[Behavior of free amino acids in severely burned patients (II: In the urine). Clinical studies].
Urinary amino acids were measured in 10 severely burned patients weekly during 4 weeks after burning. For control the same measurements have been made in 12 multiple injured patients during the first two weeks after the accident. In burned patients the renal loss of free amino acids was up to 3 g/24 h +/- 1 in the first week, together with a high excreation of sodium (450 mmol/24 h +/- 73) in the first week. Urinary output of ornithin (highest value in the 2nd week: 1093 +/- 525% of normal) and lysin (highest value in the 2nd week: 1093 +/- 525% of normal) and Lysin (highest value in the 1st week: 654 +/- 166% of normal) was increased and caused an augmented loss of cystin (645 +/- 133% of normal in the first week) and 742 +/- 64% of normal in the second week. In the first and second week after burning the excretion of valin was up to 12 times the normal. Methionine-excretion staid high (5 times the normal) during all 4 weeks. The mean rate of 3-methylhistidine output in urine (80 +/- 38 mg/24 h) was elevated from the second until fourth week, suggesting muscle protein breakdown. In the control group urinary excretion of glutamin and asparagin (1st week: 608 +/- 97% of normal), threonin (2nd week: 693 +/- 240% of normal), serin (2nd week: 517 +/- 232% of normal) and histidin (1st week: 358 +/- 115% of normal) was high. Only urinary citrullin, isoleucin, prolin and taurin were not elevated in both groups during all 4 weeks.


Epidural analgesia in Scotland: a survey of extradural opioid practice.
A postal survey of all Consultant Anaesthetists working within Scotland was conducted to establish the current state of epidural analgesia and the level of post-operative care for patients after epidural opioid administration. Of those consultants using epidurals for post-operative analgesia, 89% use extradural opioids, and the lipid soluble opioids diamorphine and fentanyl by an infusion technique were the most popular. For analgesia in labour the use of extradural opioids drops to 41% with fentanyl by bolus the commonest drug and method of administration. Monitoring requirements after extradural opioids are variable with more than half of consultants satisfied with intermittent observational measurements. Sixty-nine per cent of consultants frequently send their patients to a high dependency unit following epidural opioid administration. Additional administration of opioids on an ordinary ward setting is considered inappropriate by over half of the consultants replying. There is considerable variability amongst anaesthetists as to how patients receiving epidural opioids should be monitored and National Recommendations are required to stop the present confusion.


Selenium transport and bioaccumulation in aquatic ecosystems: a proposal for water quality criteria based on hydrological units.
Local water quality criteria for selenium should be based on an assessment of the degree of toxicological hazard to fish and wildlife, which is influenced by the spatial and temporal variation of the selenium cycle at the site under consideration. The physical area from which measurements are taken to evaluate selenium residues and biological effects, i.e., the database for setting site-specific criteria, must encompass more than an isolated segment of river, a tributary stream, etc. Because of hydrological connections between the various aquatic habitats that may be present in a watershed basin-wetlands, rivers, streams, and impoundments-the toxic threat from selenium contamination is also connected. For example, a criterion that is appropriate for a stream or river where low bioaccumulation occurs may result in seemingly harmless concentrations of selenium becoming a problem in downstream impoundments or in off-channel bays and wetlands where bioaccumulation is greater. The hydrologically connected parts of a basin downstream of a selenium discharge (natural or synthetic selenium source), extending to the point at which new sources of low-selenium water dominate the hydrology (e.g., confluence with larger tributary or river, spring or groundwater inflow), should be the area evaluated and given a specific criterion, not isolated components. Thus, a hydrological unit should be identified and used as the "site" for the purpose of setting criteria. Importantly, criteria derived in such a fashion will reflect the transport and bioaccumulation of selenium within the entire hydrological unit rather than simply focusing on a small, artificially designated segment of the system. Failure to use a hydrological unit approach can set the stage for significant biological and legal problems.


Antagonism between FOXO and MYC Regulates Cellular Powerhouse.
Alterations in cellular metabolism are a key feature of the transformed phenotype. Enhanced macromolecule synthesis is a prerequisite for rapid proliferation but may also contribute to induction of angiogenesis, metastasis formation, and tumor progression, thereby leading to a poorer clinical outcome. Metabolic adaptations enable cancer cells to survive in suboptimal growth conditions, such as the limited supply of nutrient and oxygen often found in the tumor microenvironment. Metabolic changes, including activation of glycolysis and inhibition of mitochondrial ATP production, are induced under hypoxia to promote survival in low oxygen. FOXO3a, a transcription factor that is inhibited by the phosphatidylinositol 3-kinase/Akt pathway and is upregulated in hypoxia, has emerged as an important negative regulator of MYC function. Recent studies have revealed that FOXO3a acts as a negative regulator of mitochondrial function through inhibition of MYC. Ablation of FOXO3a prevents the inhibition of mitochondrial function induced by hypoxia and results in enhanced oxidative stress. This review will focus on the antagonism between FOXO3a and MYC and discuss their role in cellular bioenergetics, reactive oxygen metabolism, and adaptation to hypoxia, raising questions about the role of FOXO proteins in cancer.


Blood pressure measuring devices: ubiquitous, essential but imprecise.
Blood pressure measurement is an essential, poorly performed skill, traditionally undertaken through auscultation and use of a mercury sphygmomanometer. However, its exclusivity to the clinical environment has changed substantially over the last 20 years with the introduction of automated blood pressure devices. This simplified self-measurement method has enabled increased patient involvement and surveillance, while also eliminating the observer error, measurement bias and white-coat effect associated with auscultatory measurement in the clinical setting. Rapid advances in technology have decreased the discrepancy between automated and auscultatory readings, evidenced by the increased number of devices to pass recognized validation standards. However, the limitation of automated device accuracy is still evident in certain patient groups, such as those with diabetes, an arrhythmia or preeclampsia. Therefore, careful consideration is warranted when selecting a noninvasive blood pressure measurement device to ensure optimum accuracy and reliability of readings.


Radiation-induced hearing impairment in patients treated for malignant parotid tumor.
Radiation-induced hearing loss was evaluated in 21 patients with unilateral malignant parotid tumors treated with surgery and radiotherapy. The contralateral ear was used as a control. Eight patients (38%) were found to have a reduction in static compliance of the tympanic membrane (type B tympanogram) in the irradiated ear. By audiometry, significant hearing loss was found in 9 patients (43%). These hearing losses were mainly sensorineural, as shown by a similar reduction in both air and bone conduction, although mixed-type hearing loss existed in some patients. A statistically significant difference in incidence of 67% versus 0% (p = .0085) was noted for patients with a cochlear dose of greater than or equal to 60 Gy, in comparison to those receiving doses of less than 60 Gy. A type B tympanogram was also found to be a prognostic factor for significant sensorineural hearing loss. Patients with type B tympanograms had a much higher incidence of significant sensorineural hearing loss than those with type A tympanograms (88% versus 15%, p = .02). This study clearly shows that radiotherapy can induce significant hearing impairment, especially when the cochlear doses are higher than 60 Gy.


Effects of dietary enrichment with conventional foods on energy and protein intake in older adults: a systematic review.
Decreased food intake is a common problem among older adults; it is a known cause of weight loss and may lead to malnutrition. The objective of this systematic review was to determine the effects of dietary enrichment with conventional foods on energy and protein intake in older adults. Studies were identified through systematic searches of the following electronic databases: MEDLINE, via PubMed; CINAHL, via EBSCO; Web of Science; Scopus; and Google Scholar. Studies in older adults were included without restrictions for sample size, length of follow-up, comparators, or date or status of publication. Eligible studies were dietary-enrichment interventions with conventional foods and powdered modules that aimed to increase the energy and protein density of meals without significantly increasing the final volume of the meals. Outcomes assessed included changes in energy intake, protein intake, nutritional status, body weight, functional status, and episodes of infection. Nine studies were included. The results suggest that dietary enrichment can improve energy intake in older adults. While dietary enrichment seems to increase protein intake, there is not enough evidence of sufficient quality to confirm this observation or to determine whether dietary enrichment improves other outcomes assessed in this population. Additional large clinical trials with long-term interventions are needed to establish the effects of dietary enrichment in older people at risk of malnutrition.


Antioxidant capacity of oat (Avena sativa L.) extracts. 2. In vitro antioxidant activity and contents of phenolic and tocol antioxidants.
Oat milling fractions were examined for concentrations of total phenolics, tocols, and phenolic acids and in vitro antioxidant activity to determine their potential as dietary antioxidants. Methanolic extracts of pearling fractions, flour and aspirations from flaking, and trichomes had high, intermediate, and low antioxidant activities, respectively, evaluated by the beta-carotene bleaching method. Pearling fractions were also highest in total phenolics and tocols. p-Hydroxybenzoic acid, vanillic acid, caffeic acid, vanillin, p-coumaric acid, and ferulic acid were identified and quantified by HPLC. Three avenanthramides and an unidentified ferulate derivative were also detected. Total phenolic content was significantly correlated with antioxidant activity, and regression equations that predicted antioxidant activity from phenolic and tocol concentrations were calculated. Antioxidant activity, evaluated by beta-carotene bleaching, was correlated with measures of oxygen radical absorbance capacity and low-density lipoprotein oxidation. These data indicate a potential for oat products, especially those enriched in outer layers of the groat, to contribute to dietary intakes of antioxidant phytonutrients.


Co-morbidity of bipolar affective disorder and obsessive compulsive disorder in a Bedford community psychiatry team.
This is a study of the prevalence and impact of co-existing bipolar affective disorder on patients with OCD, and the effect on their management within a community psychiatric team. We found that 16% of patients who visited psychiatric outpatients with a diagnosis of OCD had co-existing bipolar affective disorder. Of these the majority had bipolar affective disorder II (67%). Co-morbidity raised a number of challenges to patient management. Compared to the control group the patients with co-morbid bipolar affective disorder required a greater number of outpatients appointments, had a greater number of hospital admissions, were more likely to have been allocated a care coordinator and to have received psychological input.


