Evaluating Vitamin D levels in Rheumatic Heart Disease patients and matched controls: A case-control study from Nepal.
Diagnosis and treatment for Rheumatic Heart Disease (RHD) is inaccessible for many of the 33 million people in low and middle income countries living with this disease. More knowledge about risk factors and pathophysiologic mechanisms involved is needed in order to prevent disease and optimize treatment. This study investigated risk factors in a Nepalese population, with a special focus on Vitamin D deficiency because of its immunomodulatory effects. Ninety-nine patients with confirmed RHD diagnosis and 97 matched, cardiac-healthy controls selected by echocardiography were recruited from hospitals in the Central and Western region of Nepal. Serum 25(OH)D concentrations were assessed using dried blood spots and anthropometric values measured to evaluate nutritional status. Conditional logistic regression analysis was used to define association between vitamin D deficiency and RHD. The mean age of RHD patients was 31 years (range 9-70) and for healthy controls 32 years (range 9-65), with a 4:1 female to male ratio. Vitamin D levels were lower than expected in both RDH and controls. RHD patients had lower vitamin D levels than controls with a mean s-25(OH)D concentration of 39 nmol/l (range 8.7-89.4) compared with controls 45 nmol/l (range 14.5-86.7) (p-value = 0.02). People with Vitamin D insufficiency had a higher risk (OR = 2.59; 95% CI: 1.04-6.50) of also having RHD compared to people with Vitamin D concentrations >50 nmol/l. Body mass index was significantly lower in RHD patients (22.6; 95% CI, 21.5-23.2) compared to controls (24.2; 95% CI, 23.3-25.1). RHD patients in Nepal have lower Vitamin D levels and overall poor nutritional status compared to the non-RHD controls. Longitudinal studies are needed to explore the causality between RHD and vitamin D level. Future research is also recommended among Nepali general population to confirm the low level of vitamin D as reported in our control group.


Sequential activation of STIM1 links Ca2+ with luminal domain unfolding.
The stromal interaction molecule 1 (STIM1) has two important functions, Ca2+ sensing within the endoplasmic reticulum and activation of the store-operated Ca2+ channel Orai1, enabling plasma-membrane Ca2+ influx. We combined molecular dynamics (MD) simulations with live-cell recordings and determined the sequential Ca2+-dependent conformations of the luminal STIM1 domain upon activation. Furthermore, we identified the residues within the canonical and noncanonical EF-hand domains that can bind to multiple Ca2+ ions. In MD simulations, a single Ca2+ ion was sufficient to stabilize the luminal STIM1 complex. Ca2+ store depletion destabilized the two EF hands, triggering disassembly of the hydrophobic cleft that they form together with the stable SAM domain. Point mutations associated with tubular aggregate myopathy or cancer that targeted the canonical EF hand, and the hydrophobic cleft yielded constitutively clustered STIM1, which was associated with activation of Ca2+ entry through Orai1 channels. On the basis of our results, we present a model of STIM1 Ca2+ binding and refine the currently known initial steps of STIM1 activation on a molecular level.


A new class of DNA quadruplexes formed by oligodeoxyribonucleotides containing a 3'-3' or 5'-5' inversion of polarity site.
Unprecedented DNA quadruplex structures containing a 3'-3' or 5'-5' inversion of polarity site in the G-tract are presented; the quadruplexes are characterized by different elements of symmetry and glycosidic angle conformations.


Mobile X-ray outside the hospital: a scoping review.
For several years mobile X-ray equipment has been routinely used for imaging in patients too unwell within the hospital, when transportation to the radiology department was inadvisable. Now, mobile X-ray examinations are also used outside the hospital. The literature describes that fragile patients may benefit from mobile X-ray, but we need to provide insights into the breadth, depth and gaps in a body of literature. The scoping review was performed by searching PubMed, Cinahl, Embase, EconLit and Health Technology Assessment. English-, Danish-, Norwegian-, German-, Italian-, French- and Swedish-language studies, published 1.1.2009-1.5.2020 about mobile X-ray outside the hospital were included. Participants were patients examined using mobile X-ray as the intervention. PRISMA was used when eligible to build up the review. To extract data from the selected articles, we used a structured summary table. We included 12 studies in this scoping review. The results were divided into four topics:1. Target population 2. Population health 3. Experience of care and 4. Cost effectiveness. The main findings are that target population could be larger for instance including hospice patients for palliative care, group dwelling for people with intellectual disabilities, or psychiatric patients, population health may be improved, image quality seems to be good and mobile X-ray may be cost effective. Limitations of language, databases and grey literature may have resulted in studies being missed. Mobile X-ray may be used outside hospital. There seems to be potential benefits to both patients and health care staff. Based on the published studies it is not possible to draw a final conclusion if mobile X-ray examination is a relevant diagnostic offer and for whom. Further studies are needed to assess the feasibility of use in fragile patients, also regarding staff, relatives and societal consequences and therefore the topic mobile X-ray needs more research.


Neurotrophic and neuroprotective effects of a monomeric GLP-1/GIP/Gcg receptor triagonist in cellular and rodent models of mild traumatic brain injury.
A synthetic monomeric peptide triple receptor agonist, termed "Triagonist" that incorporates glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and glucagon (Gcg) actions, was previously developed to improve upon metabolic and glucose regulatory benefits of single and dual receptor agonists in rodent models of diet-induced obesity and type 2 diabetes. In the current study, the neurotrophic and neuroprotective actions of this Triagonist were probed in cellular and mouse models of mild traumatic brain injury (mTBI), a prevalent cause of neurodegeneration in both the young and elderly. Triagonist dose- and time-dependently elevated cyclic AMP levels in cultured human SH-SY5Y neuronal cells, and induced neurotrophic and neuroprotective actions, mitigating oxidative stress and glutamate excitotoxicity. These actions were inhibited only by the co-administration of antagonists for all three receptor types, indicating the balanced co-involvement of GLP-1, GIP and Gcg receptors. To evaluate physiological relevance, a clinically translatable dose of Triagonist was administered subcutaneously, once daily for 7 days, to mice following a 30 g weight drop close head injury. Triagonist fully mitigated mTBI-induced visual and spatial memory deficits, evaluated at 7 and 30 days post injury. These results establish Triagonist as a novel neurotrophic/protective agent worthy of further evaluation as a TBI treatment strategy.


Red blood cell distribution width-to-albumin ratio is associated with all-cause mortality in cancer patients.
Cancer causes a serious health burden on patients worldwide. Chronic low-level inflammation plays a key role in tumorigenesis and prognosis. However, the role of the red blood cell distribution width (RDW)-to-albumin (RA) ratio in cancer mortality remains unclear. In this retrospective cohort study, we collected clinical information from cancer patients from the Medical Information Mart for Intensive Care III (MIMIC-III) version 1.4 database and then calculated RA by dividing RDW by albumin concentration. The primary outcome was 30 days mortality, while secondary outcomes were 90 days and 1 year mortality. Next, we adopted Cox regression models to calculate hazard ratios (HR) together with 95% confidence intervals (CI) for all-cause mortalities associated with the RA ratio. For 30 days mortality, the HR (95% CI) for the high RA ratio (≥5.51) was 2.17 [95CI% (1.87-2.51); p = <0.0001], compared with the low RA ratio (<5.51). In Model 2, we adjusted sex and age and obtained HR (95% CI) of 2.17 [95CI% (1.87-2.52); p = <0.0001] for the high RA ratio (≥5.51) group, compared to that in the low RA ratio (<5.51). In Model 3, adjusting for age, sex, anion gap, hematocrit, white blood cell count, congestive heart failure, SOFA, liver disease, and renal failure resulted in HR (95% CI) of 1.74 [95CI% (1.48-2.04); p = <0.0001] for the high RA ratio (≥5.51) relative to the low RA ratio (<5.51). We also analyzed common diseases in cancer patients but found no significant association. To the best of our knowledge, this is the first study demonstrating that increased RA ratio is independently associated with increased all-cause mortality in cancer patients.


Application of MMPI alcoholism scales to older alcoholics and problem drinkers.
The MacAndrew and Holmes alcoholism scales differentiated older domiciled alcoholics and residents with disciplinary problems related to problem drinking from nonalcoholics. It is suggested that the scales can identify older problem drinkers along similar dimensions as alcoholics and that they might be applied to studying problem drinkrs who have as yet not received diagnoses of alcoholism.


Involvement of transcription factor GATA-4 in regulation of CYP19 gene during folliculogenesis and luteinization in buffalo ovary.
CYP19 gene encode aromatase, the key enzyme of estrogen biosynthesis, is regulated in species- and tissue-specific manner by alternate use of different promoters. Previously, we have reported the cloning and characterization of tissue-specific promoter and transcripts in buffalo ovary and placenta. In human and rat ovary, FSH induces the phosphorylation of transcription factor CREB (cAMP response element binding protein) through PKA pathway which binds to cAMP response element like sequence (CLS) in CYP19 gene ovarian promoter. However, in buffalo as well as in bovine, in silico analysis of ovary specific promoter sequence identified a single base pair deletion in CLS site and is designated as CLS-like sequence. To understand if CLS with a point mutation is still a functional cis-element and is involved in FSH stimulated transactivation of CYP19 gene in buffalo ovary, the present study was thus aimed to functionally characterize the role of buffalo CLS in CYP19 gene transactivation. We also studied the involvement of GATA-4, having consensus binding sites in CYP19 gene ovarian promoter in the vicinity of CLS during different stages of the buffalo estrus cycle. Reporter construct analyses and EMSA results showed that CLS is playing no significant role in CYP19 gene regulation in buffalo ovary. Real time absolute quantification of GATA-4 showed the differential expression of GATA-4 mRNA during folliculogenesis and luteinization with significantly higher transcript abundance in large follicle in comparison to other tissues. Western blot analysis of granulosa cells nuclear protein isolated from different stage of follicular development (small and large follicles) and differentiation (corpus luteum) showed that abundance of phosphorylated GATA-4 (Ser261) was significantly higher in granulosa cell nuclear protein of large follicles as compared to small follicles and corpora lutea. Interestingly, binding studies using ChIP showed significantly enhanced binding to the CYP19 gene promoter in large follicle which was seen to be declined in the luteal tissue. Similar results were obtained in the in vitro experiments as well. Finally, RNAi experiments were performed to validate the involvement of GATA-4 in CYP19 gene regulation. Results of RNAi showed that knockdown of GATA-4 mRNA significantly declined CYP19 gene mRNA as well as 17β-estradiol contents. In conclusion, result of the present study indicated that that in the absence of consensus CRE (cAMP response element); GATA-4 could be a downstream effector of cAMP/PKA pathway in regulation of CYP19 gene during folliculogenesis and luteinization.


