Accessing information in working memory: can the focus of attention grasp two elements at the same time?
Processing information in working memory requires selective access to a subset of working-memory contents by a focus of attention. Complex cognition often requires joint access to 2 items in working memory. How does the focus select 2 items? Two experiments with an arithmetic task and 1 with a spatial task investigate time demands for successive operations that involve 2 digits or 2 spatial positions, respectively. When both items used in an operation have been used in the preceding operation, latencies are shortened. No such repetition benefit (arithmetic) or a much smaller benefit (spatial) was found when only 1 item was repeated. The results rule out serial access to the 2 items, parallel access by expanding the focus, and parallel access by splitting the focus. They support the notion that 2 items are accessed by chunking them, so that they fit a focus limited to 1 chunk. (PsycINFO Database Record (c) 2009 APA, all rights reserved).


Evaluate the effects of platelet rich plasma (PRP) and zinc oxide ointment on skin wound healing.
In this study efficiency of platelet rich plasma (PRP) and zinc oxide on full thickness wounds created on rabbits was researched. This study conducted on 24 New Zealand rabbits divided 2 groups. A circular of 1.5 × 1.5 cm (2.5 cm2) full thickness skin wound was created under the general anesthesia. 1 ml PRP (5.503106/mm3) was applied to the one of the wounds subcutaneously. To the other wound 1 mm3 zinc oxide ointment was applied once a day during the study. Wound contraction rates were measured, biopsy materials were collected and evaluated macroscopically and histopathologically postoperatively 3rd, 7th and 15th days. As a result it is determined that PRP and zinc oxide accelerated wound contraction rates between the groups were determined as 3rd day p = 0.007, 7th day p = 0.0002 and 15th day p = 0.002.


Evaluation of the QoS policy model of an ordinary 5G smart city cluster with predominant URLLC and eMBB traffic.
A typical element of the smart city's information and communication space is a 5G cluster, which is focused on serving both new and handover requests because it is an open system. In an ordinary 5G smart city cluster, Ultra-Reliable Low-Latency Communications (URLLC) and enhanced Mobile BroadBand (eMBB) traffic types prevail. The formation of an effective QoS policy for such an object (taking into account the potentially active slicing technology) is an urgent problem. As a baseline, this research considers a Quality of Service (QoS) policy with constraints for context-defined URLLC and eMBB classes of incoming requests. Evaluating the QoS policy instance defined within the framework of the basic concept requires the formalization of both a complete qualitative metric and a computationally efficient mathematical apparatus for its calculation. The article presents accurate and approximate methods of calculating such quality parameters as the probability of loss of typed requests and the utilization ratio of the communication resource, which depend on the implementation of the estimated QoS policy. At the same time, the original parametric space includes both fixed characteristics (amount of available communication resources, load according to request classes) and controlled characteristics due to the specifics of the implementation of the basic QoS concept. The paper empirically proves the adequacy of the presented mathematical apparatus for evaluating the QoS policy defined within the scope of the research. Also, in the proposed qualitative metric, a comparison of the author's concept with a parametrically close analogue (the well-known QoS policy scheme, which takes into account the phenomenon of reservation of communication resources), determined taking into account the reservation of communication resources, was made. The results of the comparison testify in favour of the superiority of the author's approach in the proposed metrics.


Ursolic acid induces human hepatoma cell line SMMC-7721 apoptosis via p53-dependent pathway.
Ursolic acid (UA) is a ubiquitous molecule in the plant kingdom with specific anticancer effects that have been shown in vitro and in vivo. Although UA can inhibit the proliferation of liver cancer cells and induce apoptosis of many types of tumor cells, the molecular mechanism of its anti-hepatoma activity is still not well defined. The objective of this study was to investigate the inhibitory effect and mechanisms of UA on the human hepatoma cell line SMMC-7721. After treatment with UA, the growth inhibition of SMMC-7721 cells was assessed by MTT assay. Cells were also evaluated by flow cytometric analysis, Wright-Giemasa staining, Hoechst 33258 staining and transmission electron microscope after they were induced by UA. DNA microarray technology was used to investigate the gene expression pattern of SMMC-7721 cells exposed to UA 40 micromol/L. The molecular mechanism of cells death was analyzed by real-time RT-PCR and Western blotting. The proliferation of SMMC-7721 cells was significantly inhibited in a dose- and time-dependent manner after UA treatment. UA induced cell cycle arrest and apoptosis. The DNA microarray analysis indicated that 64 genes were found to be markedly up- or down-expressed, including GDF15, SOD2, ATF3, and fos. The result of Western blotting showed the apoptotic proteins p53 and Bax were up-regulated while the anti-apoptotic protein Bcl-2 was down-regulated. Real-time RT-PCR confirmed UA could up-regulate the mRNA expressions of GDF15, SOD2, ATF3 and down-regulate the mRAN expression of fos. Meanwhile these effects were partly blocked by pretreatment with the p53 inhibitor Pft-alpha. Activation of the p53 pathway is involved in UA inhibition of SMMC-7721 human hepatocellular carcinoma cell growth and induction of apoptosis.


Effects of augmented somatosensory input using vibratory insoles to improve walking in individuals with chronic post-stroke hemiparesis.
Stroke survivors suffer from hemiparesis and somatosensory impairments, which adversely impact walking performance, placing them at higher risks for trips and falls. Post-stroke, somatosensory deficits are commonly observed as impaired interpretation of afferent input and increased threshold. Diminishing or augmenting somatosensory inputs via various techniques have been demonstrated to be able to modify static and dynamic balance, postural and locomotor control in non-neurologically impaired as well as neurologically impaired individuals. We sought to investigate whether enhancing somatosensory input using vibratory insoles, can improve post-stroke gait. We hypothesized that with augmentation of somatosensory input at the soles via vibratory insoles would improve post-stroke gait via increased propulsive forces, decreased braking forces and increased ankle angle movements in the paretic legs of individuals with chronic post-stroke hemiparesis. Fifteen individuals with chronic post-stroke hemiparesis and 15 age-similar non-neurologically impaired controls participated in this cross-sectional study. Enhanced somatosensory stimulation was delivered using a pair of tactor-embedded insoles, providing suprathreshold vibratory stimulation to the bottom of the feet. Participants walked over an instrumented treadmill with self-selected speeds, under 5 conditions: no insole in shoe (NT), insoles in shoe with no vibration (BOFF), vibration under both feet (BON), vibration under one foot only (ION, CON). Kinetics and kinematics during walking were recorded and analyzed offline. Suprathreshold vibratory stimulations did not alter gait kinetics under any stimulation conditions. We observed increased paretic ankle dorsiflexions in the paretic legs, when vibratory stimuli were applied unilaterally. Vibratory stimulations applied at suprathreshold intensity to the bottom of the feet to augment somatosensory feedback can potentially be used as a low-cost solution to address the inadequate toe clearance during walking in people post-stroke, which is an important goal in post-stroke rehabilitation.


Identification of earth-abundant materials for selective dehydrogenation of light alkanes to olefins.
Selective ethane dehydrogenation (EDH) is an attractive on-purpose strategy for industrial ethylene production. Design of an effective, stable, and earth-abundant catalyst to replace noble metal Pt is the main obstacle for its large-scale application. Herein, we report an experimentally validated theoretical framework to discover promising catalysts for EDH, which combines descriptor-based microkinetic modeling, high-throughput computations, machine-learning concepts, and experiments. Our approach efficiently evaluates 1,998 bimetallic alloys by using accurately calculated C and CH3 adsorption energies and identifies a small number of new promising noble-metal-free catalysts for selective EDH. A Ni3Mo alloy predicted to be promising is successfully synthesized, and experimentally proven to outperform Pt in selective ethylene production from EDH, representing an important contribution to the improvement of light alkane dehydrogenation to olefins. These results will provide essential additions in the discovery and application of earth-abundant materials in catalysis.


Use of hyperbaric oxygen in traumatic brain injury: retrospective analysis of data of 20 patients treated at a tertiary care centre.
Traumatic brain injury (TBI) related impact results in a permanent need for help in performing daily activities. Standard treatment consists of removing the cause, restore perfusion, support metabolic requirement and limit inflammatory and oxidative damage. Hyperbaric oxygen therapy (HBOT) is one such newer promising treatment that enhances neurological recovery to some extent. HBOT is intermittent inhalation of 100% oxygen at greater than normal atmospheric pressure and is internationally accepted for its role in well-defined indications. It is hypothesised that HBO has a role in reviving 'idling neurons', also called the ischemic penumbra defined as area of reduced cerebral blood flow, abolished synaptic activity but preserved structural integrity. We carried out a retrospective analysis of medical records of 20 patients of TBI who had been treated with HBOT in addition to standard management. These were placed in Group A (test group) and received at least 30 sessions of HBO along with standard treatment. The patients were assessed along the Disability Rating Scale (DRS), Glasgow coma scale (GCS) and Rancho Los Amigos Scale (RLAS). Another 20 patients of TBI, matched in age and severity of brain injury, who received standard treatment but not HBOT, were selected as the control group (Group B). Assessment on the DRS showed maximum improvement in patients with scores of 22-24 (vegetative state).The percentage of patients in the test group fell from 45% to 5% whereas only 20% patients in Group B had similar progress. After the treatment, a significantly higher proportion of HBOT treated subjects showed a good response in cognitive functions, as measured by RLA. In group A, 90% patients had a score of ≤ 3 and in Group B 95% had a similar score, which improved to ≥ 3 in 60% patients versus 30% patients respectively. In both groups maximum patients are in 1-6 months post-injury category and within the groups this category showed the greatest recovery, with a greater improvement in the test group as compared to control group.


Developmental dissociation between visual and auditory repetition priming: the role of input lexicons.
Contrasting theories posit the source of verbal repetition priming in the activation of preexisting memory representations in the input lexicons or, alternatively, in the formation of new episodic memory traces. The two hypotheses predict different outcomes from the comparison of developmental rates of visual and auditory verbal repetition priming. The activation theory predicts a developmental dissociation between the early maturation of auditory priming and the later maturation of visuo-verbal priming, contingent upon the discrepant acquisition rates of the auditory and visual input lexicons. The episodic theory, instead, does not make such an assumption. We administered visual and auditory implicit Stem Completion to 40 reading beginners (first-graders), 40 third-graders and 20 fifth-graders. Consistent with previous reports, auditory priming was stable across different age groups. Visual priming and a measure of lexicality in reading, instead, showed a parallel developmental increase passing from reading beginners to third-graders and to fifth-graders. In the overall group, visual priming and the measure of lexicality in reading were significantly associated. These data describe a new developmental dissociation in the memory abilities of normal children and provide further support for the hypothesis that repetition priming for words reflects facilitated access to previously established memory representations.