Trends in Microbiology publications: are classic scientific journals condemned to extinction?
Scientific journals have played an essential role in the diffusion of research breakthroughs. For many years there was no competition between journals, but, in recent decades they have become categorized by a careful assessment of their published contents based on several metric parameters. Of greater note, the 'prestige index' has become an essential tool used by public and private institutions to develop their scientific policy. Thus, the evaluation of research staffs, the concession of grants or fellowships and even the scholarly reputation and academic positions are mainly founded on a given journal's 'quality'. As a consequence, the prestige of some journals has gone up, based on the assumption that they publish cutting-edge science, while the reputation of others has gone down. Within the field of Microbiology, we have carried out a direct analysis by monitoring several representative classic journals according to customary metric parameters over 20 years. This analysis also covers another set of journals of recent appearance (novel journals). Although a direct comparison between both groups is not possible, this approach serves to perceive the trends of publication among microbiologists. Our preliminary conclusion is that the continued existence of many so-termed classic journals devoted to Microbiology is seriously threatened.


Inhibitory effect of Lycium barbarum polysaccharide on sperm damage during cryopreservation.
With the development of cryopreservation technology, marked progress has been made regarding sperm cryopreservation. However, as conventional cryopreservation agents are not effective at freezing weak sperm, improved cryopreservation agents are in demand. In the present study, the addition of Lycium barbarum polysaccharides to glycerol-egg-yolk-citrate sperm cryopreservation agent was determined to improve sperm forward speed, reduce the DNA fragmentation index and improve the mitochondrial membrane potential. Furthermore, during the freezing and thawing of sperm, the improved cryopreservative increased the content of Bcl-2 while reducing the content of Bax, cytochrome C and caspase-3. These results indicated that polysaccharides added as a protective agent preserved the normal function of sperm mitochondria. Transmission electron microscopy also confirmed the protective effect of the polysaccharides on the structure of mitochondria. It was also indicated that improved cryopreservative lowered the levels of reactive oxygen species (ROS) during the freeze-thawing process. Therefore, it is hypothesized that improved cryopreservative agents may be beneficial for maintaining the structure and function of the mitochondria of weak sperm when cryopreserved, which may be facilitated via reducing the production of ROS in the freezing-thawing process, thus avoiding activation of the apoptotic pathway in sperm mitochondria and protecting mitochondrial structure and sperm function.


Echocardiography-guided pacemaker programming can improve cardiac hemodynamics in patients undergoing transcatheter aortic valve replacement.
Transcatheter aortic valve replacement (TAVR) is an effective treatment option for patients with severe aortic stenosis who are at high surgical risk because of multiple comorbidities. Many of these patients have been treated with pacemakers for concomitant conduction disease. The combination of severe aortic stenosis, cardiomyopathy, and conduction abnormalities results in a state of low cardiac output. Here, we report 2 complex TAVR cases where Doppler echocardiography was used to guide adjustment of device settings, leading to improved cardiac hemodynamic profiles.


Two-parameter leak estimation in non-invasive ventilation.
In this paper we present a method for the estimation of leaks in non-invasive ventilation. Accurate estimation of leaks is a key component of a ventilator, since it determines the ventilator performance in terms of patient-ventilator synchrony and air volume delivery. In particular, in non-invasive ventilation, the patient flow is significantly different from the flow measured at the ventilator outlet. This is mostly due to the vent orifice along the tube that is used for exhalation, but also to the non-intentional leaks that occur elsewhere in the circuit (e.g., at the mask). Such leaks are traditionally quantified via a model with two parameters, but only one of them is continually updated - the other is fixed. The new algorithm allows for breath-by-breath update of both parameters. This was made possible by leveraging a model describing the patient respiratory mechanics.


Retinoic acid suppression of endothelial nitric oxide synthase in porcine oocyte.
The presence of endothelial nitric oxide synthase (eNOS) has been found in porcine oocytes, but its mRNA and protein levels remain relatively constant during hormonal stimulation. The present study was designed to determine the effect of retinoic acid on eNOS regulation in porcine oocytes during follicle-stimulating hormone (FSH) stimulation. Cumulus-oocyte complexes (COCs), prepared from small antral follicles of immature porcine ovaries, were cultured for 15 h and treated with FSH for an additional 48 h. eNOS mRNA and its protein were analyzed by reverse transcription - polymerase chain reaction and Western blotting, respectively. Retinoic acid had an inhibitory effect on the level of oocyte eNOS mRNA in a dose-dependent manner if COCs were exposed to retinoic acid before FSH stimulation. The inhibition of FSH action was reflected in a decrease in expression of c-fos mRNA. eNOS protein also decreased to approximately 50% of the control after exposure to 10 microM retinoic acid. However, the ability of NO synthesis was abolished in the oocytes prepared from retinoic acid pretreated COCs. These results suggest that retinoic acid has a strong inhibitory action on eNOS mRNA level and NO synthesis in the porcine oocyte.


[Consequences of extrahepatic manifestations of hepatitis C viral infection (HCV)].
The hepatitis C virus (HCV) is a primarily hepatotropic virus. However, numerous extrahepatic symptoms are observed in patients chronically infected with HCV, e.g. cryoglobulinemia, lymphoproliferative disorders, kidney diseases, disturbances of the central and peripheral nervous system, thyroid gland, pancreas, lymph nodes and pituitary gland, that develop at various times after the infection. Complex mechanisms underlie these processes, both molecular, related to direct effects of the virus on cells or tissues and indirect mechanisms, resulting from the response of the immune system to infection (via cytokines or oxidative stress), and from the antiviral treatment used. Understanding these mechanisms may contribute to the definition of new prognostic factors, important for the early diagnosis of the infection, which in turn may improve treatment efficacy. This paper is a review of the incidence of selected extrahepatic manifestations of HCV infection and their underlying pathogenetic mechanisms and risk factors.


Selection and validation of castor bean (Ricinus communis) reference genes for quantitative PCR (RT-qPCR) in developing and germinating seeds and expression pattern of four ricin-family genes.
This study aims to expand the set of internal control genes used for RT-qPCR experiments with Castor bean (Ricinus communis) seeds by evaluating candidate genes across several seed tissues and developmental stages. Nine reference genes were selected, including actin-11 (ACT11), tubulin alpha-2 (Tα2), elongation factor 1-alpha (EF1-α), protein phosphatase 2A-2 (PP2A2), polyubiquitin-3 (PUB3) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Biological samples consisted of R. communis seeds in 15 stages of maturation and germination. We demonstrate that PP2A2, PUB3 and EF1-α are the most stably expressed genes across the tested conditions and therefore appropriate for RT-qPCR. Subsequently, those reference genes were used for the analysis of the expression of four R. communis ricin-family genes. In developing seeds, the highest ricin expression levels was seen in the nucellus and in the endosperm, whereas in germinating seeds a peak expression occurs 4-6 days after germination. The four tested ricin isoforms exhibited differential expression patterns across tissues and seed developmental stages, which may indicate distinct biological roles for each ricin gene.


2-Pyridinealdoxime, a new ligand for a Pd-precatalyst: application in solid-phase-assisted Suzuki-Miyaura reaction.
The preparation of a new palladium(II) complex with a 2-pyridinealdoxime ligand and its use as a Pd(0) precatalyst in the cross-coupling Suzuki-Miyaura reaction is described. Several concepts for the immobilization of this catalytic system are presented and compared in order to develop an efficient catalytic tool for high-throughput synthesis.


Differences between neurosurgeons and orthopedic surgeons in classifying cervical dislocation injuries and making assessment and treatment decisions: a multicenter reliability study.
Variability exists in the management of cervical spinal injuries. The goal of this study was to assess the effect of training specialty (orthopedic surgery vs neurosurgery) on management of cervical dislocations. Twenty-nine spine surgeons reviewed 10 cases of cervical dislocation injuries. For each of the 10 cases, the surgeons evaluated 3 clinical scenarios, which included a neurologically intact patient, a patient with an incomplete spinal cord injury (SCI), and a patient with complete SCI. Surgeons determined whether a unilateral or bilateral facet dislocation was present and whether pretreatment magnetic resonance imaging (MRI) or immediate closed reduction was indicated. Management decisions were re-assessed after review of MRIs. While spine surgeons may agree on what they see on MRI and how they classify certain cervical injuries irrespective of training, significant differences of opinion continue to exist regarding the therapeutic implications of this information, specifically, whether to order a pretreatment MRI and how to manage the injury.


CDC HIV testing guidelines and the rapid and conventional testing practices of homeless youth.
The study's aims were to describe rapid and conventional HIV testing practices and referrals/linkages to services posttest among homeless youth in New York City. We also examined variation among service-involved youth, street youth, and "nomads." Respondent-driven sampling was used to recruit 217 homeless youth who participated in structured interviews. Almost all youth were tested in the past year (82%). Most received pretest/posttest counseling (> 77%). Rapid testing was common and conducted in diverse settings. However, youth reported that rates of referral/linkage to services posttest were low (< 44.4%). Service-involved youth were significantly more likely to receive rapid testing, be tested in the past year, and be tested at a high frequency. Street youth and nomads, those at highest risk for poor health outcomes, had less access to testing and may require creative, low-threshold services. Further, a better understanding of barriers to the use of referrals/linkages to services posttest is needed.


Nematic Bond Theory of Heisenberg Helimagnets.
We study classical two-dimensional frustrated Heisenberg models with generically incommensurate ground states. A new theory for the lattice-nematic "order by disorder" transition is developed based on the self-consistent determination of the effective exchange coupling bonds. In our approach, fluctuations of the constraint field imposing conservation of the local magnetic moment drive nematicity at low temperatures. The critical temperature is found to be highly sensitive to the peak helimagnetic wave vector, and vanishes continuously when approaching rotation symmetric Lifshitz points. Transitions between symmetry distinct nematic orders may occur by tuning the exchange parameters, leading to lines of bicritical points.


The Epidemiology of Meningococcal Disease and Carriage, Genotypic Characteristics and Antibiotic Resistance of Neisseria meningitidis Isolates in Zhejiang Province, China, 2011-2021.
Neisseria meningitidis (Nm) remains a worldwide leading cause of epidemic meningitis. During 2011-July 2021, 55 meningococcal disease (MD) cases were reported with a case fatality rate of 5.45% in Zhejiang Province, China. The median age was 7 years. The annual incidence was 0.0017-0.0183 per 100,000 population. The highest age-specific incidence was observed in the group younger than 1 year. Serogroup was identified in 30 laboratory-confirmed MD cases, and MenB was most predominant. MenB was mainly observed in two age groups: younger than 5 and older than 35 years. MenB incidence was significantly increasing from 0.0018 per 100,000 in 2013 to 0.0070 per 100,000 in 2019. During 2015-2020, 17 positive samples were detected from 2,827 throat swabs from healthy population, of which 70.59% was MenB. Twenty multilocus sequence typing sequence types (STs) containing eight newly assigned STs (ST15881-ST15888) were determined in all Nm isolates. Either in MD cases or in healthy population, MenB CC ST-4821 was the predominant ST. It was worth noting that two MenY CC ST-23 cases occurred in 2019 and 2021, respectively. MenY CC ST-23 MD cases increased gradually in China. Phylogeny results based on genome sequencing indicated that Chinese MenW CC ST-11 isolates were genetically linked and grouped together with Japanese isolates, separated from MenW CC ST-11 isolates from Saudi Arabia Hajj outbreak, Europe, South Africa, South America, North America, and Oceania. MenW CC ST-11 isolates from East Asia might have evolved locally. Antibiotic susceptibility tests revealed a relatively high resistance rate (22.86%) of Nm isolates to penicillin. This study provided valuable data for Chinese public health authorities to grasp the temporal epidemiological characteristics of MD and healthy carriage.


