Differential neural projections to regions of the inferior colliculus of the cat responsive to high frequency sounds.
Iontophoretic injections of horseradish peroxidase were made in the vicinity of high best frequency neurons in the central nucleus of the inferior colliculus of the cat. Retrogradely labelled cells were found in most major auditory nuclei known to provide afferent input to the central nucleus, and were distributed in accordance with the known tonotopic organization of these nuclei. However, different injection sites gave rise to patterns of brain stem labelling that differed from one experiment to the next, in spite of the similarities in injection site best frequency. With each injection a small group of nuclei contained the majority of labelled cells. The results confirm previous anatomical findings of convergence of ascending input in relation to the tonotopic organization of the central nucleus. Additionally it is suggested that different subregions of the central nucleus may have different roles in the integration of acoustic information because of the varying patterns of brain stem terminations in each region.


Royal jelly regulates the caspase, Bax and COX-2, TNF-α protein pathways in the fluoride exposed lung damage in rats.
The study was carried out on 42 male rats divided into six groups with 7 rats in each group: two control groups, two injury groups and two treatment groups. One of the control groups received a basal diet while the other one was fed a basal diet supplemented with royal jelly (RJ) (100 mg/kg). The two injury groups were given 50 mg/kg and 100 mg/kg fluoride, respectively. The two treatment groups exposed to 50 mg/kg and 100 mg/kg fluoride were both fed basal diets with RJ (100 mg/kg). Lungs were taken for histopathological examination. Spectrophotometric analysis was utilized to determine Malondialdehyde (MDA), catalase (CAT) and glutathione (GSH) activities, and Western blotting technique was used to evaluate the levels of specific proteins. On one hand, our experiments revealed that RJ caused decreased MDA levels, and downregulation of COX-2, Bcl-2, GSK3 and TNF-α protein expressions. On the other hand, rolay jelly caused augmented GSH and CAT activities, as well as upregulated Bax, BDNF, caspase-3, caspase-6, caspase-9 protein expressions in rats injuried by the fluoride exposure. The results suggest that the application of RJ was very likely to have a healing effect on the degenerative changes seen in the examined tissue.


The active form of the cytochrome d terminal oxidase complex of Escherichia coli is a heterodimer containing one copy of each of the two subunits.
The cytochrome d complex is a component of the aerobic respiratory system of Escherichia coli. The enzyme functions as a terminal oxidase, oxidizing ubiquinol-8 within the cytoplasmic membrane and reducing oxygen to water. The enzyme is of particular interest because it is a coupling site in the electron transfer chain. The electron transfer reaction catalyzed by this enzyme is coupled to the translocations of protons across the membrane (H+/e-approximately equal to 1). The oxidase contains two subunits by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis, with molecular weights of 58,000 and 43,000. In this paper, the question of the quaternary structure is addressed. Quantitative N-terminal analysis of the isolated enzyme and relative mass quantitation following sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicate the subunits are present in equimolar amounts. Sedimentation velocity and sedimentation equilibrium studies were used to characterize the hydrodynamic properties of the purified enzyme solubilized in Triton X-100, under conditions where the enzyme is active. It is concluded that the active enzyme in Triton X-100 is a heterodimer, containing one copy of each subunit. This is likely the structure of the enzyme in the E. coli membrane.


Exome sequencing identifies a new candidate mutation for susceptibility to diabetes in a family with highly aggregated type 2 diabetes.
The aim of this study was to investigate the genetic background of familial clustering of diabetes using genome-wide linkage analysis combined with exome sequencing. We recruited a Japanese family with a 3-generation history of diabetes. The family comprised 16 members, 13 having been diagnosed with diabetes. Nine members had been diagnosed before the age of 40. Linkage analysis was performed assuming an autosomal dominant model. Linkage regions were observed on chromosomes 4q34, 5q11-q13, and 12p11-q22 and the logarithm of odds (LOD) scores were 1.80. To identify the susceptibility variants, we performed exome sequencing of an affected family member. We predicted that the familial clustering of diabetes is caused by a rare non-synonymous variant, and focused our analysis on non-synonymous variants absent in dbSNP131. Exome sequencing identified 10 such variants in the linkage regions, 7 of which were concordant with the affection status in the family. One hundred five normal subjects and 67 lean diabetes subjects were genotyped for the 7 variants; the only variant found to be significantly more frequent in the diabetes subjects than in the normal subjects was the N1072K variant of the early endosome antigen 1 (EEA1) gene (0 in normal subjects and 4 in diabetes subjects, p=0.022). We therefore propose that the N1072K variant of the EEA1 gene is a candidate mutation for susceptibility to diabetes in the Japanese population.


Estimating the mineral density of trabecular bone using Compton scattering.
This study proposes a technique based on Compton scattering to estimate trabecular bone mineral density (TBMD), which is important for understanding bone strength, and hence, is pivotal for estimating the condition of the bone. Bone phantoms (a mixture of paraffin wax and bone powder) with various concentrations of bone ash were prepared to simulate the trabecular bone. These samples were exposed to primary gamma photon flux from a137Cs (222 GBq) radioisotope source one after the other, and the scattered photon flux was detected using an NaI(Tl) detector. The presence of the cortical bone (using aluminum sheets) and fat (tertiary butyl alcohol) around the trabecular bone was also studied to determine whether the TBMD measurements had been affected. The correlation between bone ash contents and the intensity of Compton scattering was high with a coefficient of 0.97. The outcomes suggest that TBMD is independent of the presence of the cortical bone and overlying fat, with a statistical uncertainty of ±0.3% in the count rate. The intensity of Compton scattering increased by only 1.5% when the thickness of the aluminum sheet (simulating the cortical bone) becomes was increased by four times, and by less than 5% when the bone phantom was surrounded by tertiary butyl alcohol.


Alfaxalone for total intravenous anaesthesia in bitches undergoing elective caesarean section and its effects on puppies: a randomized clinical trial.
To evaluate the effects and reliability of alfaxalone constant rate infusion (CRI) in comparison to isoflurane to maintain anaesthesia in bitches undergoing elective caesarean section. Prospective, randomized, 'blinded' clinical trial. Twenty-two client-owned bitches and 94 puppies. Bitches were randomly assigned to receive an alfaxalone CRI [0.2 mg kg(-1) minute(-1) intravenously (IV), and once the last puppy was delivered, the dose was halved; n = 11] or 2% (vaporizer dial setting) isoflurane (n = 11) for maintenance of anaesthesia. All dogs were induced with alfaxalone (3 mg kg(-1) ) IV. Additional alfaxalone (0.3 mg kg(-1) IV) was administered if the depth of anaesthesia was inadequate and the total dose was calculated. Bitches were mechanically ventilated. Analgesia was administered after the delivery of puppies. Physiological variables were recorded every 5 minutes. The bitches' recovery times were also recorded. Quality of induction and recovery were evaluated. Puppies' vigour was evaluated with a modified Apgar score at 5 and 60 minutes after birth. Puppies' survival rates at 24 and 48 hours and at 15 days were recorded. Data were analysed using an anova, Student's t-test or Wilcoxon rank-sum test. The rescue dose of alfaxalone was higher (p = 0.01); bitches' recoveries were longer (p < 0.001) and puppies' Apgar scores were significantly lower at 5 and 60 minutes (p < 0.001 and p = 0.003, respectively) with alfaxalone than with isoflurane. However, no significant differences were found for puppies' survival between groups. Alfaxalone CRI seems to be a possible protocol for puppies and bitches undergoing elective caesarean sections. However, bitches recovered more slowly and puppy Apgar scores were lower in comparison to isoflurane.


Imaging of squamous cell carcinoma of the hypopharynx.
The hypopharynx is a clinically silent area and early lesions may be asymptomatic for a long period. At presentation, primary squamous cell carcinoma of this area is usually advanced. Almost all of these lesions are studied with imaging as part of the clinical work-up. The goal of this article is to help the practicing radiologist convey a report which provides information that will directly influence treatment of patients with hypopharyngeal carcinoma.


Feasibility and Cost Analysis of Ambulatory Endovascular Aneurysm Repair.
We sought to compare the costs of ambulatory endovascular aneurysm repair (a-EVAR) and inpatient EVAR (i-EVAR) at up to 1-year of follow-up. A retrospective cohort study of consecutive patients undergoing elective EVAR between April 2016 and December 2018 at two academic centers. Patients planned for a-EVAR were compared with i-EVAR. Costs at 30 days and 1 year were extracted. These included operating room (OR) use, bed occupancy, laboratory and imaging, emergency department (ED) visits, readmissions, and reinterventions. Baseline characteristics were compared. Multiple regression model was used to identify predictors of increased EVAR costs. Repeated measures analysis of variance (ANOVA) was used to compare cost differences at 30 days and 1 year via an intention-to-treat analysis. Bonferroni post hoc test compared between-group differences. A p value<0.05 was considered statistically significant. One hundred seventy patients were included. Most underwent percutaneous EVAR (>94%) under spinal anesthesia (>84%). Ambulatory endovascular aneurysm repair was successful in 84% (84/100). Ambulatory endovascular aneurysm repair patients (76±8 years) were younger than i-EVAR (78±9 years). They also had a smaller mean aneurysm diameter (56±6 mm) compared with i-EVAR (59±6 mm). Emergency department visits, readmissions, and reinterventions were similar up to 1 year (all p=NS). Ambulatory endovascular aneurysm repair costs showed a non-statistically significant reduction in total costs at 30 days and 1 year by 27% and 21%, respectively. Patients younger than 85 years and males had a 30-day cost reduction by 34% (p=0.027) and 33% (p=0.035), respectively with a-EVAR. Same-day discharge is feasible and successful in selected patients. Patients younger than 85 years and males have a short-term cost benefit with EVAR done in the ambulatory setting without increased complications or reinterventions. This study shows the overall safety of ambulatory EVAR with proper patient selection. These patient had similar post-intervention complications to inpatients. Same day discharge also resulted in short-term reduction in costs in male patients and patients younger than 85 years.


Reporting Nursing Interventions Classification and Nursing Outcomes Classification in Nursing Research: A Systematic Review.
Nursing classification systems are used to report nursing practices and maintain a unified documentation language. Nursing interventions classification (NIC) and nursing outcomes classification (NOC) are among the recognized terminology systems. To examine the extent of reporting NIC/NOC in nursing research. A systematic review following PRISMA guidelines. A literature search in three electronic databases was performed. A total of (18) articles were included. Nine studies were conducted to describe the commonly used NIC/NOC, six studies validated the effectiveness of classification systems, and two studies compared different nursing classification systems. The available evidence is limited by the quality of the studies. We recommend examining the use of NIC/NOC in nursing documentation using an experimental design.