Osteoporosis imaging.
Because osteoporotic fractures may be prevented, diagnostic techniques are essential in the assessment of osteoporosis. Conventional radiographs of the spine are not suited for diagnosing early osteoporosis, but they show fractures that may have no clinical symptoms. The radiologist should be aware of the enormous significance of these fractures for future osteoporotic fractures. Bone mass measurements are standard techniques in the diagnosis of osteoporosis, which are the basis of the WHO definition of osteoporosis. In this article the authors presented these standard techniques and newer diagnostic techniques that provide insights in the structure of trabecular bone.


Coats' disease and persistent hyperplastic primary vitreous. Role of MR imaging and CT.
Coats' disease is an idiopathic disorder in which telangiectatic and aneurysmal retinal vessels leak a lipoproteinaceous exudate, with consequent bullous retinal detachment. It is a diagnostic challenge, and CT and MR imaging provide valuable information to differentiate it from other pathologies, particularly from retinoblastoma. Typical, advanced Coats' disease shows on CT a denser substance posterior to the vitreous, which on MR is hyperintense on all pulse sequences. Contrast administration on both CT and MR might give slight linear enhancement at the boundary between vitreous and exudation. Persistent hyperplastic primary vitreous (PHPV) is a unilateral disorder in a microphthalmic eye, seen in full-term infants. PHPV rarely is bilateral in patients with Norrie's disease, Warburg syndrome, or patients with retinal dysplasia. Persistent fetal vasculature leads to fibrosis, resulting in elongation of the ciliary processes, retinal detachment, and spontaneous cataracts. The CT appearance in the disorder is quite variable; however, MR imaging may be superior in demonstrating the enhancing retrolental mass and the elongated ciliary processes.


Experimental transmission of Toxocara canis from Blattella germanica and Periplaneta americana cockroaches to a paratenic host.
The present study assessed the capacity of Blattella germanica and Periplaneta americana to disseminate and transmit infective phases of T. canis to rats, which were used as a model paratenic host. P. americana and B. germanica inoculated orally with T. canis larvated eggs shed eggs and larvae in their fecal matter during the first 6days post-inoculation. Larvae were recovered from the brain, lungs, kidneys and liver of rats that had been inoculated with either infected cockroaches or their feces. ELISAs of serum detected an increase of antibodies anti-T. canis excretion-secretion antigens, whereas Western Blot (WB) showed 4 bands (120, 50, 35 and 28kDa) that were similar to those found in positive control rats. Macroscopically, the liver and kidneys of infected rats had hemorrhagic areas with milk-spot-like lesions. The lungs showed diffuse grey protuberances. Histologically, hemorrhagic areas with leucocytic infiltrate were observed in the liver, lungs and kidneys. Some larvae were found within a granuloma that was surrounded by eosinophils and other leucocytic infiltrates. Larvae were found in the brain, but without inflammatory infiltrate. Both cockroach species that ingested larvated eggs of T. canis may shed viable larvae or eggs in their fecal matter. The induction of specific serum antibodies, presence of larvae in tissues and characteristic lesions associated with larval migration in the organs of rats that had ingested either whole adults or feces of B. germanica or P. americana demonstrate the capacity of these cockroaches to transmit toxocariosis to paratenic hosts.


Bridging The Gap in Adolescent Depression: An Action Plan Intervention.
Depression is a common diagnosis among adolescents. Routine screening for depression is recommended, yet standardization in screening and management is lacking. A care gap exists due to long wait times for referrals to counseling and other specialized care. Use of a written action plan demonstrated positive effects as an initial management tactic of elevated screening scores. A take-home action plan was provided to adolescents with elevated Patient Health Questionnaire-9 (PHQ-9) scores. Approximately 30 days after initiation, participants completed a post-intervention survey and a re-administration of the PHQ-9. Pre-intervention and post-intervention PHQ-9 scores were compared, showing a statistically significant decrease in PHQ-9 score (p = .008), with a median decrease of 4.5 points. Additionally, 92% of participants were somewhat likely or very likely to endorse the use of the action plan to a peer or friend. Using a written action plan is an effective strategy to bridge gaps in the care of adolescents with elevated depression screening scores.


Antioxidant and antiapoptotic activities of Calotropis procera latex on Catfish (Clarias gariepinus) exposed to toxic 4-nonylphenol.
Calotropis procera L. is known as medicinal plant. The Phytochemical analyzes of its latex revealed that it possessed antioxidants, namely terpenes, phenolic compounds and cardenolides, flavonoids and saponins, while tannins, alkaloids and resin were absent in moderate to high concentration. In the present study, the role of latex of Calotropis procera as antioxidant and antiapoptotic was reported. To carry out this aim, fishes were exposed to 100 µg l(-1) 4-nonylphenol as chemical pollutant. The enzymes, superoxidase dismutase, catalase, acetlycholinstrase (AchE), glutathione s-transferase, cortisol, G6PDH) and apoptotic cells increased significantly (p<0.05) accompanied by irregular disturbance of (Na(+), K(+)) ions in the presence of 4-nonylphenol. On the other hand, these enzymes, ions, and apoptotic cells decreased normally and significantly (p<0.05) in the presence of latex. Total phenol content, total capacity antioxidant, reducing power decrease significantly (p<0.05) in the presence of 4-nonylphenol and increase normally in the presence of latex. Latex was used for the first time to protect catfish after 4-nonylphenol exposure. Our study confirms that crude latex of Calotropis procera possessed antioxidant and antiapoptotic activities against the toxicity of 4-Nonylphenol.


Tautomerization of 2,6-lutidines in the presence of B(C6F5)3 using catecholborane as a precatalyst.
2,6-Lutidine and its derivatives in the presence of B(C6F5)3 undergo tautomerization to yield the corresponding enamine·B(C6F5)3 adducts when catecholborane is applied as a precatalyst. This reaction provides a straightforward way for benzylic C-H borylation of lutidines.


Near future image of orthopedics after COVID-19 pandemic.
The pandemic of the new coronavirus infection has swept the world and killed more than 5 million people, which has shocked all human beings who have believed in modern medical progress. Along with the sedation of infections, the balance between restriction and acceleration of socio-economic activities is difficult. With the spread of vaccines and the advent of viral therapeutic agents, we expect how to control this pandemic has finally become visible. In this situation, we realize that data science and robotics innovations are quite important in many medical fields. Artificial intelligence (AI) diagnosis and remote medical care are becoming a reality, and this direction will accelerate further in 2022, the first year of post-pandemic. The trend of digital transformation (Dx) will also be rushing into Orthopedics next year. In addition, research on virtual reality and augmented reality is being actively conducted, and it has become possible to use it for surgical simulation and technical training. As, in the field of abdominal surgery, remote robotic surgery will soon become available in the field of orthopedics as well. These Dx trend will prevail to our field instead of experience, and knowledge of medicine, which can change the medical care style dramatically in near future. It is crucial for orthopedic surgeons to always aim for its development and evolution.


Eutectic formation analysis of amino acid mixtures using molecular dynamics simulations.
The mechanism of eutectic formation was investigated via computer-aided molecular dynamics techniques based on experimental results. The CBZ group mixtures CBZ-l-Asp/d-AlaNH2 x HCl/methanol, CBZ-l-Asp/l-PheOMe x HCl/methanol, and CBZ-l-Tyr/l-ArgNH2 x 2HCl/methanol formed transparent eutectic melts. The non-CBZ group mixtures l-Asp/d-AlaNH2 x HCl/methanol, l-Asp/l-PheOMe x HCl/methanol, and l-Tyr/l-ArgNH2 x 2HCl/methanol did not form eutectic melts. According to molecular dynamics simulation results, increase in the kinetic energy values of eutectic forming mixtures was much larger than the increase in potential energy over a temperature shift from 298 to 333 K. However, the results for non-eutectic forming mixtures were reversed. The Coulomb interaction energies of eutectic forming mixtures significantly decreased, because eutectic melting can increase the mobility of molecules in the mixtures. The enhancement of molecular mobility was confirmed by increased self-diffusion constant values, and the change of solid-to-liquid phase was detected by radial distribution function results. The periodic boundary conditions for calculation of molecular dynamics were found to be reliable.


Simulation of pH-Dependent, Loop-Based Membrane Protein Gating Using Pretzel.
Bacterial porins often exhibit ion conductance and gating behavior which can be modulated by pH. However, the underlying control mechanism of gating is often complex, and direct inspection of the protein structure is generally insufficient for full mechanistic understanding. Here we describe Pretzel, a computational framework that can effectively model loop-based gating events in membrane proteins. Our method combines Monte Carlo conformational sampling, structure clustering, ensemble energy evaluation, and a topological gating criterion to model the equilibrium gating state under the pH environment of interest. We discuss details of applying Pretzel to the porin outer membrane protein G (OmpG).


Association Between Wearable Device-Based Measures of Physical Frailty and Major Adverse Events Following Lower Extremity Revascularization.
Physical frailty is a key risk factor associated with higher rates of major adverse events (MAEs) after surgery. Assessing physical frailty is often challenging among patients with chronic limb-threatening ischemia (CLTI) who are often unable to perform gait-based assessments because of the presence of plantar wounds. To test a frailty meter (FM) that does not rely on gait to determine the risk of occurrence of MAEs after revascularization for patients with CLTI. This cohort study included 184 consecutively recruited patients with CLTI at 2 tertiary care centers. After 32 individuals were excluded, 152 participants were included in the study. Data collection was conducted between May 2018 and June 2019. Physical frailty measurement within 1 week before limb revascularization and incidence of MAEs for as long as 1 month after surgery. The FM works by quantifying weakness, slowness, rigidity, and exhaustion during a 20-second repetitive elbow flexion-extension exercise using a wrist-worn sensor. The FM generates a frailty index (FI) ranging from 0 to 1; higher values indicate progressively greater severity of physical frailty. Of 152 eligible participants (mean [SD] age, 67.0 [11.8] years; 59 [38.8%] women), 119 (78.2%) were unable to perform the gait test, while all could perform the FM test. Overall, 53 (34.9%), 58 (38.1%), and 41 (27.0%) were classified as robust (FI <0.20), prefrail (FI ≥0.20 to <0.35), or frail (FI ≥0.35), respectively. Within 30 days after surgery, 24 (15.7%) developed MAEs, either major adverse cardiovascular events (MACE; 8 [5.2%]) or major adverse limb events (MALE; 16 [10.5%]). Baseline demographic characteristics were not significantly different between frailty groups. In contrast, the FI was approximately 30% higher in the group that developed MAEs (mean [SD] score, 0.36 [0.14]) than those who were MAE free (mean [SD] score, 0.26 [0.13]; P = .001), with observed MAE rates of 4 patients (7.5%), 7 patients (12.1%), and 13 patients (31.7%) in the robust, prefrail and frail groups, respectively (P = .004). The FI distinguished individuals who developed MACE and MALE from those who were MAE free (MACE: mean [SD] FI score, 0.38 [0.16]; P = .03; MALE: mean [SD] FI score, 0.35 [0.13]; P = .004) after adjusting by body mass index. In this cohort study, measuring physical frailty using a wrist-worn sensor during a short upper extremity test was a practical method for stratifying the risk of MAEs following revascularization for CLTI when the administration of gait-based tests is often challenging.