[Liver involvement in early secondary syphilis].
Two patients with secondary new syphilis are described, abusing alcohol, developing early syphilitic hepatitis. The manifestations of this condition are similar to those of viral hepatitis. This necessitates a thorough examination of the skin integument, visible mucosae, genitals and perianal area, and of the peripheral lymph nodes in the patients with suspected viral hepatitis, in order to timely detect a possible liver involvement in Treponema infection. When such patients consult a doctor, specific serologic tests should be carried out and case history be carefully recorded.


Reoperative insulinomas, 1927 to 1992: an institutional experience.
Between 1927 and 1992, 313 patients have undergone surgery for insulinoma(s) at our institution, 12% of which were reoperations. We retrospectively reviewed all cases (n = 39) of reoperative surgery for persistent hyperinsulinism to identify changing patterns in surgical approach, morbidity, and outcome and to evaluate the influence of preoperative and intraoperative localization studies. The diagnosis of endogenous hyperinsulinism has evolved from satisfying Whipple's triad to documenting concomitant hypoglycemia and endogenous hyperinsulinemia. Thirty-nine patients were divided into two groups for comparison: those treated before localization studies were available (1927 to 1967) (n = 17) and those treated since that time (n = 22). Initial operations were also compared with reoperations among these 39 patients. There were 26 women and 13 men (mean age, 42 years). There was at least one positive preoperative localization study in 16 of 22 patients (73%). Intraoperative ultrasonogram and careful palpation successfully identified 10 of 11 tumors in the reoperative setting. Blind or completion pancreatectomies were common before 1967 (10 of 17 patients). Since 1967, 14 of 22 patients have undergone enucleation of their primary tumor. Operative morbidity increased from 21% to 58% with reoperation but decreased from 65% to 29% (p = 0.026) when comparing the preangiography to the postangiography eras. The development of iatrogenic diabetes mellitus occurred in 13 patients (33%) after reoperation. Forty-one percent had diabetes before 1967 and 27% since that time (p = not significant). Thirty-four of 36 patients (94%) without malignant tumors were cured by reoperation. There was one operative death. Survival for patients who underwent completion or total pancreatectomy was significantly reduced (p = 0.003). Reoperations for persistent hyperinsulinism can be highly successful in experienced hands. These reoperations, however, are associated with increased morbidity and iatrogenic diabetes. With experience and the use of selected localization studies, first-time failures can be avoided in most cases thus reducing the need for reoperations and its inherent sequelae.


Psychology in national socialism: The question of "professionalization" and the case of the "Ostmark".
This article presents a contextualization and revaluation of competing narratives concerning the history of psychology in Nazi Germany. Since the 1980s, this debate revolves around the supposed "professionalization" of the discipline from Hitler's rise to power until the end of World War II. The question whether or not academic psychology has profited from collaborating with the Nazi regime during the war is not just of historical interest, but also carries strong political and moral implications. Recently, the established narrative concerning the professionalization of German psychology under National Socialism was called into question by Wolfgang Schönpflug. According to his argumentation, psychology did not benefit from the war, but had to suffer considerable losses on terms of personnel and quality in teaching and research. After reconstructing the historical context and the political implications of the debate, we propose to take a different perspective on the question of "professionalization." Three case examples of psychologists from Austria whose career advanced significantly during the war are provided to shed light on the multitude of opportunities that emerged for those who offered their psychological expertise during the war. In conclusion, it is argued that professionalization should be understood as a theoretical framework that stimulates further historical research on a local level, not as a dogmatic judgment about the state of the discipline as a whole. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Leukocyte invasion of the brain after experimental intracerebral hemorrhage in mice.
Neuroinflammatory processes contribute to secondary neuronal damage after intracerebral hemorrhage. We aimed to characterize the time course of brain immigration of different leukocyte subsets after striatal injection of either autologous blood or collagenase in mice. Intracerebral hemorrhage was induced by injection of either autologous blood (20 μL) or collagenase (0.03 U) in C57Bl/6J mice. Hematoma volumetry was performed on cryosections. Blood volume was measured by hemoglobin spectrophotometry. Leukocytes were isolated from hemorrhagic hemisphere 1, 3, 5, and 14 days after intracerebral hemorrhage, stained for leukocyte markers, and measured by flow cytometry. Heterologous blood injection from CD45.1 mice was used to investigate the origin of brain-invading leukocytes. Collagenase injection induced a larger hematoma volume but a similar blood content compared with blood injection. Cerebral leukocyte infiltration in the hemorrhagic hemisphere was similar in both models. The majority of leukocytes isolated from the brain originated from the circulation. CD4+ T lymphocytes were the predominant brain leukocyte population in both models. However, cerebral granulocyte counts were higher after collagenase compared with blood injection. Brain infiltration of systemic immune cells is similar in both murine intracerebral hemorrhage models. The pathophysiological impact of invading leukocytes and, in particular, of T cells requires further investigation.


Purine and pyrimidine contents of some desoxypentose nucleic acids.
The distribution of purines and pyrimidines in desoxypentose nucleic acids prepared from a variety of animal and plant sources has been studied. 1. The nucleic acids were prepared from calf thymus, calf kidney, sheep spleen, horse spleen, chicken erythrocyte, turtle erythrocyte, trout sperm, shad testes, sea urchin sperm, wheat germ, and Pneumococcus Type III. 2. Separate hydrolyses were carried out for the determination of purines and pyrimidines. These procedures permitted nearly quantitative recovery of nucleic acid phosphorus in many of the preparations examined. 3. In the case of those preparations where a quantitative recovery was obtained it can be concluded that no bases other than adenine, guanine, thymine, and cytosine were present in appreciable amounts. 4. The distribution of purines and pyrimidines in all the nucleic acids studied renders the tetranucleotide hypothesis untenable. 5. The results of the analyses have indicated no great differences in the composition of these nucleic acids with respect to purines and pyrimidines.


Distinct mutations in yeast TAF(II)25 differentially affect the composition of TFIID and SAGA complexes as well as global gene expression patterns.
The RNA polymerase II transcription factor TFIID, composed of the TATA-binding protein (TBP) and TBP-associated factors (TAF(II)s), nucleates preinitiation complex formation at protein-coding gene promoters. SAGA, a second TAF(II)-containing multiprotein complex, is involved in transcription regulation in Saccharomyces cerevisiae. One of the essential protein components common to SAGA and TFIID is yTAF(II)25. We define a minimal evolutionarily conserved 91-amino-acid region of TAF(II)25 containing a histone fold domain that is necessary and sufficient for growth in vivo. Different temperature-sensitive mutations of yTAF(II)25 or chimeras with the human homologue TAF(II)30 arrested cell growth at either the G(1) or G(2)/M cell cycle phase and displayed distinct phenotypic changes and gene expression patterns. Immunoprecipitation studies revealed that TAF(II)25 mutation-dependent gene expression and phenotypic changes correlated at least partially with the integrity of SAGA and TFIID. Genome-wide expression analysis revealed that the five TAF(II)25 temperature-sensitive mutant alleles individually affect the expression of between 18 and 33% of genes, whereas taken together they affect 64% of all class II genes. Thus, different yTAF(II)25 mutations induce distinct phenotypes and affect the regulation of different subsets of genes, demonstrating that no individual TAF(II) mutant allele reflects the full range of its normal functions.


The role of catastrophising in rheumatic diseases.
Pain is a common and debilitating symptom of many rheumatic diseases. Decades of research have shown that psychological factors are critical in shaping the experience of acute and chronic pain. The current review focuses on pain catastrophising, a cognitive and emotional response to pain, and its implication for the assessment and treatment of individuals with rheumatic diseases. Catastrophising is one of the most salient psychosocial predictors of a host of pain-related outcomes including heightened disability and depression, increased use of opioids, reduced response to treatment and increased chance of long-term postoperative pain. Despite being stable without treatment, catastrophising can be reduced though psychological and non-psychological interventions. Mechanisms of action including physiological, cognitive-behavioural, and social routes are discussed and a comprehensive developmental model of the combined effects of catastrophising, its biological effects and pain is suggested. Identifying patients at risk for poor outcomes through the assessment of catastrophising could enable providers to individually tailor treatment plans and improve clinical outcomes.


An Outbreak of Toxoplasmosis in an Ontario Chinchilla Herd.
An outbreak of toxoplasmosis which killed 44 of a herd of 56 chinchillas and produced 4 abortions with the loss of a total of five fetuses is reported. A wild mouse thought to be the house mouse (Mus musculus), caught in a trap in the basement housing the chinchillas, was found to be infected with Toxoplasma gondii. The suggestion is made of the existence of a reservoir of infestation in wildlife with wild rodents implicated in this case as possible transmitters of the disease. The post mortem findings, histopathological, serological, and bacteriological results of work done on 6 dead and two live chinchillas and the wild mouse are also reported. A brief review of the literature dealing with toxoplasmosis in this species (Chinchilla lanigera) is presented.


Vitamin C Enema Advances Induction of Remission in the Dextran Sodium Sulfate-Induced Colitis Model in Rats.
The current main treatment for ulcerative colitis (UC) is induction therapy by long-term administration of 5-aminosalicylic acid (5-ASA), but various side effects have been reported. Therefore, a radical cure for UC is desired. A vitamin C (VC) has anti-inflammatory effects. Therefore, this study investigated whether a VC solution enema shortens induction of remission in colitis model rats. Wistar rats (6 wk old/male) were allowed to freely ingest a 1% dextran sulfate sodium (DSS) solution for 10 d and then switched to tap water for normal breeding for 10 d (UC group). At the time of switching to tap water, an enema was performed with a 5-ASA solution (40 mg/kg/d) or VC solution (460 mg/kg/d) for 10 d. The neutrophil number, COX-2, which is an index of inflammation, and type III collagen, which is an early healing marker, were significantly increased in the UC group. However, the VC group showed decreases compared with UC groups. Furthermore, compared with UC and 5-ASA groups, the VC group showed increased expression of type I collagen, which is expressed late in healing, and significant epithelial regeneration was observed in colon tissue. The VC solution enema shortened the induction of remission by directly suppressing inflammation of damaged large intestinal tissues and promoting mucosal healing.