Characterization of opioid receptor types modulating acetylcholine release in septal regions of the rat brain.
Presynaptic opioid receptors of the delta- and mu-types have been shown to inhibit the release of acetylcholine (ACh) in the rat striatum and hippocampus, respectively, but it is unknown whether opioid receptors modulate the release of ACh also in the region of origin of the hippocampal cholinergic innervation, the septum. To answer this question, slices (350 microm) of the medial septal area and of the diagonal band of Broca, as well as (for comparison) of the hippocampus, were prepared from adult male Wistar rats. The slices were incubated with [3H]choline, superfused in the presence of hemicholinium-3 (10 microM) and stimulated twice (S1, S2) by electrical fields (360 pulses, 3 Hz, 2 ms, 60 mA); opioid receptor agonists were present during S2. The preferential mu-agonist [D-Ala2,N-Me-Phe4,Gly-ol5]enkephalin (DAMGO) inhibited the evoked ACh release by maximally about 40% in hippocampal slices and acted even more strongly in the medial septal area, or the diagonal band of Broca (about 60% or 75% maximal inhibition, respectively). These effects were reduced or abolished by the preferential mu-antagonist naloxone, which showed no effects when given alone. Using naloxone in the presence of a cocktail of peptidase inhibitors, no evidence for an endogenous tone of opioid peptides was found in the medial septal area, diagonal band of Broca or the hippocampus. Using the preferential delta-agonist [D-Pen2, D-Pen5]enkephalin (DPDPE) and the delta-antagonist naltrindole, a delta-opioid receptor inhibiting evoked ACh release was clearly detectable both in the medial septal area and the diagonal band of Broca, but not in the hippocampus, whereas the preferential kappa-agonist trans-3,4-dichloro-N-methyl-N-[2(1-pyrrolidinyl)cyclo-hexyl] benzeneacetamide (U50,488H) had only weak or no effects. In addition to the functional experiments, double in-situ hybridization studies were performed, in which cells containing mRNA for choline acetyltransferase (ChAT) were labeled by an antibody-linked enzymatic staining procedure, whereas mRNAs for mu- or delta-opioid receptors were detected with radioactive probes. These experiments revealed that in the septal region mainly mu-opioid receptors were expressed by neurons positive for ChAT mRNA, whereas in the rat striatum the expression of delta-opioid receptors prevailed in those neurons. We conclude that in the septal area of the rat brain, in contrast to the rat striatum and hippocampus, both presynaptic mu- and delta-opioid receptors modulate the evoked release of ACh. Whether presynaptic mu- and delta-opioid receptors occur on the same or on different septal cells or axon terminals remains to be clarified.


Pain assessment and general approach to management.
To manage pain successfully, assessment of the presence and degree of pain is essential. This article describes the various signs and behaviors that may be presumed to be associated with pain of varying degrees. Conditions that are associated with pain and situations that influence the severity of pain are also discussed. The general approach to management of these situations is outlined, with an introduction to the various articles in this issue dealing with specific mechanisms and modalities involved in the treatment of pain.


Caries risk after interproximal enamel reduction.
Air-rotor stripping (ARS) is a commonly used method to alleviate crowding in the permanent dentition. Its widespread acceptance, however, has been limited by the potential increase in caries risk of the abraded enamel surface. The aim of this study was to compare the susceptibility of ARS-treated enamel surfaces with intact surfaces in patients undergoing fixed orthodontic therapy. Forty patients treated with ARS were examined clinically and radiographically for caries 1 to 6 years after interproximal enamel reduction. All patients were seen by their dentists for prophylaxis at 6-month intervals during active orthodontic treatment and were exposed to fluoridated water and toothpaste. Topical fluoride agents or sealants were not applied on the abraded surface after any ARS session. Caries incidence was compared between ARS-treated and unaltered surfaces within subjects. The decayed, missing, filled tooth (DMFT) and surface (DMFS) scores were used to evaluate the subjects' overall caries risk. Totals of 376 test and 376 control surfaces were examined. The number of interproximal lesions detected was found to be low with no statistically significant difference detected between the groups (test = 3; control = 6; P = .33]. The DMFT and DMFS scores increased significantly during the study period, indicating that these patients were clearly at risk of tooth decay (P <.001). The findings indicate that the risk of caries is not affected by ARS. Furthermore, our data show that the application of topical fluoride on the enamel surfaces immediately after ARS in patients exposed to fluoridated water and fluoride-containing toothpaste may not provide any additional benefit.


A note: gut bacteria produce components of a locust cohesion pheromone.
Faecal pellets from germ-free locusts were used as culture media to determine the ability of locust gut bacteria to synthesize phenolic components of the locust cohesion pheromone. Inoculation of germ-free faecal pellets with Pantoea agglomerans, a species commonly isolated from locusts, resulted in the release of large amounts of guaiacol and small amounts of phenol, both of which are components of the locust cohesion pheromone. Two other locust-derived species, Klebsiella pneumoniae pneumoniae and Enterobacter cloacae, also produced guaiacol from germ-free faecal pellets, but the opportunistic locust pathogen, Serratia marcescens, did not. The most likely precursor for guaiacol is the plant-derived vanillic acid, which is present in large amounts in the faeces of both conventional and germ-free locusts. These observations are consistent with previous ones, that locust gut bacteria are responsible for the production of components of the locust cohesion pheromone. These findings illustrate how an insect can adapt to make use of a common bacterial metabolite produced by one or more of its indigenous gut bacterial species. This observation has implications for our appreciation of insect gut microbiota interactions.


Reversible cholestatic hepatitis caused by acetohexamide.
We report a case of cholestatic hepatitis accompanied by peripheral and hepatic eosinophilia in a patient taking acetohexamide for a period of 1.5 yr. Jaundice developed acutely and was accompanied by fever. After discontinuation of the drug, there was no evidence of further damage, with prompt normalization of liver enzymes, bilirubin, and eosinophil count.


[Application of Brain-Boy Universal Professional in preliminary assessment of auditory processing disorder].
Increasing numbers of hearing pathology is auditory processing disorders. Auditory Processing Disorders (APD) are defined as difficulty in using auditory information to communicate and learn in the presence of normal peripheral hearing. It may be recognized as a problem with understanding of speech in noise and perception disorder of distorted speech. APD may accompany to articulation disorders, language problems and difficulties in reading and writing. The diagnosis of auditory processing disorders causes many difficulties primarily due to the lack of common testing procedures, precise criteria for qualification to the group of norm and pathology. The Brain-Boy Universal Professional (BUP) is one of diagnostics tools. It enables to assess the higher auditory functions. The aim of the study was preliminary assessment of hearing difficulties that may suggest the occurrence of auditory processing disorders in children. The questionnaire of hearing difficulties and BUP was used. Study includes 20 participants 2nd grade students of elementary school. The examination of the basic central functions was carried out with BUP. The parents and teacher complete the questionnaire to evaluate the hearing problems. Studies carried out indicate that the 40% schoolchild have hearing difficulties. The high percentage of deficits in auditory functions was confirmed with research results of medical device and the questionnaire for teacher. On the basis of the studies conducted may establish that the Warnke Method can serve as preliminary assessment of hearing difficulties that may suggest the occurrence of auditory processing disorders in children.


Acute and chronic phases of unilateral inflammation in rat's ankle are associated with an increase in the proportion of calcitonin gene-related peptide-immunoreactive dorsal root ganglion cells.
Using immunocytochemical methods, the proportion of calcitonin gene-related peptide immunoreactive perikarya was determined in dorsal root ganglia L4-L6 in four control rats and in ten rats with a unilateral inflammation in the ankle region of the left hindlimb. The inflammation was induced by subdermal injection of Freund's complete adjuvant at the ankle. Swelling and cellular infiltration of the ankle region developed within 2 days, and were stable and restricted to the injected ankle for the duration of the 3-week study. In control rats approximately 24% of 20,419 perikarya showed calcitonin gene-related peptide (CGRP)-like immunoreactivity. In rats with unilateral inflammation the proportion of CGRP-positive neurons was increased on the inflamed side to approximately 32% of 11,454 cells at day 2 (P < 0.001 with respect to ganglia in normal rats) and approximately 29% of 10,739 perikarya at day 20 post inoculation (P < 0.01). By contrast, no significant changes were found between ganglia in the non-injected side (approximately 25% at day 2 and approximately 24% at day 20). These results demonstrate that peripheral inflammation is associated with an increase in the proportion of neurons in the dorsal root ganglia that synthetize CGRP. This up-regulation is already present at an early stage of inflammation but also at later stages, suggesting that the increased synthesis of CGRP is an important neurobiological reaction associated with the acute and chronic phases of inflammation.


Associations of Longitudinal Fetal Growth Patterns With Cardiometabolic Factors at Birth.
Birth weight is associated with cardiometabolic factors at birth. However, it is unclear when these associations occur in fetal life. We aimed to investigate the associations between fetal growth in different gestational periods and cord blood cardiometabolic factors. We included 1,458 newborns from the Born in Guangzhou Cohort Study, China. Z-scores of fetal size parameters [weight, abdominal circumference (AC), and femur length (FL)] at 22 weeks and growth at 22-27, 28-36, and ≥37 weeks were calculated from multilevel linear spline models. Multiple linear regression was used to examine the associations between fetal growth variables and z-scores of cord blood cardiometabolic factors. Fetal weight at each period was positively associated with insulin levels, with stronger association at 28-36 weeks (β, 0.31; 95% CI, 0.23 to 0.39) and ≥37 weeks (β, 0.15; 95% CI, 0.10 to 0.20) compared with earlier gestational periods. Fetal weight at 28-36 (β, -0.32; 95% CI, -0.39 to -0.24) and ≥37 weeks (β, -0.26; 95% CI, -0.31 to -0.21) was negatively associated with triglyceride levels, whereas weight at 28-36 weeks was positively associated with HDL levels (β, 0.12; 95% CI, 0.04 to 0.20). Similar results were observed for AC. Fetal FL at 22 and 22-27 weeks was associated with increased levels of insulin, glucose, and HDL. Fetal growth at different gestational periods was associated with cardiometabolic factors at birth, suggesting that an interplay between fetal growth and cardiometabolic factors might exist early in pregnancy.


