Corticosteroids and Mesalamine Versus Corticosteroids for Acute Severe Ulcerative Colitis: A Randomized Controlled Trial.
Corticosteroids are the mainstay of treatment for hospitalized patients with acute severe ulcerative colitis (ASUC). However, whether the addition/continuation of mesalamine with corticosteroids during hospitalization is superior to corticosteroids alone is unknown. This was a randomized controlled, investigator-blinded, clinical trial conducted in 10 centers in 7 countries. Patients hospitalized with ASUC (Lichtiger score ≥10) were eligible. Patients received corticosteroids alone or corticosteroid + mesalamine (4 g/day mesalamine) by a stratified randomization according to mesalamine use before admission. The primary outcome was the percentage of patients who responded to treatment by day 7, defined by a drop >3 points in the Lichtiger score and an absolute score <10 without the need for rescue medications or colectomy. Three hundred forty-six patients were screened, and 149 were included (70/149 female; median age, 41 years). Of these, 73 received corticosteroids + mesalamine, and 76 received corticosteroids alone. For the primary outcome, 53 of 73 patients (72.6%) receiving corticosteroids with mesalamine responded versus 58 of 76 patients (76.3%) on corticosteroids alone (odds ratio, 0.82; 95% confidence interval, 0.39-1.72; P = .60). There was no difference between groups in duration of hospitalization, C-reactive protein normalization rate, or colectomy rate up to day 90. The need for biologics among patients receiving combination of corticosteroids with mesalamine was numerically lower by day 30 (P = .11) and day 90 (P = .07). In this randomized controlled trial, combination of mesalamine with corticosteroids did not benefit hospitalized patients with ASUC more than corticosteroids alone. An exploratory signal for a reduced need for biologics at 90 days in the mesalamine group merits further evaluation. gov ID: NCT01941589.


Molecular findings in familial Parkinson disease in Spain.
Several genetic errors in alpha-synuclein (Park1) and ubiquitin carboxyl-terminal-hydrolase L1(Park5) genes cause autosomal dominant familial Parkinson disease. Mutations in the parkin gene (Park2) are the major cause of autosomal recessive Parkinson disease. To analyze the clinical and molecular data of 19 Spanish kindreds (13 with recessive, 4 with dominant, and 2 with uncertain inheritance) who have familial Parkinson disease. We searched for the previously described mutations in Park1 and Park5 genes and for new or described mutations in Park2. We used single-strand conformation polymorphism, direct sequencing, and restriction digestion of polymerase chain reaction (PCR)-amplified genomic DNA for this study. None of these families have either Park1 or Park5 mutations. We found 5 different mutations in Park2 gene in 5 of the families with recessive inheritance. To our knowledge, 2 of these mutations, V56E and C212Y, have not been previously reported. The other mutations found (deletion of exons 3 and 5 and 225delA) have been described in other ethnic groups. Heterozygous carriers of a single Park2 mutation either were asymptomatic or developed clinical symptoms in late adulthood or after brief exposure to haloperidol therapy. Mutations in Park2 gene account for 38% of the families with recessive parkinsonism in Spain. We found 2 cases of simple heterozygous Park2 mutation carriers that developed clinical symptoms, either in late adulthood or after brief exposure to parkinsonizing agents. Thus, hereditary Parkinson disease has more variable clinical phenotype and molecular defects than previously thought since heterozygous mutations could be a risk factor for parkinsonism.


Control of intrapulse frequency chirping in long-pulse CO(2) lasers employing perturbation-insensitive optical cavities.
We present the results of intrapulse frequency chirping measurements that were carried out on a TEA CO(2) laser equipped with various conventional and unconventional frequency-selective optical cavities. We experimentally demonstrate that there is a close relationship between the causes and the extent of intrapulse frequency chirping on the one hand and the type of optical configuration that is used for controlling the laser mode behavior on the other. In particular, it is shown that intrapulse chirping of the emitted frequency can be significantly reduced by employing laser cavities terminating in high-finesse reflective multipass interferometers for single-mode selection. In fact, this type of cavity can be designed in such a way to minimize the effects on the emitted frequency of perturbations affecting the cavity optical length.


A 3-month Journey: The Case of a 29-year Old Woman With Metastatic Renal Cell Carcinoma.
Early goal-oriented conversations at the end of life can help alleviate suffering and anxiety for surgical patients with cancer and their loved ones. This is especially important in the young adult population in whom there are limited patient-reported perspectives about their experiences at the end of life. We report the illustrative case of a 29-year-old woman who underwent palliative surgery for widely metastatic renal cell carcinoma. Her postoperative course was complicated by a proximal anastomotic stricture, bilateral pulmonary emboli, and delayed gastric emptying, ultimately leading to a functional decline in health and quality of life. Several wide-ranging palliative care needs arose during our patient's surgery, discharge, and subsequent readmissions. In addition to our patient's case, we discuss 3 fundamental surgical palliative care principles, and broad considerations for end-of-life management of young adults with advanced malignancies.


Alcohol response and consumption in adolescent rhesus macaques: life history and genetic influences.
The use of alcohol by adolescents is a growing problem and has become an important research topic in the etiology of the alcohol use disorders. A key component of this research has been the development of animal models of adolescent alcohol consumption and alcohol response. Because of their extended period of adolescence, rhesus macaques are especially well suited for modeling alcohol-related phenotypes that contribute to the adolescent propensity for alcohol consumption. In this review, we discuss studies from our laboratory that have investigated both the initial response to acute alcohol administration and the consumption of alcohol in voluntary self-administration paradigms in adolescent rhesus macaques. These studies confirm that adolescence is a time of dynamic change both behaviorally and physiologically, and that alcohol response and alcohol consumption are influenced by life history variables, such as age, sex, and adverse early experience in the form of peer-rearing. Furthermore, genetic variants that alter functioning of the serotonin, endogenous opioid, and corticotropin-releasing hormone systems are shown to influence both physiological and behavioral outcomes, in some cases interacting with early experience to indicate gene by environment interactions. These findings highlight several of the pathways involved in alcohol response and consumption, namely reward, behavioral dyscontrol, and vulnerability to stress, and demonstrate a role for these pathways during the early stages of alcohol exposure in adolescence.


Sex-related differences in amygdala functional connectivity during resting conditions.
Recent neuroimaging studies have established a sex-related hemispheric lateralization of amygdala involvement in memory for emotionally arousing material. Here, we examine the possibility that sex-related differences in amygdala involvement in memory for emotional material develop from differential patterns of amygdala functional connectivity evident in the resting brain. Seed voxel partial least square analyses of regional cerebral blood flow data revealed significant sex-related differences in amygdala functional connectivity during resting conditions. The right amygdala was associated with greater functional connectivity in men than in women. In contrast, the left amygdala was associated with greater functional connectivity in women than in men. Furthermore, the regions displaying stronger functional connectivity with the right amygdala in males (sensorimotor cortex, striatum, pulvinar) differed from those displaying stronger functional connectivity with the left amygdala in females (subgenual cortex, hypothalamus). These differences in functional connectivity at rest may link to sex-related differences in medical and psychiatric disorders.


Alternative descriptions of combined diffusive and convective mass transport in hemodialyzer.
Two alternative versions of the mathematical description of the combined diffusive and convective membrane transport in hemodialyzers were compared using the one-dimensional theory of hemodialyzers. The first version is based on the assumption of homogeneity of the membrane. The second version is a widely used "ad hoc" formulation, which can be interpreted as a description of the membrane as tighter at the dialysate side than at the blood side. Theoretical predictions of the increase of dialyzer clearance caused by ultrafiltration, as assessed by transmittance coefficient, were compared to experimental data about transport of small solutes (urea, creatinine, and sodium) as well as middle molecules (vitamin B12) in three types of hollow-fiber hemodialyzer. For one type of dialyzer, the theory assuming the homogeneous membrane yielded the correct predictions for the small solutes. For two other types of dialyzer, the alternative version of the theory was adequate. For vitamin B12, the experimental values of transmittance coefficient were between the values predicted by the two versions of the theory for all three types of hemodialyzer. Thus, the two versions should be considered as a possible adequate description of solute transport in hemodialyzers.


Analysis of YouTube content on substance use disorder treatment and recovery.
Emerging literature suggests the role of social media in substance use disorders (SUD). This study aimed to explore the content of YouTube videos for persons on SUD treatment/recovery, describing the users' exposure and engagement metrics and understanding viewers' perspectives. We generated a set of 10 key phrases to search on YouTube. Eighty eligible videos were analyzed using a mixed-methods approach. Content analysis of all videos and thematic analysis of 30 videos were done using the three most viewed videos from each key phrase. The reliability of videos was assessed using a modified DISCERN. The total number of views, likes, dislikes, and comments were noted and created engagement metrics. The linguistic analysis of viewers' comments was done to assess their perspectives. Sixty-three (78.8%) videos were from the US, and 59 (73.8%) were intended for persons or families with substance misuse. Persons in recovery uploaded 23 (28.7%) videos. We identified five themes - reasons for using drugs, symptoms of addiction, consequences of drug use, how to stop drug use, and expressed tone in the language. The positivity and relative positivity ratios were highest for videos developed by persons in recovery. There was a negative correlation between the relative positivity ratio and content fostering internalized stigma. Words with negative emotional experiences dominated the viewers' comments. YouTube content on SUD treatment and recovery is popular and revolves around the biopsychosocial understanding of addiction. There is an urgent need for a language policy and regulation of non-scientific content.


Understanding pregnant women's adherence-related beliefs about Nicotine Replacement Therapy for smoking cessation: A qualitative study.
Reducing smoking during pregnancy is a public health priority. Nicotine replacement therapy (NRT) is offered routinely to pregnant women who smoke in the United Kingdom. However, evidence of treatment efficacy in this population is weak, most likely due to poor adherence. Guided by the Necessity-Concerns Framework, we conducted a qualitative study to better understand pregnant women's perceived needs and concerns regarding NRT use, with consideration of combination NRT. Semi-structured interviews were conducted by telephone with 18 pregnant or recently pregnant women in England and Wales, purposively sampled for different NRT-related experiences. Participants were recruited online via Facebook adverts and through a Stop Smoking Service. A hybrid approach of deductive and inductive thematic coding was used for analysis. Findings were organized around three themes: 1) the role of motivation to stop smoking; 2) necessity beliefs about using NRT; and 3) concerns about NRT. Some women reported fluctuating motivation for stopping smoking which undermined their NRT use. Others used NRT to cut down the number of cigarettes they smoked. Reasons for low NRT necessity beliefs included a preference for quitting unassisted, low or unrealistic expectations of efficacy, and overconfidence in achieving cessation (necessity testing). Concerns included safety, particularly around increased nicotine exposure with combination NRT, addictiveness, side effects, and capability to use. Pregnant women have multiple necessity beliefs and concerns that influence their use of NRT. Targeting these, alongside increasing and maintaining motivation to quit smoking, will likely help optimize NRT use in pregnancy and improve quit rates.