Radiation Exposure in Minimally Invasive Lumbar Fusion Surgery: A Randomized Controlled Trial Comparing Conventional Fluoroscopy and 3D Fluoroscopy-based Navigation.
Randomized controlled trial. The aim of this study was to compare the dosemetrically determined radiation exposure of surgeon and patient during minimally invasive transforaminal lumbar interbody fusion (MIS TLIF) using conventional 2D fluoroscopy (FLUORO) or 3D fluoroscopy-based navigation (NAV). MIS TLIF was shown to exhibit higher radiation exposures compared to open techniques. In particular, the routinely exposed surgeon encounters the risks of increased radiation doses. With the additional use of intraoperative 3D navigation, major steps of the operation can be performed without exposing the operating room staff to ionizing radiation. Forty-four patients undergoing monosegmental MIS TLIF were randomized into the two intraoperative imaging technique groups (FLUORO or NAV). The primary endpoint was the radiation exposure of the surgeon; the secondary endpoints were the radiation exposure of the patient and C-arm readings. After exclusion of three patients, 41 patients were analyzed. In general, the average radiation exposure of the surgeon was lower in the NAV group without being statistically significant. The radiation exposure of the patient was significantly higher in the NAV group at all dosemeter sites. The average fluoroscopy time was 63 ± 36 versus 109 ± 31 sec (FLUORO versus NAV group, P < 0.001). The additional use of intraoperative 3D fluoroscopy-based navigation compared to conventional 2D fluoroscopy alone showed a nonsignificant reduction of the radiation exposure of the surgeon in monosegmental MIS TLIF, while increasing the radiation exposure of the patient. 1.


Assessing and improving public mental health literacy concerning rTMS.
Repetitive transcranial magnetic stimulation (rTMS) has received empirical support as a viable treatment alternative for treatment-resistant major depressive disorder. Nevertheless, patients and the public-at-large may be hesitant to adopt rTMS. In three studies, we sought to (1) assess and (2) improve public perceptions of rTMS as a treatment for depression. In Study 1 (N = 107), we administered questionnaires on Amazon's Mechanical Turk (MTurk) to individuals from the US and Canada in a cross-sectional design to assess perceptions of rTMS compared to psychopharmacology, electroconvulsive therapy (ECT), and talk therapy. In Study 2 (N = 106), we again used an MTurk sample and a cross-sectional design to assess perceptions of rTMS after providing participants with a relatively long description of rTMS. In Study 3 (N = 308), we conducted an experiment in undergraduate students. Participants were randomized to one of four experimental conditions manipulating participants' understanding of the causal mechanisms of depression prior to assessing their perceptions of rTMS. Public perceptions of rTMS were more negative than pharmacotherapy and talk therapy but not ECT (Study 1). rTMS perceptions were notably better when participants were given thorough information about rTMS procedures, pain, and side-effects (Study 2), compared to the previous study when they were given a very brief description of rTMS. Finally, perceptions of rTMS were significantly better when participants were given a brain circuitry-based causal explanation of depression compared to when they were given a psychological explanation of the causes of depression (Study 3). Public perceptions of rTMS are relatively poor. To improve rTMS acceptability, practitioners should carefully consider patients' prior attitudes and beliefs when explaining rTMS as a treatment alternative. Given that beliefs can have powerful effects on treatment outcome (e.g., placebo, nocebo), future research should explore whether rTMS effects on depression can be improved by facilitating less negative perceptions of rTMS.


A German Validation of Four Questionnaires Crucial to the Study of Time Perception: BPS, CFC-14, SAQ, and MQT.
We aimed to validate four established questionnaires related to time perception in German (Consideration of Future Consequences-14 scale (CFC-14), Boredom Proneness Scale (BPS), Metacognitive Questionnaire on Time (MQT), and Self-Awareness Questionnaire (SAQ)) using a back-translation method. Exploratory factor analyses were conducted on the data of 273 German-speaking participants to evaluate the factorial structures. Internal consistencies indicated good reliability values of the questionnaires and the respective subscales, except for the MQT. Intercorrelations between the questionnaires were examined to test their external validities and gain additional insight into the associations among the constructs. The consideration of future consequences was negatively linked to boredom proneness, whereas interoceptive awareness of one's bodily sensations was positively associated with boredom proneness. Additionally, interoceptive awareness was linked to metacognitive beliefs about which factors influence time perception. The results are discussed in regard to human time perception. Conclusion: The validated German questionnaires can now be used in research projects. Initial observations on how the questionnaires are related to each other fit the current knowledge on how human time perception works, yielding the first evidence for the external validity of the German versions of these established questionnaires. For evidence of criterion validity, future studies should more thoroughly investigate the external validities analyzing the correlations with other validated measures.


Single versus triple dose antimicrobial prophylaxis in elective abdominal surgery and the impact on bacterial ecology.
The results of 28 months of surveillance of postoperative wound infection rates in elective abdominal surgery using triple or single dose antimicrobial prophylaxis are reported. No significant differences in infection rates were seen in 217 patients undergoing gastric, biliary and pancreatic surgery who received either triple or single dose cefuroxime. Also, no significant differences in infection rates were seen in 198 patients undergoing jejunal, ileal and colorectal surgery who received either triple or single dose cefuroxime plus metronidazole. Our findings are consistent with those of other studies and support the conclusion that single dose prophylaxis is as effective as triple dose in elective abdominal surgery. During the study period there was no change in the pattern of bacteria isolated or in cefuroxime resistance rates from infected sites of patients from the Department of Surgery. No increased rate of cefuroxime resistance was seen in urinary isolates from patients elsewhere in the hospital.


Clinical and angiographic features of coronary artery disease after chest irradiation.
Coronary artery disease (CAD) developed in 15 patients at a mean of 16 years (range 3 to 29) after chest irradiation. The mean dose of radiation was 42 +/- 7 grays; irradiation was performed for Hodgkin's disease in 9 patients, lymphoma in 2, breast carcinoma in 3 and cystic hygroma in 1 patient. Mean age was 48 years (range 26 to 63) at diagnosis of CAD; 4 patients were younger than 35 years. Nine were women. Ten presented with angina, 3 with acute myocardial infarction, 1 patient with syncope and 1 with dyspnea. Twelve had no more than 2 risk factors of atherosclerosis. At coronary angiography, 8 had at least 50% diameter narrowing of the left main coronary artery and 4 had severe ostial stenosis of the right coronary artery. Eight patients also had valvular heart disease, 4 pericardial disease and 4 complete heart block. Mean left ventricular ejection fraction was 67 +/- 11% (range 53 to 80%). Nine had undergone coronary artery bypass grafting, but surgery was difficult or impossible in 3 because of severe mediastinal and pericardial fibrosis. Radiation-associated CAD is characterized by a high incidence of left main and right ostial coronary disease and often occurs in women with relatively few conventional risk factors for CAD.


Light-adjusted supramolecular host-guest interfacial recognition for reconfiguring soft colloidal aggregates.
The soft interfacial template-assisted confined self-assembly of block copolymers (BCPs) guiding colloidal aggregates has been extensively investigated by interfacial instability. Whether the macromolecular polymer architectonics possessed stimulus-responsive self-regulated structural controllability more readily implement the morphological diversity of colloidal aggregates. Herein, we in-situ constructed the alginate-modified β-cyclodextrin/azobenzene-functionalized alkyl chains (Alg-β-CD/AzoC12) system by supramolecular host-guest interfacial recognition-engineered strategy, in which possessed photo-stimulated responsive structural reconfigurability by modulating assembly/disassembly behaviors between CD and Azo at oil/water interface. The host-guest droplet interfaces acted as soft templates managing interfacial instability by synergistically integrating supra-amphiphilic host-guest polymers with cosurfactants, further constructing various soft supracolloidal aggregates, including soft nanoaggregates, microspheres with tunable degrees of surface roughness. Additionally, the stimuli-altering structural reconfigurability of supramolecular host-guest polymers was regulated by ultraviolet/visible irradiation, endowing soft aggregates with structural diversity. It's highly anticipated that the supramolecular host-guest interfacial recognition self-assembly establishes great bridge between supramolecular host-guest chemistry and colloid interface science.


Application of the Type, Entry Site, and Malperfusion Classification in Treatment of Aortic Dissection.
Our goal is to investigate a new practical dissection classification system, including type of dissection, location of the tear of the primary entry, and malperfusion. The outcome of 151 patients with aortic dissection between January 2019 and May 2020 retrospectively were analyzed. All cases were classified with the Stanford dissection classification (A and B) by adding type non-A non-B. They were then further classified by the new classification system, including location of the primary Entry (E) and Malperfusion (M). All cases were followed up for six months. The distribution of 151 patients was 53.0%, 27.8%, and 19.2%, respectively, in type A, B, and non-A non-B. The in-hospital mortality rate was 8.8%, 2.4%, and 3.4% in type A, B, and non-A non-B (P < 0.05) and postoperative neurological complications occurred in 33.8%, 7.1%, and 13.8% in type A, B, and non-A non-B (P < 0.05). Total arch replacement was performed in 53.8%, 4.8%, and 13.8% in type A, B, and non-A non-B. The in-hospital mortality rate was 12.0%, 10.4%, and 8.5% in type E1, E2 and E3, while it was 20.0%, 10.4%, and 8.5% in type M1, M2 and M3 (P < 0.05). The new practical dissection classification system is useful as a supplement to the Stanford dissection classification by regarding the extent of the disease process, aiding in decision-making about the operative indication and plan, and helping in anticipating prognosis.