Inoculation of sonicate fluid into blood culture bottles improves microbial detection in patients with orthopedic bone and soft tissue infections of the upper and lower extremities.
The usefulness of sonicate fluid culture for biological tissues in orthopedic bone and soft tissue infections have not been reported. We assessed whether inoculating the sonicate fluid of bone and soft tissue into a blood culture bottle could increase the diagnostic accuracy for biofilm-related orthopedic infections. Twenty consecutive patients with infections (9 purulent arthritis, 4 osteomyelitis, 4 purulent tenosynovitis, 2 purulent bursitis, and 1 cellulitis) and 10 non-infected cases (6 carpal tunnel syndrome, 3 Dupuytren contracture, and 1 soft tissue tumor) between October 2018 and December 2020 were evaluated prospectively. We analyzed a total of 107 culture submissions (87 bone and tissue specimens and 20 controls); 42 intraoperative tissue specimens (32 infected samples and 10 non-infected samples) using the conventional method, 45 sonication samples (35 infected samples and 10 non-infected samples), and 20 control samples. Intraoperative infectious tissues were cultured using sonicate fluid culture in a blood culture bottle (SFC-CB). The applications of SFC-CB and the conventional culture method and the detection rate, sensitivity, and relationship between the sensitivity of the diagnostic methods and duration of administered preoperative antibiotics were assessed. The causative microorganism was detected only by SFC-CB in five patients (25%). The sensitivity (85% vs. 60%; P = 0.077) and detection rate (80% vs. 60%; P = 0.065) were higher for SFC-CB than for the conventional culture method. The sensitivity of SFC-CB was significantly higher than that of the conventional culture method in cases in which preoperative antibiotics were administered for more than 1 week (77% vs. 39%; P = 0.047). Using SFC-CB, the diagnostic accuracy for bone and soft tissue infection was significantly improved. As biofilms are readily formed in biological tissues, sonication may also be useful for diagnosis. SFC-CB was particularly useful for cases in which preoperative antibiotics were administered.


Factors associated with adherence to provider referrals for lung cancer screening with low dose computed tomography before and during COVID-19 pandemic.
Lung cancer has been the leading cause of American deaths from cancer. Although Medicare started covering lung cancer screening (LCS) with low-dose computed tomography (LDCT) in 2015, the uptake of LDCT-LCS remains low. This study examines the changes in adherence to provider referrals for LDCT-LCS and the factors at patient, provider, and health system levels that influence the completion rate of LDCT-LCS orders before and during the COVID-19 pandemic. Our study examined electronic health record data (December 2013 - December 2020) from a large, community-based clinical healthcare delivery system in California. We plotted monthly trends in the frequency of LDCT-LCS orders and completion rate and compared the annual LDCT-LCS completion rate between LCS-eligible, LCS-ineligible, and unknown eligibility groups. We then explored multilevel factors associated with the completion of LDCT-LCS orders using hierarchical generalized linear models. There was an increase in LDCT-LCS orders (N = 12,469) from 2013 to 2019, followed by a sharp decline in March 2020 due to the onset of the COVID-19 pandemic. Thereafter, LDCT-LCS orders slowly increased again in June 2020. The completion rate of LDCT-LCS increased from 0% in December 2013 to approximately 70% in 2018-2019 but declined to 50-60% in 2020 during the pandemic. Ineligible patients had lower completion rates of LDCT-LCS. Patients who were new to the healthcare system, Black, received the LDCT-LCS order in the first few years after Medicare coverage (2016 or 2017), during the pandemic, had major comorbidities, and smoked less than 30 pack-years were less likely to complete an order. Patients were more likely to complete LDCT-LCS orders if they were younger, received the LDCT-LCS order from a physician (vs. nonphysician provider), from family medicine or other specialties (vs. internal medicine), or saw a provider with more experience in LDCT-LCS. The beginning of the COVID-19 pandemic largely decreased the volume of LDCT-LCS orders, but rates have since been slowing recovering. Future interventions to improve lung cancer screening should consider doing more targeted outreach to new patients and Black patients as well as providing additional education to nonphysician practitioners and those providers with lower rates of LDCT-LCS referral orders.


Wildlife contact rates at artificial feeding sites in Texas.
Given the popularity of feeding white-tailed deer (Odocoileus virginianus) in Texas and the increasing amount of corn that is distributed, more information is needed on the impacts of this activity on non-target wildlife. Our objectives were to report visitation, intra- and interspecific contact, and contact rates of wildlife at artificial feeding sites in Texas. Our study was conducted at three sites in Kleberg and Nueces counties, Texas. We trapped animals from February to April and August to September, 2009 and marked animals with passive integrated transponder (PIT) tags. At each site and season, we placed one feeder system containing a PIT tag reader within 600 m of trap locations. Readers detected PIT tags from a distance of 25 cm. We determined a contact event to occur when two different PIT tags were detected by feeder systems within 5 s. We recorded 62,719 passes by raccoons (Procyon lotor), 103,512 passes by collared peccaries (Pecari tajacu), 2,923 passes by feral swine (Sus scrofa), 1,336 passes by fox squirrels (Sciurus niger), and no passes by opossums (Didelphis virginiana) at feeder systems. For site-season combinations in which contact events occurred, we found intraspecific contact rates (contacts per day) for raccoons, collared peccaries, and feral swine to be 0.81-124.77, 0.69-38.08, and 0.0-0.66, respectively. Throughout our study we distributed ~2,625 kg of whole kernel corn, which resulted in 6,351 contact events between marked wildlife (2.4 contacts per kg of corn). If 136 million kg of corn is distributed in Texas annually, we would expect >5.2 billion unnatural contact events between wildlife would result from this activity each year in Texas. Consequently, we do not believe that it is wise for natural resource managers to maintain artificial feeding sites for white-tailed deer or other wildlife due to pathogen transmission risks.


miR-101-3p contributes to the progression of preeclampsia by suppressing WDR5-mediated proliferation and invasion of trophoblast.
Decreased proliferation and invasion of trophoblast were proven to be involved in the pathogenesis of preeclampsia (PE). However, the regulatory network has not been clarified yet. This study aimed to explore the role of miR-101-3p in the progression of PE. miR-101-3p expression in placentas of pregnant women with or without PE was analyzed by real-time quantitative PCR (RT-qPCR). Trophoblastic HTR-8/SVneo and HPT-8 cell lines were cultured and underwent hypoxia/reoxygenation (H/R) treatment to mimic PE in vitro. Cell proliferation and invasion were analyzed in gain-of and loss-of-function assays. Finally, we undertook in vivo studies to explore effects of miR-101-3p in the PE model. Compared to placentas from patients without PE, miR-101-3p expressed significantly higher in placentas from PE patients, and its level was positively correlated with the severity of patients. In vitro studies found that overexpression of miR-101-3p significantly suppressed cell proliferation and invasion, while knockdown of miR-101-3p reversed the impacts of H/R treatment. Further research showed that the expression of WD repeat domain 5 (WDR5) was significantly lower in placentas from patients with PE, and its level was negatively associated with the severity of patients. In vitro and in vivo studies confirmed that miR-101-3p promoted PE progression through the regulation of WD WDR5 expression. Increased expression of miR-101-3p in placenta contributes to the development of PE by suppressing WDR5-mediated proliferation and invasion of trophoblast.


The effect of light compressive and tensile mechanical forces on SOST and POSTN expressions in human periodontal ligament cells: an in vitro study.
Periodontal ligament (PDL) cells play an important role in mechanosensing and secretion of signaling molecules during bone remodeling. However, the regulatory mechanism is unknown. The aim of the present study is to investigate the expression pattern of periostin and sclerostin in response to orthodontic forces in periodontal ligament cells in vitro. PDL cells were isolated from extracted teeth and treated with compressive forces of 25 gr/cm2 or equiaxial tension forces at frequency 1 Hz for 0, 24, 48, and 72 h. qRT-PCR was applied to evaluate the gene expressions. The secretion of sclerostin and periostin was assessed using ELISA. DAPI staining was used to evaluate apoptosis. The expression of sclerostin elevated significantly at protein and gene levels under compression forces after 24 h, while the application of tensile forces induced the expression of periostin and its upstream regulator RUNX2 (p < 0.05). Gene expression up-regulation was significant for POSTN and RUNX2 after 48 and 72 h tensile forces. Also, the gene expression of sclerostin reduced in a time-dependent manner after application of tensile force. The compression forces enhanced apoptosis to 7.5 ± 3.5% and induced gene expression of apoptotic markers of CASP9, and BCL2 within 72 h of exposure. Periostin and sclerostin play an important role in orthodontic loads and their expressions are affected oppositely by compressive and tensile forces that might be suggested as a biomarker for assessment of bone remodeling during orthodontic treatment.


Acetate kinase from Veillonella alcalescens. Regulation by succinate and substrates.
The kinetic properties of acetate kinase from Veillonella alcalescens were investigated. In the presence of high concentrations of nucleotide both forward and reverse reactions were observed. In the presence of succinate the degree of cooperativity between subunits of the homodimer decreased, i.e. the Hill coefficient, n, decreased from 2.5 to 1.4 for acetyl phosphate in the presence of succinate. At low substrate concentrations hyperbolic kinetic data were observed with succinate. We have proposed a modified version of the concerted symmetry model to describe the kinetics observed with this enzyme. The primary differentiating feature of the proposed model is the requirement for activator ligand binding for catalysis. In the absence of succinate, the substrate (acetate or acetyl phosphate) also functions as an activating ligand.


The central nervous system and atherogenesis: endothelial injury.
Although it has been widely acknowledged that endothelial injury is an important contributing factor to the pathogenesis of atherosclerosis, and may even represent an initiating event, morphologic documentation of its occurrence both in humans and animals has been difficult to obtain. However, electrical stimulation of the lateral hypothalamus in conscious, unrestrained animals on normal diets induces severe endothelial damage with cell loss and denudation in both aortas and coronary arteries. Continued stimulation results in intimal lesions with features of atherosclerotic plaques. The mechanism by which stimulation leads to endothelial injury is discussed and involves the induction of vasospasm. These observations are considered in the light of recent clinical and epidemiological studies, in which the role of neuropsychological and behavioral responses to psychosocial stimuli have been considered important risk factors for the development of atherosclerosis.


Do adult eelgrass shoots rule seedling fate in a large seagrass meadow in a eutrophic bay in northern China?
We conducted field sampling over 19 months to investigate eelgrass population reproduction status and ecological interactions in a large seagrass meadow in a eutrophic bay in northern China. The results showed asexual growth played an important role in the maintenance of existing meadows, and sexual reproduction played a critical role in the colonization of new areas. We conclude that adult eelgrass shoots do rule the fate of seedlings in the large seagrass meadow. Additionally, nutrient resources (N and P) at this location were found to meet eelgrass growth demand. The N/P ratios of seawater and seagrass indicated N limitation relative to P in the eutrophic bay based on the seagrass Redfield ratio (25-30). Nutrient uptake by seagrass might be an important factor in reducing the probability of a red tide in the study area. The results of this study provide fundamental information for eelgrass restoration and conservation.