Less invasive reduction and fusion of fresh A2 and A 3 traumatic L 1-L 4 fractures with a novel vertebral body augmentation implant and short pedicle screw fixation and fusion.
The aim of this clinical study was to report on the efficacy in reduction and safety in PMMA leakage of a novel vertebral augmentation technique with PEEK and PMMA, together with pedicle screws in the treatment of fresh vertebral fractures in young adults. Twenty consecutive young adults aged 45 ± 11 years with fresh burst A3/AO or severely compressed A2/AO fractures underwent via a less invasive posterior approach one-staged reduction with a novel augmentation implant and PMMA plus 3-vertebrae pedicle screw fixation and fusion. Radiologic parameters as segmental kyphosis (SKA), anterior (AVBHr) and posterior vertebral body height ratio (PVBHr), spinal canal encroachment (SCE), cement leakage and functional parameters as VAS, SF-36 were measured pre- and post-operatively. Hybrid construct restored AVBHr (P < 0.000), PVBHr (P = 0.02), SKA (P = 0.015), SCE (P = 0.002) without loss of correction at an average follow-up of 17 months. PMMA leakage occurred in 3 patients (3 vertebrae) either anteriorly to the fractured vertebral body or to the adjacent disc, but in no case to the spinal canal. Two pedicle screws were malpositioned (one medially, one laterally to the pedicle at the fracture level) without neurologic sequelae. Solid posterolateral spinal fusion occurred 8-10 months post-operatively. Pre-operative VAS and SF-36 scores improved post-operatively significantly. This study showed that this novel vertebral augmentation technique using PEEK implant and PMMA reduces and stabilizes via less invasive technique A2 and A3 vertebral fractures without loss of correction and leakage to the spinal canal.


Measurement of the Cytoplasmic and Vacuolar Buffer Capacities in Chara corallina.
The cytoplasm and the vacuole were isolated from internodal cells of Chara corallina by using the intracellular perfusion technique, and their buffer capacities (beta(i)) were determined from the titration curves. The pH of the isolated vacuolar sap was 5.19 +/- 0.029 (mean +/- standard error). At this pH, beta(i) was minimal and amounted to 0.933 +/- 0.11 millimoles H(+)/pH unit/liter vacuolar sap. The pH of isolated cytoplasm was 7.22 +/- 0.028. beta(i) was minimal in this pH region and amounted to 14.2 +/- 0.80 millimoles H(+)/pH unit/liter cytoplasm. When 1% (volume/volume) Triton X-100 was added to the cytoplasmic solution to permeabilize the subcellular organelles, the cytoplasmic pH increased to 7.32 +/- 0.026, where beta(i) was 20.35 +/- 2.66 millimoles H(+)/pH unit/liter cytoplasm. This shows that alkaline subcellular compartments exist in the cytoplasm and also that the cytoplasmic pH before adding Triton X-100 may represent the cytosolic pH. These data indicate that the pH values of the cytoplasm and the vacuole are regulated at the values where the beta(i) values are minimal. This suggests that ATP- and inorganic pyrophosphate-dependent H(+) pumps in the plasma membrane and the tonoplast could efficiently regulate the pH of both cytoplasm and vacuole in Chara internodal cells.


Fluorescence Enhanced Optical Resonator Constituted of Quantum Dots and Thin Film Resonant Cavity for High-Efficiency Reflective Color Filter.
Conventional color filters selectively absorb a part of the backlight while reflecting or transmitting other light, resulting in the problem of low efficiency and energy wasting. For this problem, a new concept of fluorescence enhanced optical resonator was proposed and verified in this paper. The new structure consists of structural color filter and light-conversion material. Specially, a thin film resonant cavity was designed, and InP/ZnSe/ZnS quantum dots were inserted inside the resonator. When illuminated by sunlight, the novel fluorescence enhanced optical resonator could not only reflect the specific light, but also convert absorbed energy into desired light, leading to the utilization efficiency improvement of solar energy. An all-dielectric red fluorescence enhanced optical resonator was fabricated, with peak equivalent reflectance up to 105%. Compared with a thin film resonator, the enhancement coefficient of the as-proposed structure is about 124%. The new optical structure can utilize solar source efficiently, showing application potential as the next generation of reflective color filters for display.


Cord-Blood Transplantation in Patients with Minimal Residual Disease.
The majority of patients in need of a hematopoietic-cell transplant do not have a matched related donor. Data are needed to inform the choice among various alternative donor-cell sources. In this retrospective analysis, we compared outcomes in 582 consecutive patients with acute leukemia or the myelodysplastic syndrome who received a first myeloablative hematopoietic-cell transplant from an unrelated cord-blood donor (140 patients), an HLA-matched unrelated donor (344), or an HLA-mismatched unrelated donor (98). The relative risks of death and relapse between the cord-blood group and the two other unrelated-donor groups appeared to vary according to the presence of minimal residual disease status before transplantation. Among patients with minimal residual disease, the risk of death was higher in the HLA-mismatched group than in the cord-blood group (hazard ratio, 2.92; 95% confidence interval [CI], 1.52 to 5.63; P=0.001); the risk was also higher in the HLA-matched group than in the cord-blood group but not significantly so (hazard ratio, 1.69; 95% CI, 0.94 to 3.02; P=0.08). Among patients without minimal residual disease, the hazard ratios were lower (hazard ratio in the HLA-mismatched group, 1.36; 95% CI, 0.76 to 2.46; P=0.30; hazard ratio in the HLA-matched group, 0.78; 95% CI, 0.48 to 1.28; P=0.33). The risk of relapse among patients with minimal residual disease was significantly higher in the two unrelated-donor groups than in the cord-blood group (hazard ratio in the HLA-mismatched group, 3.01; 95% CI, 1.22 to 7.38; P=0.02; hazard ratio in the HLA-matched group, 2.92; 95% CI, 1.34 to 6.35; P=0.007). Among patients without minimal residual disease, the magnitude of these associations was lower (hazard ratio in the HLA-mismatched group, 1.28; 95% CI, 0.51 to 3.25; P=0.60; hazard ratio in the HLA-matched group, 1.30; 95% CI, 0.65 to 2.58; P=0.46). Our data suggest that among patients with pretransplantation minimal residual disease, the probability of overall survival after receipt of a transplant from a cord-blood donor was at least as favorable as that after receipt of a transplant from an HLA-matched unrelated donor and was significantly higher than the probability after receipt of a transplant from an HLA-mismatched unrelated donor. Furthermore, the probability of relapse was lower in the cord-blood group than in either of the other groups.


Social impressions while drinking account for the relationship between alcohol-related problems and social anxiety.
Individuals with elevated social anxiety appear particularly vulnerable to experiencing alcohol-related problems; yet we know little about factors that may account for this relationship. One possibility is that socially anxious individuals hold beliefs about the impressions they make on others while drinking and these beliefs play an important role in their drinking behaviors. The present study used exploratory factor analysis among participants with clinically elevated social anxiety (n=166) to develop a measure, the Social Impressions while Drinking Scale (SIDS), to assess beliefs regarding others' impressions of drinking behaviors that may be particularly relevant to socially anxious individuals. A valuations scale was also developed to assess the importance of each belief. Empirically-derived subscales were identified with adequate reliability. Among socially anxious participants, the Gregarious and Sexual Facilitation subscales were uniquely related to drinking problems and frequency respectively. Individuals with clinically meaningful social anxiety achieved higher scores on all SIDS subscales compared to those with lower social anxiety (n=166). Several SIDS scales mediated the relations between social anxiety group status and drinking problems (Interaction Fears, Observation Fears, Aggression, Gregariousness). Results highlight the importance of examining beliefs specific to high-risk populations in assessing their alcohol-related behaviors.


Effects of an adenoviral vector containing a suicide gene fusion on growth characteristics of breast cancer cells.
The herpes simplex virus thymidine kinase/ganciclovir (HSV‑TK/GCV) and the cytosine deaminase/5‑fluorocytosine (CD/5‑FC) systems have been widely applied in suicide gene therapy for cancer. Although suicide gene therapy has been successfully used in vitro and in vivo studies, the number of studies on the effects of recombinant adenoviruses (Ads) containing suicide genes on target cancer cells is limited. The aim of this study was to examine whether recombinant Ads containing the CD/TK fusion gene affect cell proliferation of breast cancer cells in vitro. In the present study, we explored the use of a recombinant adenoviral vector to deliver the CD/TK fusion gene to the breast cancer cell line MCF‑7. We found that the recombinant adenoviral vector efficiently infected MCF‑7 cells. Western blot analysis revealed that CD and TK proteins are expressed in the infected cells. The infected breast cancer cells did not show any significant changes in morphology, ultrastructure, cell growth, and cell‑cycle distribution compared to the uninfected cells. This study revealed that the Ad‑vascular endothelial growth factor promoter (VEGFp)‑CD/TK vector is non‑toxic to MCF‑7 cells at the appropriate titer. Our results indicate that it is feasible to use a recombinant adenoviral vector containing the CD/TK fusion gene in suicide gene therapy to target breast cancer cells.


The Institute of Medicine and its quality of healthcare in America reports.
The Institute of Medicine was founded in 1970 under the charter of the National Academy of Sciences to address the concerns of medicine and healthcare. Many members of the Institute and at least two of its former presidents are also members of the Association. For those unfamiliar with the Institute's history and purpose, I will provide a brief overview. The National Academy of Sciences was chartered in 1863 by President Lincoln and the U.S. Congress, to advise the government on scientific issues and technology. As the scope of its activities broadened, the Academy established the National Research Council to provide an operating entity and staff for the many issues studied by members of the Academy and other volunteers. The closely related National Academy of Engineering was created in the 1960's and it also utilized the staff and facilities of the National Research Council. During the 1960's there was increasing need and concern for the establishment of an entity closely affiliated with the National Academy of Sciences that could provide advice, counsel, and studies on difficult issues in medicine and in the social, economic, and political aspects of healthcare. The Institute of Medicine evolved from these deliberations and, like the National Academy of Sciences, is an independent, non-governmental, nonprofit organization with a mandate to provide the government and others with advice, counsel, and independent research on major topics in healthcare.