Time course of stimulation of renal renin messenger RNA by furosemide.
Renin secretion responds rapidly to a variety of stimuli; however, reported changes in renal renin messenger RNA (mRNA) levels in vivo have been observed only after prolonged stimulation. Studies were designed to test whether rapid changes in renin mRNA levels can be produced in vivo. In the first series, Sprague-Dawley rats received furosemide (10 mg/kg) intraperitoneally and a low sodium diet (0.05% sodium); renin secretion was significantly stimulated at 8 or 16 hours after treatment, but renin mRNA levels did not change. In a second series, rats were pretreated with deoxycorticosterone acetate (200 mg/kg) and saline drinking water for 3 days and then killed 0, 2, 4, 8, or 48 hours after furosemide administration. The renin mRNA level was unchanged at 2 hours but was stimulated twofold at 4 and 8 hours and threefold at 48 hours. In additional animals, the response of renin mRNA 4 hours after furosemide was found not to be potentiated by the converting enzyme inhibitor quinapril (5 mg/kg). The results demonstrate that with acute stimulation, renin mRNA levels lag 2-4 hours behind the change in plasma renin levels.


Evidence that Th1 lymphocytes predominate in islet inflammation and thyroiditis in the BioBreeding (BB) rat.
Th1 cytokines are thought to play a key role in islet inflammation and destruction in insulin-dependent diabetes mellitus (IDDM). We studied this hypothesis in the diabetes-prone (DP)-BB and the diabetes-resistant (DR)-BB rats that are used as a model of human IDDM. The DP-BB rat develops spontaneous autoimmune diabetes at the age of 11-14 weeks. In the DR-BB rat, diabetes is inducible by depletion of RT6+ lymphocytes and coadministration of polyinosinic:polycytidylic acid (Poly I:C). We used reverse transcriptase-polymerase chain reaction (RT-PCR) and semi-quantitative PCR techniques to examine mRNA expression of Th1 and Th2 cytokines in inflamed islets and thyroids from DP-BB and DR-BB rats. We observed that in DP-BB and in treated DR-BB rats, the levels of TCR beta, IFN-gamma and IL-12p40 mRNA increase with disease progression. In contrast, expression of message for IL-2 and IL-4 is minimal to undetectable in DP-BB and RT6-depleted DR-BB animals at any age. Message for IL-10 is detectable in DP and DR islets; however, its level of expression does not change with disease progression. A similar cytokine mRNA profile is observed in inflamed thyroids from acutely diabetic RT6-depleted DR-BB rats. Incubation of 10 wk old DP islets for 48 h in the presence of anti-CD3 antibody, followed by an incubation with rIL-2 for an additional 5-7 days, results in an expansion of T lymphocytes, and these cells express high levels of IFN-gamma and IL-10 mRNA. Our results suggest that autoimmunity in DP-BB and DR-BB rats is mediated by Th1 lymphocytes and that IFN-gamma and IL-12 are likely to play a key role in islet and thyroid inflammation and destruction in IDDM.


The impact of participatory dementia research on researchers: A systematic review.
Participatory approaches are increasingly required and used in research. In this review, we examined the impact (benefits and disadvantages) of participatory dementia research on researchers as potential key actors to sustainably implement the participatory approach. Our aim was to provide information on how the participatory process could be improved. We conducted a systematic literature review covering the Cochrane Library, PsycNet, PubMed, Scopus, and Google Scholar. The inclusion criteria for publications were as follows: research (1) involving people with dementia as co-researchers, (2) including a description or discussion of the impact of participatory research for researchers, (3) published between 2000 and 2020, and (4) in English. We performed a quality assessment of the included publications. Our final review included nine publications; three categorized as high quality, five as medium quality, and one as low quality. Four of the publications categorized as high or medium quality implemented participation at the level of partnership, and two publications implemented participation at the level of delegated power. The beneficial impact of participatory dementia research on researchers consisted of an increased understanding of people with dementia that widened researchers' theoretical knowledge and perspectives and increased their competence in working with people with dementia. Disadvantages comprised the required additional effort and time as well as the difficulty of establishing a balanced relationship between researchers and co-researchers. Disadvantages may result from the lack of a definition and structure of participatory research and a lack of training on both sides. More well-designed and transparent methods of evaluating participatory research projects are needed.


Metabolic effects of vitamin D supplementation in vitamin D deficient patients (a double-blind clinical trial).
Vitamin D has recently been given a lot of attention for its role in controlling insulin secretion. Many studies have spoken of its role in weight management, blood sugar control and many other metabolic variables. In a randomized double-blind clinical trial, 210 people with vitamin D deficiency were randomly allocated into two groups receiving vitamin D (50,000 units per week) or placebo for 8 weeks. Vitamin D levels were significantly increased in the group receiving vitamin D supplementation (13.7±5.2 unit increase versus 0.8±2.8). The increased levels of vitamin D lead to significant changes in fasting insulin levels (6.8±8.1 unit reduction versus 2.3±3.7), a 2-h insulin (31.1±34.9 unit reduction versus 4.5±24.6) and Homeostasis Model Assessment (HOMA) indices. Correction of vitamin D deficiency leads to increased insulin sensitivity that was significantly able to maintain glucose in the normal range with lower levels of insulin.


Practical Considerations for the Use of Daratumumab, a Novel CD38 Monoclonal Antibody, in Myeloma.
Monoclonal antibodies (mAbs) are a recent addition to multiple myeloma (MM) therapies and a number of mAbs directed at myeloma cell surface molecules are in development. Daratumumab is a CD38 mAb that has demonstrated substantial activity and good tolerability in four phase I, phase I/II and phase II studies as monotherapy, as well as in combination with current standard treatments in MM. The positive results obtained in the relapsed/refractory setting in patients with advanced-stage disease and in a small number of patients with newly diagnosed disease provide the rationale for the investigation of the agent in a number of ongoing phase III trials. mAbs are generally better tolerated than conventional chemotherapy; however, their use requires other special considerations. Such factors include those common to all mAbs, namely infusion-related reactions, but also factors that are observed with mAbs used in myeloma, such as interference with response assessment, or factors that are related to CD38 mAbs such as daratumumab, for instance blood typing interference. Our review provides an overview of the results from the daratumumab clinical trials conducted to date, as well as practical management considerations for the use of daratumumab based on our experience with the agent.


Local thyroid tissue ablation by high-intensity focused ultrasound: effects on thyroid function and first human feasibility study with hot and cold thyroid nodules.
The aim of this study was to assess whether high-intensity focused ultrasound (HIFU), a new and promising method for the treatment of benign hot and cold thyroid nodules using thermal ablation, has an impact on thyroid function, and to evaluate its feasibility in outpatient settings. Additionally, a possible difference in the treatment of solid and complex thyroid nodules was evaluated. Ten patients with one thyroid nodule each (six cold and four hot nodules) underwent HIFU in January 2014. Four nodules were solid and six nodules were complex. Serum levels of triiodothyronine (T3), thyroxine (T4), thyrotropin (TSH), thyroglobulin (hTg) and additionally antibodies against hTg (TAK), TSH receptors (TRAK) and thyroid peroxidase (TPO) were measured at enrolment and 24 h after the HIFU treatment. The pre- and post-thyroglobulin reduction was measured to evaluate the scale of ablation. In addition, patients' pain was recorded on a numeric rating scale from 0 to 10. The HIFU treatment did not affect thyroid function, since hormone levels stayed stable (p < 0.05). No serious immune reaction was induced. Thyroglobulin serum levels increased significantly (p < 0.05) and were correlated to the total energy emitted by HIFU (p < 0.1). The results of complex thyroid nodules did not differ from solid thyroid nodules. Similarly, the results of hot thyroid nodules did not differ from cold thyroid nodules. All patients tolerated the whole treatment and no severe complications were observed. HIFU is a safe and effective method to treat benign, solid, complex, hot and cold thyroid nodules preserving thyroid function. Further developments of the system are needed to gain suitability for daily use.


Instrumentation for Testing Whether the Icy Moons of the Gas and Ice Giants Are Inhabited.
Evidence of life beyond Earth may be closer than we think, given that the forthcoming missions to the jovian system will be equipped with instruments capable of probing Europa's icy surface for possible biosignatures, including chemical biomarkers, despite the strong radiation environment. Geochemical biomarkers may also exist beyond Europa on icy moons of the gas giants. Sulfur is proposed as a reliable geochemical biomarker for approved and forthcoming missions to the outer solar system. Key Words: JUICE mission-Clipper mission-Geochemical biomarkers-Europa-Moons of the ice giants-Geochemistry-Mass spectrometry. Astrobiology 17, 958-961.


Gastrointestinal manifestations in systemic autoimmune diseases.
In an autoimmune disease, the immune system attacks and harms the body's own tissues. The systemic autoimmune diseases include collagen vascular diseases, the systemic vasculitides, Wegener granulomatosis, and Churg-Strauss syndrome. These disorders can involve any part of the gastrointestinal tract, hepatobiliary system and pancreas. They can cause a variety of gastrointestinal manifestations that are influenced by the pathophysiologic characteristics of the underlying disease process. There is a wide variation of gastrointestinal manifestations from these autoimmune disorders including, but not limited to: oral ulcers, dysphagia, gastroesophageal reflux disease, abdominal pain, constipation, diarrhea, fecal incontinence, pseudo-obstruction, perforation and gastrointestinal bleeding. Clinical workup should be initiated by the patient's subjective complaints. In this review, we analyze the effects of autoimmune diseases on the gastrointestinal tract.


