Attainment of local drug delivery with paclitaxel-eluting balloon in porcine coronary arteries.
Our purpose was to confirm the local drug delivery of a paclitaxel-eluting balloon by percutaneous intervention of single arterial segments or bifurcations of porcine coronary arteries. Eight domestic pigs were subjected to 2 x 30 s Dior balloon dilatation of the mid left anterior descending, left circumflex and proximal right coronary arteries. Bifurcation intervention was performed in six arteries. The dilated, and the distal and proximal reference segments were prepared for tissue paclitaxel concentration measurement. Tissue samples were harvested at mean 1.5, 12, 24 and 48 h after balloon dilatation and plasma samples were taken at various time points. The tissue paclitaxel concentration of the single dilated segment was at 1.5 h postdilatation 1.82+/-1.60 micromol/l, which decreased significantly to 0.73+/-0.27 (P=0.032), 0.62+/-0.34 and 0.44+/-0.31 micromol/l at 12, 24 and 48 h. The bifurcation intervention resulted in 5.10+/-1.80 micromol/l tissue paclitaxel amount in the main branch, which at 12 h had diminished to 1.41+/-1.23 micromol/l (P=0.004). The bifurcation side contained 7.00+/-4.80 micromol/l paclitaxel at 1.5 h postdilatation, which lowered to 2.72+/-0.40 micromol/l (P=0.034). The mean paclitaxel concentration of the reference segments decreased gradually from 0.84+/-0.99 to 0.34+/-0.36 micromol/l (P=0.09), 0.28+/-0.16 and 0.19+/-0.18 micromol/l tissue at 1.5, 12, 24 and 48 h postdilatation, respectively. No paclitaxel was found in the peripheral blood at any time point. Short exposure of the coronary artery to paclitaxel with a coated balloon is sufficient for the attainment of an adequate tissue concentration of paclitaxel, which is known to be efficient in inhibiting neointimal growth.


N-Alkyl-N-arylmethylpiperidin-4-amines: novel dual inhibitors of serotonin and norepinephrine reuptake.
A series of N-alkyl-N-arylmethylpiperidin-4-amines have been prepared and are demonstrated to be inhibitors of both serotonin and norepinephrine reuptake.


Rheological and breadmaking properties of wheat samples infected withFusarium spp.
Rheological and breadmaking properties of untreated and suboptimally stored wheat samples (grain moisture: 20%, temperature: 20°C) and also of wheat which was inoculated withFusarium spp. were investigated. The deoxynivalenol (DON) content of the stored and inoculated wheat samples ranged between 820-12,000 μg/kg. Gluten proteins were isolated with different extraction solutions and the fractions obtained were analysed by means of RP-HPLC. Microextension tests and micro-baking tests were used for the determination of dough properties (maximum resistance (MR) and extensibility (EX)) and bread volume, respectively. In spite of the extremely high DON concentrations of some wheat samples contaminated withFusarium spp. they showed only a slight decrease of the amount of gluten proteins. Extension tests of dough led to a slight decrease of MR, bread volumes stayed almost the same compared with the non-contaminated grain. The contamination of wheat withAspergillus andPenicillium led to a high decrease of gluten proteins, which resulted in an extremely decreased MR of the dough and a very low bread volume.


[Production of inoculates for leguminous plants. Production of cellular suspensions of Rhizobium (Lotus group)].
The influence of culture medium composition and operative conditions on the cellular growth of Rhizobium sp (group Lotus) strain is studied. As much as 1 x 10(9) cell/ml were obtained in 16 hours using sucrose in the medium as carbon source. The best growth rate was obtained (mu = O,22 h-1) when the experiments were performed at 400 r.p.m. and one volume of air/volume of medium x minute (OAR = 793,0 ml of oxygen/1 h).


Saline irrigation for reducing the recurrence of common bile duct stones after lithotripsy: a randomized controlled trial.
Mechanical lithotripsy produces stone fragments that are not easily detected by cholangiography and is a potential cause of recurrence of common bile duct stones (CBDS). This study aims to clarify whether 100 ml saline irrigation after mechanical lithotripsy reduces the recurrent rate of CBDS. In this randomized controlled trial performed at the Surgical Endoscopy Center, the First Hospital of Lanzhou University between May 10, 2019, and Dec 31, 2020, patients undergoing endoscopic mechanical lithotripsy were randomly assigned to receive saline irrigation (study group) or no irrigation (control group). The saline irrigation was given 100 ml saline pulse irrigation after cholangiography showed no residual stones. Patients were followed up for at least 24 months after endoscopic stone removal to assess the recurrence of CBDS. This study was registered with ClinicalTrials.gov (NCT03937037). During the median follow-up period of 35.6 months (interquartile range, 26.0-40.7), 43 of the 180 patients had stone recurrence (24%). The frequency of recurrence of CBD stones was 12.22% in the saline irrigation group and 35.56% in the control group, with a difference of 23.33% between the two groups (95% confidence interval [CI], 11.35%-35.32%, p < 0.001). Multivariable Cox proportional hazards analyses showed that constipation (hazard risk [HR] 2.42; 95% CI, 1.22-4.80, p = 0.012), periampullary diverticulum (PAD) (HR 3.06; 95% CI, 1.62-5.79, p < 0.001), and total to direct bilirubin ratio (HR 1.48; 95% CI, 1.21-1.81, p < 0.001) were independent risk factors for the recurrence of CBDS. Saline irrigation was the only preventive factor for the recurrence of CBDS (HR 0.22; 95% CI, 0.11-0.44, p < 0.001). For patients with CBDS requiring mechanical lithotripsy, 100 ml saline irrigation effectively reduces the recurrent rate of CBDS after endoscopic stone removal. This work was supported by National Natural Science Foundation of China (32160255); Natural Science Foundation of Gansu Province (22JR5RA898, 20JR10RA676); Science and Technology Planning Project of Chengguan District in Lanzhou (2020JSCX0043).


Composition of eukaryotic gene loci regarding gene conversion units and the presence or the absence of intralocus reciprocal recombination.
In Sordaria fimicola, the g-locus is composed of a single convertron and does not show intralocus reciprocal recombination. On the contrary, the i-locus is composed of multiple convertrons and shows genuine intralocus reciprocal recombination.


[Alterations of salivary flow rate and oral main pathogens in miniature pig with bilateral parotid gland atrophy].
To observe the effect of bilateral parotid gland atrophy on the whole saliva flow rate and the growth of main oral pathogens in different sites of oral cavity. Ten healthy miniature pigs were divided into two groups. The parotid glands of test group (n = 5) were bilaterally ablated by methyl violet. Another healthy five miniature pigs served as the control group. Whole saliva was collected and the whole saliva flow rate detected in both groups at 12 and 24 months respectively after parotid atrophy. The total numbers of oral main pathogens in the first molar, cuspid sub-gingival bacteria plaque and whole saliva were also detected. The whole saliva flow rate was significantly decreased at both 12 and 24 months respectively after atrophy of bilateral parotid gland in miniature pig. Pathogens including Streptococcus mutans, Porphyromonas gingivalis and Fusobacterium nucleatum in different sites oral cavity were increased after bilateral parotid gland atrophy. Bilateral ablation of the parotid glands led to a significant decrease of whole saliva flow rate. The total numbers of main oral pathogens were increased in different sites of oral cavity.


The role of peritoneal lavage in severe acute pancreatitis.
Encouraged by reports of the therapeutic efficacy of peritoneal lavage in small series of five or six patients with acute pancreatitis, we have evaluated this treatment in 24 patients with "severe" pancreatitis. One hundred and three patients with "severe" pancreatitis (28% mortality) were separated from 347 with "mild" pancreatitis (0.9% mortality) by previously described early objective signs. Early treatment (Day 0-7) of "severe" pancreatitis included peritoneal lavage through catheters placed nonoperatively in 18 (Group A) and by catheters placed at laparotomy in six (Group C). Early treatment of nonlavaged patients with "severe" pancreatitis was by standard nonoperative measures in 61 (Group B) and included early operation in 18 (Group D). Lavage was continued for 48-96 hours, usually using 36-48 L/24 hours of balanced isotonic dialysate fluid, and was uncomplicated. Lavage led to striking immediate clinical improvement and no lavaged patient (Groups A and C) died during the first 10 days of treatment of pancreatitis. By contrast, 45% of deaths in nonlavaged patients (Group B and D) occurred during this early period, usually from cardiovascular or respiratory failure. Although lavage reduced mortality in subgroups of patients, ultimate overall survival was no affected (Group A, 83%; B, 84%; C, 33%; D,33%). Late peripancreatic abscesses caused most deaths in lavaged patients. These data show that peritoneal complications of severe acute pancreatitis and dramatically reduces early mortality. Lavage does not prevent the late local sequelae of peripancreatic necrosis.


Effect of metal salts on α-amylase-catalyzed hydrolysis of broken rice under a moderate electric field.
This study aimed to evaluate the effects of metal salts on α-amylase-catalyzed hydrolysis of broken rice under a moderate electric field (MEF) by monitoring changes in hydrolysis efficiency, temperature, α-amylase activity, starch-metal ion interaction, and the structural and physicochemical properties of hydrolysates. Results showed that metal salts affected the hydrolysis mainly by altering α-amylase activity rather than by inducing thermal effect or interacting with starch. Reducing sugar content reached 125.0 g/L, while α-amylase activity increased by 18.16% when treated with 0.12 mmol/L Ca2+. Holes on hydrolysates treated with Ca2+ and Mg2+ were larger than those treated with Mn2+ and Cu2+. No M-O bond was formed after the hydrolysis. The crystallinity was slightly increased with the hydrolysis and the values for Ca2+- and Mg2+-treated samples were larger. The water and oil absorption capacity of the hydrolysate treated with Ca2+ was the highest. This study extended the knowledge of the roles of metal ions on MEF-assisted enzymatic hydrolysis and will contribute to the development of an innovative technology for starch modification.


Hepatitis C and beta-thalassemia major in children: experience with glecaprevir/pibrentasvir.
Hepatitis C virus (HCV) is estimated to affect 3.26 million children worldwide, with the highest number of cases registered in Pakistan and China. Vertical transmission is the principal route in industrialized countries. However, iatrogenic transmission is relevant in low-income settings. We present the case of a 12-year-old Pakistani child who suffered from beta-thalassemia major and hepatitis C, successfully treated with glecaprevir/pibrentasvir.