A Comparative Assessment of Novel Mini-Laparoscopic Tools.
Mini-laparoscopy, or needlescopy, is an emerging minimally invasive technique that aims to improve on standard laparoscopy in the areas of tissue trauma, pain, and cosmesis. The objective of this study was to determine if there was a difference in functionality between 2 novel mini-laparoscopic instruments when compared to standard laparoscopic tools. Differences were assessed in a simulated surgical environment. Twenty participants (5 novices, 10 intermediate, 5 expert) were recruited for this institutional review board-approved study in a surgical simulation training center. Group A tools were assembled intracorporeally, and Group B tools were assembled extracorporeally. Using standard laparoscopic graspers, mini-laparoscopic graspers, or a combination of both, each participant performed 3 basic laparoscopic training tasks: a Peg Transfer, Rubber Band Stretch, and Tootsie Roll Unwrapping. Following each round of tasks, participants completed a survey evaluating the mini-laparoscopic graspers with respect to standard laparoscopic graspers. Data were analyzed using Kruskal-Wallis test with Dunn's test for post hoc comparisons. When comparing task times, both mini tools performed at the level of standard laparoscopic graspers in all participant groups. Group A tools were quicker to assemble and disassemble versus Group B tools. According to posttask surveys, all participant groups indicated that both sets of mini-laparoscopic graspers were comparable to the standard graspers. In a nonclinical setting, mini-laparoscopic instruments perform at the level of standard laparoscopic tools. Based on these results, clinical trials would be a reasonable next step in assessing feasibility and safety.


Bone vibrator placement and the cancellation technique.
An issue in the measurement of bone conduction sensitivity is the placement of the bone vibrator. The effect of bone vibrator position on the amplitude and phase of the received signal was investigated using a cancellation technique. This technique involves cancelling the signal delivered by the bone vibrator with a signal delivered acoustically via an earphone. At cancellation, the acoustic signal is equal in amplitude but opposite in phase to the bone-conducted signal. Results showed that the amplitude of the received signal did not vary significantly with bone vibrator position close to the center of the forehead whereas the phase of the received signal was critically dependent on bone vibrator position. Substantial intersubject differences were observed in the variation of phase with bone vibrator position. The precision of measurement using the cancellation technique was found to be high.


Biomimetic manganese-eumelanin nanocomposites for combined hyperthermia-immunotherapy against prostate cancer.
Pro-tumoral and immunosuppressive M2-like tumor-associated macrophages (TAMs) contribute to tumor progression, recurrence and distal metastasis. However, current TAMs-modulating therapeutic strategies often encounter challenges including insufficient immune activation, weak antigen presentation ability and unsatisfactory antitumor immune performance. Herein, cyclic RGD peptide functionalized and manganese doped eumelanin-like nanocomposites (RMnMels) are reported for combined hyperthermia-immunotherapy against PC3 prostate cancer. The RMnMels could promote M2-to-M1 macrophage repolarization via scavenging multiple reactive oxygen species and remodeling the immunosuppressive tumor microenvironment. Following near-infrared light irradiation, RMnMels-mediated thermal ablation not only could destroy tumor cells directly, but also elicit the release of damage associated molecular patterns and tumor-associated antigens, provoking robust tumor immunogenicity and strong antitumor immune responses. The results showed that RMnMels could effectively scavenge reactive oxygen species and promote M2-to-M1 macrophage repolarization both in vitro and in vivo. Synergistically enhanced anti-tumor therapeutic efficacy was achieved following single administration of RMnMels plus single round of laser irradiation, evidenced by decreased primary tumor sizes and decreased number of distant liver metastatic nodules. The as-developed RMnMels may represent a simple and high-performance therapeutic nanoplatform for immunomodulation and enhanced antitumor immune responses.


Assessment of pulse oximeter perfusion index in pediatric caudal block under basal ketamine anesthesia.
Whether pulse oximeter perfusion index (PI) may be applied to detect the onset of caudal block in pediatric patients under ketamine intravenous basal anesthesia is investigated. 40 ASA I, 2-8-year-old boys scheduled for elective circumcision surgery were randomized into two groups. Group I: 20 patients were anesthetized by 2 mg·kg(-1) ketamine intravenous injection (IV) followed by caudal block using 1 mL·kg(-1) lidocaine (1%); Group II: 20 patients were anesthetized by 2 mg·kg(-1) ketamine IV only. PI on the toe in Group II decreased by 33 ± 12%, 71 ± 9% and 65 ± 8% at 1 min, 15 min, and 30 min after ketamine injection. The maximum increase in MAP and HR after ketamine IV was 11 ± 6% at 3 min and 10 ± 6% at 2 min. Compared to the PI value before caudal injection of lidocaine, PI in Group I increased by 363 ± 318% and 778 ± 578% at 5 min and 20 min after caudal block, while no significant changes in MAP and HR were found compared to the baseline before caudal block. Thus, PI provides an earlier, more objective, and more sensitive indicator to assess the early onset of caudal block under basal ketamine anesthesia.


Comparison of intravenous and peritonsillar infiltration of tramadol for postoperative pain relief in children following adenotonsillectomy.
The aim of this study was to compare the postoperative analgesic efficacy and side-effects of intravenous tramadol with peritonsillar infiltration of tramadol in children undergoing adenotonsillectomy. Sixty-six children were randomized into two groups: group I received 2 mg kg(-1) tramadol intravenously and group II received 2 mg kg(-1) tramadol in 2 ml of normal saline (1 ml per tonsil) via peritonsillar infiltration. Modified Hannallah pain scale, nausea, vomiting, bleeding, rescue analgesia, sedation and Aldrete scores were recorded at the 1st, 15th, 30th and 60th minute postoperatively. The Aldrete score was used to determine the postanaesthesia care unit discharge criteria. Patients were evaluated for the analgesic requirement, nausea and vomiting, bleeding and sedation. There were no differences between groups during the first 1 h. In the postanaesthesia care unit, groups I and II had comparable pain scores that were not statistically significant (P > 0.05). But during the first 24 h the additional analgesic requirement of group I (141.81 mg) was more than group II (83.63 mg) (P = 0.002). Pain scores in the postoperative ward at 6, 12 and 24 h were significantly higher in group I than in group II (P < 0.001). Also four patients (12.12%) from group I and one patient (3.05%) from group II had nausea and vomiting in the postanaesthesia care unit and none of the patients had rescue analgesics. There were no differences between groups regarding nausea and vomiting, sedation and bleeding in the postoperative ward. In adenotonsillectomy cases, peritonsillar infiltration of tramadol maintains efficient pain relief with lower incidence of nausea and vomiting.


Esophageal Epithelial-Derived IL-33 Is Upregulated in Patients with Heartburn.
Interleukin-33 (IL-33) is a tissue-derived cytokine that is constitutively expressed in epithelial cells of tissues exposed to the environment and plays a role in sensing damage caused by inflammatory diseases. IL-33 acts as both a traditional cytokine and as a chromatin-associated nuclear factor in both innate and adaptive immunity. We recently showed that IL-33 in esophageal mucosa is upregulated in reflux esophagitis. However, IL-33 expression in patients with heartburn without mucosal injury and its relationship with intercellular space (ICS) have never been examined. We therefore examined the expression of cytokines and ICS in patients with heartburn. The expression of IL-33 in the middle and distal esophageal mucosa of patients with heartburn without mucosal break and control samples was examined using real-time RT-PCR and immunofluorescence. The mRNA expression of IL-6, IL-8, MCP-1, and RANTES, and ICS was also analyzed. IL-33 expression and the mean ICS were significantly increased in the mucosa of patients with heartburn compared to that of the control. IL-33 and ICS were not different between the patients who were taking a PPI and those who were not. The upregulated IL-33 expression in the heartburn group was located in the nuclei of the basal cell layer. Although IL-6, IL-8, MCP-1 and RANTES levels were not different between control and patients with heartburn samples, IL-33 mRNA levels were still significantly correlated with IL-6, IL-8, or MCP-1 mRNA levels. Nuclear IL-33 is upregulated in patients with heartburn. Upregulated IL-33 in heartburn patients is related to the symptoms.


Investigation of scavenging activities and distribution of paramagnetic species in Zanthoxylum limonella seeds.
We investigated the scavenging activities of methanol-extracted oil and the distribution of paramagnetic species in Zanthoxylum limonella (ZL) seeds using noninvasive 9 GHz electron paramagnetic resonance (EPR) imaging and continuous wave EPR. EPR detected three different stable paramagnetic species that were assigned to stable organic radicals, Mn2+, and other paramagnetic metal complexes. Two-dimensional EPR imaging showed that the stable paramagnetic species were located in the pigmented seed region with a strong intensity. Gas chromatography-mass spectrophotometric (GC-MS) analyses were then performed to identify the compound possibly related to the scavenging activity. The DPPH scavenging activities of ZL were slightly higher than those of Piper nigrum and Coriandrum sativum. Based on the results of EPR, GC-MS, and other methods, limonene in ZL is one of the major compounds that can be related to the scavenging activities.


Mobile phase effects on the retention on polar columns with special attention to the dual hydrophilic interaction-reversed-phase liquid chromatography mechanism, a review.
Hydrophilic interaction liquid chromatography on polar columns in aqueous-organic mobile phases has become increasingly popular for the separation of many biologically important compounds in chemical, environmental, food, toxicological, and other samples. In spite of many new applications appearing in literature, the retention mechanism is still controversial. This review addresses recent progress in understanding of the retention models in hydrophilic interaction liquid chromatography. The main attention is focused on the role of water, both adsorbed by the column and contained in the bulk mobile phase. Further, the theoretical retention models in the isocratic and gradient elution modes are discussed. The dual hydrophilic interaction liquid chromatography reversed-phase retention mechanism on polar columns is treated in detail, especially with respect to the practical use in one- and two-dimensional liquid chromatography separations.


A high-throughput screen for identifying transmembrane pore-forming peptides.
We have developed a visual microwell plate assay for rapid, high-throughput screening for membrane-disrupting molecules such as de novo designed pore formers, antibiotic peptides, bacterial toxins, and lipases. The detectability is based on the strong fluorescence emission of the lanthanide metal terbium(III) (Tb(3+)) when it interacts with the aromatic chelator dipicolinic acid (DPA). While Tb(3+) is not strongly fluorescent alone, the binary complex emits bright green fluorescence when irradiated with uv light. For the microwell plate assay, we prepared unilamellar phospholipid vesicles that had either Tb(3+) or DPA entrapped and the opposite molecule in the external solution. Disruption of the membranes allows the Tb(3+)/DPA complex to form, giving rise to a visibly fluorescent solution. In plates with 20-microl wells, the lower limit of visual detectability of the Tb(3+)/DPA complex in solution was about 2.5 microM. The lower limit of detectability using vesicles with entrapped Tb(3+) or DPA was about 50 microM phospholipid. We show that the membrane-disrupting effect of as little as 0.25 microM or 5 pmol of the pore-forming, antibiotic peptide alamethicin can be detected visually with this system. This sensitive, high-throughput assay is readily automatable and makes possible the visual screening of combinatorial peptide libraries for members that permeabilize lipid bilayer membranes.