Behavioral, event-related potential, and EEG/FFT changes at sleep onset.
Behavioral, event-related potential (ERP), and EEG measures were obtained to describe more fully the relationship between brain activity and arousal level during the process of falling asleep. In addition to standard polysomnographic measures, tones were presented at random intervals throughout two nights to each of nine subjects. Subjects were instructed to respond to the tones whenever they heard them. Initial sleep onset was disrupted five times following zero through four successive response failures. Sampling of EEG was initiated 5 s prior to tone onset (EEG analyses) and continued for 5 s following tone onset (ERP data). With EEG ordered as a function of response rate, significant increases in power were found across all standard frequency bands for the pretone data at sleep onset. Significant changes in amplitude were related to decreasing responsivity for all late ERP components except P2. Inasmuch as virtually all EEG frequencies and ERP components were strongly influenced by momentary changes in arousal, arousal must be considered a (possibly the) primary determinant of the characteristics of the overall electrical output of the brain. Response cessation coupled with sharp increases in EEG synchronization mark the point of sleep onset.


Parathyroid cancer in a hemodialysis patient: a case report.
An extremely rare case of parathyroid cancer in a hemodialysis patient is presented here. A 69-year-old man was operated on for secondary hyperparathyroidism due to chronic renal failure. A locally invasive tumor of the right inferior parathyroid gland and enlargement of the other three parathyroid glands were found during bilateral neck exploration. Surgical management consisted of en bloc resection of the right inferior parathyroid gland with the right thyroid lobe and part of a sternothyroid muscle along with subtotal parathyroidectomy of the three enlarged parathyroid glands. Histological examination of the resected tumor provided evidence of a parathyroid cancer in the right inferior parathyroid gland. Nodular hyperplasia was confirmed histologically in the other three glands. With less than 20 previous cases described in the literature, parathyroid cancer is a very rare condition in hemodialysis patients.


Molecular, clinicopathological, and immune correlates of LAG3 promoter DNA methylation in melanoma.
The co-receptor lymphocyte-activation gene-3 (LAG3, LAG-3, CD223) is a potential target for immune checkpoint inhibition immunotherapies. However, little is known about the biological and clinical significance of LAG3 DNA methylation in melanoma and its microenvironment. We evaluated LAG3 promoter and gene body methylation in a cohort of N = 470 melanoma patients obtained from The Cancer Genome Atlas (TCGA cohort), an independent cohort of N = 120 patients from the University Hospital Bonn, and in subsets of peripheral blood leukocytes, melanocytes, and melanoma cell lines. We validated the association of LAG3 methylation with mRNA expression in vitro in the melanoma cell line A375 treated with the hypomethylating agent 5-azacytidine and stimulated with interferon-γ. Finally, we investigated correlations between LAG3 methylation and progression-free survival in patients treated with immune checkpoint blockade (ICB cohort, N = 118). Depending on the analysed locus (promoter, gene body) we found region-dependent significant LAG3 methylation differences between monocytes, B cells, CD8+ and CD4+ T cells, regulatory T cells, melanocytes, and melanoma cell lines. In tumor tissues, methylation correlated significantly with LAG3 mRNA expression, immune cell infiltrates (histopathologic lymphocyte score and RNA-Seq signatures of distinct immune infiltrates), and an interferon-γ signature. Finally, LAG3 methylation was associated with overall survival in the TCGA cohort and progression-free survival in the ICB cohort. We detected basal LAG3 mRNA expression in the melanoma cell A375 and an interferon-γ inducible expression after demethylation with 5-azacytidine. Our study points towards an epigenetic regulation of LAG3 via promoter methylation and suggests a prognostic and predictive significance of LAG3 methylation in melanoma. Our results give insight in the tumor cell-intrinsic transcriptional regulation of LAG3 in melanoma. In perspective, our results might pave the way for investigating LAG3 methylation as a predictive biomarker for response to anti-LAG3 immune checkpoint blockage. A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.


[RESEARCH PROGRESS OF EXPERIMENTAL ANIMAL MODELS OF AVASCULAR NECROSIS OF FEMORAL HEAD].
To summarize the current researches and progress on experimental animal models of avascular necrosis of the femoral head. Domestic and internation literature concerning experimental animal models of avascular necrosis of the femoral head was reviewed and analyzed. The methods to prepare the experimental animal models of avascular necrosis of the femoral head can be mainly concluded as traumatic methods (including surgical, physical, and chemical insult), and non-traumatic methods (including steroid, lipopolysaccharide, steroid combined with lipopolysaccharide, steroid combined with horse serum, etc). Each method has both merits and demerits, yet no ideal methods have been developed. There are many methods to prepare the experimental animal models of avascular necrosis of the femoral head, but proper model should be selected based on the aim of research. The establishment of ideal experimental animal models needs further research in future.


Trends in point-of-sale tobacco marketing around college campuses: Opportunities for enhanced tobacco control efforts.
Colleges have implemented policies to limit tobacco use on-campus; however, the off-campus environment is often overlooked in tobacco control efforts. We assessed availability, marketing, and promotion of cigarettes, snus, and traditional smokeless tobacco (SLT) in a sample of communities surrounding 11 college campuses in North Carolina and Virginia. Between January-March of 2011, 2012 and 2013, 481 tobacco-selling retailers, including convenience stores, pharmacies and supermarkets, located near campuses were assessed. Trained observers completed annual point-of-sale assessments. The percentage of stores selling (81.4% to 58.6%; p < .0001) and advertising snus (80.1% to 53.11%; p < .0001) significantly decreased over time. Convenience stores increased promotions of cigarettes (65.4% to 72.8%; p = 0.04) and SLT (3.1% to 23.3%; p = 0.02). Off-campus environments have abundant tobacco availability and marketing. Colleges should collaborate with state and local tobacco control advocates to address tobacco promotion near campuses to potentially decrease product appeal and access among young adults.


Cryptococcus myelitis: atypical presentation of a common infection.
Cryptococcus neoformans is associated with as much as 45% of meningitis in patients admitted for hospital care in Zimbabwe, and it is an important opportunistic infection in patients infected with the human immunodeficiency virus. Cases of cryptococcosis presenting as a spinal cord syndrome have been reported from Zimbabwe and South Africa, but these were all cases of Cryptococcus vertebral osteomyelitis. We describe 3 unusual patients who presented with a myelitis-like syndrome without vertebral osteomyelitis.


Vascularized Ulnar Transposition and Radioulnoscapholunate Fusion With Volar Locking Plate in a Dorsal Position Following Resection of Giant Cell Tumor of the Distal Radius.
Giant cell tumor of the distal radius is a rare, locally destructive, and frequently recurrent tumor. We present a case of Campanacci Grade III giant cell tumor of the distal radius with pathologic fracture and cortical destruction which was treated with neoadjuvant denosumab. This facilitated en-bloc resection of the entire distal radius, including the articular surface, while minimizing tumor contamination. Reconstruction was accomplished using a vascularized ulnar transposition flap to facilitate radioulnoscapholunate fusion, which was fixated using a long-stem contralateral variable angle locking volar distal radius plate in a dorsal position. This case illustrates multidisciplinary management of a challenging reconstructive problem and demonstrates a novel strategy for fixation which repurposes familiar and readily available hardware to provide optimal osteosynthesis.


Past tense marking by African American English-speaking children reared in poverty.
This study examined past tense marking by African American English (AAE)-speaking children from low- and middle-income backgrounds to determine if poverty affects children's marking of past tense in ways that mirror the clinical condition of specific language impairment (SLI). Participants were 15 AAE-speaking 6-year-olds from low-income backgrounds, 15 AAE-speaking 6-year-olds from middle-income backgrounds who served as age-matched controls, and 15 AAE-speaking 5-year-olds from middle-income backgrounds who served as language-matched controls. Data were drawn from language samples and probes. Results revealed high rates of regular marking, variable rates of irregular marking, high rates of over-regularizations, and absence of dialect-inappropriate errors of commission. For some analyses, marking was affected by the phonological characteristics of the items and the children's ages, but none of the analyses revealed effects for the children's socioeconomic level. Within AAE, poverty status as a variable affects past tense marking in ways that are different from the clinical condition of SLI.


Mechanisms of GABAergic homeostatic plasticity.
Homeostatic plasticity ensures that appropriate levels of activity are maintained through compensatory adjustments in synaptic strength and cellular excitability. For instance, excitatory glutamatergic synapses are strengthened following activity blockade and weakened following increases in spiking activity. This form of plasticity has been described in a wide array of networks at several different stages of development, but most work and reviews have focussed on the excitatory inputs of excitatory neurons. Here we review homeostatic plasticity of GABAergic neurons and their synaptic connections. We propose a simplistic model for homeostatic plasticity of GABAergic components of the circuitry (GABAergic synapses onto excitatory neurons, excitatory connections onto GABAergic neurons, cellular excitability of GABAergic neurons): following chronic activity blockade there is a weakening of GABAergic inhibition, and following chronic increases in network activity there is a strengthening of GABAergic inhibition. Previous work on GABAergic homeostatic plasticity supports certain aspects of the model, but it is clear that the model cannot fully account for some results which do not appear to fit any simplistic rule. We consider potential reasons for these discrepancies.


Neuropsychological sequelae of the treatment of children with medulloblastoma.
When a malignant tumor invades the child's cerebellum, the cost of successful treatment is often significant cognitive morbidity. A review of neuropsychological outcome revealed that survivors of childhood medulloblastoma (MB) have long-term deficits in intelligence, memory, language, attention, academic skills, psychosocial function, and a compromised quality of life. These deficits varied with chronological age at tumor diagnosis and/or adjuvant treatment, type and duration of presenting symptoms, tumor extension beyond the cerebellum, a history of adjuvant radiation treatment, and time since treatment. The effects on neuropsychological outcome of other factors, such as post-surgical hydrocephalus, were less clear. To understand the interaction between two factors predictive of outcome, age at diagnosis and time since treatment, we analyzed IQ results for a new sample of 25 surgically-treated and radiated MB survivors, and found that age at diagnosis and time since treatment made separable contributions to intellectual morbidity. PIQ appeared to measure some general effects of diffuse cerebral insult because it varied with chronological age of the child at tumor diagnosis but was relatively constant in magnitude, once established. VIQ, in contrast, was somewhat less sensitive to age at diagnosis in treated MB survivors, but declined with time since treatment. These results are important for understanding the academic attainments and continuing rehabilitation needs of childhood MB survivors, because they suggest that these children progressively fail to assimilate new verbally-based knowledge at a developmentally-appropriate rate.