Intestinal and cardiac inflammatory response shows enhanced endotoxin receptor (CD14) expression in magnesium deficiency.
Substance P is elevated in plasma and in other tissues during Mg-deficiency, and was found localised to neuronal C-fibres of cardiac and intestinal tissues, where it could promote neurogenic inflammation. Plasma prostaglandin E2 (PGE2), indicative of systemic inflammation, rose significantly (>or=4 fold, p<0.01) after 1 week and remained elevated through week 2 and 3 in rat on the Mg-deficient (MgD) diet. Concomitantly, total blood glutathione decreased by 50%. Immunohistochemical staining for endotoxin (lipopolysaccaride, LPS) receptor, CD14 was prominent in macrophage-type cells in intestinal tissue; more importantly, cardiac tissue revealed both CD11b (monocyte/macrophage surface protein) and CD14 positive cells after 3 weeks in rats on MgD diet. Western blot analysis indicated a significant increase in the endotoxin receptor protein level in the 3 week MgD hearts. Since CD14 is known to be up-regulated in cells exposed to LPS, these observations suggest that prolonged Mg-deficiency results in increased intestinal permeability to bacterial products that induce the endotoxin receptor in cells localized to myocardial and intestinal tissues. These CD14 positive cells may amplify the cardiomyopathic inflammatory process by stimulating TNF-alpha and other pro-inflammatory cytokines.


Development, feasibility, and efficacy of a customized exercise device to deliver intradialytic resistance training in patients with end stage renal disease: Non-randomized controlled crossover trial.
Introduction This study assessed the feasibility and efficacy of a novel resistance training device used within an intradialytic progressive resistance training (PRT) intervention. Methods Non-randomized, within-subjects crossover design with outcomes assessed at baseline (week 0), postcontrol (week 13) and post-PRT intervention (week 26). Twenty-two hemodialysis patients (59% men, 71 ± 11 years) performed PRT three sessions per week for 12 weeks. The resistance training device was developed to enable the performance of 2 upper body and 3 lower body exercises, unilaterally and bilaterally, both before and during dialysis, with loads of 2.5 to 59 kg. Feasibility outcomes included adverse events, adherence and training load progression. Changes in upper and lower body muscular strength, six-minute walk, aspects of health-related quality of life (HRQoL) and depression were evaluated. Findings The PRT intervention was delivered without serious adverse events, resulted in 71.2% ± 23.3% adherence and significant adaptation of all training loads from pre to mid to post training (83.8%-185.6%, all P < 0.05). Lower body strength (P < 0.001) and HRQoL subscales (Role-Physical, Social Functioning, Role-Emotional) significantly increased (all P < 0.01) and a trend toward reduced depression was noted (P = 0.06). No significant changes were noted in other outcomes. Discussion PRT using the novel resistance training device was feasible and improved measures of physical and psychological health. This device can be utilized in most dialysis centers. Future studies are required to evaluate dose-response effects of PRT prescriptions in subpopulations, and the translation of PRT to standard dialysis practice.


[Ultrasound study of disorders of coordination in tongue movement in swallowing].
Ultrasound imaging of tongue movements permits real-time observation of swallowing and articulation without risk for the patient. The ultrasound images of the tongue motions were recorded on video-tape and then analyzed frame by frame. We were able to detect regular phases of tongue motion during normal swallowing. Clear deviations from normal motion patterns were found in a patient with anarthria, despite absence of swallowing difficulties in every day life.


Adrenocorticoid receptor binding in the rat hippocampus: strain-dependent covariations with arousal and habituation to novelty.
In order to investigate whether the genotype-dependent behaviour of the Naples high-(NHE) and low-excitability (NLE) rat strains was modulated by differences in the capacity of hippocampal adrenocorticoid receptors, a correlative analysis was made among behavioural scores from exposure to a Làt-maze and in vitro [3H]corticosterone hippocampal binding capacity in these rats and in their random-bred controls (NRB). As previously shown, NHE/NLE-rats differed markedly upon forced exposure to the maze, with the NRB group occupying an intermediate position. No differences were found in maximal binding capacity (Bmax) and dissociation constant (Kd), nor in the individual maximal binding capacity (IMBC) between the two strains, while both showed lower IMBC than NRB-rats. These results tend to exclude that the genetic differences in the behaviour of NHE/NLE-rats are due to distinct patterns in the adrenocorticoid binding capacity in the hippocampus (HPC). Moreover, the intrastrain correlative analysis among IMBC (in the whole HPC and in its dorsal and ventral portion) and the behavioural scores showed that (1) motor and emotional correlates of 'arousal' to novelty were positively correlated in NLE and negatively in NHE-, but not in NRB-rats; (2) a consistent correlation was found with the intertrial activity decrement (long-term habituation), which was negative in both strains, and it was positive in NRB-rats. These complex co-variations are envisioned as possibly due to the differential modulatory components of the activation and inhibition of novelty-induced arousal response. However, our findings support the hypothesized involvement of the HPC, where adrenocorticoid receptors are selectively concentrated, in the modulation of some adaptive behavioural responses.


Prognostic Value of Anemia and C-Reactive Protein Levels in Diffuse Large B-Cell Lymphoma.
To determine the prognostic value of pretreatment anemia, pretreatment elevated C-reactive protein (CRP) levels, and 6-month posttreatment anemia in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) treated with rituximab, cyclophosphamide, hydroxydaunorubicin, Oncovin, and prednisolone (R-CHOP). A total of 104 patients with newly diagnosed DLBCL were retrospectively included. Pretreatment hemoglobin and CRP levels and 6-month posttreatment hemoglobin levels were measured. Cox regression analyses were used to determine the associations of laboratory assessments and National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) risk groups with progression-free survival (PFS) and overall survival (OS). Pretreatment anemia, elevated pretreatment CRP levels, and higher risk NCCN-IPI groups were significantly associated with reduced PFS and OS (P = .001 and P = .003 for pretreatment anemia, P = .035 and P = .029 for elevated CRP, and P < .001 and P < .001 for higher risk NCCN-IPI groups). On multivariate Cox regression analysis, only the NCCN-IPI risk group remained as an independent significant predictor for PFS (P < .001) and OS (P < .001). In the subgroup of patients in complete remission 6 months after chemotherapy (n = 80), 6-month posttreatment anemia was significantly associated with reduced PFS (P = .046) but not OS (P = .062), and higher risk NCCN-IPI groups were significantly associated with both reduced PFS (P = .008) and OS (P = .017). On multivariate Cox regression analysis, only the NCCN-IPI group remained an independent significant predictor for PFS (P = .008) and OS (P = .017). Pretreatment anemia, pretreatment CRP levels, and 6-month posttreatment anemia are significantly associated with poor outcome, but were not proven to be of additional prognostic value to the current risk stratification index for DLBCL.


Ten-day empirical sequential or concomitant therapy is more effective than triple therapy for Helicobacter pylori eradication: A multicenter, prospective study.
The resistance of Helicobacter pylori to antibiotics has increased the need for new empirical, first-line treatments. However, the efficacy of sequential therapy (ST) and concomitant therapy (CT) compared with triple therapy (TT) has not been adequately evaluated. In this study, we evaluated the efficacy of these empirical three regimens. The 517 patients enrolled in the study were prospectively randomized to receive 10 days of TT (n=171), ST (n=170), and CT (n=176) at 5 university-affiliated hospitals from May 2013 to March 2015. The post-treatment H. pylori status was determined using the (13)C-urea breath test. The baseline characteristics were similar among the three groups. The intention-to-treat eradication rates were 62.6%, 70.6%, and 77.8% in the TT, ST, and CT groups, respectively (p<0.01). The corresponding per-protocol eradication rates were 82.8%, 89.5%, and 94.4%, respectively (p<0.01). There were no significant differences in the compliance, side effects, and follow-up loss rates. A higher eradication rate was achieved with empirical 10-day ST, and CT than with the TT regimen, with similar rates of compliance and treatment side effects.


Changes of gut bacteria and immune parameters in liver transplant recipients.
Liver transplantation is one of the most effective therapeutic options for patients with end-stage liver diseases, and gut microbiota is actively involved in potential infections in pretransplant and posttransplant patients. However, the diversity of gut microbiota and its relationship with the immune parameter of liver transplantation recipients are not well understood. We collected fresh feces and blood samples from 190 participants in China from November 2004 to May 2008, including 28 healthy volunteers, 51 cirrhotic patients and 111 liver-transplanted patients. Six interesting gut bacteria, plasma endotoxin, serum cytokines (i.e., tumor necrosis factor alpha and interleukin-6) and fecal secretory IgA (SIgA) were investigated by real-time quantitative PCR, chromogenic limulus amoebocyte assay, sandwich-type enzyme-linked immunosorbent assay and radioimmunoassay, respectively. All Eubacteria, Bifidobacterium spp., Faecalibacterium prausnitzii and Lactobacillus spp. were significantly lower in the liver transplantation recipients while Enterobacteriaceae and Enterococcus spp. were significantly higher (P<0.05). Except for Enterococcus spp., other bacteria showed a tendency to restore to normal level along with the time after liver transplantation. Plasma endotoxin, interleukin-6 and fecal SIgA in cirrhotic patients increased significantly, but not in liver transplantation recipients. Plasma endotoxin and interleukin-6 were negatively correlated with all Eubacteria and the Bacteroides-Prevotella group, while tumor necrosis factor alpha was not significantly correlated with these six gut bacteria in cirrhotic patients. Our study demonstrates that abundant gut bacteria were altered significantly in both cirrhotic and liver transplantation patients, while plasma endotoxin and interleukin-6 increased remarkably in cirrhotic patients, showing significant correlations with gut microbiota. Interestingly, our data show a tendency for these gut bacteria to restore to normal levels in liver transplantation recipients.


Difficulties in the prenatal diagnosis of Jarcho-Levin syndrome.
Prenatal diagnosis of Jarcho-Levin syndrome early in pregnancy has not been previously reported. We present a case in which ultrasound examination resulted in a tentative diagnosis at 22 weeks of pregnancy. The difficulties in arriving at a definite diagnosis are presented.


[CSF levels of total tau protein in patients with mild cognitive impairment and Alzheimer's disease].
In recent studies, patients diagnosed with Alzheimer's disease (AD) showed significantly elevated CSF levels of tau protein. Tau protein was therefore regarded as a putative molecular marker for AD. Since early diagnosis of AD is warranted for appropriate therapeutic intervention, investigation of total tau protein levels in patients with Aging Associated Cognitive Decline (AACD) and AD are reasonable. In our study the CSF concentrations of total tau protein were measured by ELISA in 132 patients with AD, 29 patients with AACD and 24 healthy controls. CSF concentrations were compared between the subgroups of mild, moderate and severe AD, AACD and the control group and were correlated with age and severeness of the illness. The concentration of total tau protein was increased significantly in patients with severe and moderate AD compared to all other groups. Within the group of AD patients, total tau protein correlated significantly with the severity of the dementia but not with age. Although the range of the measured tau protein concentrations is wide and overlapping between the diagnostic groups our data indicate that from a clinical point of view significantly increased tau protein levels confirm the clinical diagnosis of AD while normal values do not exclude it.