A frameshift mutation of beta subunit of epithelial sodium channel in a case of isolated Liddle syndrome.
Liddle syndrome is an autosomal dominant form of salt-sensitive hypertension caused by mutations in the epithelial sodium channel expressed in the distal nephron playing an essential role in Na absorption. All reported mutations in Liddle syndrome are either missense mutations or frameshift mutations destroying the PY motif closer to the C-terminus of the beta or gamma subunits causing the situation that the epithelial sodium channels are not degraded and sodium is pooled and thus hypertension and hypokalemia are caused. We sequenced the C-terminus of the beta or gamma subunits of the epithelial sodium channel in a Japanese family of a patient clinically diagnosed as having Liddle syndrome. As a result, we found in the proband, a frameshift mutation of the beta subunit caused by a single cytosine insertion at the codon 595, introducing a new stop codon at 605 and deleting the last 34 amino acids from the normally encoded protein. This mutation is carried by neither parent (with paternity proven) and hence confirms this has occurred as a event within this family.


Molecular basis of neuroprotective activities of rasagiline and the anti-Alzheimer drug TV3326 [(N-propargyl-(3R)aminoindan-5-YL)-ethyl methyl carbamate].
Rasagiline (N-propargyl-1-(R)-aminoindan) is a selective, irreversible monoamine oxidase B (MAO B) inhibitor which has been developed as an anti-Parkinson drug. In controlled monotherapy and as adjunct to L-dopa it has shown anti-Parkinson activity. In cell culture (PC-12 and neuroblastoma SH-SY5Y cells) it exhibits neuroprotective and anti-apoptotic activity against several neurotoxins (SIN-1, MPTP, 6-hydroxydopamine and N-methyl-(R)-salsolinol) and ischemia. In vivo, it reduces the sequelae of traumatic brain injury in mice and speeds their recovery. The neuroprotective activity of rasagaline does not result from MAO B inhibition, since its S-enantiomer, TVP1022, which has 1000-fold weaker MAO inhibitory activity, exhibits similar neuroprotective properties. Introduction of a carbamate moiety into the rasagiline molecule to confer cholinesterase inhibitory activity for the treatment of Alzheimer's disease, resulted in compounds TV3326 [(N-Propargyl-(3R)Aminoindan-5-YL)-Ethyl Methyl Carbamate] and its S-enantiomer TV3279 [(N-Propargyl-(3S)Aminoindan-5-YL)-Ethyl Methyl Carbamate], which retain the neuroprotective activities of rasagiline and TVP1022. They also antagonize scopolamine-induced impairments in spatial memory. In addition, TV3326 exhibits brain-selective MAO A and B inhibitory activity after chronic administration and has antidepressant-like activity in the forced swim test. This is associated with an increase in brain levels of serotonin. The anti-apoptotic activity of these propargylamine-containing derivatives may be related to their ability to delay the opening of voltage-dependent anion channels (VDAC), which are part of the mitochondrial permeability transition pore. The propargylamine moiety is responsible for the increase in the mitochondrial family of Bcl-2 proteins, prevention in the fall in mitochondrial membrane potential, prevention of the activation of caspase 3, and of translocation of glyceraldehyde-3-phosphate dehydrogenase from the cytoplasm to the nucleus. The latter processes are closely associated with neurotoxin-induced apoptosis. Rasagiline interacts with and prevents the binding of PKI 1195 to the pro-apoptotic peripheral benzodiazepine receptor, which together with Bcl-2, hexokinase, porin, and adenine nucleotide translocator constitutes part of the VDAC. Furthermore, rasagiline, TV3326 and TV3279 are able to influence the processing of amyloid precursor protein by activation of alpha-secretase and increasing the release of soluble alpha APP in rat PC-12 and human neuroblastoma SH-SY5Y cells and in rat and mice cortex and hippocampus. This process has been shown to involve the upregulation of PKC and MAP kinase. It is quite likely that the induction of Bcl-2 and activation of PKC by rasagiline and TV3326 is closely linked to the anti-apoptotic action of these drugs and their ability to process APP by activation of alpha-secretase.


Lipid-lowering therapy for elderly patients at risk for coronary events and stroke.
Hyperlipidemia continues to be a major risk factor for cardiovascular diseases, particularly coronary heart disease, in the elderly population. Despite the fact that hyperlipidemia does not seem to be a major risk factor for stroke, therapy for hyperlipidemia, especially with statins, has clearly been demonstrated to reduce both coronary heart disease events and stroke, with the most convincing data being for the elderly population. Although we review some safety concerns with statin therapy applicable to the elderly, statins alone or with other proved therapies, including fibrates, niacin, and exercise training, have been demonstrated to reduce major cardiovascular diseases, including coronary heart disease and stroke in the elderly. In addition, this therapy can be safely administered to most elderly patients and seems to have either neutral or slightly beneficial effects on dementia. Therefore, aggressive lipid treatment, particularly with statins, is needed in the primary and secondary prevention of cardiovascular diseases in the elderly.


Laser resurfacing: the nurse's role.
CO2 laser resurfacing is an effective alternative to dermabrasion and chemical peels in the treatment of fine wrinkles, laugh lines, photodamaged, or acne scarred and pitted skin. Nurses play an important role in educating and treating patients, and in helping them comply with therapy.


Phase I/II study of paclitaxel + carboplatin for refractory or recurrent non-small cell lung cancer.
A gene-drug correlation analysis was previously performed in lung cancer cell lines using the NC160 program. On the basis of this work, a phase I/II pilot study of weekly paclitaxel and carboplatin (CBDCA) was subsequently planned for refractory or recurrent non-small cell lung cancer (NSCLC). Safety and antitumor effects were evaluable in all 30 patients registered for this study. Seven patients were stage IIIB and 23 were stage IV. At level 5 (paclitaxel 100 mg/m2 and CBDCA AUCS), toxicities were not dose-limiting factors, but three out of the initial six cases had infusion skips. Our recommended dose was paclitaxel 100 mg/m2 and CBDCA AUC5. The response rate was 50% (9/18)(95% CI: 27-73%) in step 5. The median survival time was 12 months. This combination showed a promising clinical activity with mild toxicity and should be selected for the investigational arm of phase III trials to be compared with either docetaxel or pemetrexed.


Selective changes in thalamic and cortical GABAA receptor subunits in a model of acquired absence epilepsy in the rat.
Neonatal treatment of Long-Evans Hooded rats with the cholesterol synthesis inhibitor (CSI) AY9944 has been shown to increase occurrence of spike-waves in EEG recordings and decrease benzodiazepines sensitivity of GABA(A) receptor-mediated responses in neurons from the thalamic reticular nuclei (nRt, Wu et al., 2004). The present experiments were designed to investigate the changes in the gamma2 and alpha1 subunits of the GABA(A) receptor in CSI model rats as possible mechanisms of these changes. Western blot, immunohistochemistry and real-time PCR techniques were performed to measure the levels of GABA(A) receptor gamma2 and alpha1 subunit transcripts and protein in the nRt and ventrobasal (VB) relay nuclei of thalamus and in somatosensory cortex. In CSI model animals, Western blot results showed that gamma2 subunit expression significantly decreased in thalamus (control, n=6: 0.17+/-0.02 relative to actin vs. CSI model, n=6: 0.11+/-0.01, P<0.05) but neither in cortex nor in hippocampal tissues. Conversely, alpha1 subunit expression decreased in CSI model somatosensory cortex, but not in nRt and VB. The present results demonstrate that neonatal block of cholesterol synthesis produces region- and subunit-specific decreases in GABA(A) receptor subunits in thalamus and cortex. Selective reductions in GABA(A) receptor subunits in thalamus may play a role in pathophysiology of absence epilepsy.


Sampling in the Great Lakes for pharmaceuticals, personal care products, and endocrine-disrupting substances using the passive polar organic chemical integrative sampler.
The passive polar organic chemical integrative sampler in the pharmaceutical configuration (i.e., pharmaceutical-POCIS) was calibrated for sampling at water temperatures of 5, 15 and 25 degrees C to determine the influence of temperature on chemical-specific sampling rates (R(S)), thus providing more robust estimates of the time-weighted average concentrations of pharmaceuticals and personal care products (PPCPs) and endocrine-disrupting substances (EDS) in surface water. The effect of water temperature and flow on the R(S) of these analytes was evaluated in the laboratory with a static system. The loss of the test compounds from water by uptake into POCIS was linear over an 8-d period, and these experimental data yielded R(S) values in the range of 0.07 to 2.46 L/d across the temperature range for the 30 compounds tested. Water temperature and flow influenced POCIS uptake rates, but these effects were relatively small, which is consistent with the theory for uptake into POCIS samplers. Therefore, under a narrow range of water temperatures and flows, it may not be necessary to adjust the R(S) for POCIS. Except for acidic drugs and sulfonamide antibiotics, R(S) values were positively correlated with octanol-water partition coefficients (log K(OW)) of the test compounds. A linear relationship was also observed between R(S) and chromatographic retention times on a C18 reversed-phase column. These observations may provide a rapid method for estimating the R(S) of additional chemicals in the POCIS. The application of the R(S) to POCIS deployed for one month in Lake Ontario, Canada, during the summers of 2006 and 2008 yielded estimates of PPCP and EDS concentrations that are consistent with conventional concentration measurements of these compounds in Lake Ontario surface water.


Structural determination and population transfer of 4-nitroanisole by broadband microwave spectroscopy and tailored microwave pulses.
The rotational spectrum of 4-nitroanisole was recorded via chirped-pulse Fourier transform microwave spectroscopy in the frequency range of 2-8 GHz. The spectra of the parent molecule and all of its 13C-, 15N-, and 18O-monosubstituted species in their natural abundance were assigned, and the molecular structure was determined using Kraitchman's equations as well as a least-square fitting approach. 4-nitroanisole has a large dipole moment of 6.15 D along the inertial a-axis and a smaller dipole moment of 0.78 D along the b-axis. The large dipole moment component makes this molecule a potential candidate for deceleration experiments using static electric fields or electromagnetic radiation. Using tailored microwave pulses, we investigate the possibility of transferring population between the rotational states of 4-nitroanisole. Such a technique could be applied to selectively increase the population for specific rotational states of interest, which are then accessible for further, more advanced experiments, such as deceleration.