Impact of weight loss on plasminogen activator inhibitor (PAI-1), factor VII, and other hemostatic factors in moderately overweight adults.
Based on previous cross-sectional findings, we hypothesized that weight loss could improve several hemostatic factors associated with cardiovascular disease. In a randomized controlled trial, moderately overweight men and women were assigned to one of four weight loss treatment groups or to a control group. Measurements of plasminogen activator inhibitor-1 (PAI-1) antigen, tissue-type plasminogen activator (t-PA) antigen, D-dimer antigen, factor VII activity, fibrinogen, and protein C antigens were made at baseline and after 6 months in 90 men and 88 women. Net treatment weight loss was 9.4 kg in men and 7.4 kg in women. There was no net change (p > 0.05) in D-dimer, fibrinogen, or protein C with weight loss. Significant (p < 0.05) decreases were observed in the combined treatment groups compared with the control group for mean PAI-1 (31% decline), t-PA antigen (24% decline), and factor VII (11% decline). Decreases in these hemostatic variables were correlated with the amount of weight lost and the degree that plasma triglycerides declined; these correlations were stronger in men than women. These findings suggest that weight loss can improve abnormalities in hemostatic factors associated with obesity.


Use of a batch-stirred reactor to rationally tailor biocatalytic polytransesterification.
Despite favorable thermodynamics, high-molecular weight and low-dispersity polyesters are difficult to synthesize biocatalytically in organic solvents. We have reported previously that the elimination of solvent can improve the kinetics and apparent equilibrium significantly (Chaudhary et al., 1997a). We now present the design and use of a batch-stirred enzyme reactor to control the biocatalytic polymerization. Using the reactor, polyester having a molecular weight of 23,400 Da and a polydispersity of 1.69 was synthesized in only 1 h at 60 degrees C. Additional factors like enzyme-deactivation kinetics, enzyme specificity, and initial exothermicity were investigated to develop a better understanding of this complex reaction system.


Aminoacyl-tRNA recognition by the leucyl/phenylalanyl-tRNA-protein transferase.
We employ mutant and mischarged aminoacyl-tRNAs to characterize aminoacyl-tRNA recognition by the leucyl/phenylalanyl-tRNA-protein transferase (L/Ftransferase). Wild type Met-tRNAMetm (CAU anticodon) and mischarged Met-tRNAVal-1 (CAU anticodon) are substrates for the L/F-transferase during the NH2-terminal aminoacylation of alpha-casein, whereas Val-tRNAVal-1 (UAC), Val-tRNAMetm (UAC), and Arg-tRNAMetm (CCG, A20) are not. Mutations in the anticodon and extra arm of tRNALeu-1 do not measurably effect its ability to serve as a substrate for the L/F-transferase, and the dissociation constants of the complexes between L/F-transferase and either wild type Leu-tRNALeu-4 (UAA) or mutant Leu-tRNALeu-4 (CUA) are each 0.4 +/- 0.2 microM. The dissociation constants for the complexes between the L/F-transferase and uncharged tRNA, leucine methyl ester, and puromycin are all 10-1,000-fold greater than that of the Leu-tRNA.L/F-transferase complex. Dissociation of the Leu-tRNA.L/F-transferase complex is slow, relative to the rate calculated assuming that association is diffusion controlled. Finally, deoxyoligonucleotide.aminoacyl-tRNA hybrids (dO.AA-tRNAs) are employed to characterize the determinants of the Leu-tRNALeu-4 acceptor stem recognized by the L/F-transferase. A dO.AA-tRNA completely lacking acceptor stem base pairs remains a substrate for the L/F-transferase, whereas a dO.AA-tRNA containing a 2-base pair single-stranded region, at its 3' terminus, does not.


High-density Lipoprotein and Low-density Lipoprotein Therapeutic Approaches in Acute Coronary Syndromes.
Low-density lipoprotein cholesterol (LDL), and especially its oxidized form, renders the atherosclerotic plaque vulnerable to rupture in acute coronary syndromes (ACS). On the other hand, high-density lipoprotein (HDL) is considered an anti-atherogenic molecule. The more recent HDL-targeted drugs may prove to be superior to those used before. Indeed, delipidated HDL and HDL mimetics are efficient in increasing HDL levels, while the apoA-I upregulation with RVX-208 appears to offer a clinical benefit which is beyond the HDL related effects. HDL treatment however has not shown a significant improvement in the outcomes of patients with ACS so far, studies have therefore focused again on LDL. In addition to statins and ezetimibe, novel drugs such as PSCK9 inhibitors and apolipoprotein B inhibitors appear to be both effective and safe for patients with hyperlipidemia. Data suggest these could potentially improve the cardiovascular outcomes of patient with ACS. Yet, there is still research to be done, in order to confirm whether ACS patients would benefit from LDL- or HDL-targeted therapies or a combination of both.


Oxidative stress status during the acute phase of haemolytic uraemic syndrome.
Haemolytic uraemic syndrome (HUS) is characterized by haemolytic anaemia, thrombocytopaenia and acute renal failure. The aim of this study was to investigate the levels of oxidative stress (OS) during the acute phase of HUS. This prospective study included 18 patients diagnosed with D + HUS, 6 age-matched healthy controls and 29 children with end-stage renal disease (ESRD) not caused by HUS under regular haemodialysis. Plasma lipid peroxidation and non-enzymatic antioxidant defences were measured as thiobarbituric acid-reactive substances (TBARs) and total reactive antioxidant potential (TRAP), respectively, during hospitalization and in control individuals. TBARs were significantly higher in both oliguric and non-oliguric patients at admission (1.8 ± 0.1; 1.7 ± 0.2 μM) and discharge (1.5 ± 0.1; 1.0 ± 0.1 μM) vs controls (0.5 ± 0.1 μM, P < 0.01) following disease progression. Maximal TBARs values differed significantly between oliguric and non-oliguric groups (4.5 ± 0.9 vs 2.4 ± 0.3 μM, P < 0.01) and were significantly higher (P < 0.05) than those found in ESRD patients (1.63 ± 0.1). TRAP values were significantly higher at admission and when the disease was fully established (measured here as highest TBARs record) vs controls (675 ± 51, 657 ± 60 and 317 ± 30 μM Trolox, P < 0.01), and were similar to control values at discharge (325 ± 33 μM Trolox). We demonstrate here increased levels of OS during the acute phase of HUS, with peak plasma lipid peroxidation values well above those registered in ESRD individuals, and suggest a connection between OS and the clinical course of HUS.


Anterior windowing of the femur diaphysis for cement removal in revision surgery.
Meticulous cement removal around loosened cemented hip implants is the key to successful reconstruction. In this study, the outcome of windowing the anterior femoral diaphysis was evaluated. Cementless straight tapered revision stems not filling the medullary canal were implanted without regard to bridging the window distally. The nonvascularized cortical lids were replanted after previous periosteal stripping. Forty-one procedures done between 1991 and 2001 were reviewed after 3.5 to 11.9 (mean, 7.4) years. The implant tip was distal to the distal end of the window in 54% of cases. Except in one case, it did not project beyond the window distally by at least twice the diaphyseal width. The implant tip was proximal to the distal end of the window in 29% and level with it in 17%. None of the patients developed stress fractures. Early postoperative subsidence was observed in four instances, but was irrelevant for implant stability at followup. One patient had revision surgery for low-grade infection. All cortical lids were radiologically re-osseointegrated after 4 to 29 months. Revision stems not bridging the defect distally and cortical lids stripped of periosteum were not associated with any disadvantages. Their use can be recommended using the surgical technique described. Therapeutic study, Level IV (case series). See the Guidelines for Authors for a complete description of levels of evidence.


Clostridium asparagiforme sp. nov., isolated from a human faecal sample.
An obligatory anaerobic, Gram-positive, rod-shaped organism was isolated from faeces of a healthy human donor. It was characterized using biochemical, phenotypic and molecular taxonomic methods. The organism produced acetate, lactate, and ethanol as the major products of glucose fermentation. The G + C content was 53 mol%. Based on comparative 16S rRNA gene sequencing, the unidentified bacterium is a member of the Clostridium subphylum of the Gram-positive bacteria, and most closely related to species of the Clostridium coccoides cluster (rRNA cluster XIVa) [M.D. Collins et al., The phylogeny of the genus Clostridium: proposal of five new genera and eleven new species combinations, Int. J. Syst. Bacteriol. 44 (1994) 812-826]. Clostridium bolteae and Clostridium clostridioforme were identified as the most closely related described species. A 16S rRNA sequence divergence value of > 3% suggested that the isolate represents a new species. This was also supported by the gyrase-encoding gyrB gene sequences. Based on these findings, we propose the novel bacterium from human faeces to be classified as a new species, Clostridium asparagiforme. The type strain of C. asparagiforme is N6 (DSM 15981 and CCUG 48471).


Need to revise the national drinking water regulation for copper.
Copper is an essential micronutrient and a potential toxic metal. The USEPA current maximum contaminant level goal (MCLG, a nonenforceable aspirational health goal) and the required treatment technique action level, both set at 1.3 mg/liter of copper are not adequately protective for infants and children under 10 years of age. Infants and children up to 10 years of age have increased susceptibility to copper toxicity. The two main reasons for the high sensitivity in this population subgroup are the presence of a normally high concentration of copper in the liver during early life and the lack of a fully developed homeostatic mechanism of copper in children under 10 years of age. This sensitive group of infants and children represents approximately 17% of the total U.S. population. The adverse health effects caused by drinking water contaminated with copper are abdominal pain, nausea, vomiting, diarrhea, headache, and dizziness. The proposed drinking water guideline of 0.3 mg/liter for copper was derived by the application of the risk assessment procedures approved by the USEPA. Drinking water containing 0.3 mg/liter of copper will provide approximately 26% of the nutritional requirement of copper. This proposed drinking water guideline (0.3 mg/liter) for copper will adequately protect health of infants, children, and adults.


Junctional epithelium in rats is characterized by slow cell proliferation.
The integrity of junctional epithelium (JE) and a firm epithelial adhesion to the tooth surface are maintained by the balance between cell proliferation and cell death. Maintaining the JE structure is essential for the protection of periodontal connective tissues against oral microbes. In this study, the proliferative activity and the expression of caspase 3, a cysteine protease associated with cell death, were studied in rat JE and other epithelial structures during molar tooth development. Fourteen rats aged 10 to 70 days were injected with bromodeoxyuridine (BrdU). Samples of first and second molars were selected for immunohistochemical staining. BrdU incorporation was studied in oral epithelium (OE) covering the erupting tooth, reduced enamel epithelium (REE), and gingival epithelium (GE), sulcular epithelium (SE), and JE. Samples were also subjected to immunohistochemical analysis for proliferating cell nuclear antigen (PCNA) and caspase 3. The basal cells of the GE were actively proliferating, but in the JE, only a few cells were positive for BrdU or PCNA immunostaining. Some outer REE cells were proliferating during tooth eruption. Caspase 3 expression was in specific areas of REE after completion of amelogenesis. Results showed slow proliferative activity in the rat JE. However, specific studies on cellular turnover and cell migration are needed to understand tissue homeostasis in this area.