Distinct cerebral small vessel disease impairment in early- and late-onset Alzheimer's disease.
This study investigated cerebral small vessel disease (CSVD) damage patterns in early-onset and late-onset Alzheimer's disease (EOAD and LOAD) and their effects on cognitive function. This study included 93 participants, 45 AD patients (14 EOAD and 31 LOAD), and 48 normal controls (13 YNC and 35 ONC) from the ADNI database. All participants had diffusion tensor imaging data; some had amyloid PET and plasma p-tau181 data. The study used peak width of skeletonized mean diffusivity (PSMD) to measure CSVD severity and compared PSMD between patients and age-matched controls. The effect of age on the relationship between PSMD and cognition was also examined. The study also repeated the analysis in amyloid-positive AD patients and amyloid-negative controls in another independent database (31 EOAD and 38 LOAD), and the merged database. EOAD and LOAD showed similar cognitive function and disease severity. PSMD was validated as a reliable correlate of cognitive function. In the ADNI database, PSMD was significantly higher for LOAD and showed a tendency to increase for EOAD; in the independent and merged databases, PSMD was significantly higher for both LOAD and EOAD. The impact of PSMD on cognitive function was notably greater in the younger group (YNC and EOAD) than in the older group (ONC and LOAD), as supported by the ADNI and merged databases. EOAD has less CSVD burden than LOAD, but has a greater impact on cognition. Proactive cerebrovascular prevention strategies may have potential clinical value for younger older adults with cognitive decline.


Navigating in tissue mazes: chemoattractant interpretation in complex environments.
Guided cell movement is essential for development and integrity of animals and crucially involved in cellular immune responses. Leukocytes are professional migratory cells that can navigate through most types of tissues and sense a wide range of directional cues. The responses of these cells to attractants have been mainly explored in tissue culture settings. How leukocytes make directional decisions in situ, within the challenging environment of a tissue maze, is less understood. Here we review recent advances in how leukocytes sense chemical cues in complex tissue settings and make links with paradigms of directed migration in development and Dictyostelium discoideum amoebae.


Influence of extracellular calcium on cell permeabilization and growth regulation by the lymphokine leukoregulin.
Permeablization of human K562 leukemia cells was measured in the presence and absence of extracellular ionic calcium to examine the relationship of ionic calcium to increased membrane permeability and the inhibition of cell proliferation by this lymphokine. In the absence of extracellular calcium, the ability of leukoregulin to permeabilize the cell membrane is diminished but is fully restored by addition of 1 mM extracellular Ca++ as shown flow cytometrically by loss of intracellular fluorescein. Membrane permeability is also increased by calcium ionophore A23187 but permeablization is completely blocked in calcium-free medium despite the intramembrane presence of the calcium ionophore. Membrane permeablization by the lectin phytohemagglutinin, in contrast, is independent of extracellular calcium. A similar divergence in cell proliferation activity of the three modulators of calcium flux and membrane permeability occurs in the absence of extracellular calcium. Leukoregulin inhibition of cell proliferation is abolished, inhibition by calcium ionophore A23817 is greatly reduced, and inhibition by phytohemagglutinin is unchanged. Leukoregulin permeabilized K562 cells isolated by fluorescence activated cell sorting resume proliferation after 72 h. In contrast cells permeablized by calcium ionophore A23187 or phytohemagglutinin fail to resume proliferation by 7 days. The membrane permeablizing action of leukoregulin is, therefore, partially dependent upon extracellular calcium. It is also effected through a mechanism other than calcium ionophore transport or lectin type transmembrane signaling, and is accompanied by a reversible inhibition of cell proliferation.


In vivo degradation of polymers. I. Change of mechanical properties in polyethylene pacemaker lead insulations during long-term implantation in the human body.
The results of mechanical testing and microscopic examination of explanted clinically-used polyethylene pacemaker lead insulations are presented. An experimental set of 98 lead insulations implanted for times ranging from 7 d to 11 yr was evaluated for changes in mechanical properties during clinical use. The results showed that the polyethylene tubing suffered a gradual structural change, due to its exposure to the physiological environment of the human body. The decline of the mechanical properties with implantation time is described by empirical formulae. Abrasive deterioration was also observed and is discussed.


Ability of pleth variability index to detect hemodynamic changes induced by passive leg raising in spontaneously breathing volunteers.
Pleth Variability Index (PVI) is a new algorithm that allows continuous and automatic estimation of respiratory variations in the pulse oximeter waveform amplitude. Our aim was to test its ability to detect changes in preload induced by passive leg raising (PLR) in spontaneously breathing volunteers. We conducted a prospective observational study. Twenty-five spontaneously breathing volunteers were enrolled. PVI, heart rate and noninvasive arterial pressure were recorded. Cardiac output was assessed using transthoracic echocardiography. Volunteers were studied in three successive positions: baseline (semirecumbent position); after PLR of 45 degrees with the trunk lowered in the supine position; and back in the semirecubent position. We observed significant changes in cardiac output and PVI during changes in body position. In particular, PVI decreased significantly from baseline to PLR (from 21.5 +/- 8.0% to 18.3 +/- 9.4%; P < 0.05) and increased significantly from PLR to the semirecumbent position (from 18.3 +/- 9.4% to 25.4 +/- 10.6 %; P < 0.05). A threshold PVI value above 19% was a weak but significant predictor of response to PLR (sensitivity 82%, specificity 57%, area under the receiver operating characteristic curve 0.734 +/- 0.101). PVI can detect haemodynamic changes induced by PLR in spontaneously breathing volunteers. However, we found that PVI was a weak predictor of fluid responsiveness in this setting.


Application of an innovative design space optimization strategy to the development of liquid chromatographic methods to combat potentially counterfeit nonsteroidal anti-inflammatory drugs.
In the context of the battle against counterfeit medicines, an innovative methodology has been used to develop rapid and specific high performance liquid chromatographic methods to detect and determine 18 non-steroidal anti-inflammatory drugs, 5 pharmaceutical conservatives, paracetamol, chlorzoxazone, caffeine and salicylic acid. These molecules are commonly encountered alone or in combination on the market. Regrettably, a significant proportion of these consumed medicines are counterfeit or substandard, with a strong negative impact in countries of Central Africa. In this context, an innovative design space optimization strategy was successfully applied to the development of LC screening methods allowing the detection of substandard or counterfeit medicines. Using the results of a unique experimental design, the design spaces of 5 potentially relevant HPLC methods have been developed, and transferred to an ultra high performance liquid chromatographic system to evaluate the robustness of the predicted DS while providing rapid methods of analysis. Moreover, one of the methods has been fully validated using the accuracy profile as decision tool, and was then used for the quantitative determination of three active ingredients and one impurity in a common and widely used pharmaceutical formulation. The method was applied to 5 pharmaceuticals sold in the Democratic Republic of Congo. None of these pharmaceuticals was found compliant to the European Medicines Agency specifications.


Radiation cataract: clinicopathologic report.
We report the case of a 52-year-old woman who developed bilateral anterior and posterior subcapsular cataracts with anterior capsule fibrosis 12 years after exposure to intensive radiation therapy. The woman had uneventful cataract surgery and gained 20/20 corrected distance visual acuity in both eyes. Hematoxylin-eosin staining of the anterior capsule revealed significant subcapsular scar formation in the context of fibroblast proliferation. No author has a financial or proprietary interest in any material or method mentioned.


Hereditary ataxia and spastic paraplegia in Portugal: a population-based prevalence study.
Epidemiological data on hereditary cerebellar ataxia (HCA) and hereditary spastic paraplegia (HSP) are scarce. To present the prevalence and distribution of HCA and HSP in Portugal. Population-based, nationwide, systematic survey, from January 1, 1994, through April 15, 2004, in Portugal. Multiple sources of information were used (review of clinical files, active collaboration of neurologists and geneticists, and investigation of affected families), but the main source was active collaboration of general practitioners. Patients were examined by the same team of neurologists, using homogeneous inclusion criteria. The clinical data were registered, and all families were genetically tested. Overall, 1336 patients from a population of 10,322 million were diagnosed as having HCA or HSP, a prevalence of 12.9 per 100,000 population. Hereditary cerebellar ataxia was more prevalent (prevalence, 8.9 per 100,000 population; 5.6 for dominant and 3.3 for recessive ataxias) than HSP (prevalence, 4.1 per 100,000 population; 2.4 for dominant and 1.6 for recessive). Machado-Joseph disease (spinocerebellar ataxia type 3) (prevalence, 3.1 per 100,000 population), Friedreich ataxia (prevalence, 1.0 per 100,000 population), and ataxia with oculomotor apraxia (prevalence, 0.4 per 100,000 population) were the most frequent HCAs. Spastic paraplegia types 4 (prevalence, 0.91 per 100,000 population), 3 (prevalence, 0.14 per 100,000 population), and 11 (prevalence, 0.26 per 100,000 population) were the most prevalent HSPs. This population-based survey covered all the Portuguese territory and mobilized most general practitioners and health centers. To our best knowledge, this survey was the largest ever performed for HCA and HSP. Prevalence of autosomal dominant ataxias was high, particularly for Machado-Joseph disease (spinocerebellar ataxia type 3). The genetic cause has not been identified in 39.7% of the patients studied.


Hospital clusters of invasive Group B Streptococcal disease: A systematic review.
To characterize outbreaks of invasive Group B Streptococcal (iGBS) disease in hospitals. Systematic review using electronic databases to identify studies describing iGBS outbreaks/clusters or cross-infection/acquisition in healthcare settings where 'cluster' was defined as ≥2 linked cases. PROSPERO CRD42018096297. Twenty-five references were included describing 30 hospital clusters (26 neonatal, 4 adult) in 11 countries from 1966 to 2019. Cross-infection between unrelated neonates was reported in 19 clusters involving an early-onset (<7 days of life; n = 3), late-onset (7-90 days; n = 13) index case or colonized infant (n = 3) followed by one or more late-onset cases (median serial interval 9 days (IQR 3-17, range 0-50 days, n = 45)); linkage was determined by phage typing in 3 clusters, PFGE/MLST/PCR in 8, WGS in 4, non-molecular methods in 4. Postulated routes of transmission in neonatal clusters were via clinical personnel and equipment, particularly during periods of crowding and high patient-to-nurse ratio. Of 4 adult clusters, one was attributed to droplet spread between respiratory cases, one to handling of haemodialysis catheters and two unspecified. Long intervals between cases were identified in most of the clusters, a characteristic which potentially hinders detection of GBS hospital outbreaks without enhanced surveillance supported by genomics.