Genetic evolution of Mycoplasma capricolum subsp. capripneumoniae strains and molecular epidemiology of contagious caprine pleuropneumonia by sequencing of locus H2.
Contagious caprine pleuropneumonia (CCPP) is a major threat to goat farming in developing countries. Its exact distribution is not well known, despite the fact that new diagnostic tools such as PCR and competitive ELISA are now available. The authors developed a study of the molecular epidemiology of the disease, based on the amplification of a 2400 bp long fragment containing two duplicated gene coding for a putative membrane protein. The sequence of this fragment, obtained on 19 Mycoplasma capricolum subsp. capripneumoniae (Mccp) strains from various geographical locations, gave 11 polymorphic positions. The three mutations found on gene H2prim were silent and did not appear to induce any amino acid modifications in the putative translated protein. The second gene may be a pseudogene not translated in vivo, as it bore a deletion of the ATG codon found in the other members of the "Mycoplasma mycoides cluster" and as the six mutations evidenced in the Mccp strains would induce modifications in the translated amino acids. In addition, an Mccp strain isolated in the United Arab Emirates showed a deletion of the whole pseudogene, a further indication that this gene is not compulsory for mycoplasma growth. Four lineages were defined, based on the nucleotide sequence. These correlated relatively well with the geographical origin of the strains: North, Central or East Africa. The strain of Turkish origin had a sequence similar to that found in North African strains, while strains isolated in Oman had sequences similar to those of North or East African strains. The latter is possibly due to the regular import of goats of various origins. Similar molecular epidemiology tools have been developed by sequencing the two operons of the 16S rRNA gene or by AFLP. All these various techniques give complementary results. One (16S rRNA) offers the likelihood of a finer identification of strains circulating in a region, another (H2) of determining the geographical origin of the strains. These tools can make a very useful contribution to understanding the epidemiology of CCPP.


Human lactoferrin upregulates expression of KDR/Flk-1 and stimulates VEGF-A-mediated endothelial cell proliferation and migration.
Lactoferrin (LF) is a multifunctional iron-binding glycoprotein, which plays a variety of biological processes including immunity. In this study, we demonstrate that human LF upregulates KDR/Flk-1 mRNA and protein levels in HUVECs at an optimal concentration of 5 microg/ml, which subsequently promotes the VEGF-induced proliferation and migration of the endothelial cells. Exposure of HUVECs to LF significantly increased VEGF-induced ERK MAP kinase phosphorylation. The maximal stimulation of KDR/Flk-1 expression by LF was correlated with LF-induced increase in cell proliferation and migration. These findings suggest that LF may stimulate in vivo angiogenesis via upregulation of KDR/Flk-1 expression in endothelial cells.


Polymorphisms in genes involved in inflammatory pathways in patients with sudden sensorineural hearing loss.
Although the etiology of idiopathic sudden sensorineural hearing loss (SSNHL) remains unclear, the pathologically increased permeability of blood vessels, elucidated by gadolinium-enhanced magnetic resonance imaging (MRI), suggests the involvement of inflammation. Because SSNHL is considered a multifactorial disease, possibly caused by interactions between genetic factors and environmental factors, the authors investigated the associations of polymorphisms of inflammatory mediator genes with susceptibility to SSNHL. The authors compared 72 patients affected by SSNHL and 2010 adults (1010 men and 1000 women; mean age 59.2 years; range 40-79) who participated in the National Institute for Longevity Sciences Longitudinal Study of Aging. Multiple logistic regression was used to obtain odds ratios (ORs) for SSNHL in subjects with polymorphisms in the genes IL-6 C - 572G, IL-4R G1902A, IL-10 A - 592C, TNFα C - 863A, TNFRSF1B G593A, VEGF C936T, VEGF C - 2578A, and VEGF G - 1154A, with adjustment for age, gender, and any history of hypertension, diabetes, or dyslipidemia. The per-allele OR for the risk of SSNHL in subjects bearing IL-6 C - 572G was 1.480 (95% confidence interval [CI], 1.037-2.111) in model 1 (no adjustment), 1.463 (CI, 1.022-2.094) in model 2 (adjusted for age and gender), and 1.460 (CI, 1.016-2.097) in model 3 (adjusted for age, gender, and a history of hypertension, diabetes, or dyslipidemia). Under the dominant model of inheritance, the ORs were 1.734 (CI, 1.080-2.783) in model 1, 1.690 (CI, 1.050-2.721) in model 2, and 1.669 (CI, 1.035-2.692) in model 3. The remaining seven polymorphisms failed to show any associations with the risk of SSNHL. These data need to be confirmed on larger series of patients. In conclusion, the IL-6 C - 572G polymorphism is associated with a risk of SSNHL. Because permeability of blood vessels in the inner ear is frequently increased in patients with SSNHL, inflammation of the inner ear might be involved.


Ultrastructure of muscle spindle afferent terminations in lamina VI of the cat spinal cord.
Two group Ia muscle spindle afferents were impaled in the lumbosacral enlargement of the cat's spinal cord and intra-axonally labeled with horseradish peroxidase. Terminations in lamina VI were examined with the electron microscope. Boutons formed synaptic associations with somata and large dendritic shafts in the lamina VI neuropile and received axo-axonic contacts. It is concluded that group Ia terminals synapse with the proximal regions of lamina VI neurons and are under strong presynaptic control.


Apomorphine-induced inhibition of substantia nigra dopamine neurons: effects of unilateral injection through the internal carotid artery.
Possible indirect components in the inhibition of firing of A9 dopamine neurons induced by systemic apomorphine were studied using unilateral drug administration through the internal carotid artery, known to irrigate only the ipsilateral mid- and forebrain. When compared to intravenous injection, unilateral intracarotid administration inhibited ipsilateral neurons with a marked decrease of both the latency (less than 1 s) and the dose required for complete inhibition, whereas contralateral neurons were not affected. This suggests a first-pass central effect of apomorphine, presumably associated with brain extraction. Thus, peripheral and hindbrain targets do not seem to contribute to the inhibitory effect of low doses of systemic apomorphine. An intranigral possible mode of action is discussed in view of the particular arrangement of dopaminergic dendrites within the zona reticulata.


Serum exosomes from diabetic kidney disease patients promote pyroptosis and oxidative stress through the miR-4449/HIC1 pathway.
Diabetic kidney disease (DKD) is a major contributor to end-stage renal disease. Several microRNAs (miRNAs) have been found to be enriched in exosomes of DKD patients, but it remains unclear if any of these miRNAs play an important role in the pathogenesis of DKD. Exosomes from diabetic kidney disease (DKD) patients were isolated, and the expression of miR-4449 was measured by qRT-PCR. Reactive oxygen species (ROS) was determined by DCDFA assay kit, and pyroptosis was measured by quantifying the level of activated caspase 1. mRNA and protein levels were quantified by qRT-PCR and WB. In this study, we demonstrated that miR-4449 is enriched in the serum exosomes of DKD patients, and these exosomes regulate the expression of pro-inflammatory cytokines, ROS levels, and pyroptosis through miR-4449. Our study uncovered a novel mechanism for the progression of DKD that is mediated through miR-4449 in serum exosomes, which highlights an important role for exosomes in the pathogenesis of DKD.


Structure and biosynthesis of benzoxazinoids: Plant defence metabolites with potential as antimicrobial scaffolds.
Benzoxazinoids, comprising the classes of benzoxazinones and benzoxazolinones, are a set of specialised metabolites produced by the plant family Poaceae (formerly Gramineae), and some dicots. The family Poaceae in particular contains several important crops like maize and wheat. Benzoxazinoids play a role in allelopathy and as defence compounds against (micro)biological threats. The effectivity of benzoxazinones in these functionalities is largely imposed by the subclasses (determined by N substituent). In this review, we provide an overview of all currently known natural benzoxazinoids and a summary of the current state of knowledge of their biosynthesis. We also evaluated their antimicrobial activity based on minimum inhibitory concentration (MIC) values reported in literature. Monomeric natural benzoxazinoids seem to lack potency as antimicrobial agents. The 1,4-benzoxazin-3-one backbone, however, has been shown to be a potential scaffold for designing new antimicrobial compounds. This has been demonstrated by a number of studies that report potent activity of synthetic derivatives of 1,4-benzoxazin-3-one, which possess MIC values down to 6.25 μg mL-1 against pathogenic fungi (e.g. C. albicans) and 16 μg mL-1 against bacteria (e.g. S. aureus and E. coli). Observations on the structural requirements for allelopathy, insecticidal, and antimicrobial activity suggest that they are not necessarily conferred by similar mechanisms.


CREB/ATF3 signaling mediates indoxyl sulfate-induced vascular smooth muscle cell proliferation and neointimal formation in uremia.
Uremic patients are characterized by an increased risk of atherosclerotic cardiovascular diseases. Vascular smooth muscle cell (VSMC) proliferation contributes to neointimal formation, a main pathological feature in atherosclerosis. Activation of CREB/ATF3 signaling is pivotal in VSMC proliferation, yet its role in uremic atherosclerosis is unknown. This study aimed to explore whether CREB/ATF3 signaling is involved in the molecular mechanism underlying neointimal formation in uremia. Treatment of VSMCs with uremic toxin (indoxyl sulfate [IS]) activated cAMP/CREB/ATF3/cyclin D signaling, which was reflected by increased VSMC proliferation. Blocking cAMP/PKA/CREB/ATF3 signaling attenuated the promoting effect of IS on cyclin D1 expression and VSMC proliferation. Loss-of-function and time-dependent experiments showed that ATF3 lies downstream of the CREB signaling. Mutational analysis of cyclin D1 promoter along with chromatin immunoprecipitation assays showed that CREB/ATF3 signaling participated in IS-induced cyclin D transcription. In vivo, phosphorylated CREB (an active form of CREB) and ATF3 were prominently upregulated in the neointima of experimental uremic rats, the atherosclerotic plaques of uremic ApoE-/- mice, and the iliac arteries of uremic patients. Notably, the use of lentivirus to knock down ATF3 in the neointima of balloon-injured arteries could suppress the effect of uremia in vivo, including neointimal formation and cyclin D expression. In this study, we demonstrated that CREB/ATF3-related signaling may be involved in IS-induced VSMC proliferation and the pathogenesis of neointimal formation during uremia.


Variations in digital sensory patterns: a study of the ulnar nerve-median nerve palmar communicating branch.
Eighty percent of 50 dissected cadaver palms showed a communicating branch between the fourth and third common digital nerves (ulnar and median origins, respectively). The branch commonly crossed the palm with the superficial arterial arch and usually provided sensory fibers from a branch of the superficial ulnar nerve into the ring finger radial digital nerve. Caution should be taken during carpal tunnel release or other surgery along the axis of the fourth ray to avoid injury to this structure.