Interventions for treating chronic pelvic pain in women.
Chronic pelvic pain is common in women in the reproductive age group and it causes disability and distress and results in significant costs to health services. The pathogenesis of chronic pelvic pain is poorly understood. Often, investigation by laparoscopy reveals no obvious cause for pain. There are several possible explanations for chronic pelvic pain including undetected irritable bowel syndrome, the vascular hypothesis where pain is thought to arise from dilated pelvic veins in which blood flow is markedly reduced and altered spinal cord and brain processing of stimuli in women with chronic pelvic pain. As the pathophysiology of chronic pelvic pain is not well understood, its treatment is often unsatisfactory and limited to symptom relief. Currently, the main approaches to treatment include counseling or psychotherapy, attempting to provide reassurance using laparoscopy to exclude serious pathology, progestogen therapy such as medroxyprogesterone acetate, and surgery to interrupt nerve pathways. We aimed to identify and review treatments for chronic pelvic pain in women in the reproductive years. The review included studies of patients with a diagnosis of pelvic congestion syndrome or adhesions but excluded those with pain known to be caused by i) endometriosis, ii) primary dysmenorrhoea (period pain), iii) pain due to active chronic pelvic inflammatory disease, or iv) irritable bowel syndrome. The search strategy adopted by the Cochrane Menstrual Disorders and Subfertility Group was used. Randomised controlled trials (RCTs) with women who had chronic pelvic pain, excluding endometriosis, primary dysmenorrhoea, pain due to chronic pelvic inflammatory disease, or irritable bowel syndrome. The reviewers were prepared to consider studies of any intervention including lifestyle, physical, medical, surgical and psychological treatments. Outcome measures were pain rating scales, quality of life measures, economic analyses and adverse events. For each included trial, information was collected regarding the method of randomisation, allocation concealment, blinding, whether an intention to treat analysis could possibly be performed and relevant interventions and outcomes (see previous sections). Data were extracted independently by the two reviewers, using forms designed according to the Cochrane guidelines. Nine studies were identified of which five were of good methodological quality. Two studies were reported in a brief abstract only and were excluded. Progestogen (Medroxyprogesterone acetate) was associated with a reduction of pain during treatment. Counselling supported by ultrasound scanning was associated with reduced pain and improvement in mood. A multidisciplinary approach was beneficial for some outcome measures. Adhesiolysis was not associated with an improved outcome apart from where adhesions were severe. Sertraline was not beneficial. Further studies to confirm these observations are needed, together with full reporting of those studies which have been undertaken. Given the prevalence and health care costs associated with chronic pelvic pain in women, randomised controlled trials of other medical, surgical and psychological interventions are urgently required.


Hyaluronan fragments induce endothelial cell differentiation in a CD44- and CXCL1/GRO1-dependent manner.
Hyaluronan is a glycosaminoglycan of the extracellular matrix. In tumors and during chronic inflammatory diseases, hyaluronan is degraded to smaller fragments, which are known to stimulate endothelial cell differentiation. In this study, we have compared the molecular mechanisms through which hyaluronan dodecasaccharides (HA12), and the known angiogenic factor, fibroblast growth factor 2 (FGF-2), induce capillary endothelial cell sprouting in a three-dimensional collagen gel. The gene expression profiles of unstimulated and HA12- or FGF-2-stimulated endothelial cells were compared using a microarray analysis approach. The data revealed that both FGF-2 and HA12 promoted endothelial cell morphogenesis in a process depending on the expression of ornithine decarboxylase (Odc) and ornithine decarboxylase antizyme inhibitor (Oazi) genes. Among the genes selectively up-regulated in response to HA12 was the chemokine CXCL1/GRO1 gene. The notion that the induction of CXCL1/GRO1 is of importance for HA12-induced endothelial cell sprouting was supported by the fact that morphogenesis was inhibited by antibodies specifically neutralizing the CXCL1/GRO1 protein product. HA12-stimulated endothelial cell differentiation was exerted via binding to CD44 since it was inhibited by antibodies blocking CD44 function. Our data show that hyaluronan fragments and FGF-2 affect endothelial cell morphogenesis by the induction of overlapping but also by distinct sets of genes.


Value of a screening urinalysis in pregnancy.
In order to assess the value of a screening urinalysis in the detection of urinary tract infection, the results of routine urinalyses from 1,062 obstetric patients were compared to subsequent culture results. A positive urine culture was predicted by pyuria, bacteriuria and a positive nitrite test; the predictive values were 23%, 21% and 87%, respectively. If all the parameters were negative, 96% of the cultures were negative. These findings suggest that in the interest of cost effectiveness, the urine can be cultured only when the screening urinalysis shows pyuria, bacteriuria or a positive nitrite test.


Nosocomial COVID-19 Infection and Severe COVID-19 Pneumonia in Patients Hospitalized for Alcoholic Liver Disease: A Case Report.
BACKGROUND COVID-19 is an infectious disease caused by SARS-CoV-2. It has spread rapidly through the world, endangering human life. The main target of COVID-19 is the lungs; however, it can involve other organs, including the liver. Patients with severe COVID-19 have an increased incidence of abnormal liver function, and patients with liver disorders are considered to be at a higher risk of severe COVID-19 infection. The mechanism of liver injury reported in 14% to 53% of COVID-19 patients is poorly recognized and several possibilities need to be considered (cytokine storm, direct viral action, hypoxia). The incidence of underlying liver comorbidities in patients with a COVID-19 infection ranges from 1% to 11%. CASE REPORT This is a report of 2 nosocomial COVID-19 infections and severe COVID-19 pneumonia in 2 patients who were hospitalized during treatment for alcoholic liver disease (ALD). Case 1 and case 2 were a 31-year-old woman and a 40-year-old woman, respectively, with decompensated ALD and symptoms of the COVID-19 infection. Both patients were transferred from another hospital to our hospital after confirmation of COVID-19 during their hospitalization. The course of the infection progressed rapidly in both patients with the development of multiple-organ failure and death over a short period. CONCLUSIONS There are no clear recommendations on the management of ALD in the COVID-19 pandemic. Alcoholic hepatitis may be a risk factor for severe COVID-19 and a poor outcome. A high percentage of nosocomial COVID-19 infections are observed; therefore, special precautions should be taken to minimize the risk of COVID-19 exposure.


Level of scientific evidence underlying recommendations arising from the National Comprehensive Cancer Network clinical practice guidelines.
The level of scientific evidence on which the National Comprehensive Cancer Network (NCCN) guidelines are based has not been systematically investigated. We describe the distribution of categories of evidence and consensus (EC) among the 10 most common cancers with regard to recommendations for staging, initial and salvage therapy, and surveillance. NCCN uses a system of guideline development distinct from other major professional organizations. The NCCN definitions for EC are as follows: category I, high level of evidence with uniform consensus; category IIA, lower level of evidence with uniform consensus; category IIB, lower level of evidence without a uniform consensus but with no major disagreement; and category III, any level of evidence but with major disagreement. Of the 1,023 recommendations found in the 10 guidelines, the proportions of category I, IIA, IIB, and III EC were 6%, 83%, 10%, and 1%, respectively. Recommendations with category I EC were found in kidney (20%), breast (19%), lung (6%), pancreatic (6%), non-Hodgkin's lymphoma (6%), melanoma (6%), prostate (4%), and colorectal (1%) guidelines. Urinary bladder and uterine guidelines did not have any category I recommendations. Eight percent of all therapeutic recommendations were category I. Guidelines with the highest proportions of category I therapeutic recommendations were for breast (30%) and kidney (28%) cancers. No category I recommendations were found on screening or surveillance. Recommendations issued in the NCCN guidelines are largely developed from lower levels of evidence but with uniform expert opinion. This underscores the urgent need and available opportunities to expand evidence base in oncology.


A dataset for buffering delays due to the interaction between the Nagle algorithm and the delayed acknowledgement algorithm in cyber-physical systems communication.
In this article, we provide the research community with a dataset for the buffering delays that data packets experience at the TCP sending side in the realm of Cyber-Physical Systems (CPSs) and IoT. We focus on the buffering that occurs at the sender side due to the the adverse interaction between the Nagle algorithm and the delayed acknowledgement algorithm, which both were originally introduced into TCP to prevent sending out many small-sized packets over the network. These two algorithms are turned on (enabled) by default in most operating systems. The dataset is collected using four real-life operating systems: Windows, Linux, FreeBSD, and QNX (a real-time operating system). In each scenario, there are three separate different (virtual) machines running various operating systems. One machine, or an end-host, acts a data source, another acts as a data sink, and a third acts a network emulator that introduces artificial propagation delays between the source and the destination. To measure buffering delay at the sender side, we record for each sent packet the two time instants: when the packet is first generated at the application layer, and when it is actually sent on the physical network. In each case, 10 different independent experiment replications/runs are executed. Here, we provide the full distribution of all delay samples represented by the cumulative distribution function (CDF), which is expressed mathematically by F X ( x ) = P ( X ≤ x ) , where x is the delay measured in milliseconds, and P is the probability operator. The data exhibited here gives an impression of the amount and scale of the delay occurring at sender-side in TCP. More importantly, the data can be used to investigate the degree these delays affect the performance of cyber-physical systems and IoT or other real-time applications employing TCP.


The presence of ceramide hydrolase and synthetase in pig lens epithelium.
An enzyme that catalyzes the synthesis of ceramide and its degradation to sphingosine and fatty acid has been found in pig lens epithelium. The enzyme has been partially purified fivefold by subcellular fractionation. It is activated by Triton X-100 and sodium cholate. The pH optimum for both hydrolase and synthetase has occurred at alkaline range. The enzymatic hydrolysis of ceramide has an apparent Km of 1.0 x 10(-4) M, and its reverse reaction (via the free-acid pathway) has an apparent Km of 8.2 X 10(-5) M and 2.45 X 10(-4) M for palmitic acid and sphingosine, respectively. The hydrolysis of ceramide by this enzyme was stimulated approximately 75% in the presence of fatty acid-free bovine serum albumin at the concentration of 3.33 X 10(-5) M.