PSMD4 drives progression of hepatocellular carcinoma via Akt/COX2 pathway and p53 inhibition.
The ubiquitin-dependent proteolytic pathway is crucial for cellular regulation, including control of the cell cycle, differentiation, and apoptosis. Proteasome 26S Subunit Ubiquitin Receptor, Non-ATPase 4, (PSMD4) is a member of the ubiquitin proteasome family that is upregulated in multiple solid tumors, including hepatocellular carcinoma (HCC), and the existence of PSMD4 is associated with unfavorable prognosis. In this study, transcriptome sequencing of HCC tissues and non-tumor hepatic tissues from the public database Cancer Genome Atlas (TGCA) revealed a high expression of PSMD4. Additionally, PSMD4 loss in HCC cells suppressed the tumor development in mouse xenograft model. PSMD4, which is maintained by inflammatory factors secreted from tumor matrix cells, positively mediates cell growth and is associated with Akt/GSK-3β/ cyclooxygenase2 (COX2) pathway activation, inhibition of p53 promoter activity, and increased p53 degradation. However, the domain without the C-terminus (VWA+UIM1/2) sustained the activation of p53 transcription. Thus, our findings suggest that PSMD4 is involved in HCC tumor growth through COX2 expression and p53 downregulation. Therapeutic strategies targeting PSMD4 and its downstream effectors could be used for the treatment of PSMD4-abundant HCC patients.


Comparing functional status and community integration in severe penetrating and motor vehicle-related brain injuries.
To examine the functional status of persons surviving a severe penetrating traumatic brain injury (TBI) resulting from a gunshot wound who require inpatient rehabilitation. Data were collected prospectively at 4 different time periods: rehabilitation admission and discharge and year 1 and year 2 postinjury. Rehabilitation hospital within a Traumatic Brain Injury Model System. Forty-five persons with severe penetrating brain injury and 45 persons involved in a motor vehicle crash (MVC). Not applicable. Disability Rating Scale (DRS), FIM instrument, and Community Integration Questionnaire (CIQ). Results indicated functional improvements for both the penetrating and motor vehicle severe TBI groups on the DRS and the FIM from rehabilitation admission to discharge. Follow-up data at 1 and 2 years postinjury revealed continued improvements on the DRS and FIM measures for both groups, with the greatest improvement in recovery during the first year. In addition, improved community reintegration emerged between 1 and 2 years postinjury for both groups, as measured by the CIQ. There was a small significant difference on the outcome measures between the 2 groups in the course of their recovery. Persons who survive severe penetrating brain injuries and who require inpatient rehabilitation may show continuing improvement in functioning over time. For persons receiving inpatient rehabilitation services, initial improvement is most likely to occur during the hospital stay and continue postinjury, with the largest improvement in the first year after injury. Community reintegration can also be expected over time. One can expect similar outcomes for individuals who sustain a severe penetrating brain injury and a severe brain injury ensuing from an MVC.


Ovarian dysgerminoma: report of seven cases and review of the literature.
Seven cases of ovarian dysgerminoma are presented and the recent literature reviewed. The majority of the cases reviewed had tumor confined to one ovary at the time of diagnosis, and nearly 50% occurred in women less than 20 years of age. The 5-year survival rate was 91% for 211 patients with stage I disease and 65% for 60 patients with stage II to IV dysgerminoma. The addition of contralateral adnexectomy, abdominal hysterectomy, and radiation therapy was not beneficial when disease was confined to one ovary. The survival of patients with advanced disease treated with chemotherapy was comparable with that of patients who received radiation. Analysis of the present data suggests that the use of unilateral oophorectomy should be limited to those patients with disease confined to one ovary and no histologic evidence of lymph node metastasis. Abdominal hysterectomy, bilateral adnexectomy, and adjuvant radiation is currently the treatment of choice for patients with more advanced dysgerminoma.


Carotid reconstruction in nonagenarians: is surgery a viable option?
Because of limited longevity and perceived increased perioperative risk, the optimal treatment of significant carotid stenosis in nonagenarians is controversial. This study was conducted to evaluate our results in this demographic group. A retrospective review was performed of carotid endarterectomies (CEAs) done in nonagenarians at Cedars-Sinai Medical Center between 1996 and 2006. During this period, a total of 2,038 CEAs were performed on patients of all ages. Data abstracted included demographics, patient risk factors, indications for surgery, perioperative complications, and survival. Fifty-three (2.8%) CEAs were performed as the primary procedure on 49 patients aged 90 or greater during the study period. Of these patients, 11 (22.4%) had diabetes, 38 (77.5%) had hypertension, and 31 (63.3%) had coronary artery disease. Eleven patients (22.4%) had a history of smoking, and there were no current smokers. Renal disease was present in three (6.1%) patients, one of whom was dialysis-dependent. The median length of stay was 2 days with a range of 1 to 24 days. Five patients (10.2%) required the intensive care unit following surgery. There were no postoperative strokes, and none of the patients had suffered ipsilateral stroke during follow-up. One patient (1.8%) had a perioperative myocardial infarction. One patient died in the perioperative period (1.8%). The 1-month stroke and mortality results did not differ significantly from those in patients under the age of 90, 0.3% and 0.4%, respectively (p = nonsignificant by Fisher's exact test). Using Kaplan-Meier life-table analysis, the 1- and 5-year survival rates were 84 +/- 5% and 33 +/- 9%, respectively. Our study demonstrates that in a group of well-selected nonagenarians, CEA is a safe procedure with acceptable perioperative morbidity.


Molecular epidemiology and antimicrobial resistance profiles of Salmonella isolates from dairy heifer calves and adult lactating cows in a Mediterranean pasture-based system of Australia.
Dairy cows can be reservoirs of foodborne pathogens such as Salmonella that pose serious public health risks to humans. The study was designed to examine the molecular epidemiology and antimicrobial resistance profiles of Salmonella isolates from dairy heifer calves and adult lactating cows in the pasture-based system of Australia. A total of 838 animals (328 heifer calves and 510 lactating cows) from 22 farms were sampled. Overall, 54 Salmonella isolates were recovered (calves 28/328 and cows 26/510). A herd-level Salmonella prevalence of 50% (95% confidence interval: 31%-69%) was recorded. Within-herd prevalence for Salmonella ranged between 4%-29% and 4%-45% among the heifer calves and adult lactating cows, respectively. Three different serovars were identified with Salmonella Infantis being the most common serovar (n = 33, 61%) followed by Salmonella Kiambu (n = 20, 37.0%) and one isolate of Salmonella Cerro (2%). The highest antimicrobial resistance prevalence of Salmonella isolates was found against streptomycin (n = 31, 57%), followed by cefoxitin (n = 12, 22%), ceftriaxone (n = 2, 4%), and chloramphenicol (n = 1, 2%). Multiple class resistance was observed on 4 isolates against cefoxitin, chloramphenicol, and streptomycin. Multilocus sequence types ST32 (61%), ST309 (37%), and ST367 (2%) were strongly linked to the serovars Salmonella Infantis, Salmonella Kiambu, and Salmonella Cerro, respectively. Whole genome sequencing of Salmonella isolates detected only 2 resistance genes: aac(6') gene that confers resistance against aminoglycosides among 40.7% of the isolates, and a single isolate positive for the blaDHA-16 gene. Two distinct clusters among the serovars were observed suggesting 2 independent sources of spread. Despite the low prevalence of antimicrobial resistance among Salmonella from the dairy farms, our findings contribute to the regional and national understanding of antimicrobial resistance in dairy herds in Australia. There is need for continued antimicrobial resistance stewardship and surveillance programs to ensure the production of high-quality food products and the long-term protection of both animal and human health.


Thoracic outlet syndrome: a retrospective analysis of robotic assisted first rib resections.
Thoracic Outlet Syndrome (TOS) is caused by compression of the neurovascular bundle between the first rib and the clavicula, which can cause a large panel of symptoms and has a reported incidence of approximately 2-4/100.000. Surgical treatment consists of the resection of the first rib and is historically performed using an open, mainly transaxillary, approach. Recent developments resulted in a minimally invasive approach using Robotic Assisted Thoracic Surgery (RATS). With this study, the investigators want to provide a descriptive study of first rib resection using RATS approach at two different centers. We reviewed the files of 47 patients affected by TOS and who benefited from first rib resection using RATS approach between 2016 and 2021. Patient characteristics as well as Length of Stay (LOS), affected side, operative time (OT), complications, etiology, VAS score and post-operative QOL were gathered in the database. Statistical analysis was performed using IBM SPSS statistics 25 ®. Results were reported in mean and standard deviation. 47 patients affected by TOS received first rib resection using robotic approach. Mean age was 47 ± 12 yrs. 16 patients were operated on the left side and 31 on the right side. All the patients reported complete resolution of symptoms. At 1-year follow-up, no patient suffered from recurrence. There were no intraoperative complications. Postoperative complications occurred in two patients, one patient developed pneumothorax after chest tube removal and one patient developed recurrent pleural effusion which required surgery. Mean LOS was 3 ± 1 days and mean OT was 122 ± 40 min. First rib resection performed using a RATS approach is a safe technique with excellent outcomes and which is beneficial for the patient in terms of LOS, pain and symptom resolution.


Monitoring CAR-T cell kinetics in clinical trials by multiparametric flow cytometry: Benefits and challenges.
Exceptional clinical responses produced by the first chimeric antigen receptor T [CAR-T] cell therapies, and their entry into commercial markets prompted a logarithmic increase in the number of next generation CAR-T clinical trials. As a result, there is a growing interest in understanding the analytical approaches utilized for reliable monitoring of these "living" drugs, and the challenges encountered during their clinical development. Multiparametric flow cytometry (MFC) assays have played a crucial role in understanding the phenotype and function of first approved CAR-T therapies. Herein, three main areas for monitoring CAR-T therapies in clinical trials are discussed: (1) analytical considerations critical for development of MFC assays for the reliable enumeration of CAR-T levels, (2) operational challenges associated with clinical trial sampling and transportation, and (3) differential cellular kinetics observed by MFC and qPCR analyses and their relationship with efficacy (measurable residual disease levels). Initial experiences described here may enable design of fit-for-purpose tools and help to more rapidly advance the development of next generation CAR-T therapies.


The amino-terminal residue of glycoprotein B is critical for neutralization of bovine herpesvirus 1.
In order to address the neutralization epitope on bovine herpesvirus 1 (BHV1) glycoprotein B (gB), a panel of monoclonal antibodies (MAbs), a series of truncation forms of the glycoprotein and an MAb-escape mutant were used in this study. Immunocytochemistry on the truncations using MAbs against the glycoprotein revealed that the neutralization epitopes recognized by the MAbs lay between residues 1 and 52 of mature gB. Comparison of the sequences among the mutant, parent, and revertant viruses demonstrated that the amino-terminal residue of mature gB of the escape mutant was changed from Arg to Gln. These findings indicate that the amino-terminal residue of gB is critical for neutralization of BHV1.


