)ethyl]-N-[(4'-{[(2-phenylethyl)amino]methyl}-4-biphenylyl)methyl]propanamide dihydrochloride), to investigate 5-ht5A receptor function in guinea pig brain. SB-699551-A competitively antagonised 5-HT-stimulated [35S]GTPgammaS binding to membranes from human embryonic kidney (HEK293) cells transiently expressing the guinea pig 5-ht5A receptor (pA2 8.1+/-0.1) and displayed 100-fold selectivity versus the serotonin transporter and those 5-HT receptor subtypes (5-HT(1A/B/D), 5-HT2A/C and 5-HT7) reported to modulate central 5-HT neurotransmission in the guinea pig. In guinea pig dorsal raphe slices, SB-699551-A (1 microM) did not alter neuronal firing per se but attenuated the 5-CT-induced depression in serotonergic neuronal firing in a subpopulation of cells insensitive to the 5-HT1A receptor-selective antagonist WAY-100635 (100 nM). In contrast, SB-699551-A (100 or 300 nM) failed to affect both electrically-evoked 5-HT release and 5-CT-induced inhibition of evoked release measured using fast cyclic voltammetry in vitro. SB-699551-A (0.3, 1 and 3 mg/kg s.c.) did not modulate extracellular levels of 5-HT in the guinea pig frontal cortex in vivo. However, when administered in combination with WAY-100635 (0.3 mg/kg s.c.), SB-699551-A (0.3, 1 or 3 mg/kg s.c.) produced a significant increase in extracellular 5-HT levels. These studies provide evidence for an autoreceptor role for the 5-ht5A receptor in guinea pig brain.


Sonography of multifocal hydatidosis involving lung and liver in a female child.
Hydatid disease, caused by Echinococcus granulosus, is a zoonotic infection encountered worldwide. Though involvement of the liver and lungs is quite common, pelvic involvement is rarely reported, with the incidence being 0.2-2.2 %. Ovarian and broad ligament hydatids are rare entities and are usually seen after rupture of a hepatic hydatid cyst. These cysts are usually asymptomatic, and a high index of clinical suspicion coupled with unequivocal imaging findings is required to make an accurate and timely diagnosis. We present a case of multifocal hydatid disease in a female child involving the lungs and liver and provide an account of the quintessential radiological findings.


Pathologic disruption of the distal biceps brachii tendon by synovial sarcoma.
This article illustrates the utility of musculoskeletal magnetic resonance imaging in providing contrast resolution of soft body tissues (i.e., biceps tendon) and pathologic processes (i.e., synovial sarcoma). The evaluation of biceps tendon injury and the diagnosis/staging of synovial sarcoma are best complemented by this most sensitive, non-invasive imaging method, particularly when combined as in this unique case.


Adsorption potential of ionic liquid-modified ZnO nanoparticles for highly efficient removal of azo dye: detailed isotherms and kinetics.
In this study, bare and ionic liquid-modified ZnO nanoparticles have been fabricated using microwave irradiation method. The fabricated nanoparticles were characterized by different techniques, viz. XRD, FT-IR, FESEM, and UV-Visible spectroscopy, and were explored as adsorbent for effective sequestration of azo dye (Brilliant Blue R-250) from aqueous media. Various factors affecting the adsorption efficiency of synthesized nanoparticles (bare/ionic liquid-modified) such as concentration of dye, pH of reaction media, dose of nanoparticles, and reaction time were thoroughly investigated with varying experimental conditions; on a magnetic stirrer and in a sonicator. The results exhibited a high adsorption efficiency of ionic liquid-modified nanoparticles for removal of dye as compared to the bare one. Also, an enhanced adsorption was observed via sonication in comparison with magnetic stirring. Different isotherms such as Langmuir, Freundlich, and Tempkin were elaborated. Evaluation of adsorption kinetics showed a linear pseudo-second-order equation for adsorption process. The exothermic and spontaneous nature of adsorption was further confirmed by thermodynamic investigations. As per the results obtained, it is suggested that the fabricated ionic liquid-modified ZnO nanoparticles could successfully remediate the toxic anionic dye from aqueous media. Hence, this system can be utilized for large-scale industrial applications.


An Effective Preprocessing Method for High-Quality Pan-Genome Analysis of Bacillus subtilis and Escherichia coli.
Bacillus subtilis and Escherichia coli, as widely used microbial species, are of great significance in studying microbial community relationships, adaptive evolution in various niches, engineering cell factories that produce specific products, and designing genome reduction. The pan-genome analysis is an effective method for studying the characteristics and functions of genes among and within species. Many research directions and conclusions usually depend on accurate gene identification and reliable pan-genome results. However, there currently lack enough studies showing how to achieve high-quality pan-genome results between or within certain species. This chapter will take Bacillus subtilis as an example to introduce a stepwise manner for improving the quality of the pan-genome by gradually removing confounding strains step-by-step, and ultimately obtaining a reliable high-quality pan-genome landscape of Bacillus subtilis, which could be used as a quality control protocol in pan-genome analysis pipeline. Finally, we suggest further improving the pan-genome analysis results of Escherichia coli to prove the feasibility and credibility of the quality control protocol for obtaining high-quality pan-genome landscape.


Successful long-term management of refractory cutaneous and upper airway sarcoidosis with periodic infliximab infusion.
A clinically refractory case of cutaneous sarcoidosis was successfully treated with infliximab infusion therapy at a dose of 5mg/kg. Skin lesions cleared dramatically and remain resolved during a 3(1/2) year follow-up, the longest follow-up reported to date. Ongoing biological drug therapy has been administered at a frequency of every 8-10 weeks. Despite cost and safety concerns, infliximab should be considered in cases of cutaneous sarcoidosis refractory to standard treatment protocols.


Promotion of glycerol utilization using ethanol and 1-propanol in Schizosaccharomyces pombe.
The fission yeast Schizosaccharomyces pombe does not grow in media containing glycerol as a sole carbon source but uses glycerol in the presence of ethanol. Ethanol, but not glycerol, triggered upregulation of gld1+ and fbp1+ during glucose starvation even though gld1+ and fbp1+ are essential for growth on glycerol. This upregulation occurred at a very low concentration of ethanol. The transcriptional regulation of gld1+ was tested in the presence of various alcohols, and both ethanol and 1-propanol were found to induce gld1+ and to support growth in glycerol-containing media. We suggest that S. pombe has a novel ethanol and/or 1-propanol recognition mechanism that upregulates glycerol utilization during glucose starvation.


Age-related changes in trabecular width and spacing in human iliac crest biopsies.
Age-related changes in trabecular width and spacing have been examined in iliac crest bone obtained from 96 normal subjects. The mean trabecular plate density and separation were calculated from values of trabecular bone volume and mean trabecular plate thickness. There was an age-related decrease in mean trabecular plate thickness with age in both sexes; this was statistically significant in males (P less than 0.02) but not in females. In females, there was a significant decrease in mean trabecular plate density (P less than 0.001) and increase in mean trabecular plate separation (P less than 0.001); similar but non-significant trends were observed in the males. These results demonstrate that trabecular thinning contributes to age-related bone loss in both sexes. Loss of trabeculae also occurs in both sexes, but to a greater extent in females than in males.