Detection of antibodies to hepatitis C virus in U.S. blood donors.
An enzyme immunoassay (EIA) which utilizes a solid phase coated with a recombinant antigen (c100-3) derived from the hepatitis C virus (HCV) genome was evaluated for efficacy in the detection of antibodies to HCV (anti-HCV). The sensitivity of the antibody test was demonstrated by the detection of anti-HCV in a well-characterized panel of human specimens known to contain the infectious agent of non-A, non-B hepatitis. The specificity of the anti-HCV test was evaluated by testing 6,118 serum specimens from volunteer blood donors considered to be at low risk for exposure to HCV. The specificity of the anti-HCV EIA was demonstrated to be 99.56%, since 6,069 of 6,096 specimens from this low-risk group were nonreactive. A total of 49 (0.80%) of the 6,118 specimens were repeatedly reactive in the test, and 22 (46.81%) of the 47 specimens available for additional testing were confirmed as positive for antibodies to HCV c100-3. Among commercial plasma donors, 390 (10.49%) of 3,718 specimens were repeatedly reactive in the EIA. A total of 375 (97.40%) of the 385 specimens available for further testing were confirmed as positive. These limited data indicate that the prevalence of antibodies to HCV is 0.36% (22 confirmed positives among 6,118 specimens) among volunteer blood donors and 10.08% (375 confirmed positives among 3,718 specimens) among commercial plasma donors. The importance of confirmatory testing is discussed.


Computational limits to binary genes.
We analyse the trade-off between the speed with which a gene can propagate information, the noise of its output and its metabolic cost. Our main finding is that for any given level of metabolic cost there is an optimal trade-off between noise and processing speed. Any system with a non-vanishing leak expression rate is suboptimal, i.e. it will exhibit higher noise and/or slower speed than leak-free systems with the same metabolic cost. We also show that there is an optimal Hill coefficient h which minimizes noise and metabolic cost at fixed speeds, and an optimal threshold K which minimizes noise.


Porphyrin pi-cation and protein radicals in peroxidase catalysis and inhibition by anti-thyroid chemicals.
1. Thyroid peroxidase (TPO) catalyses the iodination and phenolic coupling reactions in the biosynthesis of thyroid hormones. 2. The two-electron oxidation of TPO by H2O2 produces an oxoferryl porphyrin pi-cation radical compound I that isomerizes spontaneously to a form of compound I that contains an oxoferryl haem and the second oxidizing equivalent as an amino acid radical. 3. The pi-cation radical compound I is the catalytic species that effects iodide ion oxidation and the protein radical compound I is most likely the catalytic species that catalyses coupling. 4. Methimazole, a therapeutic, anti-hyperthyroid drug, is a suicide substrate for TPO and effects irreversible inactivation by TPO-mediated S-oxygenation to a reactive sulphenic acid that binds covalently to the prosthetic haem. 5. Sulphamethazine and other arylamines containing electron-withdrawing substituents inhibit TPO compound I-mediated reactions by reversible, mixed-type inhibition. 6. Ethylenethiourea, a fungicide metabolite, blocks TPO-mediated iodination by reacting with the catalytic iodinating species as an alternate substrate. 7. Resorcinol and related dietary flavonoids are suicide substrates for TPO and act by covalent binding to amino acid residues, presumably those radical sites present in the compound I isomer. 8. Nitrosobenzene, a known radical-trapping agent, blocks TPO-mediated coupling but not iodination or phenolic oxidations presumably by interception of the 3,5-diiodotyrosyl radical species generated during the coupling reaction.


Identification of sequence selective receptors for peptides with a carboxylic acid terminus.
Split-and-mix libraries of resin-bound "tweezer" receptors have been prepared and screened to identify receptors for dye-labelled tripeptides. The receptors incorporate a diamidopyridine unit to serve as a specific recognition site for the CO2H group, leading to strong and selective receptors for peptide guests with a CO2H terminus. The role of the dye-label, attached to the peptide guest to allow visualisation of selective recognition events in the screening experiments, has also been examined and was found to have a significant influence on the binding selectivities.


The Effect of Obstetric Drills Training - Jamaica Core Obstetric Teaching and Training in Emergencies (JOTTIE) on Postpartum Haemorrhage at a Jamaican Teaching Hospital.
To evaluate whether the initiation of JOTTIE, a one day simulation training course focussed on the management of common obstetric emergencies, was associated with a reduction in the morbidity and mortality associated with postpartum haemorrhage (PPH) at the University Hospital of the West Indies (UHWI). We conducted a retrospective comparative study that evaluated the incidence of multiple outcomes related to maternal morbidity secondary to PPH, during the two year period immediately prior to the introduction of JOTTIE (pre course arm, N = 88) or the two year period, one year post introduction (post course arm, N = 103) for all women who had vaginal deliveries complicated by PPH at UHWI. A relationship was said to be statistically significant if p < 0.05. Additionally, the study examined risk factors in relation to severity of haemorrhage. Genital tract trauma represented the highest recorded cause of PPH (approximately 71%). The data revealed that patients in the pre training arm were similarly likely to have no adverse outcome in comparison to patients in the post training arm (p = 0.962). There was also no statistically significant relationship between the time period of patient exposure in relation to the JOTTIE course and severity of PPH (p > 0.05). Uterine fibroids and Crohn's disease were the only co-morbidities found to increase the likelihood of severe PPH, at 5.154 times (p = 0.019,OR = 5.154, CI = 1.314-20.212) and 17.848 times (p = 0.085,OR = 17.848,CI = 0.672-474.365), respectively. This study suggests that prior to the introduction of the JOTTIE the rate of maternal morbidity associated with PPH was relatively low at UHWI and there was no significant effect on its management or a significant reduction in maternal morbidity since introduction of the course. Future research on the morbidity related to the other obstetric emergencies addressed at JOTTIE is needed in order to assess the effect of the course as a whole.


2-Azetidinone cholesterol absorption inhibitors: structure-activity relationships on the heterocyclic nucleus.
A series of azetidinone cholesterol absorption inhibitors related to SCH 48461 ((-)-6) has been prepared, and compounds were evaluated for their ability to inhibit hepatic cholesteryl ester formation in a cholesterol-fed hamster model. Although originally designed as acyl CoA: cholesterol acyltransferase (ACAT) inhibitors, comparison of in vivo potency with in vitro activity in a microsomal ACAT assay indicates no correlation between activity in these two models. The molecular mechanism by which these compounds inhibit cholesterol absorption is unknown. Despite this limitation, examination of the in vivo activity of a range of compounds has revealed clear structure-activity relationships consistent with a well-defined molecular target. The details of these structure-activity relationships and their implications on the nature of the putative pharmacophore are discussed.


Diagnostic accuracy of serum (1,3)-beta-d-glucan for neonatal invasive candidiasis: systematic review and meta-analysis.
Neonatal invasive candidiasis (NIC) is a leading cause of infection-related morbidity and mortality in preterm neonates. Several studies have shown that (1,3)-Beta-d-glucan (BDG) was accurate in detecting invasive fungal infection in adults, but studies in neonates are scarce. The aim was to obtain summary estimates of the accuracy of BDG detection in serum for the diagnosis of NIC. We searched Medline, Embase, Clinicaltrials.gov, and Google Scholar (inception to July 2019). We checked the reference lists of included studies, clinical guidelines, and review articles. We included studies that assessed the accuracy of BDG against a reference standard that defined groups of patients with ordinal levels of NIC probability (e.g. proven, probable, possible) and included fungal blood culture. Participants were neonates suspected of having NIC. The intervention was BDG measurement in serum (Fungitell® assay). We assessed risk of bias and applicability using QUADAS-2. We used bivariate meta-analysis to produce summary estimates of diagnostic accuracy at prespecified positivity thresholds of 80 and 120 pg/mL. This study was registered with PROSPERO (CRD42018089545). We included eight studies (465 participants). Of these, two were judged at low overall risk of bias. There was substantial variability across studies in the reference standards used. At a positivity threshold of 80 pg/mL, summary estimates of sensitivity and specificity of BDG were 89% (95% CI: 80-94%) and 60% (53-66%), respectively; summary sensitivity for detecting proven cases of NIC was 99% (93-100%). At a positivity threshold of 120 pg/mL, summary estimates of sensitivity and specificity were 81% (71-88%) and 80% (67-88%), respectively. Because of high sensitivity, BDG seems promising to rule-out NIC. It might be too early to recommend its use because of the scarcity of reliable clinical data, heterogeneity in case definitions, and unstable accuracy estimates.


MR-guided radiotherapy for prostate cancer: state of the art and future perspectives.
Advances in radiotherapy technology have increased precision of treatment delivery and in some tumour types, improved cure rates and decreased side effects. A new generation of radiotherapy machines, hybrids of an MRI scanner and a linear accelerator, has the potential to further transform the practice of radiation therapy in some cancers. Facilitating superior image quality and the ability to change the dose distribution online on a daily basis (termed "daily adaptive replanning"), MRI-guided radiotherapy machines allow for new possibilities including increasing dose, for hard to treat cancers, and more selective sparing of healthy tissues, where toxicity reduction is the key priority.These machines have already been used to treat most types of cancer, although experience is still in its infancy. This review summarises the potential and current evidence for MRI-guided radiotherapy, with a predominant focus on prostate cancer. Current advantages and disadvantages are discussed including a realistic appraisal of the likely potential to improve patient outcomes. In addition, horizon scanning for near-term possibilities for research and development will hopefully delineate the potential role for this technology over the next decade.


Efficacy of Hydroxychloroquine for Improving Pregnancy Outcomes in a Female with Systemic Lupus Erythematosus and Antiphospholipid Syndrome.
The use of heparin and low-dose aspirin is the current conventional treatment for pregnant females with antiphospholipid syndrome (APS). However, there is no additional treatment recommended for cases where the standard treatment cannot prevent obstetric complications such as fetal loss and placental insufficiency. Recently, the addition of a novel antimalarial, hydroxychloroquine (HCQ), to the conventional treatment has shown the potential to prevent obstetric complications. Herein, we report a case in which the addition of HCQ improved adverse pregnancy outcomes in a pregnant female with systemic lupus erythematosus and aspirin-heparin-resistant APS.


[Clinical and experimental research on a massage cream in physiotherapeutic practice].
New Bulgarian preparations from mioton series (A, B and C) have of late attracted the attention of clinicians. Of a special interest for physiotherapists is mioton B. Broad-scale clinical and experimental trials (41 patients and 75 animals) demonstrated high clinical efficacy of the cream mioton B (Extr. caps. spis. 1.01% 01. bergamotae u ol. lavandulae) induced by ultraphonophoresis. No side effects were registered.


[Short bowel syndrome and limits of small intestinal resections].
Short bowel syndrome (SBS) is a malabsorption syndrome resulting from anatomical or functional loss of a significantly long small intestinal segment. A loss over 80% of the small intestinal length is associated with increased urgency for supportive parenteral nutrition and results in reduced overall survival of the patients. The ileocaecal valve (valvula Bauhini) loss results in bacterial contamination of the small intestine, affecting tolerability of the oral, ev. enteral nutrition. The authors present a case review of a 27-year-old patient with repetitive small intestinal resections. The last procedure included the Bauhini valve and, finally, the patient has only 70 cm of the jejunum preserved.