Phloretin and phlorizin promote lipolysis and inhibit inflammation in mouse 3T3-L1 cells and in macrophage-adipocyte co-cultures.
Previous studies found that phloretin (PT) and phlorizin (PZ) could inhibit glucose transport, with PT being a better inhibitor of lipid peroxidation. This study aimed to evaluate the antiobesity effects of PT and PZ in 3T3-L1 cells and if they can modulate the relationship between adipocytes and macrophages. Differentiated 3T3-L1 cells were treated with PT or PZ. Subsequently, transcription factors of adipogenesis and lipolysis proteins were measured. In addition, RAW 264.7 macrophages treated with PT or PZ were cultured in differentiated media from 3T3-L1 cells to analyze inflammatory mediators and signaling pathways. PT significantly enhanced glycerol release and inhibited the adipogenesis-related transcription factors. PT also promoted phosphorylation of AMP-activated protein kinase and increased activity of adipose triglyceride lipase and hormone-sensitive lipase. PT suppressed the nuclear transcription factor kappa-B and mitogen-activated protein kinase pathways when RAW 264.7 cells were cultured in differentiated media from 3T3-L1 cells. PZ improved lipolysis and inhibited the macrophage inflammatory response less effectively than PT. This study suggests that PT is more effective than PZ at increasing lipolysis in adipocytes. In addition, PT also suppresses inflammatory response in macrophage that is stimulated by differentiated media from 3T3-L1 cells.


Supporting Women Planning a Vaginal Breech Birth: An International Survey.
The aim of this study was to explore the experiences of women who planned a vaginal breech birth. An online survey was developed consisting of questions regarding women's experiences surrounding planned vaginal breech birth. The survey was distributed between April 2014 and January 2015 to closed membership Facebook groups that had a consumer focus on vaginal breech birth. In total, 204 unique responses to the survey were obtained from women who had sought the option of a vaginal breech birth in a previous pregnancy. Most women (80.8%) stated that they were happy with the birth choices they made, and a significant proportion (89.4%) would attempt a vaginal breech birth in subsequent pregnancies. Less than half of women were formally referred to a clinician skilled in vaginal breech birth when their baby was diagnosed breech (41.8%), while the remainder sourced a clinician themselves. Half of the women felt supported by their care provider (56.7%) and less than half (42.3%) felt supported by family and friends. The women who responded to this international survey sought the option of a vaginal breech birth, were subsequently happy with this decision, and would attempt a vaginal breech birth in their next pregnancy. Access to vaginal breech birth is important for some women; however, this choice may be challenging to achieve. Consistent information and support from clinicians is important to assist decision-making.


[Quality of a life of military seamen of Northern fleet].
Research of quality of a life of military seamen with use of the Russian-speaking version of the general questionnaire of health "Medical Outcomes Study-Short Forms" (SF-36) is conducted. 600 military men at the age from 18 till 55 years are surveyed. Military seamen have highly appreciated the quality of a life. Absolute values of indicators of quality of a life on all scales 70 points that is considered, how very high there are more. The physical component of health is estimated by military men above, than psychological. Values of indicators of quality of a life on all scales of questionnaire SF-36 at men were above, than at women, with preservation of the general tendency more an appreciation of a physical component of health. Military men on an appeal have estimated the quality of a life above, than military men under the contract. Essential distinctions in an estimation of quality of a life in group of military men under the contract it is not revealed.


Synthesis and fungicidal activity of lipophylic N- and O-acyl derivatives of beta-hydroxy DL-alpha-amino acids.
Synthesis of N- and O-acyl derivatives of DL-serine and threo-DL-phenylserine was accomplished by a regioselective acylation of the corresponding amino acid. The residues introduced into amino acid structure contain hydrophobic long chain or aromatic, namely lauroyl, myristoyl and phenylacetyl moieties. The fungicidal activity against six strains of fungi was studied. Several compounds were found to be effective against growth of fungi, and O-myristoyl-DL-serine 2 and N-phenylacetyl-threo-DL-phenylserine 8 completely inhibited the growth of the mycelium of the fungus Verticillium dahliae.


Carcinogenicity of antihypertensive therapy.
Several studies have suggested that antihypertensive treatment may promote cancer through unknown mechanisms. Early retrospective studies implicated reserpine in breast cancer, but data from prospective studies and meta-analysis of several case-controlled studies showed only a weak association between reserpine and breast cancer which, although statistically significant, is of little clinical concern. Data from case-controlled studies and several cohort studies suggested an association between the use of a diuretic and the occurrence of renal cell cancer, particularly in women. A recent study showed an association between the use of a diuretic and the occurrence of colon cancer. Several prospective studies showed that treatment with atenolol may increase mortality from malignancy. However, other studies that analyzed data from several thousand patients could not confirm this association. In three prospective and a few case-controlled studies, angiotensin converting enzyme inhibitors were not associated with increased mortality from malignancy. In addition, a recent retrospective study showed that long-term use of angiotensin converting enzyme inhibitors had a protective effect against malignancy. Data from three large case-controlled studies and the combined data from eight randomized controlled studies and seven longitudinal studies showed a similar risk for malignancy among users and nonusers of calcium antagonists. Until further data from prospective clinical trials are available, we advise caution about long-term diuretic therapy in women. With regard to other antihypertensive drug classes, we suggest continuing the management of hypertension according to current treatment guidelines with little fear of any substantial cancer risk.


Characterizing topological charge of optical vortices by using an annular aperture.
We explore the spatial frequency property of the far-field diffraction intensity pattern of an optical vortex after passing through an annular aperture in detail. The result reveals that the spatial spectrum consists of alternate bright and dark rings and, in particular, the number of the bright rings is nicely identical to the absolute value of the topological charge. Based on this property, we present and demonstrate a simple technique to characterize the topological charge of an optical vortex through its diffraction intensity pattern after an annular aperture.


Simultaneous high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS-MS) analysis of cyanide and thiocyanate from swine plasma.
An analytical procedure for the simultaneous determination of cyanide and thiocyanate in swine plasma was developed and validated. Cyanide and thiocyanate were simultaneously analyzed by high-performance liquid chromatography tandem mass spectrometry in negative ionization mode after rapid and simple sample preparation. Isotopically labeled internal standards, Na(13)C(15)N and NaS(13)C(15)N, were mixed with swine plasma (spiked and nonspiked), proteins were precipitated with acetone, the samples were centrifuged, and the supernatant was removed and dried. The dried samples were reconstituted in 10 mM ammonium formate. Cyanide was reacted with naphthalene-2,3-dicarboxaldehyde and taurine to form N-substituted 1-cyano[f]benzoisoindole, while thiocyanate was chemically modified with monobromobimane to form an SCN-bimane product. The method produced dynamic ranges of 0.1-50 and 0.2-50 μM for cyanide and thiocyanate, respectively, with limits of detection of 10 nM for cyanide and 50 nM for thiocyanate. For quality control standards, the precision, as measured by percent relative standard deviation, was below 8 %, and the accuracy was within ±10 % of the nominal concentration. Following validation, the analytical procedure successfully detected cyanide and thiocyanate simultaneously from the plasma of cyanide-exposed swine.


Pertrochanteric fractures in the elderly: are there indications for primary prosthetic replacement?
During a 10-year period (1978-1988), 565 patients, aged greater than or equal to 70 years, who sustained a fresh pertrochanteric fracture, were treated in the Department of Traumatology at the University Hospitals of Leuven, Belgium. Three hundred eighty-eight fractures were complex and unstable, according to the Evans-Jensen system and the AO system. Special attention was given to the 324 cases of type IC and ID in Evans' system, type A2 in the AO system. The method of treatment changed greatly during the period of study. All patients were followed prospectively during 1 year. Our study showed that for these unstable fractures, fixation with an angled plate or Ender nails should be forsaken. The overall results of the compression hip screw treatment were good (reoperation rate 2%, good functional results in 64%), but as this treatment has a risk for serious collapse and pain in about 80% of all type ID fractures, one could suggest treating these complex multifragment fractures primarily with an endoprosthesis. This treatment need no longer be considered severe intervention, as the danger of mechanical complications is minimal (less than 1%).


Nonconformity defines the self: the role of minority opinion status in self-concept clarity.
Drawing on distinctiveness and social identity theories, the present studies tested whether minority opinion holders would have a more clearly defined sense of self than majority opinion holders. In Study 1, participants who were induced to believe that they held a minority opinion on a controversial issue had higher subsequent self-concept clarity scores than did those who were induced to believe that they held a majority opinion, controlling for self-esteem. Furthermore, the relationship between minority opinion status and self-concept clarity was strongest among participants whose opinions were highly expressive of their values (Studies 2 and 3), as well as among participants who identified strongly with the group in which they were a minority (Study 3). Theoretical and practical implications of these results are discussed.


Electrochemical deposition and formation mechanism of single-crystalline cu(2)o octahedra on aluminum.
A simple electrochemical deposition was developed to synthesize the cuprous oxide (Cu(2)O) octahedra on aluminum foils. The average edge length of the octahedra is about 300 nm. The chemical composition of the octahedra was determined using energy dispersive X-ray spectroscopy and electron energy-loss spectroscopy. The microstructure of the octahedra was investigated using transmission electron microscopy. The formation mechanism of the octahedra is proposed.


Prevalence and feasibility of assessing the frailty phenotype among hemodialysis patients in a dialysis unit.
Frailty increases risk of morbidity and mortality in hemodialysis patients. Frailty assessments could trigger risk reduction interventions if broadly adopted in clinical practice. We aimed to assess the clinical feasibility of frailty assessment among Veteran hemodialysis patients. Hemodialysis patients' ≥50 years were recruited from a single dialysis unit between 9/1/2021 and 3/31/2022.Patients who consented underwent a frailty phenotype assessment by clinical staff. Five criteria were assessed: unintentional weight loss, low grip strength, self-reported exhaustion, slow gait speed, and low physical activity. Participants were classified as frail (3-5 points), pre-frail (1-2 points) or non-frail (0 points). Feasibility was determined by the number of eligible participants completing the assessment. Among 82 unique dialysis patients, 45 (52%) completed the assessment, 13 (16%) refused, 18 (23%) were not offered the assessment due to death, transfers, or switch to transplant or peritoneal dialysis, and 6 patients were excluded because they did not meet mobility criteria. Among assessed patients, 40(88%) patients were identified as pre-frail (46.6%) or frail (42.2%). Low grip strength was most common (90%). Those who refused were more likely to have peripheral vascular disease (p = 0.001), low albumin (p = 0.0187), low sodium (p = 0.0422), and ineligible for kidney transplant (p = 0.005). Just over half of eligible hemodialysis patients completed the frailty assessment suggesting difficulty with broad clinical adoption expectations. Among those assessed, frailty and pre-frailty prevalence was high. Given patients who were not tested were clinically high risk, our reported prevalence likely underestimates true frailty prevalence. Providing frailty reduction interventions to all hemodialysis patients could have high impact for this group.