Bone level change of extraction sockets with Bio-Oss collagen and implant placement: a clinical study.
To compare the reaction of the alveolar bone to the preservation of the extraction socket by Bio-Oss Collagen with and without combination of implant treatment. To evaluate whether early implant insertion 8-10weeks thereafter could be a suitable time point for long term bone stability around the implant. A total of 25 patients were divided into three groups: The first group (seven patients) received Bio-Oss Collagen after extraction and 8-10weeks later an implant, the second group (eight patients) received only Bio-Oss Collagen without implantation thereafter, while the third group was considered as a control (eleven patients), where the sockets healed without any treatment. The change in the vertical bone level of the alveolar crests were measured from panoramic radiographs and statistically analysed. Bone level change was significantly less for Group 1 than Group 3 (P<0.001), while was not significantly different for Group 2 and Group 3 (P=0.23). However, the rate of bone level change per year was statistically smaller for Group 1 compared to Group 3 (P=0.019) and as well as for Group 1 than for Group 2 (P=0.003), whereas the change per year was not significantly different for Group 2 vs. Group 3 (P=0.122). Bone level preservation of extraction sockets using Bio-Oss Collagen with implantation is significantly better compared to using Bio-Oss Collagen only and untreated sockets. Implant insertion 8-10weeks after extraction is a suitable time point after socket augmentation.


Start-of-day oculomotor screening demonstrates the effects of fatigue and rest during a total immersion training program.
Investigating changes in sleep and fatigue metrics during intensive surgical and trauma skills training, this study explored the dynamic association between oculomotor metrics and fatigue. Specifically, alterations in these relations over extended stress exposure, the influence of time of day, and the impact of fatigue exposure on sleep metrics were examined. Thirty-nine military medical students participated in 6 days of immersion, hyper-realistic, and high-stress experiential casualty training. Participants completed surveys assessing the state of sleepiness with oculomotor tests performed each morning and evening, analyzing eye movement and pupillary change to characterize fatigue. Participants wore Fitbit TM devices to measure overall time asleep and time in each sleep stage during the training. Fitbit data showed increased average minutes in rapid eye movement, deep sleep, and less time in light sleep from day 1 to day 4. The microsaccade peak velocity-to-displacement ratio exhibited a morning decrease but not in afternoon sessions, indicating repeated but temporary effects of accumulated fatigue. There were no findings regarding pupil reactivity to illumination changes. This study describes characteristics of fatigue measured by rapid and individually calibrated oculomotor tests. It demonstrates oculomotor relationships to fatigue in start-of-day testing, providing a direction for timing for optimal fatigue testing. These data suggest that improved sleep could signal resilience to fatigue during afternoon testing. Further investigation with more participants and longer duration is warranted. A deeper understanding of the interrelationships between training, sleep, and fatigue could improve surgical and military fitness.


Transient opacification of the urinary pathways by amorphous debris in children with leukemia.
Our index patient, a 14-year-old male on chemotherapy for acute lymphatic leukemia had extensive opacification of the urinary tract on the preliminary film for an intravenous urogram. Sonography and computed tomography also demonstrated dense material in the calyces, renal pelves and ureters. Since then, we have found another patient, a 9-year-old female with acute lymphatic leukemia who was not receiving chemotherapy, with a similar pattern on sonography and computed tomography. These densities unlike those in our first patient were not visible on a plain film of the abdomen. All of the material disappeared spontaneously in both patients.


A novel strategy for analyzing RNA-protein interactions by surface plasmon resonance biosensor.
Surface plasmon resonance (SPR) biosensor is a promising technology for its various advantages including the real-time measurement of biomolecular interactions without labeling. A method of hybridizing RNAs on the surface of the streptavidin-coated (SA) sensor chip to study RNA-protein interactions was described in this paper. In our study, it has been shown that the nucleocapsid (N) protein of severe acute respiratory syndrome coronavirus (SARS-CoV) has a high binding affinity for the leader sequence of SARS-CoV genome. Effect of temperature on the RNA-DNA hybridization was also examined. This method can provide the affinity of interactions with high sensitivity. Therefore, it will be useful in screening binding candidates for a given RNA target motif with one chip.


An electrochemical glutathione biosensor: ubiquinone as a transducer.
In this paper, coenzyme Q10 (Ubiquinone, CoQ10) was used for the first time as a transducer to construct electrochemical biosensor for effectively detecting γ-L-glutamyl-L-cysteinyl-glycine (glutathione, GSH). CoQ10 modified electrode was fabricated by attaching its gel mixed with multi-walled carbon nanotubes (MWNTs)/ionic liquid (IL). In the optimum conditions, based on the increasing of reduction peak current of CoQ10 caused by GSH through voltammetric technology, it was found that the peak current of CoQ10 was linear with the concentration of GSH in the range from 4.0×10(-9) to 2.0×10(-7)mol L(-1) at the pH 7.00, and the limit of detection was 3.2×10(-10)mol L(-1) (S/N=3). The results revealed that this method could be used to determine GSH in actual blood samples with the superiority of excellent selectivity, high stability and sensitivity. The strategy explored here might provide a new pathway to design novel multi-function transducers for detecting GSH, which has unique characteristic and potential application in the fields of sensor and medical diagnosis.


[Chorea, lupus and antiphospholipid antibodies].
Chorea may occur in patients with SLE with a frequency estimated at 1 to 3% in adults and up to 9% in paediatric lupus. Chorea is frequently a presenting feature, and is strongly related to the presence of antiphospholipid antibodies. A treatment with antiplatelet agents and hydroxychloroquine is generally sufficient. During follow-up, the patients with chorea have a significant higher risk to develop thrombotic events (mainly arterial). They also have an excess risk of obstetric morbidity and valvular disease. The prescription of antiplatelet agents and adequate management, especially during pregnancy, can probably reduce this risk.


Odontogenic Tumors.
Odontogenic tumors are a group of neoplastic growths that originate from the tissues responsible for tooth formation and the periodontal apparatus of the jaw. Odontogenic tumors usually present as radiolucent defect, which makes diagnosis somewhat confusing while differentiating them from cysts. Although cystic lesions are surrounded by sclerotic borders, few odontogenic tumors share similar features. This article reviews clinical concepts of several odontogenic tumors that occur in the proximity or in association with teeth and not merely focusing on relatively common conditions.


Selection or random picking? Foraminiferal tests in Sabellaria alveolata (Linnaeus, 1767) bioconstructions.
This work investigates whether the honeycomb worm Sabellaria alveolata (Polychaeta) actively selects foraminiferal tests to build its arenaceous bioconstructions and if the tests are chosen based on a defined criterion. To this purpose, both foraminiferal content and structure of communities were compared across samples of bioconstructions and samples of neighbouring sediment collected from two sites of southern Sicily (Central Mediterranean). Results document a higher concentration of foraminiferal tests within the tubes than in sediment, with a clear preference for biconvex and spherical morphologies. We hypothesize that the high proportion of biconvex and spherical tests in the bioconstruction is probably due to the active selection operated by the polychaete combined with the different buoyancy of foraminiferal tests kept in suspension by the wave motion. Among the grains agglutinated in the tubes, we also observed sporadic specimens of Amphistegina lobifera Larsen, a non-indigenous foraminifer native to the Red Sea.


Analysis of Human Dopamine D3 Receptor Quaternary Structure.
The dopamine D3 receptor is a class A, rhodopsin-like G protein-coupled receptor that can form dimers and/or higher order oligomers. However, the molecular basis for production of these complexes is not well defined. Using combinations of molecular modeling, site-directed mutagenesis, and homogenous time-resolved FRET, the interfaces that allow dopamine D3 receptor monomers to interact were defined and used to describe likely quaternary arrangements of the receptor. These were then compared with published crystal structures of dimeric β1-adrenoreceptor, μ-opioid, and CXCR4 receptors. The data indicate important contributions of residues from within each of transmembrane domains I, II, IV, V, VI, and VII as well as the intracellular helix VIII in the formation of D3-D3 receptor interfaces within homo-oligomers and are consistent with the D3 receptor adopting a β1-adrenoreceptor-like quaternary arrangement. Specifically, results suggest that D3 protomers can interact with each other via at least two distinct interfaces: the first one comprising residues from transmembrane domains I and II along with those from helix VIII and a second one involving transmembrane domains IV and V. Moreover, rather than existing only as distinct dimeric species, the results are consistent with the D3 receptor also assuming a quaternary structure in which two transmembrane domain I-II-helix VIII dimers interact to form a "rhombic" tetramer via an interface involving residues from transmembrane domains VI and VII. In addition, the results also provide insights into the potential contribution of molecules of cholesterol to the overall organization and potential stability of the D3 receptor and possibly other GPCR quaternary structures.


Enhanced mixing and mass transfer in a recirculation loop results in high cell densities in a roller bottle reactor.
A recirculation loop added to a large-scale roller bottle reactor resulted in high cell densities as compared to standard roller bottles. Four different mammalian cell lines reached an average maximum density equal to 5.4 x 10(6) cells /mL (sigma = 0.263), which was between 2.13 and 2.95 times greater than the densities in roller bottles without recirculation using the same cell lines. The high densities were maintained over long durations (>25 days) while the reactor operated with continuous perfusion. The increased densities are attributed to enhanced liquid mixing and oxygen transfer that occur as a result of the recirculation loop. Models were developed that describe axial liquid flow and oxygen transfer in both the sample loop and the reactor growth chamber. Axial dispersion and oxygen transfer coefficients are presented for a variety of operating conditions. The increased oxygen transfer characteristics of the reactor allow for easy scale-up of roller bottle cultures by operating at larger volumes with greater liquid depths than conventional roller bottles permit. The surface-area-to-volume ratio in the tests performed was 0.206 versus 1.16 cm(-1) in a standard roller bottle.


Knowledge on drug dosages of ward physicians.
Dosing errors are a common source for preventable adverse drug events. This study evaluated the knowledge of German hospital physicians with respect to the daily dosage of frequently used drugs. A questionnaire survey was carried out among 168 ward physicians from three university and four municipal hospital departments of internal medicine asking for the daily dosage of 17 frequently used drugs. One hundred twenty-seven of 168 physicians returned a completed questionnaire, a response rate of 75.6%. Only 50% of the dose estimates were within the therapeutic range. Even in cases of frequent prescription 7% of the stated doses were overdosed and 15% were underdosed. The results of this survey suggest that adverse drug events and the lack of therapeutic effect due to dosing errors could be prevented by an improved knowledge of daily dosages.


Protective conditioning for acute graft-versus-host disease.
Conditioning with total lymphoid irradiation plus antithymocyte serum protects mice against acute graft-versus-host disease (GVHD) after hematopoietic-cell transplantation. We tested this strategy in humans. Thirty-seven patients with lymphoid malignant diseases or acute leukemia underwent an experimental conditioning regimen with 10 doses of total lymphoid irradiation (80 cGy each) plus antithymocyte globulin, followed by an infusion of HLA-matched peripheral-blood mononuclear cells from related or unrelated donors who received granulocyte colony-stimulating factor. Of the 37 transplant recipients, only 2 had acute GVHD after hematopoietic-cell transplantation. Potent antitumor effects in patients with lymphoid malignant diseases were shown by the change from partial to complete remission. In the transplant recipients who underwent conditioning with total lymphoid irradiation and antithymocyte globulin, the fraction of donor CD4+ T cells that produced interleukin-4 after in vitro stimulation increased by a factor of five, and the proliferative response to alloantigens in vitro was reduced, as compared with normal control subjects and control subjects who underwent conditioning with a single dose of total-body irradiation (200 cGy). A regimen of total lymphoid irradiation plus antithymocyte globulin decreases the incidence of acute GVHD and allows graft antitumor activity in patients with lymphoid malignant diseases or acute leukemia treated with hematopoietic-cell transplantation.