Filling the Core EPA 10 assessment void: A framework for individual assessment of Core Entrustable professional activity 10 competencies in medical students.
The goal of this study was to develop and evaluate a novel curriculum and assessment tool for Core Entrustable Professional Activity (EPA) 10 competencies and entrustment scoring in a cohort of medical students in their emergency medicine (EM) clerkship using a framework of individualized, ad hoc, formative assessment. Core EPA 10 is an observable workplace-based activity for graduating medical students to recognize a patient requiring urgent or emergent care and initiate evaluation and management. This is a prospective, pretest-posttest study of medical students during their EM clerkship. Using the Thomas and Kern framework, we created a curriculum of simulation cases about chest pain/cardiac arrest and respiratory distress, which included novel assessment checklists, and instructional videos about recognizing and managing emergencies. Students were individually pretested on EPA 10 competencies using the simulation cases. Two raters scored students using standardized checklists. Students then watched instructional videos, underwent a posttest with the simulation cases, and were scored again by the two raters using the checklists. Differences between pretest and posttest scores were analyzed using paired t-tests and Wilcoxon signed-rank tests. Seventy-three out of 85 (86%) students completed the curriculum. Mean scores from pretest to final posttest in the chest pain/cardiac arrest and respiratory distress cases significantly improved from 14.8/19 (SD 1.91), to 17.1/19 (SD = 1.00), t(68) = 10.56, p < 0.001, and 8.5/13 (SD 1.79), to 11.1/13(SD 0.89), t(67) = 11.15, p < 0.001, respectively. The kappa coefficients were 0.909 (n = 2698, p < 0.001) and 0.931 (n = 1872, p < 0.001). Median modified Chen entrustment scores improved from 1b (i.e., "Watch me do this") to 2b (i.e., "I'll watch you") for the chest pain/cardiac arrest case (p < 0.001) and 1b/2a (i.e., "Watch me do this"/ "Let's do this together") to 3a (i.e. "You go ahead, and I'll double-check all of your findings") for the respiratory distress case (p < 0.001). A new directed curriculum of standardized simulation cases and asynchronous instructional videos improved medical student performance in EPA 10 competencies and entrustment scores. This study provides a curricular framework to support formative individualized assessments for EPA 10.


Comparison of genetic groups determined by molecular and immunological analyses of Giardia isolated from animals and humans in Switzerland and Australia.
Nine axenic isolates of Giardia originating from four different host species in Switzerland were subjected to genetic analysis using the polymerase chain reaction (PCR) to amplify segments of genes encoding different trophozoite variant surface proteins (VSPs). Three genotypes were identified on the basis of product yield, size, and restriction-fragment-length polymorphisms (RFLPs). Five G. duodenalis isolates (O1, B1, B2, B3-1A1 and C1--from a sheep, three calves and a dog, respectively) were classified as belonging to genetic group I of Andrews et al. (1989). DNA amplified from the VSP genes tsp11, tsa417 and vsp1267 of these isolates was indistinguishable in size and restriction characteristics from that amplified from group-I Giardia isolated from humans in Australia. One human-derived Swiss isolate (H2-17A1), typed as belonging to genetic group II, yielded a vsp1267-specific PCR product that was indistinguishable by size or restriction sites from the equivalent 1.6-kb product amplified from human-derived Australian group-II organisms. This isolate also yielded 1.8-kb tsp11 and 0.52-kb tsa417/tsp11-like PCR products possessing RFLPs typical of group-II organisms. Three isolates (O2-4A1, O3 and H3-15K2--originating from two sheep and a human, respectively) represent a novel genotype that is closely related to genetic groups I and II. These three isolates exhibited identical RFLPs in their tsp11 PCR products and failed to yield a vsp1267 PCR product. An antiserum specific for the 90-kDa VSP of the sheep-derived clone O2-4A1 reacted strongly by immunofluorescence and on Western blots with surface proteins from the O2, O3 and H3 isolates only--consistent with the genetic classification determined above. The data provide no evidence for the occurrence of host-specific genotypes.


Kocuria kristinae infection associated with acute cholecystitis.
Kocuria, previously classified into the genus of Micrococcus, is commonly found on human skin. Two species, K. rosea and K. kristinae, are etiologically associated with catheter-related bacteremia. We describe the first case of K. kristinae infection associated with acute cholecystitis. The microorganism was isolated from the bile of a 56-year old Chinese man who underwent laparoscopic cholecystectomy. He developed post-operative fever that resolved readily after levofloxacin treatment. Our report of K. kristinae infection associated with acute cholecystitis expands the clinical spectrum of infections caused by this group of bacteria. With increasing number of recent reports describing the association between Kocuria spp. and infectious diseases, the significance of their isolation from clinical specimens cannot be underestimated. A complete picture of infections related to Kocuria spp. will have to await the documentation of more clinical cases.


Written spelling agraphia.
When a disorder of single word writing is seen in conjunction with preserved oral spelling and intact written grapheme formation ("written spelling agraphia"), the deficit may be presumed to lie somewhere between letter choice and written motor output. Two potential deficits are considered: (1) visual letter codes are not activated properly and (2) the information contained within properly activated visual letter codes fails to reach intact graphic motor patterns. Two patients with written spelling agraphia were each given a series of tests aimed at distinguishing between the two possibilities. Results suggest that the written spelling agraphia seen in these two patients arises from different underlying deficits. The results are discussed in terms of the patients' CT scan lesion sites, which were markedly different.


Case of Barrett's adenocarcinoma with marked endoscopic morphological changes in Barrett's esophagus over a long follow-up period of 15 years.
The natural history of Barrett's esophagus (BE) is unclear. We herein describe a case of Barrett's adenocarcinoma (BAC) in which we could closely observe marked morphological changes in BE over a long follow-up period of 15 years. A man in his seventies received routine esophagogastroduodenoscopy (EGD) and was diagnosed as having reflux esophagitis and short-segment BE. The BE gradually became elongated, and BAC was detected 9 years following the initial EGD examination with continued administration of a proton pump inhibitor. We witnessed that BE elongated sporadically over time and mucosal breaks of reflux esophagitis were detectable several years before elongation. The patient underwent endoscopic submucosal dissection for BAC and has been monitored by EGD every year thereafter. These remarkable morphological changes may be representative of the natural history of BE and aid in deciding long-term disease management.


Investigating Factors Influencing Nurses' Behavioral Intention to Use Mobile Learning: Using a Modified Unified Theory of Acceptance and Use of Technology Model.
The purpose of this study was to develop and empirically test a model for predicting the key factors affecting nurses' behavioral intention to use mobile learning (m-learning). We explored behavioral intention from users' perspectives by applying an extended unified theory of acceptance and use of technology (UTAUT) model with the addition of information quality, system quality, technostress, and satisfaction. We conducted a survey of the district and regional hospitals in central Taiwan. Data were derived from 434 respondents. Structural equation modeling was applied to analyze the causal effects of 15 hypothesized predictive factors. We determined that satisfaction, social influence, performance expectancy, facilitating conditions, and effort expectancy positively impacted nurses' behavioral intention to use m-learning. In addition, technostress was a negative antecedent of effort expectancy. Information quality and system quality had significantly positive effects on satisfaction, performance expectancy, and effort expectancy. This study provides hospital managers with a reference when assessing future developments and informs approaches to promote m-learning.


Neurogenic cardiac outcome in patients after acute ischemic stroke: The brain and heart connection.
Neurogenic cardiac impairment can occur after acute ischemic stroke (AIS), but the mapping of the neuroanatomic correlation of stroke-related myocardial injury remains uncertain. This study aims to identify the association between cardiac outcomes and middle cerebral artery (MCA) ischemic stroke, with or without insular cortex involvement, as well as the impact of new-onset atrial fibrillation (AF) after AIS on recurrent stroke. Serial measurements of high sensitivity troponin T (TnT), brain natriuretic peptide (BNP), electrocardiography (ECG), echocardiogram, and cardiac monitoring were performed on 415 patients with imaging confirmed MCA stroke, with or without insular involvement. Patients with renal failure, recent cardiovascular events, or congestive heart failure were excluded. One hundred fifteen patients (28%) had left MCA infarcts with insular involvement, 122 (29%) had right MCA infarcts involving insular cortex, and 178 (43%) had no insular involvement. Patients with left MCA stroke with insular involvement tended to exhibit higher BNP and TnI, and transient cardiac dysfunction, which mimicked Takotsubo cardiomyopathy in 10 patients with left ventricular ejection fraction (LVEF) of 20-40%. Incidence of new-onset AF was higher in right MCA stroke involving insula (39%) than left MCA involving insula (4%). Nine out of fifty-three patients with new-onset AF were not on anticoagulant therapy due to various reasons; none of them experienced recurrent AF or stroke during up to a 3-year follow-up period. Statistically significant correlations between BNP or TnT elevation and left insular infarcts, as well as the incidence of AF and right insular infarcts, were revealed using linear regression analysis. The present study demonstrated that acute left MCA stroke with insular involvement could cause transient cardiac dysfunction and elevated cardiac enzymes without persistent negative outcomes in the setting of health baseline cardiac condition. The incidence of new-onset AF was significantly higher in patients with right MCA stroke involving the insula. There was no increased risk of recurrent ischemic stroke in nine patients with newly developed AF who were not on anticoagulant therapy, which indicated a need for further research on presumed neurogenic AF and its management.


Microbiota-sensitive drug delivery systems based on natural polysaccharides for colon targeting.
Colon targeting is an ongoing challenge, particularly for the oral administration of biological drugs or local treatment of inflammatory bowel disease (IBD). In both cases, drugs are known to be sensitive to the harsh conditions of the upper gastrointestinal tract (GIT) and, thus, must be protected. Here, we provide an overview of recently developed colonic site-specific drug delivery systems based on microbiota sensitivity of natural polysaccharides. Polysaccharides act as a substrate for enzymes secreted by the microbiota located in the distal part of GIT. The dosage form is adapted to the pathophysiology of the patient and, thus, a combination of bacteria-sensitive and time-controlled release or pH-dependent systems can be used for delivery.


Evaluation of Cryopreservation Media for the Preservation of Human Corneal Stromal Stem Cells.
Introduction: Human corneal stromal stem cells (CSSCs) have gained increasing attention in the treatment of corneal stromal scars. In view of this, the preparation and storage of CSSCs are critical to maintaining the regenerative potential of CSSCs. The goal of the study was to investigate the human serum (HS) concentration in the cryomedia that could best preserve CSSCs. Materials and Methods: Three different cryopreservation media, varying in HS concentration were evaluated in their ability to preserve the viability and phenotype of CSSCs: 2% HS (FS1), 4% HS (FS2), and 90% HS (FS3). After thawing, CSSCs morphology, recovery rate, cell proliferation, relative gene expression of CSSC markers (ABCG2, SOX2, NANOG, PAX6, and SIX3), and their anti-inflammatory response (level of TNFAIP6) were compared with those of unfrozen CSSCs (control). Results: Cryopreserved CSSCs had similar cell morphology as the control. Cell viability was significantly higher using FS2 (92.7 ± 1.3%) compared with FS1 (88 ± 0.8%, p = 0.018). Doubling times of CSSCs were maintained in all cryopreserved conditions, as in the control (p > 0.05), which were 0.9 ± 0.1 days and 1.8 ± 0.0 days at passages 3 and 4, then increased to 18.2 ± 1.9 days at passage 6 (p > 0.05). The expression level of stem cell/progenitor cell markers investigated was not affected by the cryopreservation with any of the three media. In addition, cryopreserved CSSCs have a similar expression level of TNFAIP6 after stimulation with proinflammatory cytokines as the control (p > 0.05). Conclusion: Our results indicated that all three cryopreservation media maintained CSSCs phenotype after undergoing one freezing/thawing cycle. Impact Statement Corneal stromal stem cells (CSSCs) offer an alternative for the treatment of corneal stromal scars. Cryopreservation of CSSCs is necessary as it enables feasibility of using CSSCs as a cell therapy candidate. The current study shows that media used to cryopreserve CSSCs could be optimized to maintain cell viability, phenotype, and potency of CSSCs after thawing.