Content of adenosine phosphates and adenylate energy charge in germinating ponderosa pine seeds.
An average of 540 picomoles of total adenosine phosphates was found in the embryo of mature seeds of ponderosa pine (Pinus ponderosa Laws.) and 1140 picomoles in the gametophyte. Adenylate energy charges were 0.44 and 0.26, respectively. After stratification, total adenosine phosphates increased 7-fold and 6-fold in embryo and gametophyte, respectively, and energy charges rose to 0.85 and 0.75. During germination, total adenosine phosphates increased to a 20-fold peak on the 9th day in gametophytic tissue, parallel with the peak of reserve regradation and organellar synthesis, and then decreased. In embryo and seedling, total adenosine phosphates elevated 80-fold with two distinct oscillating increases of AMP and ADP. The oscillating increases occurred before the emergence of radicle and cotyledons during which the highest mitotic index prevailed in all tissues. Energy charges fluctuated between 0.65 at the rapid cell dividing stage to 0.85 at the fully differentiated stage of the seedling, while energy charges remained around 0.75 in the gametophyte. These data indicated that the content of adenosine phosphates of germinating seeds reflects growth, organogenesis, and morphogenesis, and that a compartmentalized energy metabolism must exist in dividing and growing plant cells.


Molecular structure of the Menkes disease gene (ATP7A).
We report a detailed molecular analysis of the genomic structure of the Menkes disease gene (MNK; ATP7A). There are 23 exons in ATP7A covering a genomic region of approximately 140 kb. The size of the individual coding exons varies between 77 and 726 bp, and introns vary in size between 196 bp and approximately 60 kb. All of the splice sites obey the consensus GT-AG rule except the splice donor of intron 9, which is GC instead of GT. The exon following this rare splice donor variant is alternatively spliced. A PGAM pseudogene and two highly polymorphic CA repeats map to introns within the gene. The structure is very similar to that of the closely related Wilson disease gene (WND; ATP7B). From exon 5 (exon 3 in ATP7B) to the end, all of the splice sites occur at exactly the same nucleotide positions as in the WND gene, except for the boundary between exons 17 and 18 (exons 15 and 16 in ATP7B) and a single codon difference at the boundary between exons 4 and 5 of the MNK gene (exons 2 and 3 in ATP7B). In contrast to the WND gene, in which the first four of six metal binding domains are contained in 1 exon, metal binding domains 1 to 4 are divided over 3 exons. The striking similarity of the MNK and WND genes at the genomic level is consistent with their relatively recent divergence from a common ancestral gene.


Purification of fibroblast-derived celiac disease autoantigen molecules.
We have recently purified autoantigen polypeptides reacting with celiac disease patient sera IgA from the extracellular noncollagenous matrix compartment of fetal lung tissue. These molecules trigger the production of different tissue antibodies, the so-called antireticulin and antiendomysium antibodies in celiac disease. In the present report, we show that fibroblasts synthesize and secrete celiac disease autoantigen molecules. The secretion product, reactive with IgA from celiac disease patients, is a large-molecular-weight protein aggregate. When the protein complex was treated with 4 M guanidinium hydrochloride and 0.1% SDS, 11 monocomponent polypeptides could be detected by PAGE. Of these, four single polypeptides with molecular weights of 17,000-39,500 and isoelectric points of 5.0-7.0 were observed to react with IgA separated from sera of children with celiac disease. The polypeptide molecules produced by fibroblasts in vitro bound to antireticulin and antiendomysium antibodies but not to antigliadin antibodies. The present observations show that tissue antibodies found to be specifically associated with celiac disease are generated against a synthesis product of fibroblasts, a cell-type known to synthesize a number of biologically active polypeptides. The fibroblast-derived extracellular matrix proteins and the formed autoantibodies may be important in the pathogenesis of gluten-sensitive enteropathy.


[Spectral analysis of cyanobacteria chlorophyll in polluted water].
The polluted water with abundant nourishment cause phytoplankton, such as cyanobacteria, to grow rapidly, which brings great harm to environment. In the present paper, the absorption spectrum of cyanobacteria was measured and analyzed in order to estimate the content of the chlorophyll accurately. The same amount of cyanobacteria was separately cultured in pure water and lake water for different time. The chlorophyll was extracted from the cyanobacteria for the same time by 95% of ethanol. Then the ethanol extract was tested by ultraviolet visible spectrometry. The results show that the absorption spectrum of the chlorophyll has three absorption peaks at 279.5, 436.0 and 664.5 nm respectively. However, the absorbency at 279.5 nm cannot reflect the content of the chlorophyll. The absorbencies at 436.0 and 664.5 nm have linear relationship with the content of chlorophyll. Moreover, the dispersion between the absorbency at 436.0 nm and the absorbency at 664. 5 nm can reflect the content of chlorophyll more accurately. The research provides the experimental and theoretical basis for the highly accurate detection of the water quality.


[Commercial capture with long line in the exclusive economic zone in La Guajira, Colombian Caribbean Sea].
Pelagic fish were collected with long line in the 20-22 degrees C isotherms from 1986 to 1988 off Guajira, Colombia. Thirteen species of pelagic fish were found including four new records: Lampris guttatus, Lepidocybium flavobrunneum, Tetrapturus pfluegeri, Eumegistius brevorti. The occurrence of the orca (Orcinus orca Linnaeus) is confirmed in the Colombian Caribbean waters.


Antibiotic resistance in the intensive care unit.
The increase in antibiotic resistance over the past 10 years can be traced to several factors. This includes exogenous transmission of bacteria, usually by hospital personnel. The use of potent antibiotics also can select for resistant bacteria initially present in low quantities. Strategies to reduce antibiotic resistance can be tailored to specific outbreaks in a given ICU. General strategies for reducing antibiotic resistance, on the other hand, include varying the agents used in the ICU over time. Reduction of the duration of therapy may prove to be another method of reducing antibiotic resistance.


Cell surface expression of the HIV-1 envelope glycoproteins is directed from intracellular CTLA-4-containing regulated secretory granules.
The envelope glycoprotein (Env) of HIV-1 is incorporated into virions that bud from the cell surface of infected T cells. With immunofluorescence microscopy and subcellular membrane fractionation techniques, the intracellular fate of Env in the secretory pathway of HIV-1-infected T cells was evaluated. Rather than trafficking constitutively from the Golgi to the cell surface, Env is directed to intracellular CTLA-4-containing granules, whose recruitment to the cell surface is regulated. The use of the regulated pathway for intracellular Env storage before virion assembly holds implications for the staging of Env exposure at the cell surface of infected cells and of coordinating HIV virion assembly.


Determination of Phenolic Compounds and Bioactive Potential of Plum (Prunus salicina) Peel Extract Obtained by Ultrasound-Assisted Extraction.
Ultrasound-assisted extraction (UAE) of bioactive compounds from black plum peels was optimized by response surface methodology (RSM). Temperature (35-55°C), time (15-45 min), and ethanol concentration (50-90%) were selected as independent extraction parameters, whereas total anthocyanin content (TAC), total phenolic content (TPC), and 2,2-diphenyl-1-picrylhydrazyl (DPPH) inhibition were kept as response variables. The optimized extraction conditions were determined by RSM as extraction at 49°C for 37 min with 68% ethanol, which corresponded to TAC, TPC, and DPPH inhibition values of 5.42 ± 0.61 mg/g, 6.217 ± 0.76 mg GAE/g, and 89 ± 2.13%, respectively. Fourier-transform infrared spectrometer (FTIR), high-performance liquid chromatography (HPLC), and gas chromatography mass spectrometer (GCMS) were used for chemical characterization of optimized plum peel extract (PPE). Optimized PPE was further evaluated for antibacterial, antioxidant, anticancer, and food preservation potential. PPE showed 92.31% DPPH inhibition with IC50 value of 360.6 μg/ml. Optimized PPE extract was effective in the inhibition of cancer cell proliferation and migration, and IC50 values were in the range 1.85-3.96 mg/ml for different human cancer cell lines. Major phenolics identified in PPE were ferulic acid (47.87 mg/kg), sinapic acid (9.15 mg/kg), quercetin (7.44 mg/kg), gallic acid (3.24 mg/kg), m-coumaric acid (2.59 mg/kg), and vanillic acid (1.12 mg/kg). PPE extract inhibited the growth of various foodborne bacterial pathogens and increased the shelf life of PPE coated fresh grapes. PPE due to antibacterial, anticancer, antioxidant, and food preservation potential can be used in developing functional food and pharmaceutical products.


Directed biopsy during contrast-enhanced sonography of the prostate.
We evaluated the value of directed biopsy for the detection of prostate cancer during contrast-enhanced endorectal sonography. Forty patients were evaluated with harmonic gray-scale sonography. The evaluation was performed before administration of contrast agent, during continuous IV infusion of perflutren lipid microspheres, and again during bolus administration of the microspheres. Sextant biopsy sites were scored prospectively on a six-point scale for suggestion of malignancy at baseline during contrast infusion and after bolus administration. An additional directed core was obtained at 20 of the sextant biopsy sites based on contrast-enhanced imaging. Cancer was identified in 30 biopsy sites in 16 of the patients (40%). A suspicious site identified during contrast-enhanced transrectal sonography was 3.5 times more likely to have positive biopsy findings at than an adjacent site that was not suggestive of malignancy (p < 0.025). When a suspicious site was evaluated with an additional biopsy core, the site was five times more likely to have a biopsy with positive findings than a standard sextant site (p < 0.01). We found no difference in diagnostic accuracy between continuous infusion of contrast material and bolus administration. Contrast-enhanced transrectal sonography improves the sonographic detection of malignant foci in the prostate. The performance of multiple biopsies of suspicious enhancing foci significantly improves the detection of cancer. There is no advantage to additional examination of the gland after bolus administration of contrast material.


Hematologic parameters in raptor species in a rehabilitation setting before release.
To be considered for release, raptors undergoing rehabilitation must have recovered from their initial injury in addition to being clinically healthy. For that purpose, a good understanding of reference hematologic values is important in determining release criteria for raptors in a rehabilitation setting. In this study, retrospective data were tabulated from clinically normal birds within 10 days of release from a rehabilitation facility. Hematologic values were compiled from 71 red-tailed hawks (Buteo jamaicensis), 54 Eastern screech owls (Megascops asio), 31 Cooper's hawks (Accipiter cooperii), 30 great-horned owls (Bubo virginianus), 28 barred owls (Strix varia), 16 bald eagles (Haliaeetus leucocephalus), and 12 broad-winged hawks (Buteo platypterus). Parameters collected included a white blood cell count and differential, hematocrit, and total protein concentration. Comparisons were made among species and among previously published reports of reference hematologic values in free-ranging birds or permanently captive birds. This is the first published report of reference values for Eastern screech owls, barred owls, and broad-winged hawks; and the first prerelease reference values for all species undergoing rehabilitation. These data can be used as a reference when developing release criteria for rehabilitated raptors.