Poly(3-methylpyrrole): vibrational dynamics, phonon dispersion and heat capacity.
Normal modes of vibration and their dispersions in poly(3-methylpyrrole) (P3MPy) based on the Urey-Bradley force field are reported. It provides a detailed interpretation of previously reported I.R. spectra. Characteristic features of dispersion curves, such as regions of high density-of-states, repulsion, and character mixing of dispersive modes are discussed. Predictive values of heat capacity as a function of temperature are calculated from dispersion curves via density-of-states.


Comparison of measurements of canine plasma creatinine, glucose, proteins, urea, alanine aminotransferase, and alkaline phosphatase obtained with Spotchem SP 4430 and Vitros 250 analyzers.
The suitability of the Spotchem 4430 benchtop biochemistry analyzer for canine blood samples was tested for creatinine, glucose, proteins, urea, alkaline phosphatases and alanine aminotransferase. Results obtained from whole blood and corresponding heparin plasma were identical except for proteins which were higher in plasma (n=10). Between series imprecision (n=10) was <5% for substrates and <10% for enzymes. Comparison of results from 100 Li-heparin samples with those measured with a Vitros 250 analyzer showed good correlation (r>0.93). The slopes of the Passing-Bablock's regression ranged from 0.90 to 1.20 and intercepts were low. The mean biases were low, except for creatinine for which the results obtained by Spotchem (Jaffe reaction) were about 20 micromol/L higher than with the Vitros (enzymatic reaction). The results of this study show that the Spotchem analyzer is suitable for use in canine whole blood or plasma when small numbers of tests are to be performed and large analyzers are not available.


Wollastonite as filler of an experimental dental adhesive.
The aim of this study was to formulate experimental dental adhesives with wollastonite and evaluate the physical, chemical, and bioactivity properties of the resins. Wollastonite was characterized by Fourier transform infrared spectroscopy, X-ray and laser diffraction analyses, and scanning electronic microscopy. An experimental adhesive resin was formulated, and wollastonite was used as filler at 0 (control group), 0.5, 1, or 2 wt.%. Radiopacity, degree of conversion (DC%), microhardness, softening in solvent, ultimate tensile strength (UTS), 24 h- and 1 year- microtensile bond strength (μTBS), mineral deposition, and color of the adhesives were evaluated. Wollastonite particles showed a needle-like shape, a mean diameter of 70 (± 30) μm, characteristic chemical peaks, and pure crystalline β-CaSiO3 phase. There were no significant differences (p > 0.05) for radiopacity, softening in solvent, and color change. The group with 2 wt.% of wollastonite showed higher microhardness and UTS in comparison to the control group (p < 0.05). After one year, the control group showed reduced μTBS compared to the immediate value (p < 0.05). The groups with wollastonite presented stable μTBS after one year in comparison to the immediate μTBS (p > 0.05). Wollastonite induced mineral deposition on the adhesive surface over the time of storage in simulated body fluid. The addition of wollastonite improved the mechanical behavior of the adhesive without changing the analyzed chemical properties. The adhesives with this filler presented mineral deposition and acceptable clinical color. Moreover, dentin treated with wollastonite-doped adhesives showed higher bonding stability after one year of aging. Wollastonite, a silicate-based material, provided bioactivity for the adhesives, which assists in producing therapeutic tooth-restoration interfaces. Moreover, the incorporation of this mineral improOfiller to improve the biological properties of adhesives and assist in dentin-restoration stability.


How do magnetic resonance cholangiopancreatography findings predict conversion from laparoscopic cholecystectomy for acute cholecystitis to bailout procedures?
Acute cholecystitis is one of the most prevalent surgical abdominal conditions. The Tokyo Guidelines describe the management of acute cholecystitis and recommend bailout procedures for "difficult" cholecystitis cases. This study aimed to identify risk factors for conversion from laparoscopic cholecystectomy to bailout procedures in patients with acute cholecystitis. This retrospective cohort study was conducted at a single center between January 2017 and December 2021. Patients who underwent laparoscopic cholecystectomy for acute cholecystitis were enrolled and classified into bailout and non-bailout groups. The patients' characteristics and perioperative data were compared between the 2 groups. In total, 161 patients who underwent laparoscopic cholecystectomy for acute cholecystitis were reviewed. Fourteen were excluded because of a lack of preoperative magnetic resonance cholangiopancreatography; thus, 147 patients were enrolled (bailout group, 21; non-bailout group, 126). Age (74 vs 67 years old; P = .048), days from onset to surgery (3 vs 2 days; P = .02), or defect of cystic duct in magnetic resonance cholangiopancreatography (57% vs 29%; P = .02) were significantly associated with conversion to bailout procedures. In the logistic regression analysis, a defect of the cystic duct in magnetic resonance cholangiopancreatography was an independent predictor for bailout procedures (odds ratio, 2.793; P = .04). In this study, defect of the cystic duct in the magnetic resonance cholangiopancreatography can predict conversion to bailout procedures. To the best of our knowledge, this is the first report to describe magnetic resonance cholangiopancreatography finding of the cystic duct as a predictor of surgical difficulty in patients with acute cholecystitis.


Treatment with Radix Euphorbiae Ebracteolatae Significantly Decreases the Expression of E6 and L1, and Increases the Expression of p53 and Rb in HPV18-infected Human Foreskin Keratinocytes.
Radix Euphorbiae Ebracteolatae (REE) was recently reported to be significantly superior to vitamin A acid ointment in treating multiple plantar warts. However, the effects of REE on HPV18 remain unclear. Therefore, the current study aimed to investigate the effects of REE on the proliferation of HPV18, and explore possible molecular mechanisms underlying the effects. HFK and HFK-HPV18 were treated with water-extracted single or compound REE, ethanol-extracted single or compound REE, TNF-α and IFN for 3 days, respectively. In addition, the organotypic rafts containing HFK-HPV18 and HFK were treated with REE, IFN and TNF-α for 7 days, respectively. Cell proliferation rates were measured with Brdu. mRNA expression of E6, L1, p53 and Rb was detected by qPCR. Protein expression of p53, Rb and L1 was detected by Western blot. Compared to HFK group, HFK-HPV18 group had significantly higher expression of E6 and L1. Compared to the control group, HFK-HPV18 treated with REE, TNF-α and IFN displayed significantly lower proliferation rates. The mRNA expression of E6 was markedly lower, and mRNA expression of p53 and Rb was significantly higher after treatment of REE in HFK-HPV18 or in organotypic rafts containing HFK-HPV18. Treatment with REE markedly increased the protein expression of p53 and Rb, and decreased the protein expression of L1 in HFK-HPV18 or in organotypic rafts containing HFK-HPV18. Among all formula of REE, the inhibition of proliferation rates and expression of E6 and L1, and the increase in expression of p53 and Rb in HFK-HPV18 was highest in ethanol-extracted compound REE group. The proliferation rates are significantly lower in HFK-HPV18 treated with REE. The expression of E6 and L1 is markedly lower, and expression of p53 and Rb is significantly higher after REE treatment in HFK-HPV18 or organotypic rafts containing HFK-HPV18. Among all formula of REE, ethanol-extracted compound REE displays the highest protection against HPV18.


Hyperglycemia as a risk factor in the perioperative patient.
Bodily injury and stress associated with surgical interventions increase glucose levels not only in individuals diagnosed with diabetes mellitus but also in patients without a preoperative diagnosis of diabetes. Whatever the cause, hyperglycemia is becoming an increasingly important indicator of perioperative patient outcomes. An elevated blood glucose level affects the body's defense systems and the body's ability to heal after surgical intervention. Perioperative nurses should closely monitor the patient's blood glucose levels and watch for signs of hyperglycemia throughout the perioperative experience. Perioperative nurses should work collaboratively with other perioperative team members to identify and treat perioperative hyperglycemia.


Polymorphonuclear counts in ascitic fluid and microorganisms producing spontaneous bacterial peritonitis: an under-recognized relationship.
BACKGROUND AND AIMS. In cirrhotic patients with spontaneous bacterial peritonitis (SBP) higher polymorphonuclear (PMN) count in ascitic fluid have been reported in infections caused by Gram-negative bacilli (GNB) as opposed to Gram-positive cocci (GPC). However, the influence of other associated factors on the PMN count, such as the specific microorganism causing the episode of SBP, has not been well established. METHODS. Retrospective observational study of 194 episodes of positive ascitic and/or blood culture SBP in 159 patients with liver cirrhosis (2001-2009). Parameters associated with PMN count in ascitic fluid at diagnosis were evaluated. RESULTS. The multivariate analysis (model 1) showed that a virulent etiology of the infection [coefficient 3.941 (95% confidence interval (95 CI): 0.421-7.461)] and the model for end-stage liver disease (MELD) score [coefficient 0.196 (95 CI: 0.007-0.384)] were positively associated with the PMN count in ascites, while a nosocomial acquisition was inversely associated [coefficient -3.546 (95 CI: -6.855 - -0.238)]. A nonsignificant trend toward higher PMN count was found in GNB versus GPC, but there were differences between groups of microorganisms: pyogenic streptococci [median (p25-p75): 3211 (1615-8004)], Enterobacteriaceae [2958 (917-7690)], Vibrionaceae [9215 (375-17280)], nonfermenting GNB [1384 (565-3865)], viridans group streptococci [1044 (503-2354)] and enterococci [1050 (476-4655)](p = 0.005). No clear cut-offs of ascitic PMN count predicting a particular etiology could be calculated out of these data. CONCLUSIONS. In cirrhotic patients with SBP, the causing microorganism, the place of acquisition of the infection and the host liver condition were the main factors determining PMN count in ascitic fluid. Third-generation cephalosporin resistance was associated with low PMN count probably because this group included bacteria with inherent low virulence.