Studies On The Lungfluke, Paragonimus Iloktsuenensis: IV. A Mathematical Analysis On Metacercarial Density Of Paragonimus Iloktsuenensis In Crab Host, Sesarma Dehaani.
Mathematical models such as the negative binomial, Poisson and Polya-Eggenberger distributions were applied to the observed data of the number of metacercariae of Paragonimus iloktsuenensis in crab hosts, Sesarma dehaani which were collected in Hadong, South Kyong-sang Do, Korea. From the above analysis, it was found that the pattern of density of metacercariae of this lungfluke among the crab hosts was well fitted to the negative binomial distribution, rather than to the Poisson or Polya-Eggenberger distribution.


Differences between mesial and neocortical magnetic-resonance-imaging-negative temporal lobe epilepsy.
The aim of this study was to assess clinical and electrophysiological differences within a group of patients with magnetic-resonance-imaging-negative temporal lobe epilepsy (MRI-negative TLE) according to seizure onset zone (SOZ) localization in invasive EEG (IEEG). According to SOZ localization in IEEG, 20 patients with MRI-negative TLE were divided into either having mesial SOZ-mesial MRI-negative TLE or neocortical SOZ-neocortical MRI-negative TLE. We evaluated for differences between these groups in demographic data, localization of interictal epileptiform discharges (IEDs), and the ictal onset pattern in semiinvasive EEG and in ictal semiology. Thirteen of the 20 patients (65%) had mesial MRI-negative TLE and 7 of the 20 patients (35%) had neocortical MRI-negative TLE. The differences between mesial MRI-negative TLE and neocortical MRI-negative TLE were identified in the distribution of IEDs and in the ictal onset pattern in semiinvasive EEG. The patients with neocortical MRI-negative TLE tended to have more IEDs localized outside the anterotemporal region (p=0.031) and more seizures without clear lateralization of ictal activity (p=0.044). No other differences regarding demographic data, seizure semiology, surgical outcome, or histopathological findings were found. According to the localization of the SOZ, MRI-negative TLE had two subgroups: mesial MRI-negative TLE and neocortical MRI-negative TLE. The groups could be partially distinguished by an analysis of their noninvasive data (distribution of IEDs and lateralization of ictal activity). This differentiation might have an impact on the surgical approach.


Current Status of Radiotherapy for the Management of Regional Nodes in Breast Cancer.
Worldwide, breast cancer is the most common invasive cancer in women. Breast cancer constitutes about 23% of invasive cancers in women. The management of breast cancer depends on various factors, including the cancer stage and patient age. Breast cancer is usually treated with surgery, which can be followed by chemotherapy or radiation therapy, or both. Until recently, the standard procedure for axillary study was axillary dissection. Sentinel lymph node biopsy has been validated as a less-aggressive axillary treatment without an impact on survival. In the present report, we review the current management of the axillary lymph nodes, especially from the viewpoint of an oncology radiotherapist.


Blockade of neuronal tryptamine receptors by metoclopramide.
Metoclopramide (0.13, 0.51, 2.0 and 8.1 X 10(-6) M) caused parallel, rightward, shifts in the dose response curves to 5-HT on the isolated rabbit heart. A significant straight line relationship was found between log (5-HT dr--1) and log [metoclopramide] (molar) with a slope of 1.08 +/- 0.13 and giving a pA2 value of 7.20. Metoclopramide did not significantly alter responses to noradrenaline and was 575 times less effective as an inhibitor of DMPP than of 5-HT. The results indicate that metoclopramide is a potent, surmountable and selective antagonist of tryptamine receptors on rabbit cardiac sympathetic nerves.


Shuttle box learning in zebrafish (Danio rerio).
Zebrafish is used in forward genetic and drug screening and is gaining popularity in behavioral brain research but high throughput learning paradigms are lacking. The sight of conspecifics has been shown to be rewarding in zebrafish. Here, in a novel paradigm, subjects learn to respond to alternating presentation of computer-animated zebrafish images. The simplicity and computerization of the paradigm will make it useful for high throughput screening.


Catheter-based radiofrequency renal sympathetic denervation for resistant hypertension.
To evaluate the feasibility, efficacy, and safety of catheter-based radiofrequency renal sympathetic denervation for treatment of resistant hypertension. Twenty-four patients with essential hypertension unresponsive to at least three antihypertensive agents underwent renal denervation (RDN). Three patients had variant renal anatomy. Comorbidities included diabetes (n = 11), renal failure (n = 4), and obstructive sleep apnea (n = 2). The effect on 24-hour ambulatory blood pressure (BP) was assessed at 6 months. Patients with a decrease in systolic BP of at least 10mm Hg were considered responders. RDN was bilateral in 19 patients and single-sided in five. The 19 patients with bilateral RDN showed mean reductions in 24-hour ambulatory BP of 20.7/8.7mm Hg±18.1/9.9 (systolic/diastolic; P = .0001/P = .0012). Sixteen bilaterally treated patients (84.2%) showed a systolic BP reduction of at least 10mm Hg and were considered responders, whereas only one of the five patients with single-sided RDN showed a response. Two responders with sleep apnea showed improvement in polysomnography indices, and one with left concentric ventricular hypertrophy showed complete cardiac remodeling 11 months after the RDN procedure. Renal function remained unchanged in all patients, including those with renal failure. Optical coherence tomography of the renal arteries in one patient showed sporadic endothelial scarring. Renal angiograms at 9 months (one patient) and 12 months (two patients) had normal findings. Catheter-based RDN was carried out safely, even in patients with comorbidities, abnormal renal arteries, or anatomic variants. The response rate for bilateral RDN (84.2%) was comparable to previous reports.


Acceptability of sexual health discussion and testing in the pediatric acute care setting.
The objective of this study was to determine acceptability of sexual health discussion and testing among adolescents, parents, and health care providers (HCPs). We conducted a cross-sectional study of acute care patients (aged 14-19 years), parents, nurses, and physicians/nurse practitioners. Subjects rated sexual health discussion, sexually transmitted disease and pregnancy testing as acceptable/unacceptable and verbally explained their reasoning. Reasons were transcribed verbatim, coded, and analyzed. Agreement with individual adolescent responses was determined. Controlling for visit type, logistic regression was used to evaluate association between location and acceptance with odds ratios (ORs). Visits were categorized as reproductive/nonreproductive. Subjects included 127 adolescents, 90 parents, and 190 HCP responses. Mean adolescent age was 15.5 years; 57% were female; 43% reported previous intercourse; 43% were black, and 39% were white. Most visits (76%) were nonreproductive. Adolescents and parents were highly accepting of discussion and testing and were more accepting than HCPs. Acceptance was more likely for reproductive versus nonreproductive visits (P ≤ 0.05). Emergency department HCPs were more likely to accept discussion (OR, 2.8) and sexually transmitted disease testing (OR, 3.1) than urgent care HCPs. Acceptance themes among adolescents were comfort with system/HCP, confidentiality concerns, and desire for good health; among parents, acceptance themes were identification as a safe place for disclosure and desire for adolescent good health and information; and among HCPs, these were relevance to chief complaint and perception of appropriate care. In contrast to HCPs, adolescents and parents expressed broad support for sexual health discussion and testing, which may inform HCP practice to improve access to care.


Morphology of feedback neurons in the mushroom body of the honeybee, Apis mellifera.
The anatomy of gamma-aminobutyric acid (GABA)-immunoreactive, recurrent feedback neurons in the mushroom body (MB) of the honeybee, Apis mellifera, was investigated by using intraneuropilar injections of cobalt ions and light microscopic techniques. Each MB contains approximately 110 GABA-immunoreactive neurons, and approximately 50% of them are feedback neurons, i.e., they connect the MB output regions--the alpha-lobe, beta-lobe, and pedunculus--with its input regions--the calyces. Their somata are located in the lateral protocerebral lobe, and their primary neurites project medially and bifurcate near the alpha-lobe. In the alpha-lobe feedback neurons form narrow banded, horizontal arborizations in the dorsal and median alpha-lobe; each cell innervates a certain alpha-lobe layer. The neurons form additional branches in the pedunculus and the beta-lobe. All calycal subcompartments--the lip, collar, and basal ring--are innervated by feedback neurons. However, individual feedback neurons innervate exclusively a certain subcompartment in both the median and lateral calyx. Due to the arrangement of intrinsic Kenyon cells, each calycal subcompartment is connected to its specific, corresponding layer in the alpha-lobe. Feedback neurons interconnect the alpha-lobe and the calyces in either a corresponding or a noncorresponding fashion. With respect to their branching pattern in the alpha-lobe, the basal ring and the collar neuropil receive input from feedback neurons innervating the corresponding dorsal and median alpha-lobe layers. By contrast, the lip region, which receives olfactory antennal input, is innervated by feedback neurons with arborizations in a noncorresponding dorsal alpha-lobe layer.


Knowledge of human papillomavirus and cervical cancer among young women recruited using a social networking site.
Human papillomavirus (HPV) is the commonest sexually transmitted infection. Despite the significant morbidity and mortality associated with HPV-related diseases, previous studies have demonstrated low HPV knowledge in the general population. The objectives of this study were to assess knowledge of cervical cancer and HPV among young women and investigate predictors of high knowledge. Female subjects, aged 16-25 years living in Victoria, Australia, were recruited using targeted advertising on Facebook from May to September 2010. A web-based questionnaire was used in a cross-sectional pilot study for a large longitudinal study on women's health, The Young Female Health Initiative. A total of 278 women completed the questionnaire. The geographic region, indigenous status and socio-economic status of participants were representative of the target population. Overall, 63% knew what HPV was, but only 48% knew it was a common virus. Predictors of high HPV knowledge on multivariate analyses were older age (adjusted OR (aOR) 2.78, 95% CI 0.77 to 10.04), higher socio-economic status (aOR 1.39, 95% CI 0.66 to 2.95), being Australian-born (aOR 3.10, 95% CI 1.15 to 8.36), older age at first vaginal intercourse (aOR 1.84, 95% CI 0.66 to 5.14), awareness of HPV vaccines (aOR 2.16, 95% CI 0.68 to 6.85) and chlamydia (aOR 2.57, 95% CI 1.11 to 5.94), and self-reported HPV vaccination status (aOR 1.83, 95% CI 0.76 to 4.41). HPV and cervical cancer knowledge among participants were relatively high compared with other studies conducted both worldwide and in Australia. However, deficits in knowledge exist and warrant address in educational initiatives.