Ways of coping with obesity stigma: review and conceptual analysis.
There is clear documentation of bias and discrimination aimed at overweight persons, but less is known about methods individuals use to cope with weight stigma. This paper provides an analysis of such methods, integrating work on weight stigma with what is known from other relevant areas (e.g., race and gender bias). Multiple means of coping have been studied, ranging from attempts to change the stigmatizing condition (losing weight) to taking pride in the condition and mobilizing social action to prevent discrimination. The most promising areas for future research, methodological challenges, and the importance of individual difference and situational factors as moderating variables are discussed.


Echocardiography in infective endocarditis: reassessment of prognostic implications of vegetation size determined by the transthoracic and the transesophageal approach.
In 105 patients with active infective endocarditis, disease-associated complications defined as severe heart failure (New York Heart Association class IV), embolic events and in-hospital death were correlated to the vegetation size determined by both transthoracic and transesophageal echocardiography. A detailed comparison between anatomic and echocardiographic findings, performed in a subgroup of 80 patients undergoing surgery or necropsy, revealed that true valvular vegetations can be reliably identified by echocardiography in the vast majority of patients; the detection rate was significantly higher for the transesophageal (90%) than for the transthoracic (58%) approach, particularly when infected prosthetic valves were evaluated. However, an accurate echocardiographic differentiation between true vegetations and other endocarditis-induced valve destruction (ruptured leaflets or chordae) is impossible. The correlation of vegetation size with endocarditis-associated complications showed that patients with a vegetation diameter greater than 10 mm had a significantly higher incidence of embolic events than did those with a vegetation diameter less than or equal to 10 mm (22 of 47 versus 11 of 58; p less than 0.01). Particularly for patients with mitral valve endocarditis, a vegetation diameter greater than 10 mm was highly sensitive in identifying patients at risk for embolic events. Vegetation size, however, was not significantly different in patients with and without severe heart failure or in patients surviving or dying during acute endocarditis. In addition, no significant correlation was found between vegetation size and location of endocarditis or type of infective organism.(ABSTRACT TRUNCATED AT 250 WORDS)


Biochemical characterization of postsynaptically localized cyclic nucleotide phosphodiesterase.
This study demonstrates the postsynaptic localization of one of the isozymes of cyclic nucleotide phosphodiesterase (PDE) activity at asymmetrical, axospinous terminals in the rat corpus striatum and neocortex. Characterization of this enzymatic activity demonstrates that the PDE form surviving aldehyde fixation for electron cytochemistry can be considered to preferentially hydrolyze cyclic 3'5'-guanosine monophosphate, and it requires calcium and a heat-stable calcium-dependent regulator protein (CDR) for full hydrolytic activity. Ion exchange chromatographic analysis of extracts of corresponding unfixed brain regions demonstrates that only one enzyme activity peak exhibits similar aldehyde resistance and calcium and regulator protein activatibility.


Evolution: Fruit Fly Clocks on the Edge.
Fruit flies evolved in tropical regions under stable light-dark cycles. However, their photosensitive circadian clock had to adapt to extreme seasonal photoperiods during their colonisation of temperate regions. This was achieved by changing the neuronal expression of two key clock-related components.


People post-stroke perceive movement fluency in virtual reality.
We investigated the visual perception of biological movement by people post-stroke, using minimal kinematic displays. A group of twenty patients and a group of twelve age-matched healthy controls were asked to judge movement fluency. The movements to judge were either displayed as an end-point dot or as a stick-figure of the arm and trunk. It was found that the perception of movement fluency was preserved post-stroke, however, with an increase in the variability of judgment. Moreover, the end-point dot representation ameliorated what was perceived and judged, presumably by directing attention to the important kinematic cues: smoothness and directness of the trajectory. We conclude that, despite perception of actions is influenced by the ability of the observer to execute the observed movement, hemiparesis has a mild effect on the perception of biological movement. Yet, a valuable virtual learning environment for upper-limb rehabilitation should be implemented to provide the observer with neither too much, nor too little information to maximize learning.


Dual-cutoff of sFlt-1/PlGF ratio in the stratification of preeclampsia: a systematic review and meta-analysis.
To systematically review the approach of using two independent sFlt-1/PlGF cutoffs that has better sensitivity (cutoff-sen) and specificity (cutoff-spe) separately for risk stratification in the detection of preeclampsia. PubMed and Embase databases and reference lists were searched up to June 2016. Inclusion criteria were blood samples for sFlt-1/PlGF with separate cutoffs (cutoff-sen and cutoff-spe) provided. Six relevant studies were identified. Pooling of results was done based on three studies and a systematic review was performed based on all six. The strategy of using a cutoff of ≤33 and ≥85 for early onset preeclampsia, and ≤33 and ≥110 for the late onset preeclampsia was proposed and examined. The pooled sensitivity for cutoff-sen was: 95.3% (90.6-98.1%) and 88.6% (82.9-92.9%) for early and late onset preeclampsia, respectively. The pooled specificity for cutoff-spe was: 97.6% (95.2-98.9%) and 94.2% (91.4-96.3%) for early and late onset preeclampsia respectively. The pooled estimation of the early onset pre-eclamptic pregnancies and control normal pregnancies classified in the equivocal zone was 4.9% (2.0-8.8%) and 32.4% (25.7-39.5%), respectively, and 26.8% (10.3-47.6%) and 8.7% (3.0-17.6%) for late onset patients. The new dual-cutoff diagnostic system optimizes the predictive performance of the single cutoff system. Further studies are required to assess the performance of this system and to define the approach and frequency at which subjects in the equivocal zone should be screened.


c-kit mutations in gastrointestinal stromal tumors occur preferentially in the spindle rather than in the epithelioid cell variant.
Gastrointestinal stromal tumors (GISTs) coexpress CD34 and the Kit tyrosine-kinase receptor (CD117). A subset of GISTs carry gain-of-function mutations of the c-kit proto-oncogene in its juxtamembrane domain. The relationship between the mutational status and histological as well as immunohistochemical features has not been assessed in detail. 36 GISTs and 14 other gastrointestinal mesenchymal tumors were investigated for their morphology and immunophenotype as well as for the presence of c-kit mutations. DNA was extracted from formalin-fixed, paraffin-embedded tissue. Exons 9, 11, 13, and 17 of c-kit were analyzed by SSCP. Bands with altered mobility were excised, reamplified, and sequenced. C-kit mutations in Exon 11 encoding the juxtamembrane domain were identified in 19 cases (52.8%), with deletions in 12 cases, insertions in 3 cases (2 of these as duplications), and point mutations in 4 cases. The mutations clustered between Codons 553 and 561, pinpointing the critical region for deregulated Kit receptor activation. In both Exons 9 and 13, single mutations could be identified, whereas no mutations were found in Exon 17. There were c-kit mutations in 66.6% of benign GISTs (14/21), 83.3% of the malignant (5/6), and 40% of the cases of intermediate malignancy (2/5). A low frequency of mutations in benign GISTs, as reported previously by other researchers, could not be observed in our panel. Interestingly, all GISTs with c-kit mutations displayed a spindle cell phenotype, whereas mutations were absent in all 7 tumors with an epithelioid component (P =.03). This finding suggests a relationship between c-kit mutation and histological subtype in GISTs.


The prognostic importance of triple negative breast carcinoma.
There is a current debate on whether triple negative breast carcinomas (estrogen receptor--ER-negative, progesterone receptor--PR-negative and HER2-negative) have a poor prognosis. Our aim in this retrospective study was to determine whether triple negative feature is a prognostic factor for disease-free survival (DFS) in 322 breast carcinoma patients, of whom 80 (24.8%) had triple negative tumor histology. In the multivariate analysis, tumor subgroup (triple vs non-triple, p<0.0001; hazard ratio [HR], 4.2; 95% confidence interval [95%CI], 2.2-8.2) was a significant factor related to relapse, in addition to number of metastatic nodes (>4 vs <or=4, p=0.04; HR, 1.6; 95%CI, 1.2-2.4), lymphatic vascular invasion (yes vs no, p=0.002; HR, 2.0; 95%CI, 1.3-3.1) and HER2 (positive vs negative, p<0.0001; HR, 5.9; 95%CI, 3.0-10.0). This result indicated that patients with triple negative histology had a poor disease-free survival and this histology was an independent significant prognostic factor for DFS.


Meal frequency differentially alters postprandial triacylglycerol and insulin concentrations in obese women.
The aim of this study was to compare postprandial lipemia, oxidative stress, antioxidant activity, and insulinemia between a three and six isocaloric high-carbohydrate meal frequency pattern in obese women. In a counterbalanced order, eight obese women completed two, 12-h conditions in which they consumed 1,500 calories (14% protein, 21% fat, and 65% carbohydrate) either as three 500 calorie liquid meals every 4-h or six 250 calorie liquid meals every 2-h. Blood samples were taken every 30 min and analyzed for triacylglycerol (TAG), total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, oxidized low-density lipoprotein cholesterol, myeloperoxidase, paraoxonase-1 activity, and insulin. The TAG incremental area under the curve (iAUC) during the three meal condition (321 ± 129 mg/dl · 12 h) was significantly lower (P = 0.04) compared with the six meal condition (481 ± 155 mg/dl · 12 h). The insulin iAUC during the three meal condition (5,549 ± 1,007 pmol/l · 12 h) was significantly higher (P = 0.05) compared with the six meal condition (4,230 ± 757 pmol/l(.) 12 h). Meal frequency had no influence on the other biochemical variables. Collectively, a three and six isocaloric high-carbohydrate meal frequency pattern differentially alters postprandial TAG and insulin concentrations but has no effect on postprandial cholesterol, oxidative stress, or antioxidant activity in obese women.


The identification of placenta praevia.
Placenta praevia is frequently misdiagnosed because of an overdistended bladder at the time of ultrasound examination. Other incorrectly diagnosed cases may be related to placental migration due to the result of differential growth of the uterus and placenta. By recognizing these potential errors, the ultrasound diagnostic accuracy of placenta praevia will improve.