Impairment of endothelium-independent vasodilation in patients with hypercalcemia.
Patients with primary hyperparathyroidism (PHPT) and/or hypercalcemia are at increased risk for myocardial ischemia. Whether PHPT is associated with altered endothelium-dependent dilation, vascular smooth muscle cell function, or both is unknown. This study was performed to test the hypothesis that endothelium-dependent, flow-mediated dilation (FMD) and/or endothelium-independent, nitroglycerin-induced dilation (NMD) is impaired in the preclinical phase of vascular disease in patients with PHPT. Twenty-six PHPT patients (mean +/- SD; age 55 +/- 15 y, serum calcium 3.00 +/- 0.37 mmol/l, serum phosphate 0.79 +/- 0.21 mmol/l, iPTH 249 +/- 262 pg/ml) with no evidence of coronary artery disease (CAD) as well as 26 normocalcemic control subjects (CTL; age 51 +/- 12 y) were studied. FMD following reactive hyperemia and NMD after 0.8 mg nitroglycerin (NTG) were assessed in the brachial artery by using high resolution ultrasound (7 MHz). NMD was impaired in PHPT patients compared to CTL (11.9 +/- 3.9% vs. 15.6 +/- 5.7%; p = 0.012). FMD was similar in both study groups (11.6 +/- 4.6% vs. 12.6 +/- 4.9; NS). The ratio of FMD to NMD was significantly different between PHPT patients and CTL (0.98 +/- 0.19 vs 0.81 +/- 0.25, p = 0.0009). On multiple stepwise regression analysis serum calcium was independently associated with the FMD/NMD ratio (r = 0.34, p = 0.017). Endothelium-independent vasodilation is impaired in PHPT patients without clinical evidence of coronary artery disease compared to normocalcemic CTL, while endothelium-dependent dilation was similar in both study groups. Thus, altered arterial reactivity in the course of PHPT may predominantly involve the arterial media and not the endothelium as observed previously in patients with various stages of atherosclerosis.


Constipation and clinical outcomes in peritoneal dialysis: Results from Thailand PDOPPS.
Patient-reported outcome measures (PROMs) are widely recognized as valuable predictors of clinical outcomes in peritoneal dialysis (PD). Our study aimed to explore the connections between patient-reported constipation and clinical outcomes. We assessed constipation in patients across 22 facilities participating in the Thailand Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS) from 2014 to 2017. Constipation diagnosis utilized objective assessment tools such as the Bristol stool form scale (BSFS) and a self-reported questionnaire known as the constipation severity score (CSS). The BSFS is a 7-level scale that visually inspects feces based on texture and morphology, while the CSS measures constipation duration and severity using a 5-point Likert scale for various factors. We employed Cox proportional hazards model regression to determine the associations between constipation and clinical outcomes, including mortality, hemodialysis (HD) transfer and peritonitis. Among 975 randomly selected PD patients from 22 facilities, 845 provided written informed consent, and 729 completed CSS questionnaire. Constipation was prevalent in the PD population (13%), particularly among older patients, those who were caregiver dependent, had diabetes and poorer nutritional status (indicated by lower time-averaged serum albumin, potassium, creatinine and phosphate concentrations). Twenty-seven percent of which experiencing symptoms of constipation for over a year. Notably, self-reported constipation at baseline was significantly associated with a shorter time to first peritonitis and higher rates of peritonitis and death. However, no significant association was found between constipation and HD transfer after adjusting for various factors, including age, gender, PD vintage, comorbidities, shared frailty by study sites and serum albumin. Patient-reported constipation independently correlated with increased risks of peritonitis and all-cause mortality, though no such correlation was observed with HD transfer. These findings underscore the need for further investigation to identify effective interventions for constipation in PD patients.


Determination of organophosphorus pesticides in peanut oil by dispersive solid phase extraction gas chromatography-mass spectrometry.
The organophosphorus pesticides including phorate, diazinon, tolclofos-methyl, fenitrothin, malathion, fenthion, isocarbophos, quinalphos and phenamiphos, in peanut oils were determined by liquid-liquid extraction coupled with dispersive solid phase extraction and gas chromatography-mass spectrometry (GC-MS). The mixture of multi-walled carbon nanotubes and alumina was used as adsorbent in dispersive solid phase extraction. The effects of some experimental conditions, such as types of multi-walled carbon nanotubes, amount of adsorbents and extraction time were examined. The limits of detection for the analytes were between 0.7 and 1.6 μg kg(-1). The obtained recoveries of the analytes in the samples were between 85.9 and 114.3% and relative standard deviations were lower than 8.48%.


Ultraviolet and COVID-19 pandemic.
COVID-19 virus causes coronavirus disease. It is a highly contagious viral infection. In this article, we will discuss the potential phototherapy problems and also alternative options for dermatologists, ultraviolet treatment against COVID-19 virus, and vitamin D-associated problems in these coronavirus days.


Vultures and Livestock: The Where, When, and Why of Visits to Farms.
Recent changes in European legislation have legalized the abandonment of carcasses around livestock farms, but our understanding of how vultures exploit these semi-predictable food sources is still very limited. For filling this gap, we determine the individual and ecological drivers influencing vulture visits to farms. We assessed the effects of individual characteristics of both birds and farms on the frequency of vultures' visits to livestock facilities using data collected from 45 GPS-tagged Egyptian Vultures (Neophron percnopterus) and 318 farms (>94% of livestock) on Fuerteventura Island, Spain. Farms were more visited during the vultures' breeding season. Farms located closer to highly predictable feeding places (i.e., vulture restaurants and garbage dumps) or with more available feeding resources were visited by more vultures, whereas those located close to roads and vultures' breeding territories received fewer visits. Younger territorial birds visited a farm more frequently than older territorial ones, whereas older non-territorial individuals concentrated those visits on farms closer to their activity core areas compared with younger ones. Our findings indicate that visits to farms were determined by their spatial distribution in relation to the age-specific birds' activity centers, the availability of carcasses, seasonality, and individual characteristics of vultures. These interacting factors should be considered in vulture conservation, avoiding very general solutions that ignore population structure.


Normal values for respiratory resistance using forced oscillation in subjects>65 years old.
The aim of the present study was to determine reference values and predictive variables for respiratory impedance (Zrs) by the forced oscillation technique (FOT) in subjects aged>65 yrs. The investigation involved a prospective study of nonsmoking subjects, with normal forced expiratory volumes. The Zrs parameters, which included average resistance between 4-16 Hz (R4-16), average resistance between 4-30 Hz (RM), resonant frequency (FN), capacitance (C) and inertance (I), were measured along with forced expiratory manoeuvres. Every subject had each parameter measured in the same sequence using FOT and spirometry. A total of 223 subjects aged 83+/-8 yrs were included in the study. The mean values for forced expiratory volume in one second (FEV1) % predicted were 110+/-23. The forced vital capacity (FVC) % pred was 114+/-21 and the FEV1/FVC % pred was 112+/-11. The mean values for the Zrs parameters were: R4-16: 0.25+/-0.07 kPa.s-1.L-1; RM: 0.25+/-0.06 kPa.s-1.L-1; FN: 11.0+/-2.8 Hz; I: 1.17+/-0.26 Pa.L-1.s-2; and C: 20.5+/-9.0 mL.hPa-1. In multiple regression models adjusted for age, sex, height and weight, height was the most influential predictor for Zrs parameters based on the magnitude of the regression coefficient. In conclusion, it was found that height was the best predictor for respiratory impedance parameters. Contribution of age and weight was negligible. However, the level of predictability for respiratory impedance parameters by regression equations was low.


Synthesis of the enantiomers of the bioreductively-activated cytotoxin RSU-1069 and its prodrug RB6145 and lack of stereoselectivity in their cytotoxicity and radiosensitization in vitro.
The R(+)- and S(-)-enantiomers of the radiosensitizer and bioreductively-activated cytotoxin RSU-1069 and their prodrugs have been synthesised. The parent drugs were evaluated as radiosensitizers and bioreductively-activated cytotoxins in vitro. No stereoselectivity in the activities in vitro of the two enantiomers was evident and both compounds were potent hypoxia-selective agents.


In vitro toxicity assessment of chitosan oligosaccharide coated iron oxide nanoparticles.
Iron oxide nanoparticles (INPs) have potential biological, biomedical and environmental applications. These applications require surface modification of the iron oxide nanoparticles, which makes it non-toxic, biocompatible, stable and non-agglomerative in natural and biological surroundings. In the present study, iron oxide nanoparticles (INPs) and chitosan oligosaccharide coated iron oxide nanoparticles (CSO-INPs) were synthesized to evaluate the effect of surface coating on the stability and toxicity of nanoparticles. Comparative in vitro cytotoxicity of nanoparticles was evaluated in HeLa (human cervix carcinoma), A549 (human lung carcinoma) and Hek293 (human embryonic kidney) cells by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay along with flow cytometry study for cell viability, membrane integrity, mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) production. Morphological alteration in nanoparticles treated cells was analyzed by Acridine orange/ethidium bromide double staining and electron microscopy. Synthesized nanoparticles were found to be spherical in shape, well dispersed and stable at various pH values, making them suitable for biomedical and environmental applications. The present study also indicates that the chitosan oligosaccharide coating on iron oxide nanoparticles results in the decrease in cellular damage and moderate ROS production, thereby, significantly decreasing the cytotoxic impact of bare iron oxide nanoparticles.


Electron microscope fluoro-autoradiography: improvement of efficiency.
The fluorographic process for enhancement of the autoradiographic detection of beta-ray emitted by tritium has been successfully adapted to electron microscope autoradiography. An original scintillator plastic film helped to increase the detection yield of electrons up to 80% without alteration of the morphological aspect of the autoradiograms, and without increasing background fog or causing apparent loss of resolution.


How do junior doctors working in a multicultural context make sense of somatisation?
Physicians' explanatory models of commonly encountered clinical problems reflect not only formal medical training, but also personal and professional experience. In situations where formal training is absent, the clinical context of informal learning is likely to have an important influence on junior doctors' evolving knowledge and practice. The purpose of this study was to explore junior doctors' explanatory models of somatisation in the absence of formal training, and in particular the influence of working with a large proportion of immigrants (asylum seekers and refugees) on their understanding and practice. Semi-structured interviews were conducted with all 14 junior doctors working at the Geneva University Hospitals general medicine outpatient clinic. Interviews explored junior doctors' definitions, understanding and management of somatisation. Interviews were tape-recorded, transcribed verbatim and analyzed for key themes. In the absence of formal training, somatisation evoked considerable uncertainty and frustration in terms of diagnosis and management. Junior doctors' understanding of somatisation was heavily influenced by their contact with immigrant patients. They primarily attributed somatisation to psychosocial stresses related to migration and tended to label certain socio-cultural groups as more prone to somatisation than others. It is important to recognize that contextual factors have an important influence on physicians' evolving explanatory models for commonly encountered problems, especially in the absence of formal training. Results from this study suggest that formal training in management of somatisation should be offered in order to broaden junior doctors' understanding of somatisation and avoid cultural stereotyping.