Deep learning-based thin-section MRI reconstruction improves tumour detection and delineation in pre- and post-treatment pituitary adenoma.
Even a tiny functioning pituitary adenoma could cause symptoms; hence, accurate diagnosis and treatment are crucial for management. However, it is difficult to diagnose a small pituitary adenoma using conventional MR sequence. Deep learning-based reconstruction (DLR) using magnetic resonance imaging (MRI) enables high-resolution thin-section imaging with noise reduction. In the present single-institution retrospective study of 201 patients, conducted between August 2019 and October 2020, we compared the performance of 1 mm DLR MRI with that of 3 mm routine MRI, using a combined imaging protocol to detect and delineate pituitary adenoma. Four readers assessed the adenomas in a pairwise fashion, and diagnostic performance and image preferences were compared between inexperienced and experienced readers. The signal-to-noise ratio (SNR) was quantitatively assessed. New detection of adenoma, achieved using 1 mm DLR MRI, was not visualised using 3 mm routine MRI (overall: 6.5% [13/201]). There was no significant difference depending on the experience of the readers in new detections. Readers preferred 1 mm DLR MRI over 3 mm routine MRI (overall superiority 56%) to delineate normal pituitary stalk and gland, with inexperienced readers more preferred 1 mm DLR MRI than experienced readers. The SNR of 1 mm DLR MRI was 1.25-fold higher than that of the 3 mm routine MRI. In conclusion, the 1 mm DLR MRI achieved higher sensitivity in the detection of pituitary adenoma and provided better delineation of normal pituitary gland than 3 mm routine MRI.


Daidzein-metabolizing phenotypes in relation to serum hormones and sex hormone binding globulin, and urinary estrogen metabolites in premenopausal women in the United States.
Blood and urine concentrations of hormones are implicated in the etiology of some cancers. Small studies have assessed relationships between production of the daidzein metabolites equol and O-desmethylangolensin (ODMA) and hormones, but findings are unclear. We evaluated relationships between daidzein-metabolizing phenotypes and follicular phase concentrations of estrogens, androgens, sex hormone binding globulin (SHBG), and urinary estrogen metabolites in premenopausal women. Two-hundred women collected a first-void urine sample after a 3-day soy challenge, and 191 and 193 provided fasting blood and spot urine samples, respectively, during days 5-9 of their menstrual cycle. Soy challenge urines were analyzed for isoflavones; serum was analyzed for estrogens, androgens, and SHBG; spot urines were analyzed for 2-hydroxyestrone and 16alpha-hydroxyestrone. Data were log-transformed and multiple regression analyses were conducted to assess relationships between daidzein-metabolizing phenotypes and hormones and SHBG. Data from 187 and 189 women were included in analyses of serum and urine hormones, respectively. 55 (27.5%) and 182 (91%) of the 200 women who provided a soy challenge urine sample were equol- and ODMA-producers (>87.5 ng/ml urine), respectively. In unadjusted analyses, equol-producers (n = 52) had lower free testosterone than equol non-producers (n = 137, p = 0.02). In adjusted analyses, there were no differences between producers and non-producers of either daidzein metabolite. In the absence of a soy intervention, we found no difference in serum or urine hormone concentrations between producers and non-producers of equol or ODMA.


Successful treatment of severe Behçet's disease with infliximab in an Italian Olympic athlete.
An Italian Olympic athlete with a severe form of Behçet's disease was given infliximab. He had oral aphthosis, papulopustular and follicular lesions, and a bilateral cystoid macular edema. After the first 3 infusions, the mucocutaneous lesions disappeared and cystoid macular edema was much improved. Cyclosporine was stopped and the prednisone dose was progressively tapered until the cystoid macular edema disappeared.


Heliothrips haemorrhoidalis and its relatives, with one new species and one new genus (Thysanoptera: Thripidae).
Heliothrips similis sp.n. is described as a close relative of the greenhouse thrips, Heliothrips haemorrhoidalis. This is the third species recognized here in the Neotropical genus Heliothrips. A pest species described from South Africa as Heliothrips sylvanus is transferred to a new genus, Neoheliothrips gen.n., as Neoheliothrips sylvanus (Faure) comb.n.


Selective inhibition of STAT3 signaling using monobodies targeting the coiled-coil and N-terminal domains.
The transcription factor STAT3 is frequently activated in human solid and hematological malignancies and remains a challenging therapeutic target with no approved drugs to date. Here, we develop synthetic antibody mimetics, termed monobodies, to interfere with STAT3 signaling. These monobodies are highly selective for STAT3 and bind with nanomolar affinity to the N-terminal and coiled-coil domains. Interactome analysis detects no significant binding to other STATs or additional off-target proteins, confirming their exquisite specificity. Intracellular expression of monobodies fused to VHL, an E3 ubiquitin ligase substrate receptor, results in degradation of endogenous STAT3. The crystal structure of STAT3 in complex with monobody MS3-6 reveals bending of the coiled-coil domain, resulting in diminished DNA binding and nuclear translocation. MS3-6 expression strongly inhibits STAT3-dependent transcriptional activation and disrupts STAT3 interaction with the IL-22 receptor. Therefore, our study establishes innovative tools to interfere with STAT3 signaling by different molecular mechanisms.


Sigmund Freud's evolution from neurology to psychiatry: evidence from his La Salpêtrière library.
To analyze the parallel between the scientific evolution of Sigmund Freud and his French library during and after his stay with Jean-Martin Charcot at La Salpêtrière in 1885-1886. Systematic review of all identified volumes of Freud's personal library, and comparison with his life data and publications. The largest part of Freud's 125 French medical books up to 1900 (of 3,725 books overall) are devoted to hysteria and hypnotism, published mainly between 1885 and 1895. Over one-third (50) of the neurology (94) and alienism (22) books have Charcot or one of his direct pupils (Janet, Féré, Babinski, Gilles de la Tourette, Richer, Pitres, Sollier, Raymond, Marie, Binet, Ball, Bourneville, Blocq, Berbez, Guinon, and Souques) as author. During that period, Freud evolved from the clinical-anatomic method (after mainly experimental histologic studies) to theoretical neurology (using hysteria and aphasia models) and psychology, a process which subsequently led to the birth of psychoanalysis. The library of Freud gives an interesting account on his own evolving thinking, which led him to leave neurology for psychology and psychoanalysis.


2,3,7,8-Tetrachlorodibenzo-p-Dioxin Alters Lipid Metabolism and Depletes Immune Cell Populations in the Jejunum of C57BL/6 Mice.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent aryl hydrocarbon receptor agonist that elicits dose-dependent hepatic fat accumulation and inflammation that can progress to steatohepatitis. To investigate intestine-liver interactions that contribute to TCDD-elicited steatohepatitis, we examined the dose-dependent effects of TCDD (0.01, 0.03, 0.1, 0.3, 1, 3, 10, or 30 µg/kg) on jejunal epithelial gene expression in C57BL/6 mice orally gavaged every 4 days for 28 days. Agilent 4x44K whole-genome microarray analysis of the jejunal epithelium identified 439 differentially expressed genes (|fold change| ≥ 1.5, P1(t) ≥ 0.999) across 1 or more doses, many related to lipid metabolism and immune system processes. TCDD-elicited differentially expressed genes were associated with lipolysis, fatty acid/cholesterol absorption and transport, the Kennedy pathway, and retinol metabolism, consistent with increased hepatic fat accumulation. Moreover, several major histocompatibility complex (MHC) class II genes (H2-Aa, H2-Ab1, H2-DMb1, Cd74) were repressed, coincident with decreased macrophage and dendritic cell levels in the lamina propria, suggesting migration of antigen-presenting cells out of the intestine. In contrast, hepatic RNA-Seq analysis identified increased expression of MHC class II genes, as well as chemokines and chemokine receptors involved in macrophage recruitment (Ccr1, Ccr5, Ccl5, Cx3cr1), consistent with hepatic F4/80 labeling and macrophage infiltration into the liver. Collectively, these results suggest TCDD elicits changes that support hepatic lipid accumulation, macrophage migration, and the progression of hepatic steatosis to steatohepatitis.


Decrease in oxidative phosphorylation yield in presence of butyrate in perfused liver isolated from fed rats.
Butyrate is the main nutrient for the colonocytes but the effect of the fraction reaching the liver is not totally known. A decrease in tissue ATP content and increase in respiration was previously demonstrated when livers were perfused with short-chain fatty acids (SCFA) such as butyrate, or octanoate. In fed rats the oxidative phosphorylation yield was determined on the whole isolated liver perfused with butyrate in comparison with acetate and octoanoate (3 mmol/L). The rate of ATP synthesis was determined in the steady state by monitoring the rate of ATP loss after inhibition of (i) cytochrome oxidase (oxidative phosphorylation) with KCN (2.5 mmol/L) and (ii) glyceraldehyde 3-phosphate dehydrogenase (glycolysis) with IAA (0.5 mmol/L). The ATP flux, estimated by 31P Nuclear Magnetic Resonance, and the measured liver respiration allowed the ATP/O ratio to be determined. ATP turnover was significantly lower in the presence of butyrate (0.40 +/- 0.10 micromoles/min.g, p = 0.001, n = 7) and octanoate (0.56 +/- 0.10 micromoles/min.g, p = 0.01, n = 5) than in control (1.09 +/- 0.13 micromoles/min.g, n = 7), whereas perfusion with acetate induced no significant decrease (0.76 +/- 0.10 micromoles/min.g, n = 7). Mitochondrial oxygen consumption was unchanged in the presence of acetate (1.92 +/- 0.16 vs 1.86 +/- 0.16 for control) and significantly increased in the presence of butyrate (p = 0.02) and octanoate (p = 0.0004) (2.54 +/- 0.18 and 3.04 +/- 0.15 micromoles/min.g, respectively). The oxidative phosphorylation yield (ATP/O ratio) calculated in the whole liver was significantly lower with butyrate (0.07 +/- 0.02, p = 0.0006) and octanoate (0.09 +/- 0.02, p = 0.005) than in control (0.30 +/- 0.05), whereas there was no significant change with acetate (0.20 +/- 0.02). Butyrate or octanoate decrease rather than increase the rate of ATP synthesis, resulting in a decrease in the apparent ATP/O ratio. Butyrate as a nutrient has the same effect as longer chain FA. An effect on the hepatic metabolism should be taken into account when large quantities of SCFA are directly used or obtained during therapeutic or nutritional strategies.