Isolation of the Drosophila segmentation gene runt and analysis of its expression during embryogenesis.
runt is one of the genes required for establishment of the segmented body pattern of the Drosophila embryo. We have isolated DNA sequences containing this gene using P-element transposon tagging. Southern blot analyses of six different DNA rearrangements that are associated with runt mutations revealed a minimal region of 8.5-kb of DNA that was important for function. In germ line transformation experiments, a 14.5-kb segment of DNA that spanned this minimal region provided significant, although not full, levels of runt activity. The runt gene encoded a 2.6-kb poly(A)+ RNA that underwent a series of dynamic changes in its spatial and temporal patterns of accumulation during embryogenesis. The runt RNA was most abundant at the blastoderm stage when it showed the seven stripes of expression characteristic of other Drosophila pair-rule genes.


Surface-length index: a novel index for rapid detection of right ventricles with abnormal ejection fraction using cardiac MRI.
To validate a new index, the surface-length index (SLI) based on area change in a short-axis view and length reduction in the horizontal long-axis view, which is used to quickly (<1 min) detect right ventricles with an abnormal ejection fraction (EF) during a cardiac MRI examination. SLI can be used to avoid a complete delineation of the endocardial contours of normal right ventricles. Sixty patients (group A) were retrospectively included to calibrate the SLI formula by optimisation of the area under the ROC curves and SLI thresholds were chosen to obtain 100 % sensitivity. Another 340 patients (group B) were prospectively recruited to test SLI's capacity to detect right ventricles (RVs) with an abnormal EF (<0.5). The appropriate threshold to obtain 100 % sensitivity in group A was 0.58. In group B, with the 0.58 threshold, SLI yielded a sensitivity of 100 % and specificity of 51 %. SLI would have saved 35 % of the RV studies in our population, without inducing any diagnostic error. SLI and EF correlation was good (r (2) = 0.64). SLI combines two simple RV measures, and brings significant improvement in post-processing efficiency by preselecting RVs that require a complete study. • Assessment of right ventricle ejection fraction (RVEF) with cine-MRI is time consuming. • Therefore, RVEF is not always assessed during cardiac MRI. • Surface-length index (SLI) allows rapid detection of abnormal RVEF during cardiac MRI. • SLI saves one third of the operator time. • Every cardiac MRI could include RVEF assessment by means of SLI.


Case management in capitated long-term care.
For a very impaired population needing multiple interrelated services, the case management approach used by On Lok Senior Health Services in San Francisco, California, produces a responsive, flexible service system. Case management in On Lok's consolidated model has three key characteristics: (1) a true multidisciplinary team of medical as well as nonmedical personnel who separately assess, then, as a group, plan with the client and/or the family the services to be given; (2) use of the same team to assess needs and deliver services; and (3) team access to a potentially unlimited array of services, with freedom to adapt or create needed services.


A comparative study of mini-external fixation systems used to treat unstable metacarpal fractures.
We compared the biomechanical properties, clinical versatility, application ease, and financial cost of 7 mini-external fixation systems used to treat unstable metacarpal shaft fractures with segmental bone loss. Attached to a maple dowel fracture model, each fixator was tested in axial compression, lateral 4-point bending, 45 degrees apex-dorsal 4-point bending, and torsion. The EBI DynaFix system had the highest overall rigidity values and was highly versatile; the Synthes/AO Mini-External Fixator had intermediate rigidity values and was the lightest system tested; the Howmedica Mini-Hoffmann fixator was substantially less rigid than all the other tested constructs but was the most versatile. Devices constructed with polymethylmethacrylate and Kirschner wires were rigid, lightweight, and inexpensive. Routine use of these devices is discouraged, however, because of unacceptable loosening at the pin-cement interface during testing and because of difficulties encountered during construction and application. None of the external fixation systems tested was superior in all the parameters analyzed.


Clinical Remission in a 72-Year-Old Patient with a Massive Primary Cutaneous Peripheral T-Cell Lymphoma-NOS of the Eyelid, Following Combination Chemotherapy with Etoposide Plus COP.
Peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) is the rarest subtype of primary cutaneous lymphoma, accounting for approximately 2% of cutaneous lymphomas. The rarity of primary cutaneous PTCL-NOS means that there is a paucity of data regarding clinical and histopathological features and its clinical course. This malignancy is an aggressive and life-threatening hematological malignancy that often presents mimicking other less severe plaque-like skin conditions. Due to the nonspecific nature of these lesions, CD4-positive cutaneous T-cell lymphoma (CTCL) is often misdiagnosed as either mycosis fungoides or Sezary syndrome. We describe a patient who presented with a large tumoral mass in the right frontal area, with involvement of the right upper eyelid and the ocular globe, causing loss of vision greatly impacting the quality of life. Biopsy revealed primary cutaneous PTCL-NOS, treated successfully with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) plus etoposide combination chemotherapy. As elderly patients are indicated to receive attenuated doses of chemotherapy, CHOP-based regimens represent viable options.


Mean Glenoid Defect Size and Location Associated With Anterior Shoulder Instability: A Systematic Review.
There is a strong correlation between glenoid defect size and recurrent anterior shoulder instability. A better understanding of glenoid defects could lead to improved treatments and outcomes. To (1) determine the rate of reporting numeric measurements for glenoid defect size, (2) determine the consistency of glenoid defect size and location reported within the literature, (3) define the typical size and location of glenoid defects, and (4) determine whether a correlation exists between defect size and treatment outcome. Systematic review; Level of evidence, 4. PubMed, Ovid, and Cochrane databases were searched for clinical studies measuring glenoid defect size or location. We excluded studies with defect size requirements or pathology other than anterior instability and studies that included patients with known prior surgery. Our search produced 83 studies; 38 studies provided numeric measurements for glenoid defect size and 2 for defect location. From 1981 to 2000, a total of 5.6% (1 of 18) of the studies reported numeric measurements for glenoid defect size; from 2001 to 2014, the rate of reporting glenoid defects increased to 58.7% (37 of 63). Fourteen studies (n = 1363 shoulders) reported defect size ranges for percentage loss of glenoid width, and 9 studies (n = 570 shoulders) reported defect size ranges for percentage loss of glenoid surface area. According to 2 studies, the mean glenoid defect orientation was pointing toward the 3:01 and 3:20 positions on the glenoid clock face. Since 2001, the rate of reporting numeric measurements for glenoid defect size was only 58.7%. Among studies reporting the percentage loss of glenoid width, 23.6% of shoulders had a defect between 10% and 25%, and among studies reporting the percentage loss of glenoid surface area, 44.7% of shoulders had a defect between 5% and 20%. There is significant variability in the way glenoid bone loss is measured, calculated, and reported.


A human putative lymphocyte G0/G1 switch gene homologous to a rodent gene encoding a zinc-binding potential transcription factor.
G0S24 is a member of a set of genes (putative G0/G1 switch regulatory genes) that are expressed transiently within 1-2 hr of the addition of lectin or cycloheximide to human blood mononuclear cells. Comparison of a full-length cDNA sequence with the corresponding genomic sequence reveals an open reading frame of 326 amino acids, distributed across two exons. Potential phosphorylation sites include the sequence PSPTSPT, which resembles an RNA polymerase II repeat reported to be a target of the cell cycle control kinase cdc2. Comparison of the derived protein sequence with those of rodent homologs allows classification into three groups. Group 1 contains G0S24 and the rat and mouse TIS11 genes (also known as TTP, Nup475, and Zfp36). Members of this group have three tetraproline repeats. Groups 1 and 2 have a serine-rich region and an "arginine element" (RRLPIF) at the carboxyl terminus. All groups contain cysteine- and histidine-rich putative zinc finger domains and a serine-phenylalanine "SFS" domain similar to part of the large subunit of eukaryotic RNA polymerase II. Comparison of group 1 human and mouse genomic sequences shows high conservation in the 5' flank and exons. A CpG island suggests expression in the germ line. G0S24 has potential sites for transcription factors in the 5' flank and intron; these include a serum response element. Protein and genomic sequences show similarities with those of a variety of proteins involved in transcription, suggesting that the G0S24 product has a similar role.


BRCA1 promoter methylation in sporadic breast cancer is associated with reduced BRCA1 copy number and chromosome 17 aneusomy.
To explore the molecular mechanisms for the similarities between inherited and noninherited forms of breast cancer, we tested the hypothesis that inactivation of BRCA1 by promoter hypermethylation is associated with reduced gene copy number and chromosome 17 aneusomy as observed in tumors from BRCA1 mutation carriers. Using a combination of methylation-specific PCR analysis and fluorescence in situ hybridization, we observed varying degrees of promoter methylation in 39 of 131 (29.8%) primary tumors. Despite significant tumor heterogeneity, mean copy numbers of BRCA1 and CEP17 per cell were lower in methylated cases compared with unmethylated cases [1.78 versus 2.30 (P = 0.001) and 1.85 versus 2.29 (P = 0.005), respectively]. Methylation was more frequently observed in younger women (P = 0.05) with high-grade (P = 0.001), estrogen receptor-negative (P = 0.04), and progesterone receptor-negative (P = 0.01) tumors. Moreover, methylation was associated with reduced or absent BRCA1 transcripts, which was reversible in the heavily BRCA1-methylated cell line UACC3199 following treatment with 5-aza-2'-deoxycytidine and trichostatin A. We identified five CpGs at positions -533, -355, -173, -21, and +44 as critical in the reexpression of BRCA1. We conclude that BRCA1 methylation contributes to a subset of sporadic breast cancers with the resulting molecular and clinicopathologic phenotype similar to that of hereditary BRCA1-associated breast cancers. Our data support a model of carcinogenesis in which BRCA1 promoter methylation may serve as a "first hit," much like an inherited germ line mutation, and promote tumor progression down a restricted set of molecular pathways.