Morphology and kinetics of asphalt binder microstructure at gas, liquid and solid interfaces.
We combined optical and atomic force microscopy to observe morphology and kinetics of microstructures (typically referred to as bees) that formed at free surfaces of unmodified Performance Graded (PG) 64-22 asphalt binders upon cooling from 150°C to room temperature (RT) at 5°C min-1 , and changes in these microstructures when the surface was terminated with a transparent solid (glass) or liquid (glycerol) overlayer. The main findings are: (1) at free binder surfaces, wrinkled microstructures started to form near the crystallization temperature (∼45°C) of saturates such as wax observed by differential scanning calorimetry, then grew to ∼5 µm diameter, ∼25 nm wrinkle amplitude and 10-30% surface area coverage upon cooling to RT, where they persisted indefinitely without observable change in shape or density. (2) Glycerol coverage of the binder surface during cooling reduced wrinkled area and wrinkle amplitude three-fold compared to free binder surfaces upon initial cooling to RT; continued glycerol coverage at RT eliminated most surface microstructures within ∼4 h. (3) No surface microstructures were observed to form at binder surfaces covered with glass. (4) Submicron bulk microstructures were observed by near-infrared microscopy beneath the surfaces of all binder samples, with size, shape and density independent of surface coverage. No tendency of such structures to float to the top or sink to the bottom of mm-thick samples was observed. (5) We attribute the dependence of surface wrinkling on surface coverage to variation in interface tension, based on a thin-film continuum mechanics model. LAY DESCRIPTION: Asphalt binder, or bitumen, is the glue that holds aggregate particles together to form a road surface. It is derived from the heavy residue that remains after distilling gasoline, diesel and other lighter products out of crude oil. Nevertheless, bitumen varies widely in composition and mechanical properties. To avoid expensive road failures, bitumen must be processed after distillation so that its mechanical properties satisfy diverse climate and load requirements. International standards now guide these mechanical properties, but yield varying long-term performance as local source composition and preparation methods vary. In situ diagnostic methods that can predict bitumen performance independently of processing history are therefore needed. The present work focuses on one promising diagnostic candidate: microscopic observation of internal bitumen structure. Past bitumen microscopy has revealed microstructures of widely varying composition, size, shape and density. A challenge is distinguishing bulk microstructures, which directly influence a binder's mechanical properties, from surface microstructures, which often dominate optical microscopy because of bitumen's opacity and scanning-probe microscopy because of its inherent surface specificity. In previously published work, we used infrared microscopy to enhance visibility of bulk microstructure. Here, as a foil to this work, we use visible-wavelength microscopy together with atomic-force microscopy (AFM) specifically to isolate surface microstructure, to understand its distinct origin and morphology, and to demonstrate its unique sensitivity to surface alterations. To this end, optical microscopy complements AFM by enabling us to observe surface microstructures form at temperatures (50°C-70°C) at which bitumen's fluidity prevents AFM, and to observe surface microstructure beneath transparent, but chemically inert, liquid (glycerol) and solid (glass) overlayers, which alter surface tension compared to free surfaces. From this study, we learned, first, that, as bitumen cools, distinctly wrinkled surface microstructures form at the same temperature at which independent calorimetric studies showed crystallization in bitumen, causing it to release latent heat of crystallization. This shows that surface microstructures are likely precipitates of the crystallizable component(s). Second, a glycerol overlayer on the cooling bitumen results in smaller, less wrinkled, sparser microstructures, whereas a glass overlayer suppresses them altogether. In contrast, underlying smaller bulk microstructures are unaffected. This shows that surface tension is the driving force behind formation and wrinkling of surface precipitates. Taken together, the work advances our ability to diagnose bitumen samples noninvasively by clearly distinguishing surface from bulk microstructure.


Association of CYP2D6 100 C > T and 2850 C > T polymorphisms with generalized tonic clonic seizures among Indians.
Multiple avenues of research have provided evidence for the role of genetic and environmental factors in epilepsy. Previous studies indicated an association of debrisoquine hydroxylase (CYP2D6) with susceptibility to epilepsy. In this study, association of CYP2D6 100C > T and 2850C > T polymorphisms with generalized tonic clonic seizures (GTCS) among Indians has been analysed using case-control approach. A significant association of 2850C > T (P = 0.015) has been observed. Comparison between phenytoin toxic and others among patients showed no association of these polymorphisms with phenytoin toxicity.


Anaphylaxis induced by pine nuts in two young girls.
Pine nuts are the seeds of Pinus pinea. There are few reported cases of allergy to pine nut. We describe two young girls with anaphylaxis caused by small amounts of pine nuts. Specific IgE to pine nut was demonstrated by skin prick tests and RAST but no IgE to other nuts and pine pollen was detected. The patients had IgE against a pine nut protein band with apparent molecular weights of approximately 17 kDa that could be considered as the main allergen. Our patients were monosensitized to pine nut and the 17-kDa protein could be correlated with the severe clinical symptoms.


A fluorescent redox dye. Influence of several substrates and electron carriers on the tetrazolium salt-formazan reaction of Ehrlich ascites tumour cells.
This study was performed to elaborate the best conditions for measuring the redox activity of Ehrlich ascites tumour cells by using a new tetrazolium salt, cyantolyl tetrazolium chloride (CTC). This tetrazolium salt forms a fluorescent water-insoluble formazan on reduction on the surface of intact vital cells. The influences of fixation and of various substrates and electron carriers on the cellular reduction of CTC were investigated quantitatively using an elution technique. The amount of formazan obtained after incubating vital cells with Meldola Blue as electron carrier was greater than that obtained with Methylene Blue, menadione, 2,6-dichloroindophenol, 1-methoxyphenazine methosulphate or phenazine methosulphate. Using flow cytometry, the formazan production per cell and, after staining the nuclear DNA, the distribution of the redox activity in the cell population can be visualized with satisfactory resolution. We conclude from our findings that dehydrogenases are only partially involved in the reduction of tetrazolium salts by intact cells and that a redox activity, probably related to a cell membrane-bound NAD(P)H-oxidase system, is mainly measured.


Pregnancy in a uterine scar sacculus--an unusual cause of postabortal haemorrhage. A case report.
A patient who presented with incomplete abortion developed severe persistent haemorrhage from the genital tract after evacuation of the uterus, as a result of erosion of a major vessel in a sacculus in a previous caesarean section scar. Detection and management of this condition are discussed.


A versatile and sensitive method for measuring oxygen.
Oxygen dependence of the lifetime of the excited triplet state of phosphorescent molecules can be used to measure the oxygen concentration in aqueous media. These measurements are insensitive to much of the optical interference that limits the usefulness of measurements based on the oxygen dependent quenching of luminescence intensity. The measurements also extend to significantly lower oxygen concentrations than are normally attainable using oxygen electrodes. The phosphorescence lifetimes can be accurately measured from a few microseconds to seconds, permitting a wide dynamic range of oxygen concentration measurements. With currently available probes, for example, it is possible to make continuous measurement of oxygen concentrations from 10(-4) M to 10(-8) M in a single experiment.


Microtubules regulate hypoxia-inducible factor-1α protein trafficking and activity: implications for taxane therapy.
Disruption of the microtubule cytoskeleton impairs tumor angiogenesis by inhibiting the hypoxia-inducible factor (HIF-1α) pathway. However, the signaling cascade linking microtubule disruption to HIF-1α inactivation has not been elucidated. Here, we show that microtubule-targeting drug (MTD) treatment impaired HIF-1α protein nuclear translocation, which significantly down-regulated HIF transcriptional activity. We provide strong evidence that HIF-1α protein associates with polymerized microtubules and traffics to the nucleus, with the aid of the dynein motor protein. Together, these data suggest that microtubules are critically involved in the nuclear trafficking and transcriptional activity of HIF-1α. We also show that the connection between the microtubule cytoskeleton and HIF-1α regulation is lost in renal cell carcinoma (RCC), where HIF-1α is overexpressed because of mutations in the von Hippel Lindau (VHL) tumor suppressor protein. Specifically, we show that MTD treatment of RCC cells did not impair HIF-1α nuclear accumulation or transcriptional activity, and had no effect on the polysome association profile of HIF-1α. Interestingly, we found that HIF-1α protein did not bind microtubules in RCC. Moreover, restoration of VHL function failed to restore the ability of MTDs to inhibit HIF-1α, suggesting that VHL does not contribute to this phenotype. Together, these results suggest that HIF-1α regulation is microtubule-independent, and likely contributes to the chemoresistant nature of RCCs. Further understanding of the microtubule-dependent HIF-1α regulation, and lack thereof in RCC, is essential given the importance of HIF-1α in tumor biology, and the widespread use of MTDs in clinical oncology.


The effect of socioeconomic factors on patient outcomes in cardiac surgery.
Healthcare delivery is heterogenous; the reasons for this are numerous and complex. Patient-specific factors including geography, income, insurance status, age, and gender have been shown to bias surgical outcomes. Utilizing a prospectively collected all-payer database, we aim to evaluate the influence of socioeconomic factors on mortality and length of stay (LOS) after common cardiac surgical procedures. We utilized the National Inpatient Sample, Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality for the year 2019. We included patients undergoing coronary artery bypass grafting (CABG), aortic valve replacement (AVR), transcatheter aortic valve replacement (TAVR), and combined AVR/CABG using the 10th revision of the International Classification of Diseases procedure codes. AVR and CABG were combined into a separate cohort as this was felt to represent a different pathology than isolated valvular or coronary arterial disease. Baseline demographics were summarized. Multivariable regression was performed within each procedure group to model the odds of in-hospital mortality and hospital LOS with age, sex, insurance, zip-code median household income, and location as predictors. Baseline patient characteristics including gender, income, geography, and payer status were similar between CABG, AVR, and AVR/CABG. TAVR patients had a higher proportion of female sex and Medicare as the primary payer, with an overall greater age. Multivariable Cox proportional hazards regression found that higher income was strongly associated with decreased LOS following AVR and CABG, and moderately associated in TAVR and AVR/CABG. Private insurance was associated with a decreased LOS in patients undergoing CABG, AVR, TAVR, and AVR/CABG. Female sex and increased age were associated with increased odds of mortality in TAVR, CABG, and AVR/CABG. Private insurance was associated with a decreased odds of mortality in patients undergoing AVR. These findings reveal significant disparities in patient outcomes after routine cardiac operations that are associated with socioeconomic status. Patients who did not have private insurance or had lower incomes were found to be at risk for increased LOS. Women were at a higher risk of mortality for several operations, a finding which has been previously described elsewhere. Private insurance conveyed a decreased odds of mortality in patients undergoing AVR. This data set serves to highlight differences in healthcare outcomes based on a variety of socioeconomic, geographic, and other inherent factors. Additional research is needed to identify the mechanisms behind these disparities with the goal of providing equitable care to all patients.