Mechanistic insights into accelerated α-synuclein aggregation mediated by human microbiome-associated functional amyloids.
The gut microbiome has been shown to have key implications in the pathogenesis of Parkinson's disease (PD). The Escherichia coli functional amyloid CsgA is known to accelerate α-synuclein aggregation in vitro and induce PD symptoms in mice. However, the mechanism governing CsgA-mediated acceleration of α-synuclein aggregation is unclear. Here, we show that CsgA can form stable homodimeric species that correlate with faster α-synuclein amyloid aggregation. Furthermore, we identify and characterize new CsgA homologs encoded by bacteria present in the human microbiome. These CsgA homologs display diverse aggregation kinetics, and they differ in their ability to modulate α-synuclein aggregation. Remarkably, we demonstrate that slowing down CsgA aggregation leads to an increased acceleration of α-synuclein aggregation, suggesting that the intrinsic amyloidogenicity of gut bacterial CsgA homologs affects their ability to accelerate α-synuclein aggregation. Finally, we identify a complex between CsgA and α-synuclein that functions as a platform to accelerate α-synuclein aggregation. Taken together, our work reveals complex interplay between bacterial amyloids and α-synuclein that better informs our understanding of PD causation.


Simulated effects of dryland cropping intensification on soil organic matter and greenhouse gas exchanges using the DAYCENT ecosystem model.
We present evidence to show that DAYCENT can reliably simulate soil C levels, crop yields, and annual trace gas fluxes for various soils. DAYCENT was applied to compare the net greenhouse gas fluxes for soils under different land uses. To calculate net greenhouse gas flux we accounted for changes in soil organic C, the C equivalents of N2O emissions and CH4 uptake, and the CO2 costs of N fertilizer production. Model results and data show that dryland soils that are depleted of C due to conventional till winter wheat fallow cropping can store C upon conversion to no till, by reducing the fallow period, or by reversion to native vegetation. However, model results suggest that dryland agricultural soils will still be net sources of greenhouse gases although the magnitude of the source can be significantly reduced and yields can be increased upon conversion to no till annual cropping.


Spatial data analysis of malnutrition among children under-five years in Ethiopia.
Childhood malnutrition is a major cause of child mortality under the age of 5 in the sub-Saharan Africa region. This study sought to identify the risk factors and spatial distribution of the composite index of anthropometric failure (CIAF). Secondary data from 2000, 2005, 2011, and 2016 Ethiopian Health and Demographic Survey (EDHS) were used. The generalized geo-additive mixed model was adopted via the Integrated Nested Laplace Approximation (INLA) with a binomial family and logit link function. The CIAF status of children was found to be positively associated with the male gender, the potency of contracting a disease, and multiple births. However, it was negatively associated with family wealth quartiles, parental level of education, place of residence, unemployment status of mothers, improved sanitation, media exposure, and survey years. Moreover, the study revealed significant spatial variations on the level of CIAF among administrative zones. The generalized geo-additive mixed-effects model results identified gender of the child, presence of comorbidity, size of child at birth, dietary diversity, birth type, place of residence, age of the child, parental level of education, wealth index, sanitation facilities, and media exposure as main drivers of CIAF. The results would help decision-makers to develop and carry out target-oriented programs.


Cytochromes P450: terpene detoxification and pheromone production in bark beetles.
Bark beetles (family: Curculionidae; subfamily: Scolytinae) in the Dendroctonus and Ips genera are the most destructive forest pests in the Northern hemisphere. They use cytochromes P450 (P450s) to detoxify tree-produced terpenes to produce pheromones, in de novo pheromone production and to oxidize odorants on antennae. Many Dendroctonus spp. use trans-verbenol as an aggregation pheromone, and it is formed from host-tree produced α-pinene hydroxylated by CYP6DE1 during larval stages, stored as verbenyl ester of fatty acids, and then released when the female begins feeding on a new host tree. Ips spp. hydroxylate de novo produced myrcene to form ipsdienol. Subsequent steps form the appropriate enantiomeric composition of ipsdienol and convert ipsdienol to ipsenol. In this article we review recent progress in elucidating the functions of P450s in Ips and Dendroctonus species and in doing so provide insights into the role of these enzymes in host phytochemical detoxification and pheromone production.


FGSI: distant supervision for relation extraction method based on fine-grained semantic information.
Relation extraction is one of the important steps in building a knowledge graph. Its main objective is to extract semantic relationships from identified entity pairs in sentences, playing a crucial role in semantic understanding and knowledge graph construction. Remote supervised relation extraction aligns knowledge bases with natural language texts and generates labeled data, which alleviates the burden of manually annotating datasets. However, the labeled corpus obtained from remote supervision contains a large amount of noisy data, which greatly affects the training of relation extraction models. In this paper, we propose the hypothesis that key semantic information within the sentence plays a crucial role in entity relation extraction in the task of remote supervised relation extraction. Based on this hypothesis, we divide the sentence into three segments by splitting it according to the positions of entities, starting from within the sentence. Then, using intra-sentence attention mechanisms, we identify fine-grained semantic features within the sentence to reduce the interference of irrelevant noise information. We also improved the intra-bag attention mechanism by setting a threshold gate to filter out low-relevant noisy sentences, minimizing the impact of noise on the relation extraction model, and making full use of available positive semantic information. Experimental results show that the proposed relation extraction model in this paper achieves improvements in precision-recall curve, P@N value, and AUC value compared to existing methods, demonstrating the effectiveness of this model.


The persistence of teacher-reported behavioral problems among children aged 8 to 12.
This investigation assessed psychiatric symptoms in children reported by teachers at two points of time, and the persistence of symptom groups over an interval of four years. 1128 children born in 1981 (mean age 8.5 yr in Study 1 and 12.5 yr in Study 2) were studied, using the Rutter Scale B2 questionnaires in both studies. The frequencies of teacher-reported problems generally decreased over an interval of four years. Hyperkinetic symptoms were the most prevalent at both occasions. Gender differences were seen in both studies, boys outnumbering girls on most items. Symptoms were classified into five groups representing hyperactivity, internalizing and externalizing behaviour, relationship difficulties, and habits. The correlations of these different groups in Study 1 with those in Study 2 were moderate. Among deviant girls, correlations were high or moderate for externalizing, hyperactivity and internalizing behavior between the two studies. For deviant boys, high correlations between the studies were found for hyperactivity and habits. Externalizing behavior was also highly correlated with relationship difficulties among deviant boys. Two symptom groups (hyperactivity and relationship difficulties) and low performance level in Study 1 increased the probability of being deviant in Study 2 among boys, and four interactional terms (hyperactivity by relationship difficulties, hyperactivity by performance level, internalizing by performance level, and externalizing by relationship difficulties) also had an effect. Among girls, the probability of being deviant in Study 2 was increased if they were hyperactive or had relationship difficulties in Study 1. Furthermore, one interactional term (hyperactivity by performance level) had an impact on deviance among girls.


Relationships between age and symptom severity among women seeking medical treatment for premenstrual symptoms.
Age at the time of seeking treatment for premenstrual symptoms (PMS) was examined in a sample of 332 women who reported severe distress and met criteria for Late Luteal Phase Dysphoric Disorder (LLPDD). The mean age of the sample was 33.1 (+/- 5.3) years. Severity of symptoms decreased with age and was not associated with the duration of symptoms. Depression-related factors were associated with the severity of PMS, and together with the duration of symptoms, were the best discriminators between the younger (ages 20-35) and older (ages 36-44) women in this sample. These data suggest that the years of the late twenties through mid-thirties are the most vulnerable time for distressing PMS and fail to support the clinical premise that PMS worsens with age until menopause. Further longitudinal study should be conducted to confirm and extend these findings.


Refocusing pulses: A strategy to improve efficiency of phase-modulated heteronuclear decoupling schemes in MAS solid-state NMR.
The strategy of using π pulses in conjunction with continuous-wave radio-frequency fields to refocus spin interactions has lead to robust and efficient family of heteronuclear decoupling schemes in magic-angle spinning solid-state NMR, denoted as, rCW schemes. Here, we investigate the generality of the application of such refocussing pulses in other phase-modulated decoupling schemes, notably the super-cycled XiX decoupling. XiX is a commonly used heteronuclear decoupling scheme under conditions of fast MAS and low-amplitude radio-frequency irradiation. The refocussing of interactions is achieved by inserting π pulses with a phase of 135° in the supercycled XiX scheme. The refocussed XiX, rXiX, scheme has improved decoupling efficiency, better offset tolerance, and easier experimental setup compared to the XiX scheme.


Short and mid-term characteristics of COVID-19 disease course in athletes: A high-volume, single-center study.
At the pandemic's beginning, significant concern has risen about the prevalence of myocardial involvement after SARS-CoV-2 infection. We assessed the cardiovascular burden of SARS-CoV-2 in a large cohort of athletes and identified factors that might affect the disease course. We included 633 athletes in our study on whom we performed extensive cardiology examinations after recovering from SARS-CoV-2 infection. More than half of the athletes (n = 322) returned for a follow-up examination median of 107 days after the commencement of their infection. Troponin T positivity was as low as 1.4% of the athletes, where the subsequently performed examinations did not show definitive, ongoing myocardial injury. Altogether, 31% of the athletes' rapid training rebuild was hindered by persistent or reoccurring symptoms. Female athletes reported a higher prevalence of return to play (RTP) symptoms than their male counterparts (34% vs. 19%, p = 0.005). The development of long COVID symptoms was independently predicted by increasing age and acute symptoms' severity in a multiple regression model (AUC 0.75, CI 0.685-0.801). Athletes presenting with either or both cough and ferritin levels higher than >150 μg/L had a 4.1x (CI 1.78-9.6, p = 0.001) higher odds ratio of developing persistent symptoms. While SARS-CoV-2 rarely affects the myocardium in athletes, about one in three of them experience symptoms beyond the acute phase. Identifying those athletes with a predisposition to developing long-standing symptoms may aid clinicians and trainers in finding the optimal return-to-play timing and training load rebuild pace.


Effects of ventromedial nucleus lesions on the display of lordosis behavior in the male rat. Interactions with facilitory effects of male urine.
Previous observations showed that exposure to the odor of male urine prior to mating could enhance the display of lordosis behavior in male rats feminized with ovarian hormones. This study was performed to determine in feminized male rats whether the control of lordosis behavior by the olfactory system was mediated by the ventromedial nucleus (VMN) of the hypothalamus. Male rats were orchidectomized (ORCH) as adults and primed with 25 micrograms estradiol benzoate (EB) and 150 micrograms progesterone (P) 40 hr apart. Lordosis behavior was tested 9 +/- 1 hr after P injection. VMN lesions were shown to completely suppress the display of lordosis behavior as compared to sham VMN operated and dorsomedial nucleus (DMN) lesioned animals. Exposure of feminized rats to the odor of male urine by 9 +/- 1 hr before mating significantly increased the proportion of ORCH rats that displayed lordosis behavior in response to male mounts. This effect was abolished by VMN lesions but was maintained in the sham VMN operated and DMN lesioned animals. These results were discussed in the light of the present knowledge on the neuroendocrine and olfactory structures which mediate lordosis behavior in the male rat.