Psychomotor and intellectual development (Neurocognitive Function) of children born small for gestational age (SGA). Transversal and longitudinal study.
Although much is now known about the effects of intrauterine growth retardation (IUGR) on children born SGA with regard to anthropometric and biochemical parameters and their treatment, there are still many gaps associated with its impact on neurocognitive functions. In our experience published several years ago, IUGR has a negative effect on neurocognitive development, regardless of whether these children showed evidence of catch-up growth or not or of the socio-economic conditions that might contribute to the situation. We have now accumulated a large number of cases, many of whom have been followed longitudinally, some for up to 7 years, many having been treated with GH from the time when this therapy was first approved by the EMA. Apart from the cases mentioned, other confounding factors such as gestational age, Apgar score, neonatal comorbidity and the possible effects of GH treatment have also been included. In addition and using our own reference standards, we now present our experience, which confirms what we had already noted in the past, that IUGR is in itself a condition that often causes psychomotorintellectual impairment, may be extremely severe and tends to worsen. This negative impact of IUGR on neurocognitive development does not depend on how the child grows,spontaneous growth is better and when growth is not altered by GH therapy. Later studies will be able to confirm whether early treatment with GH throughout the 2nd year of life, or an early specific stimulation programme, or the sum of both, can improve the neurocognitive development of these children. IUGR prevention, acting on causal factors that are partly avoidable such as smoking, working conditions and stress during pregnancy (see the corresponding article in this supplement) proves once again to be the best way to stop this negative impact on the IQ of many children born SGA.


Detection of neuropeptide Y and its mRNA in megakaryocytes: enhanced levels in certain autoimmune mice.
Neuropeptide tyrosine (neuropeptide Y, NPY) is a potent vasoconstrictor with a wide distribution in the central and peripheral nervous systems. Here we show that high levels of rat NPY mRNA are also found in peripheral blood cells, bone marrow, lung, and spleen. Furthermore, radioimmunoassay revealed high levels of NPY-like peptide in these tissues. In mice, the levels of splenic NPY mRNA and immunoreactive peptide differed extensively between strains and were greatly elevated in several strains (NZB, NZBxW, and BXSB) that develop a disease resembling human systemic lupus erythematosus. Like the rat, the NZB mouse showed a high content of NPY mRNA in peripheral blood cells and bone marrow. Immunohistochemical staining revealed NPY-like immunoreactivity in large cells morphologically identifiable as megakaryocytes in rat bone marrow and in the spleen of the NZB mouse strain. Expression of NPY mRNA in megakaryocytes in rat bone marrow and NZB mouse spleen was confirmed by in situ hybridization. These results indicate that NPY is synthesized in megakaryocytes, implying that NPY can be released from platelets and function as a vasoconstrictor during blood-vessel damage. In addition, the increase in splenic NPY in certain autoimmune mouse strains adds to the list of abnormalities associated with these strains.


Revelation in the field of tissue preservation - a preliminary study on natural formalin substitutes.
The quest for formalin substitutes has long been going on due to its health hazards. Honey has been proven as a safe alternative to formalin. However, we explored more economical, eco-friendly & readily available substances like sugar & jaggery as natural substitutes for formalin. The aim of this study was to compare the tissue fixation abilities of honey, sugar syrup & jaggery syrup with that of formalin using H & E stain and to determine the best fixative among the three. Commercially available fresh goat meat (buccal mucosa) was cut into five bits & each bit was placed in five different containers containing 10% buffered formalin, distilled water, 20% honey, 20% sugar syrup & 30% jaggery syrup with formalin as positive control & distilled water as negative control. 24 hours tissue fixation was attained at room temperature followed by conventional processing and staining. The tissue sections were assessed for cytoplasmic, nuclear details & staining quality under light microscopy. Each criteria was rated on a scale of 1- 4 (1 for poor & 4 for excellent) & the whole procedure was blinded. RESULTS were analysed by Kruskal Wallis ANOVA test. Inter-observer variability was determined by Kappa statistics. The preservation of tissue by honey, sugar & jaggery syrup was comparable to that of formalin. Among the three natural fixatives, jaggery syrup excelled. Our effort of using sugar and jaggery for tissue fixation is first of its kind and yielded good results. Hence they can be successfully adopted in routine histopathology laboratories in place of formalin. Natural fixatives can be used in place of the hazardous formalin with equal efficiency. Also, jaggery being highly economical and universally available can be employed in large scale as in screening camps. How to cite this article: Patil S, Premalatha B R, Rao R S, Ganavi B S. Revelation in the Field of Tissue Preservation - A Preliminary Study on Natural Formalin Substitutes. J Int Oral Health 2013; 5(1):31-38.


Microscopy in electron diffraction apparatus.
A simple method was devised for observing electron micrographs as well as diffraction figures from a given object. A dielectric emulsion composed of paraffin and barium titanate acted here as an electrostatic lens when charged up with the incident electrons. Electron diffraction figures could immediately be observed from the same object as for microscopy when the lens was mechanically removed out of the electron path.


The effects of using stimuli from three different dimensions on autoshaping with a complex negative patterning discrimination.
In two experiments pigeons received a complex negative patterning discrimination, using autoshaping, in which food was made available after three stimuli if they were presented alone (A, B, C), or in pairs (AB, AC, BC), but not when they were all presented together (ABC). Subjects also received a positive patterning discrimination in which three additional stimuli were not followed by food when presented alone (D, E, F), or in pairs (DE, DF, EF), but they were followed by food when presented together (DEF). Stimuli A and D belonged to one dimension, B and E to a second dimension, and D and F to a third dimension. For both problems, the discrimination between the individual stimuli and the triple-element compounds developed more readily than that between the pairs of stimuli and the triple-element compound. The results are consistent with predictions that can be derived from a configural theory of conditioning.


2-Chloro-4-nitro-benzoic acid-quinoline (1/1).
In the title compound, C(7)H(4)ClNO(4)·C(9)H(7)N, the two components are connected by an O-H⋯N hydrogen bond. In the hydrogen-bonded unit, the dihedral angle between the quinoline ring system and the benzene ring of benzoic acid is 3.15 (7)°. In the crystal, units are linked by inter-molecular C-H⋯O hydrogen bonds, forming a tape along the c axis. The tapes are stacked along the b axis through a C-H⋯O hydrogen bond into a layer parallel to the bc plane.


Atlas of fluorescein angiographic findings in eyes undergoing laser for retinopathy of prematurity.
We sought to examine the clinical features of severe retinopathy of prematurity (ROP) using fluorescein angiography (FA). Retrospective case series of eyes with severe acute-phase ROP that underwent FA at the time of laser photocoagulation. We included 22 eyes of 11 infants that developed ROP stage 3 in zone 1 with plus disease, 8 eyes of 4 infants classified as ROP stage 3 in zone 1 without plus disease, and 21 eyes of 11 infants that developed ROP stage 3 in zone 2 with plus disease. All eyes underwent laser photocoagulation. A total of 51 sets of digital images including FA were obtained immediately before treatment. RetCam (Clarity, Pleasanton, CA) fundus images and video digital FAs were performed under general anesthesia right before laser treatment. A 10% solution of fluorescein was intravenously administered as a bolus at a dose of 0.1 ml/kg, followed by an isotonic saline flush. Fluorescein angiograms were examined retrospectively to catalog different retinal and choroidal findings In eyes with severe ROP, FA clearly shows extreme variability in both retinal circulation and choroidal filling pattern. Different patterns of vessels branching at the junction between vascular and avascular retina (V-Av junction) are noted. Posterior to the V-Av junction, hypoperfused retinal areas with or without hyperfluorescent "cotton-wool-like" or "popcorn-like" lesions due to dye leakage are documented by FA. Focal dilatation of capillaries, capillary tufts formations, and rosary-bead-like hyperfluorescent lesions inside the vessels were seen; sometimes all 3 are noted. Various macular abnormalities are noted including absence of foveal avascular area and significant exudative component. Fluorescein angiography was useful to distinguish the deceptively featureless zone 1 junction between the vascularized and nonvascularized retina. Further studies are needed to understand the role of vascular abnormalities observed in zone 1 vascularized retina.


Myocardial remodeling is controlled by myocyte-targeted gene regulation of phosphodiesterase type 5.
we tested the hypothesis that bi-directional, gene-targeted regulation of cardiomyocyte cyclic guanosine monophosphate-selective phosphodiesterase type 5 (PDE5) influences maladaptive remodeling in hearts subjected to sustained pressure overload. PDE5 expression is up-regulated in human hypertrophied and failing hearts, and its inhibition (e.g., by sildenafil) stimulates protein kinase G activity, suppressing and reversing maladaptive hypertrophy, fibrosis, and contractile dysfunction. Sildenafil is currently being clinically tested for the treatment of heart failure. However, researchers of new studies have questioned the role of myocyte PDE5 and protein kinase G (PKG) to this process, proposing alternative targets and mechanisms. mice with doxycycline-controllable myocyte-specific PDE5 gene expression were generated (medium transgenic [TG] and high TG expression lines) and subjected to sustained pressure overload. Rest myocyte and heart function, histology, and molecular profiling were normal in both TG lines versus controls at 2 months of age. However, upon exposure to pressure overload (aortic banding), TG hearts developed more eccentric remodeling, maladaptive molecular signaling, depressed function, and amplified fibrosis with up-regulation of tissue growth factor signaling pathways. PKG activation was inhibited in TG myocytes versus controls. After establishing a severe cardiomyopathic state, high-TG mice received doxycycline to suppress PDE5 expression/activity only in myocytes. This in turn enhanced PKG activity and reversed all previously amplified maladaptive responses, despite sustained pressure overload. Sildenafil was also effective in this regard. these data strongly support a primary role of myocyte PDE5 regulation to myocardial pathobiology and PDE5 targeting therapy in vivo and reveal a novel mechanism of myocyte-orchestrated extracellular matrix remodeling via PDE5/cyclic guanosine monophosphate-PKG regulatory pathways.


Lack of association between CTLA-4 gene polymorphism and IDDM in Japanese subjects.
Susceptibility to insulin-dependent diabetes mellitus (IDDM) is determined by both environmental and genetic factors. The main gene associated with predisposition to IDDM is HLA. Recent studies have described linkage and association of IDDM to the CTLA-4 gene (IDDM12) in Caucasians. CTLA-4 is a candidate gene for T-cell-mediated autoimmune diseases because it is a negative regulator of T-cell proliferation. We investigated the distribution of a CTLA-4 gene polymorphism in 110 Japanese patients with IDDM and 200 control subjects. In 84 patients, we also investigated associations between this CTLA-4 gene polymorphism and GAD65 antibody positivity. An A/G transition at position 49 of exon 1 was analyzed by the polymerase chain reaction-restriction fragment length polymorphism method. GAD65 antibody was detected using a radioligand binding assay. There was no significant difference in the distribution of CTLA-4 alleles in patients and controls and no difference was observed in prevalence of CTLA-4 alleles when GAD65 antibody-positive and -negative individuals in the IDDM groups were compared. The present study did not support an association between the CTLA-4 gene and IDDM in the Japanese population.