Correlation of apparent diffusion coefficient values and peritumoral edema with pathologic biomarkers in patients with breast cancer.
To investigate the relationship between breast cancer imaging features on magnetic resonance imaging (MRI) and histopathological characteristics. We prospectively enrolled 46 patients who underwent 1.5-T MRI with 68 breast malignant lesions from 2017 until 2019. Peritumoral edema was determined based on visual assessment on T2 weighted imaging. Lesions were categorized into two groups: A: with edema (48 lesions) and B: without edema (20 lesions). The tumor size was not different among two groups but multifocal-multicentric lesions were more common in the group A (70% vs. 35%). The axillary lymph nodes are most involved in group A. ER and PR positive lesions were more common in group B (90% vs. 56.3%) but in the group A, HER2 positive lesions were found to be more common (31.3% vs. 15%). The mean ADC value in tumors and peritumoral regions were lower (0.97 × 10-3 mm2/s, P = 0.023) and higher (1.85 × 10-3 mm2/s, P < 0.0001) in group A, respectively. Peritumoral ADC value was significantly higher in HER2-positive group. Breast carcinomas with peritumoral edema were found to be more multifocal-multicentric, with higher prevalence of axillary lymph node involvement, more HER 2-positive, with lower prevalence of ER/PR-positive, lower tumoral ADC and higher peritumoral ADC values.


Plant uptake and translocation of air-borne chlordane and comparison with the soil-to-plant route.
In order to assess fully the impact of persistent organic pollutants (POPs) on human health, pollutant exchange at the interface between terrestrial plants, in particular food crops, and other environmental compartments must be thoroughly understood. In this regard, transfers of multicomponent and chiral pollutants are particularly informative. In the present study, zucchini (Cucurbita pepo L.) was planted in containerized, uncontaminated soil under both greenhouse and field conditions and exposed to air-borne chlordane contamination at 14.0 and 0.20 ng/m(3) (average, greenhouses), and 2.2 ng/m(3) (average, field). Chiral gas chromatography interfaced to an ion trap mass spectrometer was used to determine the chiral (trans-chlordane, TC, and cis-chlordane, CC) and achiral (trans-nonachlor, TN) chlordane components in vegetation, air, and soil compartments. The chlordane components of interest were detected in all vegetation tissues examined--root, stem, leaves, and fruits. When compared with the data from a soil-to-plant uptake study, the compositional profile of the chlordane components, i.e. the component fractions of TC, CC, and TN, in plant tissues, showed significantly different patterns between the air-to-plant and soil-to-plant pathways. Changes in the enantiomer fractions of TC and CC in plant tissues relative to the source, i.e. air or soil, although observed, were not markedly different between the two routes. This report provides the first comprehensive comparison between two distinct plant uptake routes for POPs and their subsequent translocation within plant tissues.


Nursing interventions for patients with Alzheimer's disease.
Common nursing concerns and patient needs within the physical, emotional, cognitive, and social dimensions are addressed. Nursing interventions that help the patients maintain the maximum level of independence for as long as possible are suggested.


Arabidopsis ALTERED MERISTEM PROGRAM 1 negatively modulates plant responses to abscisic acid and dehydration stress.
Abscisic acid (ABA) is an important signaling molecule with multiple biological functions in seed germination, plant development and stress responses. ALTERED MERISTEM PROGRAM 1 (AMP1), encoding a putative glutamate carboxypeptidase, is involved in plant growth, morphogenesis and seed dormancy. In this study, we assigned new role for AtAMP1 in ABA signaling and dehydration stress. AtAMP1 was transcriptionally down-regulated by ABA. Loss-of-function mutant of AtAMP1 (amp1-1, encoding a premature stop codon in AtAMP1) resulted in hypersensitive phenotypes toward ABA-mediated seed germination and primary root elongation. The amp1-1 mutant also exhibited enhanced dehydration resistance, as evidenced by the changes of electrolyte leakage (EL), water loss rate and survival rate. Notably, the amp1-1 lines exhibited higher expression levels of ABA-responsive genes (RAB18, RD29A and RD29B), higher concentration of proline and lower reactive oxygen species (ROS) levels (H2O2 and O2(-)) after ABA and dehydration treatments than those of wild type. Taken together, these observations indicated a negative role for AtAMP1 in ABA-mediated seed germination, seedling development and dehydration stress response.


Effects of alismol isolated from Alismatis Rhizoma on calcium-induced contraction in the rabbit thoracic aorta.
We examined the inhibitory effects of alismol, a sesquiterpenoid isolated from Alismatis Rhizoma, on vascular contractions induced by high concentrations of K+ and Ca2+, and on 45Ca2+ retention in normal and in high K+-containing medium. Alismol affected neither the resting tension nor the 45Ca2+ retention in normal medium, but it inhibited sustained contraction and increased 45Ca2+ retention induced by high K+ concentrations. Alismol did not affect norepinephrine-induced contractions in normal medium, nor phasic contractions in Ca2+-free medium. These results suggested that alismol inhibited mainly Ca2+ influx through a voltage-dependent Ca2+ channel.


Synthesis of Fluorinated Imidazole[4,5f][1,10]phenanthroline Derivatives as Potential Inhibitors of Liver Cancer Cell Proliferation by Inducing Apoptosis via DNA Damage.
Phenanthroline derivatives containing fluorinated imidazole ring are effective anti-neoplastic agents. Herein, a series of four fluorinated imidazole[4,5f][1,10]phenanthroline derivatives were synthesized and investigated as potential inhibitors to fight against the growth of liver cancer cells. The in vitro antitumor activity of targeted compounds have been evaluated by using MTT assay, and results showed that compound 4 (2-(2,3-difluorophenyl)-1H-imidazo[4,5-f][1,10]phenanthroline) exhibited excellent inhibitory effect against the growth of various tumor cells, particularly for HepG2 cells, with IC50 value of approximately 0.29 μM. This result has been further confirmed by colony formation assay, showing that compound 4 suppressed the proliferation of HepG2 cells. Moreover, cell apoptosis (AO/PI dual staining and flow cytometry) analyses as well as comet assay showed that compound 4 may induce apoptosis of HepG2 cells through triggering DNA damage. Furthermore, the in vivo anti-tumor activity were evaluated on zebrafish bearing HepG2 cells showed that compound 4 can observably block the growth of liver cancer cells. All in together, these compounds, particularly compound 4, may be developed as a potential agent to treat liver cancer in the future.


Characterization of metal ligand mutants of phenylalanine hydroxylase: Insights into the plasticity of a 2-histidine-1-carboxylate triad.
The iron atom in the nonheme iron monooxygenase phenylalanine hydroxylase is bound on one face by His285, His290, and Glu330. This arrangement of metal ligands is conserved in the other aromatic amino acid hydroxylases, tyrosine hydroxylase and tryptophan hydroxylase. A similar 2-His-1-carboxylate facial triad of two histidines and an acidic residue are the ligands to the iron in other nonheme iron enzymes, including the alpha-ketoglutarate-dependent hydroxylases and the extradiol dioxygenases. Previous studies of the effects of conservative mutations of the iron ligands in tyrosine hydroxylase established that there is some plasticity in the nature of the ligands and that the three ligands differ in their sensitivity to mutagenesis. To determine the generality of this finding for enzymes containing a 2-His-1-carboxylate facial triad, the His285, His290, and Glu330 in rat phenylalanine hydroxylase were mutated to glutamine, glutamate, and histidine. All of the mutant proteins had low but measurable activities for tyrosine formation. In general, mutation of Glu330 had the greatest effect on activity and mutation of His290 the least. All of the mutations resulted in an excess of tetrahydropterin oxidized relative to tyrosine formation, with mutation of His285 having the greatest effect on the coupling of the two partial reactions. The H285Q enzyme had the highest activity as tetrahydropterin oxidase at 20% the wild-type value. All of the mutations greatly decreased the affinity for iron, with mutation of Glu330 the most deleterious. The results complement previous results with tyrosine hydroxylase in establishing the plasticity of the individual iron ligands in this enzyme family.


Virulence may determine the necessary duration and dosage of oseltamivir treatment for highly pathogenic A/Vietnam/1203/04 influenza virus in mice.
Control of highly pathogenic avian H5N1 influenza viruses is a major public-health concern. Antiviral drugs could be the only option early in the pandemic.METHODS. BALB/c mice were given oseltamivir (0.1, 1, or 10 mg/kg/day) twice daily by oral gavage; the first dose was given 4 h before inoculation with H5N1 A/Vietnam/1203/04 (VN1203/04) virus. Five- and 8-day regimens were evaluated.RESULTS. Oseltamivir produced a dose-dependent antiviral effect against VN1203/04 in vivo (P<.01). The 5-day regimen at 10 mg/kg/day protected 50% of mice; deaths in this treatment group were delayed and indicated the replication of residual virus after the completion of treatment. Eight-day regimens improved oseltamivir efficacy, and dosages of 1 and 10 mg/kg/day significantly reduced virus titers in organs and provided 60% and 80% survival rates, respectively (P<.05). Overall, the efficacy of the 5- and 8-day regimens differed significantly (death hazard ratio, 2.658; P<.01). The new H5N1 antigenic variant VN1203/04 was more pathogenic in mice than was A/HK/156/97 virus, and a prolonged and higher-dose oseltamivir regimen may be required for the most beneficial antiviral effect.CONCLUSIONS. Oseltamivir prophylaxis is efficacious against lethal challenge with VN1203/04 virus in mice. Viral virulence may affect the antiviral treatment schedule.


Reduction of plasma levels of betathromboglobulin and platelet factor 4 during hemodialysis: a possible role for a short acting inhibitor of platelet aggregation.
Plasma levels of the platelet markers betathromboglobulin and platelet factor 4 are elevated in patients with chronic renal failure, and their levels in hemodialysis patients increase further during exposure to the dialysis membrane. The effectiveness of a short acting inhibitor of platelet aggregation in reducing the blood levels of betathromboglobulin and platelet factor 4 was assessed by means of a double blind cross over study. A statistically significant reduction of betathromboglobulin and platelet factor 4 levels was observed during treatment with the platelet inhibitor.


An effective method for improving the permeation flux of a ceramic membrane: Single-matrix spherical ceramic membrane.
A single-matrix hydrophobic ceramic membrane (HCM) was prepared via gel-casting and membrane grafting. Fly ash cenospheres and 1H,1H,2H,2H-perfluorooctyl trichlorosilane were used as the single-matrix material. The results showed that when the sintering temperature was 1300℃, the porosity was 75.56 %, and flexural strength was 11.1 MPa; this means that the material meets the requirements for mechanical properties. After grafting 1H,1H,2H,2H-perfluorooctane trichlorosilane, the Si-CH3 peak increased and the Si-OH peak was weaker. Also, the contact angle of the droplet increased from 56° to 126°, and this indicates that the droplet was successfully chemically adsorbed to the surface of the ceramic membrane. The results of computational fluid dynamics simulation show that a gaussian spherical wall greatly improved the permeation flux of foamed ceramic membranes, and the permeation flux of the microchannel increased by 26.5 %∼76.2 % at the same transmembrane pressure. Pure water permeation flux and heavy metal adsorption experiments shows excellent high permeation flux and satisfactory heavy metal adsorption performance of HCM. From the perspective of membrane cost, HCM is suitable to be promoted. In summary, HCM has the potential for commercial application.