Evaluating the User Performance and Experience with a Re-Engineered 4 mm × 32G Pen Needle: A Randomized Trial with Similar Length/Gauge Needles.
Since insulin pens were first introduced in 1985, many advances have been made in pen needles (PNs). In this study we evaluated patient-reported outcomes of an investigational newly re-engineered 4 mm × 32G PN, the BD Nano™ 2nd Gen (also known by its "PRO" brand extension in many markets outside of the USA). In place of a conventional cylindrical posted hub, the investigational PN's hub is contoured with an expanded surface area. The investigational PN also includes a redesigned inner shield that includes tactile ridges and a remodeled outer cover with improved proportions and attachment grips. This was a multi-site, prospective, open-label, two-period crossover trial. Individuals with type 1 and type 2 diabetes using 32G PNs of ≤ 6 mm in length for ≥ 4 months were eligible. Subjects using 31G PNs of a similar length were eligible after a 2-week wash-in period. Subjects were assigned to one of four groups, with each group using a commercially available PN to which the investigational PN was compared. Each of the two study periods were 15 days: one with the investigational PN and the other with a comparator PN. After completing both study periods, subjects compared experiences between the two PN types. A 150-mm comparative visual analog scale (VAS) was used to evaluate overall preference (primary endpoint) and several secondary endpoints, including overall comfort, injection pain, and ease of use. Data from the four PN groups were combined after poolability was verified. Subgroup analyses were also conducted on each PN group. For VAS responses, a two-sided 95% confidence interval (CI) was calculated for average rating. Threshold for non-inferiority or superiority was established at the lower bound CI of > - 10 mm or > 0 mm, respectively. At baseline, average age of subjects was 55.6 years; 51.6% were female; and 85.1% has type 2 diabetes mellitus. Average diabetes duration was 14.2 years, and average duration of injecting was 7.8 years. The investigational PN demonstrated superiority for all outcomes, both primary and secondary, for all groups combined (p < 0.05). The investigational PN was rated as being overall preferred, more comfortable, less painful, and easier to use when compared to comparator PNs of similar gauge and length, in all groups combined. Clinicaltrials.gov (NCT03267264). BD (Becton, Dickinson, and Company).


Complete genome sequencing and antibiotics biosynthesis pathways analysis of Streptomyces lydicus 103.
More and more new natural products have been found in Streptomyces species, which become the significant resource for antibiotics production. Among them, Streptomyces lydicus has been known as its ability of streptolydigin biosynthesis. Herein, we present the genome analysis of S. lydicus based on the complete genome sequencing. The circular chromosome of S. lydicus 103 comprises 8,201,357 base pairs with average GC content 72.22%. With the aid of KEGG analysis, we found that S. lydicus 103 can transfer propanoate to succinate, glutamine or glutamate to 2-oxoglutarate, CO2 and L-glutamate to ammonia, which are conducive to the the supply of amino acids. S. lydicus 103 encodes acyl-CoA thioesterase II that takes part in biosynthesis of unsaturated fatty acids, and harbors the complete biosynthesis pathways of lysine, valine, leucine, phenylalanine, tyrosine and isoleucine. Furthermore, a total of 27 putative gene clusters have been predicted to be involved in secondary metabolism, including biosynthesis of streptolydigin, erythromycin, mannopeptimycin, ectoine and desferrioxamine B. Comparative genome analysis of S. lydicus 103 will help us deeply understand its metabolic pathways, which is essential for enhancing the antibiotic production through metabolic engineering.


Diffusive gradients in thin films (DGT) probe for effectively sampling of per- and polyfluoroalkyl substances in waters and sediments.
The passive sampling technique, diffusive gradients in thin films (DGT) has attracted increasing interests as an in-situ sampler for organic contaminants including per- and polyfluoroalkyl substances (PFAS). However, its effectiveness has been questioned because of the small effective sampling area (3.1 cm2). In this study, we developed a DGT probe for rapid sampling of eight PFAS in waters and applied it to a water-sediment system. It has a much larger sampling area (27 cm2) and as a result lower method quantification limits (0.15 - 0.21 ng/L for one-day deployment and 0.02 - 0.03 ng/L for one-week deployment) and much higher (by > 10 factors) sampling rate (100 mL/day) compared to the standard DGT (piston configuration). The sampler could linearly accumulate PFAS from wastewater, was sensitive enough even for a 24 hr deployment with performance comparable to grab sampling (500 mL). The DGT probe provided homogeneous sampling performance along the large exposure area. The use of the probe to investigate distributions of dissolved PFAS around the sediment-water interface was demonstrated. This work, for the first time, demonstrated that the DGT probe is a promising monitoring tool for trace levels of PFAS and a research tool for studying their distribution, migration, and fate in aquatic environments including the sediment-water interface.


High arsenic metabolic efficiency in AS3MT287Thr allele carriers.
Epidemiological data indicate the existence of wide interindividual differences in arsenic metabolism. It has recently been shown that arsenic(III)methyltransferase (AS3MT) enzyme catalyses the methylation of arsenite and monomethylarsonous acid (MMA). Thus, genetic variations in the AS3MT gene could explain, at least partly, the interindividual variation in the response to arsenic exposure. In an earlier study, we have demonstrated that the AS3MT Met(287)Thr (C/T) polymorphism affected the urinary arsenic profile in a Chilean group of men (n=50) occupationally exposed to arsenic. To confirm, the influence of the Met(287)Thr polymorphism in the metabolism of arsenic, a total of 207 Chilean men working at the copper industry were genotyped and their urinary profiles determined. The results confirm that Met(287)Thr polymorphism does influence arsenic metabolism in this population. Those carriers of the variant ((287)Thr) had a higher methylation efficiency, excreting 4.63% more MMA in urine (P=0.0007) and presenting a 2.98 times higher odd of excreting levels of MMA over the standard (P=0.011) than the participants homozygous for the normal allele. We can conclude that individuals with the (287)Thr variant display increased arsenic methylation; thus, those participants might be at increased risk for the toxic and genotoxic effects of arsenic exposure.


Pathways to improve nephrologist comfort in managing patients on in-center or home self-care dialysis.
In end-stage kidney disease (ESKD), patient engagement and empowerment are associated with improved survival and complications. However, patients lack education and confidence to participate in self-care. The development of in center self-care hemodialysis can enable motivated patients to allocate autonomy, increase satisfaction and engagement, reduce human resource intensiveness, and cultivate a curiosity about home dialysis. In this review, we emphasize the role of education to overcome barriers to home dialysis, strategies of improving home dialysis utilization in the COVID 19 era, the significance of in-center self-care dialysis (e.g., cost containment and empowering patients), and implementation of an in-center self-care dialysis as a bridge to home hemodialysis (HHD).


Dissemination with malignant changes from a pineal tumor through the corpus callosum after total removal.
Within the germinal neoplasms of the central nervous system, the embryonal carcinoma is a very rare tumor. The authors report such a lesion arising on the corpus callosum in a child 8 months after a differentiated teratoma was totaly removed from the pineal region. The classification of the germ cell tumors of the central nervous system and their relation with similar tumors of the gonads are discussed. The treatment of the pineal tumors is also discussed.


Repeated exposure to social stress has long-term effects on indirect markers of dopaminergic activity in brain regions associated with motivated behavior.
The visible burrow system (VBS) is a chronic social stress paradigm in which a dominance hierarchy forms among male rats housed with females. Males in the VBS undergo behavioral and physiological changes thought to be manifestations of chronic social stress. Since it is unclear whether chronic social stress affects motivation and reward behavior, brain areas related to these regions were examined. Long-term effects of a single or repeated VBS exposure on mesolimbic subregions were investigated by exposing rats to the VBS either once (one cycle of VBS housing and recovery) or repeatedly (three cycles). Behavior in the VBS was observed and rats were classified as dominants or subordinates. Subordinates were further sub-classified on the basis of stress hormone (corticosterone) response to an acute stressor (i.e. restraint stress). Normal responders were categorized as stress-responsive subordinates (SRS) and animals with a blunted hypothalamic-pituitary-adrenal axis response were designated as non-responsive subordinates (NRS). Controls males were pair-housed with a single female during VBS periods and alone during recovery. Lowered enkephalin-mRNA levels were observed in the nucleus accumbens (Acb) after single VBS exposure in SRS and repeated VBS exposure both subordinate groups (i.e. SRS + NRS) compared with controls. Decreased dopamine transporter density was detected after single VBS exposure in the dorsolateral caudate putamen (DLCPu) of NRS and after repeated VBS exposure in the Acb of NRS compared with controls. Dopamine D2 receptor density was elevated after single VBS exposure in the Acb of both subordinate groups (SRS + NRS) and after repeated VBS exposure in the DLCPu, dorsomedial CPu, and Acb of NRS compared with controls. No changes in dopamine D1 receptor binding were observed in any group. These results suggest that long-term changes in dopamine activity in mesolimbic structures persist after repeated exposures to chronic social stress and may provide insight into the neurochemical basis of depressive illness and subsequent comorbidity with drug abuse vulnerability.


African American adolescents' experiences with unplanned pregnancy and elective abortion.
Abortion is a controversial topic in American society, yet abortion experiences have not been studied in great detail. We used a focused ethnographic method to interview 12 adolescents (ages 15-18 years) as they awaited elective abortion. Two follow-up interviews were conducted 6 and 8 months after the elective abortion. Major domains included relationships with partners, confiding in others and finding support, unselfish decision for self, and resolution of the crises. Empowerment was the integrating theme that unified the four domains.


Micronutrient composition, antioxidant properties, and mineral safety index of selected Nigerian cooked foods.
The need to update the Nigerian food composition database (FCD) and provide information on dietary factors contributing to chronic diseases is essential to managing health conditions. This study is analytical. Standardized Nigerian cooked foods were analyzed for minerals, β-carotene, vitamins, phytate, and oxalate contents. Mineral, phytate-mineral interactions, and mineral toxicities in foods were evaluated. Results showed that okazi soup and akara & agidi had the highest potassium, sodium, and calcium (449.60 and 236.36; 1087.12 and 359.49; 568.55 and 481.05 mg/100 g respectively) contents. Miyan taushe, gbegiri, and groundnut soups had the highest β-carotene content when compared to others. The Sodium-potassium ratio of the foods exceeded standard values, while most soups including ogbono, ila alasepo, egusi, and gbegiri, had poor predicted bioavailability for iron, calcium, and zinc. Also, Akara & agidi, okazi, and groundnut soups contained excess doses of iron and sodium compared to the standard. These findings are useful to update Nigerian FCD.