Simple alignment technique for polarisation maintaining fibres.
We describe a simple technique for rapid alignment of input state of polarisation with respect to the preferred axis of polarisation maintaining fibres. In this technique a combination of a half-wave and a quarter-wave plate is used to turn the polarisation of incoming beam and to compensate for stress-induced perturbation of polarisation states in a laid-out fibre, respectively. The angular alignment technique is tested with temperature excursion on the fibre. The technique is easy to implement, affordable, and gives quick and accurate alignment.


Construction and expression of an enzymatically active form of PECAM-1 containing the phosphatase domain of the protein tyrosine phosphatase, SHP-2.
Platelet endothelial cell adhesion molecule-1 (PECAM-1; CD31) is a 130-kDa transmembrane glycoprotein that is expressed on the surfaces of platelets, endothelial cells, and certain leukocyte subsets. The extracellular region of PECAM-1 contains six immunoglobulin homology domains, two of which (domains 1 and 2) mediate PECAM-1 homophilic interactions. Recent evidence suggests that a major function of the extracellular region of PECAM-1 is to determine its localization within the plane of the plasma membrane. The cytoplasmic domain of PECAM-1 contains an immunoreceptor tyrosine-based inhibitory motif that, upon tyrosine phosphorylation, supports recruitment of the Src homology 2 domain-containing protein tyrosine phosphatase, SHP-2. However, neither the targets of this PECAM-1/SHP-2 complex nor the significance of localizing SHP-2 to the borders of opposing PECAM-1-expressing cells is yet known. As a first step in addressing these issues, we designed a cDNA encoding a chimeric protein composed of the PECAM-1 extracellular domain fused to the phosphatase domain of SHP-2, which we call PECAM-1/PhD2. When immunopurified from stably transfected HEK293 cell lines expressing this recombinant protein, PECAM-1/PhD2 was found to possess constitutive enzymatic activity and appropriate border localization. This constitutively active chimeric protein will be useful in future studies designed to define the components of signal transduction pathways modulated by PECAM-1/SHP-2 signaling complexes.


The thermodynamics and electronic structure analysis of P-doped spinel Co3O4.
The thermodynamics of phosphorus (P) doping to spinel Co3O4, for both bulk cases and (100) and (110) surface cases, is studied using first principles calculations. The doping energies of the P atom at different doping sites are carefully calculated and compared. It is shown that P doping at Co sites, at either tetrahedral or octahedral sites, is energetically favorable, while P doping and replacing O atoms are energetically unfavorable. The doping energy difference is large enough to conclude that P doping has a very strong preference to take the Co sites, rather than the O sites in spinel Co3O4. Even when O-vacancy is available, P doping and taking the O-vacancy site is thermodynamically unfavorable. The physical/chemical mechanism behind this phenomenon is carefully analyzed. Electronic structure analysis shows that P doping and replacing the Co atom brings excess electrons to the Co3O4 system, which is beneficial to enhance the electrochemical and catalytic performance of the spinel Co3O4. Our results clarified the misleading results of P doping and replacing O atoms in spinel Co3O4 reported in the literature.


Dyslexia and dysgraphia: more than written language difficulties in common.
A dual-task paradigm involving concurrent finger tapping and line orientation judgment was used to investigate brain processing differences in early adolescent good readers/poor spellers (dysgraphia), poor readers/poor spellers (dyslexia) and good readers/good spellers. Whereas all groups were similarly affected during the left-hand tapping condition, in the right-hand tapping condition the good spelling group displayed significantly less tapping disruption than both poor spelling groups, who did not differ significantly from each other. From these results, it can be inferred that individuals with dyslexia and dysgraphia share a left-hemisphere processing limitation that is not confined to written language. In light of other relevant research findings, I suggest that this limitation is due to the absence of a disembedding scanning mechanism for converting spatial arrays (e.g., spelling patterns) to temporal form-an impairment putatively caused by attempting to teach written language to children who are late in establishing left-hemisphere motor dominance.


Laparoscopic mucosectomy for large choledochal cyst.
The laparoscopic excision of the choledochal cyst is feasible, but it entails certain difficulties while dealing with huge cysts because of the risk of injury of important surrounding structures. Mucosectomy of these large cysts is described in open surgery for huge adherent cysts, and the idea can be applied for laparoscopic excision. Over a period of 5 years, 5 of 30 patients with a large choledochal cyst underwent the laparoscopic mucosectomy. The procedure was done under general anesthesia, with an initial operative cholangiography to delineate the anatomy of the cyst. The common hepatic duct at its junction with the cyst was dissected and cut, leaving the distal end attached to the cystic duct and gallbladder. The cyst was opened at its upper part, and the upper half with the attached gallbladder was excised en block. A plane between the mucosa and the covering of the cyst was found, and the mucosa was peeled by traction and countertraction with proper hemostasis. The procedure was completed by performing hepatico-duodenostomy. Five patients were operated on by this technique. Their age ranged from 3 months to 8 years. The procedure was done successfully in all patients, but a conversion was needed in 1 patient due to a difficult hepatico-duodenostomy. The operative time ranged from 125 to 180 minutes (mean, 140). The follow-up ranged from 4 months to 5 years, with a relief of symptoms in all cases and with no evidence of cholangitis or jaundice. Mucosectomy can be performed safely with the laparoscopy. The technique is easy, avoiding the difficult dissection of the huge adherent cyst from the surrounding important structures.


Heightened pressor effect and dipsogenicity to intracerebroventricularly applied angiotensin II and III in spontaneously hypertensive rats.
The effect of acute intracerebroventricular (i.c.v.) injections of angiotensin II and III (ANG II and ANG III; 0, 1, 10 and 100 pmol in 2 microliters artificial cerebrospinal fluid (CSF) on blood pressure and water consumption was investigated in Okamoto-Aoki spontaneously hypertensive rats (SHR), and Wistar-Kyoto (WKY) and Sprague-Dawley (SD) normotensive controls. Heightened sensitivity to i.c.v. ANG II and ANG III was observed in the SHR compared with the WKY and SD strains (P less than 0.001), for both pressor and drinking responses. In addition, i.c.v. treatment with an aminopeptidase B inhibitor, bestatin (20 nmol in 1 microliter artificial CSF) significantly potentiated the heightened pressor response to i.c.v.-injected ANG II and ANG III (100 pmol) in SHR and to a lesser degree in WKY animals compared with SD controls (P less than 0.001). These results suggest that a dysfunction in central aminopeptidase activity results in an extended life of endogenous angiotensins, and perhaps other peptides that may contribute to the high blood pressure seen in this animal model of human essential hypertension.


Angiotensin 1-7 stimulates brown adipose tissue and reduces diet-induced obesity.
The renin-angiotensin system is a key regulator of metabolism with beneficial effects of the angiotensin 1-7 (Ang 1-7) peptide. We hypothesized that the antiobesity effect of Ang 1-7 was related to the stimulation of brown adipose tissue (BAT). We administered Ang 1-7 (0.54 mg kg-1 day-1) for 28 days via implanted micro-osmotic pumps to mice with high-fat diet (HFD)-induced obesity. Ang 1-7 treatment reduced body weight, upregulated thermogenesis, and ameliorated impaired glucose homeostasis without affecting food consumption. Furthermore, Ang 1-7 treatment enlarged BAT and the increased expression of UCP1, PRDM16, and prohibitin. Alterations in PRDM16 expression correlated with increased AMPK and phosphorylation of mTOR. Ang 1-7 treatment elevated thermogenesis in subcutaneous white adipose tissue without altering UCP1 expression. These changes occurred in the context of decreased lipid accumulation in BAT from HFD-fed mice, preserved insulin signaling concomitant with phosphorylation of hormone-sensitive lipase and decreased expression of perilipin. These data suggest that Ang 1-7 induces brown adipocyte differentiation leading to upregulation of thermogenesis and improved metabolic profile in diet-induced obesity. Enhancing Ang 1-7 action represents a promising therapy to increase BAT and to reduce the metabolic complications associated with diet-induced obesity.


Radioiodine-Refractory Thyroid Cancer: Molecular Basis of Redifferentiation Therapies, Management, and Novel Therapies.
Recurrent, metastatic disease represents the most frequent cause of death for patients with thyroid cancer, and radioactive iodine (RAI) remains a mainstay of therapy for these patients. Unfortunately, many thyroid cancer patients have tumors that no longer trap iodine, and hence are refractory to RAI, heralding a poor prognosis. RAI-refractory (RAI-R) cancer cells result from the loss of thyroid differentiation features, such as iodide uptake and organification. This loss of differentiation features correlates with the degree of mitogen-activated protein kinase (MAPK) activation, which is higher in tumors with BRAF (B-Raf proto-oncogene) mutations than in those with RTK (receptor tyrosine kinase) or RAS (rat sarcoma) mutations. Hence, inhibition of the mitogen-activated protein kinase kinase-1 and -2 (MEK-1 and -2) downstream of RAF (rapidly accelerated fibrosarcoma) could sensitize RAI refractivity in thyroid cancer. However, a significant hurdle is the development of secondary tumor resistance (escape mechanisms) to these drugs through upregulation of tyrosine kinase receptors or another alternative signaling pathway. The sodium iodide symporter (NIS) is a plasma membrane glycoprotein, a member of solute carrier family 5A (SLC5A5), located on the basolateral surfaces of the thyroid follicular epithelial cells, which mediates active iodide transport into thyroid follicular cells. The mechanisms responsible for NIS loss of function in RAI-R thyroid cancer remains unclear. In a study of patients with recurrent thyroid cancer, expression levels of specific ribosomal machinery-namely PIGU (phosphatidylinositol glycan anchor biosynthesis class U), a subunit of the GPI (glycosylphosphatidylinositol transamidase complex-correlated with RAI avidity in radioiodine scanning, NIS levels, and biochemical response to RAI treatment. Here, we review the proposed mechanisms for RAI refractivity and the management of RAI-refractive metastatic, recurrent thyroid cancer. We also describe novel targeted systemic agents that are in use or under investigation for RAI-refractory disease, their mechanisms of action, and their adverse events.