Bone marrow mesenchymal stromal cells stimulate skeletal myoblast proliferation through the paracrine release of VEGF.
Mesenchymal stromal cells (MSCs) are the leading cell candidates in the field of regenerative medicine. These cells have also been successfully used to improve skeletal muscle repair/regeneration; however, the mechanisms responsible for their beneficial effects remain to be clarified. On this basis, in the present study, we evaluated in a co-culture system, the ability of bone-marrow MSCs to influence C2C12 myoblast behavior and analyzed the cross-talk between the two cell types at the cellular and molecular level. We found that myoblast proliferation was greatly enhanced in the co-culture as judged by time lapse videomicroscopy, cyclin A expression and EdU incorporation. Moreover, myoblasts immunomagnetically separated from MSCs after co-culture expressed higher mRNA and protein levels of Notch-1, a key determinant of myoblast activation and proliferation, as compared with the single culture. Notch-1 intracellular domain and nuclear localization of Hes-1, a Notch-1 target gene, were also increased in the co-culture. Interestingly, the myoblastic response was mainly dependent on the paracrine release of vascular endothelial growth factor (VEGF) by MSCs. Indeed, the addition of MSC-derived conditioned medium (CM) to C2C12 cells yielded similar results as those observed in the co-culture and increased the phosphorylation and expression levels of VEGFR. The treatment with the selective pharmacological VEGFR inhibitor, KRN633, resulted in a marked attenuation of the receptor activation and concomitantly inhibited the effects of MSC-CM on C2C12 cell growth and Notch-1 signaling. In conclusion, this study provides novel evidence for a role of MSCs in stimulating myoblast cell proliferation and suggests that the functional interaction between the two cell types may be exploited for the development of new and more efficient cell-based skeletal muscle repair strategies.


Post-translational import of protein into the endoplasmic reticulum of a trypanosome: an in vitro system for discovery of anti-trypanosomal chemical entities.
HAT (human African trypanosomiasis), caused by the protozoan parasite Trypanosoma brucei, is an emerging disease for which new drugs are needed. Expression of plasma membrane proteins [e.g. VSG (variant surface glycoprotein)] is crucial for the establishment and maintenance of an infection by T. brucei. Transport of a majority of proteins to the plasma membrane involves their translocation into the ER (endoplasmic reticulum). Thus inhibition of protein import into the ER of T. brucei would be a logical target for discovery of lead compounds against trypanosomes. We have developed a TbRM (T. brucei microsome) system that imports VSG_117 post-translationally. Using this system, MAL3-101, equisetin and CJ-21,058 were discovered to be small molecule inhibitors of VSG_117 translocation into the ER. These agents also killed bloodstream T. brucei in vitro; the concentrations at which 50% of parasites were killed (IC50) were 1.5 microM (MAL3-101), 3.3 microM (equisetin) and 7 microM (CJ-21,058). Thus VSG_117 import into TbRMs is a rapid and novel assay to identify 'new chemical entities' (e.g. MAL3-101, equisetin and CJ-21,058) for anti-trypanosome drug development.


Effects of a Passive Back Support Exoskeleton when Lifting and Carrying Lumber Boards.
Passive back support exoskeletons, which support the human trunk using elements like springs and elastic bands, have demonstrated positive results in laboratory-based studies, but have seen significantly less field testing. As an intermediate step between generic lab evaluations and field tests, we conducted a single-session lab evaluation of the HeroWear Apex exoskeleton with mockup construction tasks: 20 adult men (without extensive construction experience) lifted, carried and raised lumber boards (265 cm length, up to 18 kg total load). The exoskeleton significantly reduced mean erector spinae electromyograms, with effect sizes (Cohen's d) ranging from -0.2 to -0.55 - corresponding to reductions of 5-25% relative to noexoskeleton electromyogram values. In asymmetric carrying tasks, the exoskeleton provided more assistance to the more heavily loaded erector spinae muscle. Additionally, in lifting tasks, the exoskeleton decreased trunk/hip flexion/extension range of motion and increased knee range of motion, indicating changes in lifting strategy. These results indicate potential exoskeleton benefits for lumber board carrying and will serve as the basis for further evaluations with workers in the field.Clinical Relevance- This study establishes that a passive back exoskeleton reduces erector spinae electromyograms by 525% when lifting and carrying lumber boards used in construction work.


False positive troponin result caused by a true macrotroponin.
A 35-year-old female presented with complaints of tiredness, shortness of breath and recent onset of chest pain. The cardiac troponin I (cTnI) concentration was elevated at 6.4 μg/L (Abbott Architect reference value: <0.03 μg/L) with a normal ECG. Physical examination, radiological imaging and routine laboratory investigations did not provide an explanation for the elevated cTnI concentration. Use of different troponin assays, dilutions with assay diluent, addition of mouse serum, polyethylene glycol (PEG) precipitation and gel filtration chromatography (GFC) were used to investigate possible interference. Troponin concentrations were below the level of detection when measured using all other troponin immunoassays. Serial dilutions of sample and addition of mouse serum did not alter the results. However, PEG precipitation and GFC showed the presence of a high molecular weight immunoreactive protein. Using GFC and protein-A IgG precipitation, the interference could be identified as a macrocomplex containing IgG and (fragments of) cTnI. We report a false positive cTnI result caused by a true macrotroponin, containing IgG and (fragments of) cTnI. This macrotroponin was only immunoreactive in the Abbott Architect cTnI immunoassay. Clinicians should be aware of analytical interference when troponin results are constantly elevated in the absence of (non)coronary causes of an increased troponin.


Whole-body nitrogen and tyrosine metabolism in surgical patients receiving branched-chain amino acid solutions.
Fifteen patients undergoing gastric bypass surgery for morbid obesity received preoperatively a standard crystalline amino acid solution containing 15.6% branched-chain amino acids. During the first five postoperative days, the patients were randomized to receive one of three amino acid solutions (9.0 to 10.3 g of nitrogen per day) of different branched-chain amino acid content. The branched-chain amino acid concentrations of the mixtures were 15.6%, 50%, and 100% by weight with five patients in each group. Whole-body amino acid appearance and oxidation were estimated using a continuous intravenous infusion of L-(U-14C)-tyrosine preoperatively and on the third postoperative day. Daily postoperative nitrogen balance, fractional albumin renewal rate, and whole-body tyrosine appearance, oxidation, and incorporation into protein were not significantly different among the three groups. This study suggests that an adequate nitrogen intake of a balanced amino acid mixture, as well as a solution enriched with branched-chain amino acids, maintains protein homeostasis and supports protein synthesis similarly in well-nourished patients following major abdominal surgery. A diet containing only branched-chain amino acids in isomolar ratios was as effective at maintaining protein retention and whole-body protein synthesis and albumin renewal postoperatively when compared with a standard amino acid formula.


Probing steric and hydrophobic effects on enzyme-substrate interactions by protein engineering.
Steric and hydrophobic effects on substrate specificity were probed by protein engineering of subtilisin. Subtilisin has broad peptidase specificity and contains a large hydrophobic substrate binding cleft. A conserved glycine (Gly(166)), located at the bottom of the substrate binding left, was replaced by 12 nonionic amino acids by the cassette mutagenesis method. Mutant enzymes showed large changes in specificity toward substrates of increasing size and hydrophobicity. In general, the catalytic efficiency (k(cat)/K(m)) toward small hydrophobic substrates was increased (up to 16 times) by hydrophobic substitutions at position 166 in the binding cleft. Exceeding the optimal binding volume of the cleft ( approximately 160 A(3)), by enlarging either the substrate side chain or the side chain at position 166, evoked precipitous drops in catalytic efficiency (k(cat)/K(m)) (up to 5000 times) as a result of steric hindrance.


Microwave-assisted technology for the clearing and staining of arbuscular mycorrhizal fungi in roots.
The use of microwave irradiation as a source of energy to clear and stain intra-radical arbuscular mycorrhizal fungi propagules has been tested on a variety of indigenous and cultivated herbaceous plants. The aim of the study was to evaluate the efficiency of microwave irradiation on root softening, fungi tissue staining, and preservation of DNA integrity for subsequent molecular analyses. The proposed methodology has been adapted from the standard procedures used to detect and quantify mycorrhizal root colonization levels. Using a domestic microwave oven, tissue clearing and staining required together between 30 s and 1.5 min of microwave treatment to be completed, depending the diameter size of the roots. The well-performing chemical stains tested were acid fuchsin, trypan blue, and aniline blue. The acid fuchsin clearing and staining processes, as performed, were also demonstrated to preserve DNA integrity for further molecular analyses. Irradiation by microwaves has been used with success in our laboratory within the frame of several studies. It offers considerable time saving over traditional method, reducing processing times from several hours to a few minutes while decreasing considerably the amount of chemicals and energy required to perform analyses.


Effectiveness of the Tobacco Tactics Program in the Trinity Health System.
This study determined the effectiveness of the Tobacco Tactics intervention. This was a pragmatic, quasi-experimental study conducted from 2010 to 2013 and analyzed from 2014 to 2015 in five Michigan community hospitals; three received the Tobacco Tactics intervention, and two received usual care. Smokers (N=1,528) were identified during hospitalization, and sent surveys and cotinine tests after 6 months. Changes in pre- to post-intervention quit rates in the intervention sites were compared with usual care control sites. The toolkit for nurses included: (1) 1 continuing education unit contact hour for training; (2) a PowerPoint presentation on behavioral and pharmaceutical interventions; (3) a pocket card entitled "Helping Smokers Quit: A Guide for Clinicians"; (4) behavioral and pharmaceutical protocols; and (5) a computerized template for documentation. The toolkit for patients included: (1) a brochure; (2) a cessation DVD; (3) the Tobacco Tactics manual; (4) a 1-800-QUIT-NOW card; (5) nurse behavioral counseling and pharmaceuticals; (6) physician reminders to offer brief advice to quit coupled with medication sign-off; and (7) follow-up phone calls by trained hospital volunteers. The effectiveness of the intervention was measured by 6-month 30-day point prevalence; self-reported quit rates with NicAlert(®) urinary biochemical verification (48-hour detection period); and the use of electronic medical record data among non-responders. There were significant improvements in pre- to post-intervention self-reported quit rates (5.7% vs 16.5%, p<0.001) and cotinine-verified quit rates (4.3% vs 8.0%, p<0.05) in the intervention sites compared with no change in the control sites. Propensity-adjusted multivariable analyses showed a significant improvement in self-reported 6-month quit rates from the pre- to post-intervention time periods in the intervention sites compared to the control sites (p=0.044) and a non-statistically significant improvement in the cotinine-verified 6-month quit rate. The Tobacco Tactics intervention, which meets the Joint Commission standards for inpatient smoking, has the potential to significantly decrease smoking among inpatient smokers. This study is registered at www.clinicaltrial.gov NCT01309217.