[Hereditary ataxias, spastic parapareses and neuropathies in Eastern Canada].
It has been demonstrated, for many inherited diseases, that historical events have shaped the various regional gene pools of Eastern Canada. In so doing, it has given rise to the increased prevalence of some rare diseases due, to founder effects. The following neurogenetic disorders were first identified in patients from Eastern Canada: AOA-2, Arsacs, HSN-2, Arca-1, HMSN/ACC and Arsal. The population of Eastern Canada, we are convinced, will still allow the identification of new rare forms of hereditary ataxias, spastic parapareses and neuropathies as well as contribute to the uncovering of their mutated genes. We have summarized our current knowledge of the various hereditary ataxias, spastic parapareses and neuropathies in Eastern Canada. The study of the more common and homogenous features of these diseases has been largely completed.


Novel approach for a pulmonary bronchogenic cyst: a report of a case.
We present a case of a bronchogenic pulmonary cyst in a 48-year-old patient. We performed [corrected] mucoclasis using argon laser photocoagulation following resection of mucosa, closure of some drainage bronchus, and covering of the inner surface by the intrapulmonary bronchogenic cyst with an [corrected] absorbable vicryl mesh. At [corrected] 4-year [corrected] follow-up, the patient had no signs of recurrence.


Hypertrophy of the posterior longitudinal ligament in the thoracic spine.
This is a case report of a patient with hypertrophy of the posterior longitudinal ligament (HPLL) in the thoracic spine. This patient was followed for 10 years after surgery. The purpose of this study was to report the long-term outcome of HPLL in the thoracic spine. Department of orthopedic surgery, Hiroshima Red Cross and Atomic-bomb Survivors Hospital, Hiroshima, Japan. A 58-year-old-woman with thoracic HPLL was reported. Magnetic resonance image (MRI) and computed tomography (CT) showed the expanded spinal cord compression from Th4 to Th12 due to HPLL. Anterior decompression and fusion (Th10-12) was performed. Histological findings of the surgical specimens showed thickening of the posterior longitudinal ligament with proliferation of chondroid tissue. The clinical outcome and the radiological findings (CT and MRI) were evaluated 10 years after surgery. The patient was asymptomatic postoperatively. However, the subsequent CT examination revealed ossification of the previously hypertrophied posterior longitudinal ligament. HPLL in the thoracic spine is a rare pathological condition causing myelopathy. The results of this study support the hypothesis that HPLL is one of the prodromal conditions of HPLL.


Effects of fenoprofen and benoxaprofen on human lymphocytes: inhibition of tritiated thymidine uptake.
The effects of the related nonsteroidal anti-inflammatory agents, fenoprofen and benoxaprofen, on in vitro responses of normal human peripheral blood lymphocytes were examined. Drugs caused dose-related inhibition of stimulated cell responses. Fifty percent inhibition occurred at 400 microgram/ml calcium fenoprofen and 250 microgram/ml sodium benoxaprofen. Drugs affected not only responses to soluble phytomitogens but also responses to specific antigens and allogeneic lymphocytes. Numbers of viable cells in cultures with and without mitogens and drugs were similar at beginnings and ends of experiments, excluding drug-related cytotoxicity. Inhibition by drugs was greater when cells were cultured in medium alone than in medium with plasma. Cells that were exposed overnight to drugs and then washed and stimulated did not respond as well as did cells not exposed to drugs. These data indicated that fenoprofen and benoxaprofen exhibited noncytotoxic, incompletely reversible inhibition of nonspecific, specific, soluble and insoluble, mitogen-stimulated lymphocyte responses. These findings may pertain to the anti-inflammatory efficacy of these drugs.


Evidence that nigral substance P controls the activity of the nigrotectal GABAergic pathway.
The unilateral intranigral application of either of two substance P (SP) analogs with antagonist properties ( [DPro2,D-Phe7,D-Trp9]-SP and [D-Pro2,D-Trp7,9]-SP) induced a significant (37%) decrease in GABA turnover in the target region of the nigrotectal projections, namely the deep layers of the superior colliculus in the homolateral hemisphere, and was without any effect in the superficial layers. This action was not prevented by coinjection of the GABA antagonist bicuculline-methiodide. There was no effect of these SP analogs on GABA turnover in the deep layers of superior colliculus when they were microinjected in the ipsilateral median forebrain bundle or in the contralateral substantia nigra. These results are consistent with the proposal that nigral SP exerts a tonic excitatory action on efferent GABAergic projections from pars reticulata of substantia nigra.


Partial control of Core Data Set measures and Disease Activity Score (DAS) measures of inflammation does not prevent long-term joint damage: evidence from longitudinal observations over 5-20 years.
Several reports concerning outcomes of rheumatoid arthritis (RA) document that measures of inflammatory activity [such as swollen joint count, tender joint count, and acute phase reactant, which are included in the Core Data Set or Disease Activity Score (DAS)] may be stable or improved over 5-10 years, while measures of damage (such as radiographic progression and joint deformity) may show contemporaneous progression. Therefore, studies which include only improvement in measures of disease activity cannot document overall improvement in patient status over 5-10 years. Studies designed to document favorable long-term effects of therapy in RA must include, at baseline and later follow-up evaluation, measures of damage, such as a radiograph, joint deformity, comorbidities, and extra-articular disease, in addition to measures of disease activity. The one prognostic measure which appears to detect both activity and damage in RA over short, intermediate, and long periods is a disability score on a patient questionnaire, which might be used by all rheumatologists at all patient encounters. The need for inclusion of accurate and relevant measures of damage appears of particular importance in the current era of biological drugs, in which the slowing or prevention of damage now appears a realistic goal in most patients with RA.


Hypothermia down-regulates the LPS-induced norepinephrine (NE) release in ischaemic human heart cells.
Hypothermia has been widely acknowledged as the fundamental component of myocardial protection during cardiac operations. In this work, we studied in human atrial tissue the effect of the common hypothermic protection used in cardiac surgery, and we assessed this effect by comparing catecholamine release among normoxic, ischaemic, and inflammatory conditions. Our results provide the first evidence that lipopolysaccharide treatment results in an extremely dramatic and significant increase in the resting norepinephrine release under ischaemic conditions that can be normalised by hypothermia. These findings demonstrate that inflammatory conditions increase the temperature sensitivity of the norepinephrine transporter in human cardiac tissue. When the possible pharmacological interventions are taken into consideration, the results presented here provide new insight into the protection against ischaemia/reperfusion injury during cardiac surgery.


Minimally invasive locking screw plate fixation of non-articular proximal and distal tibia fractures.
Intramedullary nailing of proximal and distal quarter tibia fractures is known to be a challenging procedure due to the metaphyseal enlargement, the reduced contact between implant and cortex and fracture comminution. Therefore, some authors suggest preferring the use of plate internal fixation in the management of these challenging fractures. The purpose of this manuscript is to present and describe our technique of minimally invasive locking plate osteosynthesis in the treatment of extra-articular proximal and distal tibia fractures. Osteosynthesis was performed by means of a locking screw plate system which construct characteristics usually allow immediate weight-bearing and early functional mobilization. This minimally invasive surgical procedure advantageously combines the principles of closed fixation with construct stability.


Silencing SARS-CoV Spike protein expression in cultured cells by RNA interference.
The severe acute respiratory syndrome (SARS) has been one of the most epidemic diseases threatening human health all over the world. Based on clinical studies, SARS-CoV (the SARS-associated coronavirus), a novel coronavirus, is reported as the pathogen responsible for the disease. To date, no effective and specific therapeutic method can be used to treat patients suffering from SARS-CoV infection. RNA interference (RNAi) is a process by which the introduced small interfering RNA (siRNA) could cause the degradation of mRNA with identical sequence specificity. The RNAi methodology has been used as a tool to silence genes in cultured cells and in animals. Recently, this technique was employed in anti-virus infections in human immunodeficiency virus and hepatitis C/B virus. In this study, RNAi technology has been applied to explore the possibility for prevention of SARS-CoV infection. We constructed specific siRNAs targeting the S gene in SARS-CoV. We demonstrated that the siRNAs could effectively and specifically inhibit gene expression of Spike protein in SARS-CoV-infected cells. Our study provided evidence that RNAi could be a tool for inhibition of SARS-CoV.


No independent association of serum phosphorus with risk for death or progression to end-stage renal disease in a large screen for chronic kidney disease.
Whether higher serum phosphorus levels are associated with a higher risk for death and/or progression of chronic kidney disease (CKD) is not well established, and whether the association is confounded by access and barriers to care is unknown. To answer these questions, data of 10,672 individuals identified to have CKD (estimated glomerular filtration rate <60 ml/min per 1.73 m(2)) from those participating in a community-based screening program were analyzed. Over a median follow-up of 2.3 years, there was no association between quartiles of serum phosphorus and all-cause mortality (adjusted hazards ratio for serum phosphorus over 3.3 to 3.7, over 3.7 to 4.1, and over 4.1 mg/dl, respectively: 1.22 (0.95-1.56), 1.00 (0.76-1.32), and 1.00 (0.75-1.33); reference, serum phosphorus of 3.3 mg/dl and below). Individuals in the highest quartile for serum phosphorus had a significantly higher risk for progression to end-stage renal disease (ESRD) (unadjusted hazards ratio, 6.72 (4.16-10.85)); however, the risk became nonsignificant on adjustment for potential confounders. There was no appreciable change in hazards ratio with inclusion of variables related to access and barriers to care. Additional analyses in subgroups based on 12 different variables yielded similar negative associations. Thus, in the largest cohort of individuals with early-stage CKD to date, we could not validate an independent association of serum phosphorus with risk for death or progression to ESRD.


Immunoreactivity for beta-endorphin in LH-RH neurons of the fetal human hypothalamus.
A peptide immunochemically related to beta-endorphin was detected in some LH-RH neurons of the fetal human hypothalamus by comparison of adjacent sections stained for beta-endorphin and for LH-RH. In the same section, by successive staining and after antibody elution, both peptides were again revealed in the same neuron. The significance of the presence of the beta-endorphin-like material in LH-RH neurons is discussed.


Generation of human induced pluripotent stem cells from peripheral blood mononuclear cells of a Senior-Loken syndrome patient.
Senior-Loken syndrome (SLS) is a rare disorder primarily associated with kidney and retinal dysfunction. We generated a human induced pluripotency stem cell (hiPSC) line, designated DKHi005-A, from peripheral blood mononuclear cells of a patient with SLS using a Sendai virus reprogramming method. We confirmed that DKHi005-A cells harbor the same mutation as the patient and show a normal karyotype. DKHi005-A also has pluripotency and the capacity for differentiation into the three germ layers. This cell line is registered and available at the National Stem Cell Bank, Korea National Institute of Health.