First use of a compound-specific stable isotope (CSSI) technique to trace sediment transport in upland forest catchments of Chile.
Land degradation is a problem affecting the sustainability of commercial forest plantations. The identification of critical areas prone to erosion can assist this activity to better target soil conservation efforts. Here we present the first use of the carbon-13 signatures of fatty acids (C14 to C24) in soil samples for spatial and temporal tracing of sediment transport in river bodies of upland commercial forest catchments in Chile. This compound-specific stable isotope (CSSI) technique was tested as a fingerprinting approach to determine the degree of soil erosion in pre-harvested forest catchments with surface areas ranging from 12 to 40ha. For soil apportionment a mixing model based on a Bayesian inference framework was used (CSSIAR v.2.0). Approximately four potential sediment sources were used for the calculations of all of the selected catchments. Unpaved forestry roads were shown to be the main source of sediment deposited at the outlet of the catchments (30-75%). Furthermore, sampling along the stream channel demonstrated that sediments were mainly comprised of sediment coming from the unpaved roads in the upper part of the catchments (74-98%). From this it was possible to identify the location and type of primary land use contributing to the sediment delivered at the outlet of the catchments. The derived information will allow management to focus efforts to control or mitigate soil erosion by improving the runoff features of the forest roads. The use of this CSSI technique has a high potential to help forestry managers and decision makers to evaluate and mitigate sources of soil erosion in upland forest catchments. It is important to highlight that this technique can also be a good complement to other soil erosion assessment and geological fingerprinting techniques, especially when attempting to quantify (sediment loads) and differentiate which type of land use most contributes to sediment accumulation.


Isothermal titration calorimetry studies of neutral salt effects on the thermodynamics of micelle formation.
Isothermal titration calorimetry, ITC, was used to determine the enthalpy and heat capacity changes that accompany micelle formation of decyldimethylphosphine oxide, APO10, from 15-79 degrees C in the presence of representative neutral salts from the Hofmeister series. The solutions investigated were water, 0.2, 0.5, and 1.0 NaCl, 0.5 M NaF, KCl, KI, guanidinium chloride (GuHCl) and mannitol, and 0.333 M Na2SO4. The heat capacity change at 25 degrees C (but not the cmc) and the parameter that describes the temperature dependence of the heat capacity change, B (cal/(mol K2)), appear to be correlated. Calculated values of the ion effects on micelle formation from a recent salt ion partitioning model (SPM) of Pegram and Record [J. Phys. Chem. B 2007, 111, 5411-5417] were quantitatively related to the experimental value of the solute free energy increment (SFEI). Use of this model requires a calculation of the solvent accessible area (ASA), which yields values for the extent of hydration of the micelle interior. An alternate method to determine the ASA based on the heat capacity change for micelle formation at 25 degrees C of APO8-12 yielded values for the number of buried carbon atoms (5-12) versus previous estimates (4-8) from analysis of the B parameter.


Intoxicated behavioral disinhibition and the heart rate response to alcohol.
This study examined the association between the heart rate (HR) response to alcohol intoxication, which is thought to reflect sensitivity to alcohol-induced reward and alcohol-induced behavioral disinhibition. High- and low-HR responders to alcohol participated in a go/no-go task, under sober and intoxicated conditions. Errors of commission on this task have previously been related to behavioral disinhibition. High-HR responders made more intoxicated commission errors as compared with low-HR responders. High-HR responders also reported increased alcohol consumption, and controlling for the latter did not alter the significant association between high-HR responders and increased intoxicated errors of commission. These results are consistent with previous findings of an increased risk for addictive and disinhibited behavioral propensities in individuals with a high-HR response to alcohol intoxication.


Outbreak of Neisseria meningitidis C in workers at a large food-processing plant in Brazil: challenges of controlling disease spread to the larger community.
SUMMARYAn outbreak of meningococcal disease (MD) with severe morbidity and mortality was investigated in midwestern Brazil in order to identify control measures. A MD case was defined as isolation of Neisseria meningitidis, or detection of polysaccharide antigen in a sterile site, or presence of clinical purpura fulminans, or an epidemiological link with a laboratory-confirmed case-patient, between June and August 2008. In 8 out of 16 MD cases studied, serogroup C ST103 complex was identified. Five (31%) cases had neurological findings and five (31%) died. The attack rate was 12 cases/100 000 town residents and 60 cases/100 000 employees in a large local food-processing plant. We conducted a matched case-control study of eight primary laboratory-confirmed cases (1:4). Factors associated with illness in single variable analysis were work at the processing plant [matched odds ratio (mOR) 22, 95% confidence interval (CI) 2·3-207·7, P<0·01], and residing <1 year in Rio Verde (mOR 7, 95% CI 1·11-43·9, P<0·02). Mass vaccination (>10 000 plant employees) stopped propagation in the plant, but not in the larger community.


Effect of saline 0.9% or Plasma-Lyte 148 therapy on feeding intolerance in patients receiving nasogastric enteral nutrition.
To compare the effect of Plasma-Lyte (PL)-148 and saline 0.9% (saline) on gastrointestinal (GI) feeding intolerance in mechanically ventilated patients receiving nasogastric (NG) feeding in an intensive care unit. A single-centre pilot study, nested within a multicentre, double-blind, cluster-randomised, double-crossover trial, performed in a mixed medical and surgical ICU. All adult patients who required crystalloid fluid therapy as part of the 0.9% Saline versus Plasma-Lyte 148 for Intensive Care Unit Fluid Therapy (SPLIT) trial, were expected to need mechanical ventilation for more than 48 hours and were receiving enteral nutrition exclusively by NG tube were eligible. We enrolled 69 patients and assigned 35 to PL-148 and 34 to saline. We randomly allocated saline or PL-148 for four alternating 7-week blocks, with staff blinded to the solution. The primary outcome was the proportion of patients with GI feeding intolerance, defined as high gastric residual volume (GRV), diarrhoea or vomiting while receiving NG feeding in the ICU. The proportions of patients with each of high GRV, diarrhoea and vomiting were secondary outcomes. In the PL-148 group, 21 of 35 patients (60.0%) developed GI feeding intolerance, compared with 22 of 34 patients (64.7%) in the saline group (odds ratio [OR], 0.82; 95% CI, 0.31-2.17; P = 0.69). A high GRV was seen in four of 35 patients (11.4%) in the PL-148 group, and in 11 of 34 patients (32.4%) in the saline group (OR, 0.27; 95% CI, 0.08-0.96; P = 0.04). Among mechanically ventilated patients receiving NG feeding, the use of PL-148, compared with saline, did not reduce the proportion of patients developing GI feeding intolerance, but was associated with a decreased incidence of high GRV.


Wnt-1 regulates free pools of catenins and stabilizes APC-catenin complexes.
The Wnt-1 proto-oncogene induces the accumulation of beta-catenin and plakoglobin, two related proteins that associate with and functionally modulate the cadherin cell adhesion proteins. Here we have investigated the effects of Wnt-1 expression on the tumor suppressor protein APC, which also associates with catenins. Expression of Wnt-1 in two different cell lines greatly increased the stability of APC-catenin complexes. The steady-state levels of both catenins and APC were elevated by Wnt-1, and the half-lives of both beta-catenin and plakoglobin associated with APC were also markedly increased. The stabilization of catenins by Wnt-1 was primarily the result of a selective increase in the amount of uncomplexed, monomeric beta-catenin and plakoglobin, detected both by affinity precipitation and size-exclusion chromatography of cell extracts. Exogenous expression of beta-catenin was possible in cells already responding to Wnt-1 but not in the parental cells, suggesting that Wnt-1 inhibits an essential regulatory mechanism for beta-catenin turnover. APC has the capacity to oppose this Wnt-1 effect in experiments in which overexpression of the central region of APC significantly reduced the size of the monomeric pool of beta-catenin induced by Wnt-1. Thus, the Wnt-1 signal transduction pathway leads to the accumulation of monomeric catenins and stabilization of catenin complex formation with both APC and cadherins.


Differentiation of human macrophages with anaphylatoxin C3a impairs alternative M2 polarization and decreases lipopolysaccharide-induced cytokine secretion.
Anaphylatoxin C3a is a small signaling polypeptide that is generated during complement activation. C3a is involved in the regulation of various innate and adaptive immune system processes; however, the role of C3a in macrophage differentiation and polarization is poorly elucidated. Here we showed that C3a impairs alternative M2 polarization of human macrophages and suppressed CD206, IL1Ra and CCL22 expression. C3a leads to a decrease of nuclear receptor PPARγ expression via the ERK1/2 signaling pathway, resulting in repressed PPARγ-dependent activation of CD36, FABP4 and LXRα genes and blunted response to an LXR ligand TO901317. Using small interfering RNA and agonist/antagonist approaches we showed that C3a decreases CD206, IL1Ra and CCL22 transcription at least partly in a PPARγ-dependent manner in M2 macrophages. Moreover, C3a impairs efferocytosis by M2 macrophages and inhibits their migratory activity. By contrast, macrophages treated with C3a during differentiation show blunted response to lipopolysaccharide stimulation owing to downregulation of TLR4 and lipid raft content. At the same time, differentiation of macrophages with C3a does not change M1 polarization in interferon gamma (IFNγ) and IFNγ + lipopolysaccharide-treated macrophages. These data provide a novel role of complement system and C3a in the regulation of M2 macrophage polarizations and suggest crosstalk between C3a, TLR4, PPARγ and LXR signaling pathways.


Pancreatic Cancer Incidence, Mortality, and Survival in Puerto Rico, 2001-2015.
To perform an epidemiologic profile of pancreatic cancer (PC) in Puerto Rico (PR) with data gathered from 2001 to 2015. Using data from the PR Central Cancer Registry we estimated incidence and mortality rates and trends of PC in PR, and performed survival analyses. We also compared the age-standardized incidence and mortality rates of PC in people in PR with those of Hispanics, non-Hispanic whites, and non Hispanic blacks in the United States (US). From 2011 to 2015, 7.8 per 100,000 persons were diagnosed with PC in PR; higher rates were observed in men than in women (9.2 vs. 6.7 per 100,000, respectively) and in persons 65 years old and older (42.7 per 100,000 persons). For the same period, 6.7 per 100,000 persons died from PC; men and persons 65 years and older had higher mortality rates. Incidence and mortality trends of PC in PR increased from 2001-2015 (annual percent change [APC] = 3.8% and 1.9%, respectively (p<0.05). Lower risk of being diagnosed with and dying from PC was seen in PR than in members of several racial/ethnic groups in the US. The median survival time for PC cases diagnosed in PR during the period of 2008 to 2012 was 5.3 months. We observed increasing mortality rates and low survival in PC patients in PR. Research on access and response to treatment is needed to elucidate the reasons for the observed results and have a positive impact on PC burden and survival.