Plasma levels of opioid analgesics determined by radioreceptor assay.
Plasma levels of opioid drugs, Mr 1268 MS (3-(2-methyl-3-furylmethyl)-1,2,3,4,5,6-hexahydro-6 alpha,11 alpha-dimetyl-2,6-methano-3-benzazocin-8-ol methane sulfonate), Mr 2033 CL ( [2 alpha, 3(S*), 6 alpha, 11 R*]-(+/-)-1,2,3,4,5,6-hexahydro-6,11-dimethyl-3-[(tetrahydro-2-furanyl) methyl]-2,6-methano-3-benzazocin-8-ol hydrochloride), MRZ 2549 BR ( (2-methoxypropyl)-1,2,3,4,5,6-hexahydro-6 alpha, 11 alpha-dimethyl-2,6-methano-3-benzazocin-8-ol hydrobromide), and pentazocine, have been determined by a radioreceptor assay after enteral and parenteral administration to human volunteers as well as to laboratory animals (monkeys and dogs), using [3H]dihydromorphine as radioligand and freshly prepared membrane homogenates of rat brains. The concentration of parent compound drug has been evaluated after a specific extraction from plasma. The method described presents a universal possibility for the determination of opioid drugs of different structures in plasma and other body fluids.


Reduction of nucleosome assembly during new DNA synthesis impairs both major pathways of double-strand break repair.
Assembly of new chromatin during S phase requires the histone chaperone complexes CAF-1 (Cac2p, Msi1p and Rlf2p) and RCAF (Asf1p plus acetylated histones H3 and H4). Cells lacking CAF-1 and RCAF are hypersensitive to DNA-damaging agents, such as methyl methanesulfonate and camptothecin, suggesting a possible defect in double-strand break (DSB) repair. Assays developed to quantitate repair of defined, cohesive-ended break structures revealed that DSB-induced plasmid:chromosome recombination was reduced approximately 10-fold in RCAF/CAF-1 double mutants. Recombination defects were similar with both chromosomal and plasmid targets in vivo, suggesting that inhibitory chromatin structures were not involved. Consistent with these observations, ionizing radiation-induced loss of heterozygosity was abolished in the mutants. Nonhomologous end-joining (NHEJ) repair proficiency and accuracy were intermediate between wild-type levels and those of NHEJ-deficient yku70 and rad50 mutants. The defects in NHEJ, but not homologous recombination, could be rescued by deletion of HMR-a1, a component of the a1/alpha2 transcriptional repressor complex. The findings are consistent with the observation that silent mating loci are partially derepressed. These results demonstrate that defective assembly of nucleosomes during new DNA synthesis compromises each of the known pathways of DSB repair and that the effects can be indirect consequences of changes in silenced chromatin structure.


Inclusion of palliative care in health care policy for older people: A directed documentary analysis in 13 of the most rapidly ageing countries worldwide.
Palliative care is insufficiently integrated in the continuum of care for older people. It is unclear to what extent healthcare policy for older people includes elements of palliative care and thus supports its integration. (1) To develop a reference framework for identifying palliative care contents in policy documents; (2) to determine inclusion of palliative care in public policy documents on healthcare for older people in 13 rapidly ageing countries. Directed documentary analysis of public policy documents (legislation, policies/strategies, guidelines, white papers) on healthcare for older people. Using existing literature, we developed a reference framework and data extraction form assessing 10 criteria of palliative care inclusion. Country experts identified documents and extracted data. Austria, Belgium, Canada, Czech Republic, England, Japan, Mexico, Netherlands, New Zealand, Singapore, Slovenia, South Korea, Spain. Of 139 identified documents, 50 met inclusion criteria. The most frequently addressed palliative care elements were coordination and continuity of care (12 countries), communication and care planning, care for family, and ethical and legal aspects (11 countries). Documents in 10 countries explicitly mentioned palliative care, nine addressed symptom management, eight mentioned end-of-life care, and five referred to existing palliative care strategies (out of nine that had them). Health care policies for older people need revising to include reference to end-of-life care and dying and ensure linkage to existing national or regional palliative care strategies. The strong policy focus on care coordination and continuity in policies for older people is an opportunity window for palliative care advocacy.


Intrathecal administration of substance P in the rat: spinal transection or morphine blocks the behavioural responses but not the facilitation of the tail flick reflex.
Substance P (10 micrograms) was administered intrathecally (i.t.) via a chronic catheter to the L5 vertebral level in rats with spinal cords transected at the T10-12 level (n = 11) and in intact rats pretreated 25 min earlier with morphine (5 micrograms i.t., n = 5). In both experimental paradigms, substance P decreased the reaction time in the tail flick test at 1 min after injection; the magnitude of this effect resembled that which occurs in intact rats given substance P alone. In both paradigms, substance P failed to produce the behavioural responses typically observed in untreated rats given substance P. These results indicate that substance P-induced facilitation of the tail flick reflex may occur via spinal mechanisms alone. The results also suggest that in the spinal cord morphine preferentially blocks the relay of substance P-induced information to supraspinal structures. Finally, as the behavioural response is blocked by the analgesic and by spinal transection, this is interpreted as further support for the proposal that this behavioural response indicates that the animal has perceived a noxious stimulus.


Additivity in perception of affect from limb motion.
In this study, the notion of additivity in perception of affect from limb motion is investigated. Specifically, we examine whether the impact of multiple limbs in perception of affect is equal to the sum of the impacts of each individual limb. Several neutral, happy, and sad walking sequences are first aligned and averaged. Four distinct body regions or limbs are defined for this study: arms and hands, legs and feet, head and neck, and torso. The three average walks are used to create the stimuli. The motion of each limb and combination of limbs from the neutral sequence are replaced with those of the happy and sad sequences. Through collecting perceptual ratings for when individual limbs contain affective features, and comparing the sums of these ratings to instances where multiple limbs of the body simultaneously contain affective features, additivity is investigated. We find that while the results are highly correlated, additivity does not hold in the classical sense. Based on the results, a mathematical model is proposed for describing the observed relationship.


Screening and confirmation of 62 drugs of abuse and metabolites in urine by ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry.
An ultra-high-performance liquid chromatography--quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) method for the screening and confirmation of 62 drugs of abuse and their metabolites in urine was developed in this study. The most commonly abused drugs, including amphetamines, opioids, cocaine, benzodiazepines (BZDs) and barbiturates, and many other new and emerging abused drugs, were selected as the analytes for this study. Urine samples were diluted 5-fold with deionized water before analysis. Using a superficially porous micro-particulate column and an acetic acid-based mobile phase, 54 basic and 8 acidic analytes could be detected within 15 and 12 min in positive and negative ionization modes, respectively. The MS collision energies for the 62 analytes were optimized, and their respective fragmentation patterns were constructed in the in-house library for confirmatory analysis. The coefficients of variation of the intra- and inter-day precision of the analyte responses all were <17.39%. All analytes, except barbital, showed matrix effects of 77-121%. The limits of detection of the 62 analytes were between 2.8 and 187.5 ng/mL, which were lower than their respective cut-off concentrations (20-500 ng/mL). Ten urine samples from patients undergoing methadone treatment were analyzed by the developed UHPLC-QTOF-MS method, and the results were compared with the immunoassay method.


Intermittent oscillopsia in a case of congenital nystagmus. Dependence upon waveform.
Spontaneous reports of oscillopsia are rare in cases of congenital nystagmus (CN). We examined the relationship between nystagmus waveform characteristics and oscillopsia in one such case. To reduce the patient's nystagmus, she was fitted with contact lenses. We examined the effects of tactile feedback by applying local anesthetic while she wore the lenses. When she was without lenses, we provided tactile feedback by applying gentle finger pressure to one eyelid. She was also asked to look at a peripheral afterimage. Nystagmus was analyzed for frequency, amplitude, foveation duration, and drift velocity, if foveation was not perfectly stable. Perceived target stability was recorded. The patient noted oscillopsia during the initial baseline recording and with lid pressure. The image was stable with contact lenses with and without anesthesia and during the second session baseline; at these times, drift velocity was less than 4 degrees/sec and foveation duration was greater than 100 msec. No oscillopsia of the afterimage in dark was noted; she perceived it moving with her gaze as she attempted to look at it. It appears that in some CN patients, the suppression of oscillopsia operates only within fixed limits of foveation stability and duration. When, because of internal or external factors, their nystagmus exceeds these, oscillopsia results.


Functional food science and behaviour and psychological functions.
The impact of ingesting various foods on psychological and behavioural functions is a topic of both interest and concern to the general public. In this article, the scientific literature concerning demonstrated cause-and-effect relationships is reviewed, beginning with methodological considerations specific to the quantification of particular behaviours and psychological events. The essential function of food is to satisfy hunger and the need for essential nutrients. The contributions of macronutrients to appetite and satiety are described, as well as their impact on metabolism and energy balance. Functional properties of macronutrient substitutes (high-intensity sweeteners, fat replacers) and flavour enhancers are examined in relation to their contribution to hunger, satiety, and energy balance. The effects of foods and individual nutrients on the performance of diverse psychomotor tasks are studied with consideration given to the various validated quantitative tools used to assess behaviour. The effects of food components on activation, sedation, and affective states such as dysphoria are also reviewed, with special attention given to brain function and neuroactive substances such as serotonin and the endorphins. The case of hyperactivity in children is given special emphasis with reference to the potential influence of sugar and food additives. Safety issues related to food constituents and additives are discussed. Finally, a set of criteria is proposed for the evaluation and elaboration of studies in the behavioural and psychological fields, along with suggestions for future research.