Model-based quantification of EELS spectra: Including the fine structure.
An extension to model-based electron energy loss spectroscopy (EELS) quantification is reported to improve the possibility of modelling fine structure changes in electron energy loss spectra. An equalisation function is used in the energy loss near edge structure (ELNES) region to model the differences between a single atom differential cross section and the cross section for an atom in a crystal. The equalisation function can be shown to approximate the relative density of unoccupied states for the given excitation edge. On a set of 200 experimental h-BN spectra, this technique leads to statistically acceptable models resulting into unbiased estimates of relative concentrations and making the estimated precisions come very close to the Cramér-Rao lower bound (CRLB). The method greatly expands the useability of model-based EELS quantification to spectra with pronounced fine structure. Another benefit of this model is that one also gets an estimate of the unoccupied density of states for a given excitation edge, without having to do background removal and deconvolution, making the outcome intrinsically more reliable and less noisy.


Distribution of different cell types within the rat thymus in the neonatal period of life.
This study attempted to define reciprocal positions of cell types within the thymus. Random or non-random contacts between specific cell types were analyzed by means of graph theory. For analysis, thymus blocks were sectioned serially and, then, thymus cells were categorized into types, based on morphological criteria. The distribution of individual cell types within the cortex, cortico-medullary zone and medulla was presented in form of a map. In the analysis, three types of epithelial cell, characteristic of each thymus zone, macrophages, Langerhans-like cells and lymphocytes were found in non-random relations to one another. Moreover, characteristic groups of cells associated with one another were also demonstrated.


[The common celiacomesenteric trunk: about one case].
The discovery of a coeliacomesenteric trunk is often fortuitous in a context of morphological or vascular exploration. About one case of this rare arterial remind us of its characteristic and different type. We emphasize the interest of not being unaware of this variation in radiological practice and vascular pathology. In our observation, the coeliacomesenteric trunk's ostium is oval with a tall axis of 14 mm; its route of 8mm is median and its arterial ending divide into hepatosplenogastric trunk and superior mesenteric trunk. It is a type I coeliacomesenteric trunk which is the most frequent type of this arterial variation in Higashi's classification.


Electromagnetic navigation bronchoscopy versus virtual bronchoscopy navigation for improving the diagnosis of peripheral lung lesions: analysis of the predictors of successful diagnosis.
To investigate if electromagnetic navigation bronchoscopy (ENB) improves the diagnostic yield for peripheral lung lesions from that achieved by virtual bronchoscopy navigation (VBN). This retrospective study compared the results of 100 ENB-transbronchial lung biopsies (TBLBs) with those of 50 VBN-TBLBs at a single institution. ENB improved the diagnostic yield significantly compared with VBN (64.0% for 19.4 ± 9.0 mm tumors vs. 46.0% for 27.6 ± 8.9 mm tumors; p < 0.0001). Irrespective of the bronchus sign, ENB was more favorable than VBN, with 81.0% (47/58) achieved by ENB vs. 60.0% (21/35) achieved by VBN in the presence of the positive bronchus sign (p = 0.0283), and 40.5% (17/42) achieved by ENB vs. 13.3% (2/15) achieved by VBN in the absence of the bronchus sign (p = 0.0431). Univariate analysis identified tumor size (p = 0.0048), amount of intravenous sedation (p = 0.0182), registration time (p = 0.0111), minimum distance to target (p = 0.0244), and the bronchus sign (p < 0.0001) as factors that affected the yield significantly for ENB. Multivariate analysis identified the bronchus sign (odds ratio 6.74; 95% CI 1.84-24.7) and the registration time (OR 1.01; 95% CI 1.00-1.02) as significant factors. Despite the bronchus sign being a significant factor, ENB improved the diagnostic yield of smaller lesions significantly, compared with VBN, regardless of the bronchus sign.


Race-Dependent Differences in Risk, Genomics, and Epstein-Barr Virus Exposure in Monoclonal Gammopathies: Results of SWOG S0120.
Risk of multiple myeloma is increased in African American (AA) populations compared with European American (EA) cohorts. Current estimates of risk of progression of monoclonal gammopathy of undetermined significance (MGUS) are based largely on studies in EA cohorts. Prospective analyses of this risk in AA cohorts are lacking. Between 2003 and 2011, 331 eligible patients with IgG/A monoclonal gammopathy were enrolled in a prospective observational trial (SWOG S0120). Of 331 eligible patients, 57 (17%) were of AA descent. The risk of transformation to clinical malignancy in AA patients was significantly lower than in non-AA cohort (2-year risk 5% vs. 15%; 5-year risk 13% vs. 24%; log-rank P = 0.047). Differences in risk were evident for both MGUS and asymptomatic multiple myeloma. Gene expression profile (GEP) of CD138-purified plasma cells revealed that all molecular multiple myeloma subsets can be identified in both cohorts. However, the proportion of patients with high-risk GEP risk score (GEP-70 gene risk > -0.26) was lower in the AA cohort (0% vs. 33%, P = 0.01). AA cohorts also have higher levels of antibodies against Epstein-Barr nuclear antigen-1 (EBNA-1; P < 0.001). These data provide the first prospective evidence that multiple myeloma precursor states in AA patients may have lower risk of disease compared with non-AA counterparts with lower incidence of high-risk GEP and increased EBV seropositivity. Race-dependent differences in biology and clinical risk of gammopathy may impact optimal management of these patients.


Cementless short stem hip arthroplasty METHA® as an encouraging option in adults with osteonecrosis of the femoral head.
The implantation of a total hip arthroplasty is the standard treatment for patients with progressive osteonecrosis. However, there is uncertainty about the type of arthroplasty that provides the best outcome and whether short stem arthroplasty represents a reasonable alternative for young patients in order to have more options in case of revision. This uncertainty exists due to the lack of studies analysing contemporary short stem arthroplasty in osteonecrosis. The aim of this study was to determine the outcome of the METHA(®) short stem arthroplasty in patients with progressive osteonecrosis. This study evaluated the clinical and radiological short- to midterm results after implantation of the cementless short stem arthroplasty METHA(®). 73 hips in 64 patients with progessive osteonecrosis after implantation of the METHA(®) arthroplasty were investigated by measuring the clinical outcome, the Harris Hip Score (HHS) and visual analogue pain scale for the preoperative stage and follow-up. Radiological analyses of X-rays were conducted to assess the bone ingrowth as well as subsidence, osteolysis or fracture. The pain scale improved from preoperatively 7.8 to postoperatively 1.7, while the HHS increased from 41.4 to 90.6 points 34 months post-surgery. Complications associated with revision of the METHA(®) short stem included two traumatic femoral shaft fracture and one deep infection. The radiological assessment showed good bone ingrowth in all patients despite osteonecrosis. The study confirms encouraging results as well as good bone ingrowth of the cementless short stem arthroplasty METHA(®) even in patients with osteonecrosis.


Unique biochemical and biological features of cathepsin D in rodent lymphoid tissues.
Cathepsin D, an enzyme consistently found to be lysosomal in many cells, has an unusual localization in rat thoracic duct lymphocytes (TDL). After fractionation of homogenates of rat TDL, most of the enzyme activity, as measured at pH 3.6 on denatured bovine hemoglobin, is distributed differently from the other lysosomal enzymes. The enzyme also has some unique properties: it is not inhibited by an antiserum inhibitory for rat liver cathepsin D; it exists in two molecular weight forms (approximately 45,000 and approximately 95,000) both of which have a higher specific activity than rat liver cathepsin D, as determined by studies using the irreversible inhibitor, sodium pepstatin; the high molecular weight form converts to the low molecular weight form after treatment with beta-mercaptoethanol without any loss in activity. These enzymes appear to be restricted to rodent lymphoid tissues. Reasons for considering them to be a type of cathepsin D are given in the text.


Effect of delay in processing and storage temperature on diagnosis of SARS-CoV-2 by RTPCR testing.
A large number of new molecular or virology laboratories have been established to increase the testing capacity for SARS-CoV-2. Due to heavy workload, there is delay in testing of samples. In order to avoid the negative effect of delayed testing on RTPCR results guidelines are issued from WHO and CDC to transport samples in cold chain. However, in pandemic situations the recommended guidelines for transport and storage conditions are often compromised. This study was conducted to evaluate the effect of sample storage conditions at different temperatures on the results of RT PCR test. Total 275 samples were included in this study, among these 126 samples tested positive and 149 samples tested negative. All samples were aliquoted into two and the aliquotes stored in duplicate at 4 °C and room temperature. All aliquots stored at both the temperatures were tested by RTPCR every 24 hours up to 5 days. Diagnostic accuracy decreased from day1 to day 5 at both the storage temperatures i,e 4 °C and room temperature in comparison to the initial day results. Positivity decreased on an average of 9.02% at 4 °C and at 9.27% at room temperature per day. Among total 126 positive samples on an average false negative and failure of internal control at 4 °C and room temperature was 8.86%, 8.22% and 3.64%, and 4.12%, respectively. All the samples with CT value < 30 remained positive at both temperatures up to 5 days. Few samples with >30 CT value showed variable results i.e. positive, negative or internal control failure from day 1 (2nd day after sample collection) onwards. There was no significant difference between RT PCR results of samples stored at 4 °C and room temperature up to 5 days of collection. However internal control failure was more in samples stored at room temperature. Therefore, samples received without cold chain also may be processed by RTPCR and should not be rejected.


Response elimination, reinforcement rate and resurgence of operant behavior.
The effects of reinforcement rate of alternative responding on resurgence were studied in six experiments with pigeons. In Experiment 1A, key pecking was maintained on a multiple variable-interval (VI) VI schedule in the Training phase. In the Response-Elimination phase, a variable differential-reinforcement-of-other-behavior (DRO) schedule was in effect in each component. Reinforcement rates were equal and then, higher in one (rich) component, and lower in the other (lean), than in the Training phase. More resurgence occurred in the lean component, but this could have resulted from response-rate differences between components in the Training-phase. Experiment 1B was a replication of Experiment 1A, but with experimentally-naïve pigeons. Response-Elimination phase reinforcement rates were manipulated systematically in subsequent experiments: In Experiment 2, reinforcement rate was equal, in one component, and lower or higher in the other, than in the Training phase. In Experiment 3, reinforcers were discontinued before differential reinforcement rates were effected. In Experiment 4, reinforcement rates first were differential and, then, equal to those in the Training phase. In Experiments 5 and 6, differential reinforcement rates were arranged by using fixed-DROs and VIs for pecking a different key, respectively. Even though resurgence was not obtained with every pigeon, at least some small-magnitude resurgence occurred in each experiment and was not related systematically to reinforcement rates of alternative responding. Schedule differences, response topography, order of conditions and the length of each phase were not sufficient to account for these results.