Investigation of photoexcited states in porcine eumelanin through their transient radical products.
Time-resolved electron paramagnetic resonance was used to monitor the photochemistry of radical pairs from melanin in porcine retinal pigment epithelial cells on the sub-microsecond time scale. Two distinct signals were found: one of enhanced absorption/emission at early times and one mostly emissive at later times. The emissive character of the longer lived feature suggests participation of an excited triplet precursor, something not generally thought to exist in melanins. The radicals in the early time signal were separated by about 21 A and those in the later time signal were separated by about 22-24 A.


Anti-inflammatory activity of N-(3-florophenyl)ethylcaffeamide in mice.
In this study, we evaluated the anti-inflammatory activity of one synthetic product, N-(3-Florophenyl)ethylcaffeamide (abbrev. FECA), by using animal model of λ-carrageenan-induced paw edema in mice. The anti-inflammatory mechanism of FECA was determined by measuring the levels of cyclooxygenase-2 (COX-2), nitric oxide (NO), tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), and malondialdehyde (MDA) in the edema paw tissue, and the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GRd) in the liver. The results showed that FECA reduced the paw edema at three, four and five hours after λ-carrageenan administration. The levels of COX-2, NO, TNF-α, and MDA in the λ-carrageenan-induced edema paws were reduced and the activities of SOD, GPx, and GRd in liver tissues were raised by FECA. These results suggested that FECA possessed anti-inflammatory activities and the anti-inflammatory mechanisms might be related to the decrease of the levels of COX-2, NO, and TNF-α in inflamed tissues and the increase in the MDA level by increasing the activities of SOD, GPx, and GRd.


A strategy for generating and testing models of migration and urban growth.
"In this paper, it is argued that to identify the appropriate conditions under which the traditional gravity-type migration model should be tested, it is necessary to consider the wider demographic-economic framework in which such models play an essential part. The traditional model and attempts to make it more realistic in an ad hoc way are first sketched, and then the model is embedded in a dynamic framework based on nonlinear differential equations of the logistic kind describing the growth of population and employment. The role of the gravity model in coupling these equations is then developed." A theoretical analysis of this framework is then presented using simulation. "The simplest possible two-region case involving urban and rural regions is developed and after preliminary simulations, a more realistic version involving urban core, suburb and rural hinterland is proposed. A number of variants of this model are tested using simulation and it is concluded that in devising an appropriate test for this type of migration model, attention should be switched from spatial to temporal variation in migration using highly polarized spatial situations such as city regions." (summary in FRE, GER)


Recovery of early postoperative muscle strength after deep neuromuscular block by means of ultrasonography with comparison of neostigmine versus sugammadex as reversal drugs: study protocol for a randomised controlled trial.
Despite the use of quantitative neuromuscular monitoring together with the administration of reversal drugs (neostigmine or sugammadex), the incidence of residual neuromuscular blockade defined as a train-of-four ratio (TOFr) <0.9 remains high. Even TOFr >0.9 cannot ensure adequate recovery of neuromuscular function when T1 height is not recovered completely. Thus, a mathematical correction of TOFr needs to be applied because the return of a normal TOFr can precede the return of a normal T1 twitch height. On the other hand, different muscles have different sensitivities to neuromuscular blockade agents; thus, complete recovery of one specific muscle group does not represent complete recovery of all other muscles. Therefore, our study aims to assess the muscle strength recovery of respiratory-related muscle groups by ultrasound and evaluate global strength using handgrip dynamometry in the early postoperative period when TOFr=0.9 and corrected TOFr (cTOFr)=0.9 with comparison of neostigmine versus sugammadex as reversal drugs. This study will be a prospective, single-blinded, randomised controlled trial involving 60 patients with American Society of Anesthesiologists physical status I-II and aged between 18 and 65 years, who will undergo microlaryngeal surgery. We will assess geniohyoid muscle, parasternal intercostal muscle, diaphragm, abdominal wall muscle and handgrip strength at four time points: before anaesthesia, TOFr=0.9, cTOFr=0.9 and 30 min after admission to the post anaesthesia care unit. Our primary objective will be to compare the effects of neostigmine and sugammadex on the recovery of muscle strength of different muscle groups in the early postoperative period when TOFr=0.9 and cTOFr=0.9. The secondary objective will be to observe the difference of muscle strength between the time points of TOFr=0.9 and cTOFr=0.9 to find out the clinical significance of cTOFr >0.9. The protocol was reviewed and approved by the Ethics Committee of The First Affiliated Hospital, Sun Yat-sen University. The findings will be disseminated to the public through peer-reviewed scientific journals. ChiCTR2000033832.


Analysis of allelic loss as an adjuvant tool in evaluation of malignancy in uterine smooth muscle tumors.
Uterine smooth muscle tumors of uncertain malignant potential (STUMPs) are difficult both from the diagnostic and patient management standpoint because they cannot be classified as benign or malignant by conventional histologic criteria. This study's aim was to determine the diagnostic utility of allelic imbalance (AI) analysis in uterine smooth muscle tumors. Using microdissection and genotyping, we tested 5 leiomyomas, 6 STUMPs, and 10 leiomyosarcomas with follow-up for AI across a panel of seven tumor suppressor genes (p16, p21, p53, VHL, XRCC3, RB, and NM-23). None of the 6 patients with STUMP experienced recurrent disease, whereas 8 of the 10 patients diagnosed with leiomyosarcoma died of disease at follow-up. The mean frequency of allelic loss (FAL) for leiomyomas (18%) was not significantly different from that of STUMPs (21%) (P = 1), whereas leiomyosarcomas displayed a significantly higher FAL (52%) than both leiomyomas (P = 0.001) and STUMPs (P = 0.002). Loss of NM-23, a reported tumor metastasis suppressor gene, was found only in leiomyosarcomas (5 of 9, or 56%), and 4 of 5 (80%) of these were the only cases that demonstrated distant metastases (P = 0.04). Additionally, an FAL of >50% correlated with both NM-23 loss (P = 0.008) and distant metastatic disease (P = 0.04). In conclusion, leiomyomas and STUMPs displayed similar mean FALs and all were clinically benign, whereas uterine leiomyosarcomas had significantly higher frequencies of allelic loss than both leiomyomas and STUMPs. Molecular profiling may thus provide a valuable tool in assessment of malignancy in uterine smooth muscle tumors. Additionally, NM-23 is a promising candidate gene for determination of metastatic potential in these tumors.


Association of aflatoxin B1 levels with mean CD4 cell count and uptake of ART among HIV infected patients: A prospective study.
Aflatoxin suppresses cellular immunity and accentuates HIV-associated changes in T- cell phenotypes and B- cells. This prospective study was conducted to examine the association of aflatoxin levels with CD4 T-cell count and antiretroviral therapy uptake over time. Sociodemographic and food data were collected from antiretroviral therapy naïve HIV-infected patients. CD4+ counts were collected from participants' medical records. Plasma samples were tested for aflatoxin B1 albumin adducts, hepatitis B surface antigen, and HIV viral load. Participants were separated into high and low aflatoxin groups based on the median aflatoxin B1 albumin adduct level of 10.4 pg/ml for data analysis. Participants with high aflatoxin B1 albumin adduct levels had lower mean CD4 at baseline and at each follow-up period. Adjusted multivariable logistic regression analysis showed that higher baseline aflatoxin B1 adduct levels were associated with statistically significant lower CD4 counts (est = -66.5, p = 0.043). Not starting ART and low/middle socioeconomic status were associated with higher CD4 counts (est = 152.2, p<0.001) and (est = 86.3, p = 0.027), respectively. Consistent correlations of higher aflatoxin B1 adduct levels with lower CD4 over time indicate that there is an independent early and prolonged effect of aflatoxin on CD4 even with the initiation of antiretroviral therapy. The prospective study design, evaluation of baseline and follow-up measures, extensive control for potential confounders, and utilization of objective measures of aflatoxin exposure and CD4 count provide compelling evidence for a strong epidemiologic association that deserves careful attention in HIV care and treatment programs.


Long-term treatment with GM-CSF in patients with chronic lymphocytic leukemia and recurrent neutropenic infections.
In this prospective study we evaluated the multiple effects of long-term GM-CSF therapy on blood counts, granulocyte functions and disease progression in patients with chronic lymphocytic leukemia (CLL) with chronic neutropenia and recurrent bacterial infections. The treatment duration varied from 2 to 12 weeks. The neutrophil count was raised in all patients, by the median of 6.6-fold. The neutrophil level of 1.0 x 10(9)/l was usually reached after two weeks. The initial dose of GM-CSF was 5 microg/kg/day, and 1-7 microg/kg/day was required to maintain the neutrophil level above 1.0 x 10(9)/l. Granulocyte functions, i.e. chemiluminescence (CL), random migration, and fMLP-stimulated chemotaxis were initially depressed in all patients when compared to healthy controls. GM-CSF enhanced significantly CL even when given at small doses (less than 1 microg/kg/day), even lower than the dose required to promote granulopoiesis. We conclude that GM-CSF is effective in improving CLL associated chronic neutropenia and also enhances impaired granulocyte chemiluminescence. Thus, GM-CSF could be helpful for giving chemotherapy without neutropenic delays and for prophylaxis of infectious complications in CLL patients.


[The rheumatoid wrist. Pathobiomechanics and therapy].
A stable and pain-free wrist is a prerequisite for normal hand function. Since the wrist joint is involved early in rheumatoid disease and progress is rapid, operative treatment is of major importance. It is indicated not only for treatment of established osseous changes with instability, deformation, and extensor tendon ruptures but for early treatment of drug-resistant synovitis and monarthritis of the wrist.A considerable number of operative procedures is available: arthroscopic or open synovectomy of the radio- and midcarpal as well as the distal radioulnar joint, possibly with resection of the ulna head, partial arthrodeses, complete arthrodeses,and arthroplasty. When choosing the procedure, type and stage of wrist changes as well as the pathobiomechanic situation have to be considered. The individual course of the disease and patient requirements have to be taken into account.Thus, for long periods of time a pain-free stable wrist can be preserved, albeit sometimes with only limited but functional mobility.