Human islet allografts in patients with type 2 diabetes undergoing liver transplantation.
Most patients with cirrhosis have insulin resistance and impaired glucose tolerance, and 20% eventually develop diabetes. Although diabetes in this setting may be reversible after orthotopic liver transplantation (OLTx), immunosuppressive agents administered after transplantation could exacerbate this disease. We report the results of the first pilot trial of islet cell transplantation (ICTx) in patients with diabetes undergoing OLTx. Five patients with diabetes and liver cirrhosis underwent OLTx and ICTx. Donor bone marrow cells were also infused to enhance the acceptance of the graft. We identified seven patients who received only OLTx and donor bone marrow cells as historical controls. Preliminary results suggest that ICTx in conjunction with OLTx may improve glucose metabolism (insulin requirement, hemoglobin A1c) in patients with liver cirrhosis. However, there was virtually no change in pre- and posttransplant basal C-peptide levels in the recipients of OLTx + ICTx. We are planning to further evaluate the effect of OLTx with or without ICTx in a randomized prospective trial, using euglycemic insulin clamp studies.


Three-dimensional structure of an antibody-antigen complex.
We have determined the three-dimensional structure of two crystal forms of an antilysozyme Fab-lysozyme complex by x-ray crystallography. The epitope on lysozyme consists of three sequentially separated subsites, including one long, nearly continuous, site from Gln-41 through Tyr-53 and one from Gly-67 through Pro-70. Antibody residues interacting with lysozyme occur in each of the six complementarity-determining regions and also include one framework residue. Arg-45 and Arg-68 form a ridge on the surface of lysozyme, which binds in a groove on the antibody surface. Otherwise the surface of interaction between the two proteins is relatively flat, although it curls at the edges. The surface of interaction is approximately 26 X 19 A. No water molecules are found in the interface. The positive charge on the two arginines is complemented by the negative charge of Glu-35 and Glu-50 from the heavy chain of the antibody. The backbone structure of the antigen, lysozyme, is mostly unperturbed, although there are some changes in the epitope region, most notably Pro-70. One side chain not in the epitope, Trp-63, undergoes a rotation of approximately 180 degrees about the C beta--C gamma bond. The Fab elbow bends in the two crystal forms differ by 7 degrees.


Contrasting effects of Deadend1 (Dnd1) gain and loss of function mutations on allelic inheritance, testicular cancer, and intestinal polyposis.
Certain mutations in the Deadend1 (Dnd1) gene are the most potent modifiers of testicular germ cell tumor (TGCT) susceptibility in mice and rats. In the 129 family of mice, the Dnd1Ter mutation significantly increases occurrence of TGCT-affected males. To test the hypothesis that he Dnd1Ter allele is a loss-of-function mutation; we characterized the consequences of a genetically-engineered loss-of-function mutation in mice, and compared these results with those for Dnd1Ter. We found that intercrossing Dnd1+/KO heterozygotes to generate a complete loss-of-function led to absence of Dnd1KO/KO homozygotes and significantly reduced numbers of Dnd1+/KO heterozygotes. Further crosses showed that Dnd1Ter partially rescues loss of Dnd1KO mice. We also found that loss of a single copy of Dnd1 in Dnd1KO/+ heterozygotes did not affect baseline occurrence of TGCT-affected males and that Dnd1Ter increased TGCT risk regardless whether the alternative allele was loss-of-function (Dnd1KO) or wild-type (Dnd1⁺). Finally, we found that the action of Dnd1Ter was not limited to testicular cancer, but also significantly increased polyp number and burden in the Apc+/Min model of intestinal polyposis. These results show that Dnd1 is essential for normal allelic inheritance and that Dnd1Ter has a novel combination of functions that significantly increase risk for both testicular and intestinal cancer.


Emergence of Ixodes scapularis and Borrelia burgdorferi, the Lyme disease vector and agent, in Ohio.
Lyme disease, the most common vector-borne disease in the United States, is caused by a tick-borne infection with Borrelia burgdorferi. Currently, Ohio is considered by the Centers for Disease Control and Prevention (CDC) to be non-endemic for Lyme disease. The low incidence of Lyme disease in this state was largely attributed to the absence of the transmitting vector, Ixodes scapularis, commonly known as the blacklegged tick. However, a tick surveillance program established by Ohio Department of Health indicated that the number of I. scapularis in Ohio had increased sharply in recent years, from 0 - 5 ticks per year during 1983-2008 to 15 in 2009, 40 in 2010, and 184 in 2011. During the fall deer hunting season, examination of deer heads submitted to Ohio Department of Agriculture found 29 I. scapularis from 7 counties in 2010 and 1,830 from 25 counties in 2011. As of 2012, the tick had been found in 57 of the 88 counties of Ohio. In addition, all three active stages (larva, nymph, and adult) of I. scapularis were found in Tiverton Township of Coshocton County, demonstrating the presence of established tick populations at this central Ohio location. Of 530 nymphal or adult I. scapularis analyzed by quantitative polymerase chain reaction (qPCR), 32 (6.1%) tested positive for the B. burgdorferi flaB gene, ranging from 36 to 390,000 copies per tick. Antibodies to B. burgdorferi antigens were detected in 2 of 10 (20%) field-captured Peromyscus leucopus from Tiverton Township, and in 41 of 355 (11.5%) dogs residing in Ohio. Collectively, these data suggest that the enzootic life cycle of B. burgdorferi has become established in Ohio, which poses risk of Lyme disease to people and animals in the area.


Urgent vs. elective endoscopy for acute non-variceal upper-GI bleeding: an effectiveness study.
Urgent endoscopy in patients with acute upper-GI bleeding identifies many patients who may be safely treated without hospitalization. The aim of this multicenter trial was to determine whether urgent endoscopy effectively decreases health care resource utilization in a real-life setting where primary care providers determine the course of care. Ninety-three outpatients with acute upper-GI bleeding were randomized to either urgent endoscopy (before hospitalization) or elective endoscopy after admission. The results of urgent endoscopy and a recommendation regarding patient disposition were provided to the attending physician. Medical outcomes and resource utilization were measured. The timing of endoscopy did not affect resource utilization or patient outcomes. Length of stay was similar (urgent endoscopy, OR 3.98 days: 95% CI[2.84, 5.11] vs. elective endoscopy, OR 3.26 days: 95% CI[2.32, 4.21], p=0.45). The mean number of days in an intensive care unit was the same (1.2 days). The urgent endoscopy group had more high-risk endoscopic lesions (15 vs. 9; p=0.031). Outpatient care was recommended for 19 patients (40%). Only 4 patients were discharged. Urgent endoscopy did not reduce hospitalization or resource utilization because the results of early endoscopy did not impact the decision by attending physicians regarding admission. For early (triage) endoscopy to impact resource utilization, the results of endoscopy must change subsequent patient care.


Direct visualization of critical hydrogen atoms in a pyridoxal 5'-phosphate enzyme.
Enzymes dependent on pyridoxal 5'-phosphate (PLP, the active form of vitamin B6) perform a myriad of diverse chemical transformations. They promote various reactions by modulating the electronic states of PLP through weak interactions in the active site. Neutron crystallography has the unique ability of visualizing the nuclear positions of hydrogen atoms in macromolecules. Here we present a room-temperature neutron structure of a homodimeric PLP-dependent enzyme, aspartate aminotransferase, which was reacted in situ with α-methylaspartate. In one monomer, the PLP remained as an internal aldimine with a deprotonated Schiff base. In the second monomer, the external aldimine formed with the substrate analog. We observe a deuterium equidistant between the Schiff base and the C-terminal carboxylate of the substrate, a position indicative of a low-barrier hydrogen bond. Quantum chemical calculations and a low-pH room-temperature X-ray structure provide insight into the physical phenomena that control the electronic modulation in aspartate aminotransferase.Pyridoxal 5'-phosphate (PLP) is a ubiquitous co factor for diverse enzymes, among them aspartate aminotransferase. Here the authors use neutron crystallography, which allows the visualization of the positions of hydrogen atoms, and computation to characterize the catalytic mechanism of the enzyme.


Gilles de la Tourette's syndrome: tics and central nervous system stimulants in twins and nontwins.
Thirty-four of 170 surveyed individuals with Tourette's syndrome (TS) were treated with CNS stimulants before age 18. In 24% of treated individuals, persistent exacerbation of tics was closely associated with treatment. In 3%, tic response was transient, and in 24%, tics were not obviously associated with treatment. Six pairs of monozygotic twins were discordant for stimulant treatment, and all untreated co-twins also developed TS. The number of individuals in whom stimulants permanently exacerbate tics may be small, but the risk appears to be real. Genetic vulnerability and duration and timing of treatment may mediate response.


Uncoupling of epidermal growth factor-dependent proliferation and invasion in a model of squamous carcinoma progression.
Cell lines pairs were established from a primary squamous carcinoma of tongue and a lymph node metastasis and their biological behavior characterized. HN12 cells, derived from metastatic SCC, formed tumors upon subcutaneous transplantation to athymic mice, whereas HN4, derived from a primary lesion in the same individual, were non-tumorigenic in this assay. EGF stimulated proliferation of HN4 cells; in comparison, not only were metastatic HN12 cells refractory to the stimulatory effects of this growth factor but showed inhibition at higher growth factor concentrations. However, in contrast to the effects on proliferation, EGF (10 ng/ml) readily induced HN12 cells to invade in Boyden chamber assays whereas HN4 were non-invasive under these conditions. The invasive properties of HN12 cells were apparently independent of MMP-2 activity, as levels of active MMP-2 were higher in the non-invasive cells. However, EGF stimulated MMP-9 activity in invasive cells. Additionally, HN12 cells expressed constitutively high levels of active MMP-7 and MMP-3/10. The pharmacological agents LY294002, PD098059, SP600125, or SB202190 inhibited invasion of HN12 cells, suggesting requirement for phosphoinositide 3-OH kinase- and mitogen activated protein kinase-dependent pathways in the process. The data indicate that distinct biochemical differences distinguish metastatic squamous carcinoma cells from those derived from corresponding primary tumors, resulting in their contrasting biological properties.


Investigation of a nosocomial outbreak of severe acute respiratory syndrome (SARS) in Toronto, Canada.
Severe acute respiratory syndrome (SARS) was introduced into Canada by a visitor to Hong Kong who returned to Toronto on Feb. 23, 2003. Transmission to a family member who was later admitted to a community hospital in Toronto led to a large nosocomial outbreak. In this report we summarize the preliminary results of the epidemiological investigation into the transmission of SARS between 128 cases associated with this hospital outbreak. We collected epidemiologic data on 128 probable and suspect cases of SARS associated with the hospital outbreak, including those who became infected in hospital and the next generation of illness arising among their contacts. Incubation periods were calculated based on cases with a single known exposure. Transmission chains from the index family to hospital contacts and within the hospital were mapped. Attack rates were calculated for nurses in 3 hospital wards where transmission occurred. The cases ranged in age from 21 months to 86 years; 60.2% were female. Seventeen deaths were reported (case-fatality rate 13.3%). Of the identified cases, 36.7% were hospital staff. Other cases were household or social contacts of SARS cases (29.6%), hospital patients (14.1%), visitors (14.1%) or other health care workers (5.5%). Of the 128 cases, 120 (93.8%) had documented contact with a SARS case or with a ward where there was a known SARS case. The remaining 8 cases without documented exposure are believed to have had exposure to an unidentified case and remain under investigation. The attack rates among nurses who worked in the emergency department, intensive care unit and coronary care unit ranged from 10.3% to 60.0%. Based on 42 of the 128 cases with a single known contact with a SARS case, the mean incubation period was 5 days (range 2 to 10 days). Evidence to date suggests that SARS is a severe respiratory illness spread mainly by respiratory droplets. There has been no evidence of further transmission within the hospital after the elapse of 2 full incubation periods (20 days).


The effects of acute and chronic morphine treatment and of morphine withdrawal on rat brain in vivo.
1. The effects of morphine, nalorphine, acetazolamide, and 10% CO(2) on brain metabolite concentrations of 24h-starved rats were studied. 2. A single dose of morphine (20mg/kg body wt.) caused an increase in brain glucose concentration (42%) and decreased concentrations of lactate (24%), pyruvate (29%), citrate (20%), alpha-oxoglutarate (16%), malate (14%) and creatine phosphate (10%) after 30min. No changes were found in adenine nucleotide concentrations. 3. The same dose of morphine increased arterial CO(2) from 5.07 to 7.60 kN/m(2) (38 to 57 Torr), decreased the pH from 7.41 to 7.31 and decreased O(2) from 14.1 to 10.8kN/m(2) (106 to 81 Torr) at 30min. 4. Rats injected with morphine three times daily (20mg/kg body wt.) for 2 weeks had no changes in brain metabolite concentrations or in blood gases 30min after their last injection. 5. Nalorphine (an antagonist of morphine) caused essentially no changes in brain metabolite concentrations in normal rats. When nalorphine (20mg/kg) was administered to rats previously treated with morphine three times daily for 2 weeks, there was an increase in brain glucose (100%), lactate (23%), pyruvate (18%) and citrate (10%) concentrations. 6. Acetazolamide (an inhibitor of carbonic anhydrase) and 10% CO(2) increased the arterial CO(2) from 4.79 to 6.78kN/m(2) (36 to 51 Torr) and from 5.32 to 10.8kN/m(2) (40 to 81 Torr) respectively. 7. Both acetazolamide and 10% CO(2) caused changes in brain metabolite concentrations similar to those for acutely administered morphine. Thus 10% CO(2) caused increased brain glucose concentration (123%) and decreased brain lactate (46%), pyruvate (34%), citrate (26%), alpha-oxoglutarate (33%), malate (45%) and creatine phosphate (7%) concentrations. No changes in adenine nucleotide concentrations were found. 8. The results indicate that the effect of morphine on brain metabolite concentrations may be accounted for by the increased [CO(2)]. 9. These findings constitute a consistent pattern of metabolic changes after acute morphine administration, morphine addiction, and withdrawal from morphine addiction.


Perioperative Mortality Does Not Explain Racial Disparities in Gastrointestinal Cancer.
Racial minorities with gastrointestinal cancer suffer disproportionately poor overall and disease-specific survival. We used a nationally representative sample to examine the relationship between race/ethnicity and mortality and determine whether these disparities were observed in the perioperative period. The Nationwide Inpatient Sample (NIS) was used to examine patients undergoing surgery for cancers of the esophagus, stomach, pancreas, colon and rectum ("GI cancer") between 2008 and 2012. Logistic regression was used to evaluate whether race/ethnicity was associated with perioperative mortality after adjusting for sociodemographic characteristics, perioperative factors and presentation (ER vs elective). A total of 110,044 subjects were identified, including 75.8% Whites, 10.5% Black patients, 7.2% Hispanic patients, and 3.1% Asian/Pacific Islanders (API). Whites were generally older than minorities. In adjusted multivariable generalized linear mixed logistic models, no increase in perioperative mortality was seen for minorities. Worse outcomes were observed for those with higher Elixhauser comorbidity score (OR 6.90, CI 5.96-7.99), lower income region (OR 1.24, CI 1.10-1.40), males (OR 1.54, CI 1.42-1.68), and those without private insurance (Medicare OR 1.34, CI 1.16-1.55; Medicaid OR 1.27, CI 1.02-1.58; self-pay OR 1.64, CI 1.24-2.17). Differences in mortality were predominantly driven by comorbidities (pseudo %ΔR2 = 38.56%) and only minimally by race (pseudo %ΔR2 = 0.49%). Minority groups do not suffer higher rates of perioperative mortality for GI cancer surgeries after controlling for clinical and demographic factors. Future work to address cancer disparities should focus on areas in the cancer care trajectory such as cancer screening, surveillance, socioeconomic factors, and access.


Cerebrospinal fluid amine metabolites. Relationships with behavioral measurements in depressed, manic, and healthy control subjects.
We studied 99 hospitalized depressed, 14 manic, and 61 healthy control subjects and evaluated relationships during a drug-free baseline period between behavioral measures (postulated to be associated with brain norepinephrine, dopamine, and serotonin function) and metabolites of these neurotransmitters sampled from lumbar cerebrospinal fluid (CSF): 3-methoxy-4-hydroxyphenylglycol (MHPG), homovanillic acid, and 5-hydroxyindoleacetic acid. Depressed subjects with increased anxiety, agitation, somatization, and sleep disturbance were found to have significantly elevated concentrations of CSF MHPG; this relationship was not found in the healthy controls. A correlation between CSF MHPG level and an anxiety/agitation dimension measured in all subjects was statistically significant but explained a modest portion of the total variance. No consistent relationships were found between CSF MHPG and depression/retardation, hostility/interpersonal sensitivity, and global severity, nor did any of these measures correlate significantly with the levels of the other monoamine metabolites, although some trends were found. Other factors did not account for the relationships between CSF MHPG and some behavioral measures, including diagnostic subgroup, motor movement, age, sex, and premenopausal or postmenopausal status in women. Suggested relationships among drug treatment modality, eventual treatment outcome, behavioral and mood state at baseline, and these metabolite levels will require further analyses.


Merkel cell polyomavirus small T antigen mRNA level is increased following in vivo UV-radiation.
Merkel cell carcinoma (MCC) is a rare but aggressive skin cancer involving Merkel cells. Recently, a new human polyomavirus was implicated in MCC, being present in 80% of the samples analyzed. In virus-positive MCC, the Merkel cell polyomavirus (MCPyV) is clonally integrated into the patients DNA, and carries mutations in its large T antigen, leading to a truncated protein. In non-symptomatic tissue MCPyV can reside at very low levels. MCC is also associated with older age, immunosuppression and sun exposure. However, the link with solar exposure remains unknown, as the precise mechanism and steps involved between time of infection by MCPyV and the development of MCC. We thus investigated the potential impact of solar simulated radiation (SSR) on MCPyV transcriptional activity. We screened skin samples of 20 healthy patients enrolled in a photodermatological protocol based on in vivo-administered 2 and 4 J/cm(2) SSR. Two patients were infected with two new variants of MCPyV, present in their episomal form and RT-QPCR analyses on SSR-irradiated skin samples showed a specific and unique dose-dependent increase of MCPyV small t antigen transcript. A luciferase based in vitro assay confirmed that small t promoter is indeed UV-inducible. These findings demonstrate that solar radiation has an impact on MCPyV mRNA levels that may explain the association between MCC and solar exposure.


Low-coverage MiSeq next generation sequencing reveals the mitochondrial genome of the Eastern Rock Lobster, Sagmariasus verreauxi.
The complete mitochondrial genome of the Eastern Rock lobster, Sagmariasus verreauxi, is reported for the first time. Using low-coverage, long read MiSeq next generation sequencing, we constructed and determined the mtDNA genome organization of the 15,470 bp sequence from two isolates from Eastern Tasmania, Australia and Northern New Zealand, and identified 46 polymorphic nucleotides between the two sequences. This genome sequence and its genetic polymorphisms will likely be useful in understanding the distribution and population connectivity of the Eastern Rock Lobster, and in the fisheries management of this commercially important species.


Kinetics of Cl-dependent K influx in human erythrocytes with and without external Na: effect of NEM.
The majority of the ouabain-insensitive K influx in human erythrocytes is dependent on the presence of Cl. Recent studies have shown that a portion of the Cl-dependent K influx persists in the absence of external Na (Nao). It has been suggested that this Nao-independent component represents (K + Cl) cotransport, whereas the remainder of the Cl-dependent K influx seen on addition of external Na represents (Na + K + 2Cl) cotransport. In the present studies, the kinetics of Cl-dependent K influx were examined in the presence and absence of external Na, by varying external K and external Cl. Our studies suggest that the Nao-independent Cl-dependent pathway has a relatively low affinity for external K (Km 17-30 mM) in contrast to the high affinity of the Nao-augmented component (Km 3-4 mM). N-ethylmaleimide (NEM) stimulates the maximal velocity of the Nao-independent Cl-dependent K influx achievable without alteration of intracellular solutes but does not alter its Km for external K. In contrast, NEM has no stimulatory effect on the Nao-augmented component. The Cl dependence of the Nao-independent K influx is best described by a relatively flat curve with a mild upward concavity. The kinetic properties of the Nao-independent component of Cl-dependent K transport are very similar to those of the putative (K + Cl) cotransport pathway seen in low-K sheep erythrocytes.(ABSTRACT TRUNCATED AT 250 WORDS)