A new distinctive species of pagurid hermit crab (Crustacea: Decapoda: Anomura) from Japan.
A new species of pagurid hermit crab, Pagurus decimbranchiae, is described and illustrated based on 20 specimens collected from shallow waters of the Pacific coast of Japan ranging from Boso Peninsula to Tanegashima Island. It is quite distinctive in having the rudimentary arthrobranch on the third maxilliped represented by a single bud, however close morphological similarity is found between the new species and P. moluccensis Haig and Ball. Comparisons are also made among other species, including P. boriaustraliensis Morgan, P. sp. cf. boriaustraliensis sensu Rahayu and Komai (2000) and the members of the P. anachoretus group. The present generic assignment of the new species should be considered provisional, as more extensive study is needed to investigate phylogenetic relationships of the new species and the other species of Pagurus.


TbKINX1B: a novel BILBO1 partner and an essential protein in bloodstream form Trypanosoma brucei.
The flagellar pocket (FP) of the pathogen Trypanosoma brucei is an important single copy structure that is formed by the invagination of the pellicular membrane. It is the unique site of endo- and exocytosis and is required for parasite pathogenicity. The FP consists of distinct structural sub-domains with the least explored being the flagellar pocket collar (FPC). TbBILBO1 is the first-described FPC protein of Trypanosoma brucei. It is essential for parasite survival, FP and FPC biogenesis. In this work, we characterize TbKINX1B, a novel TbBILBO1 partner. We demonstrate that TbKINX1B is located on the basal bodies, the microtubule quartet (a set of four microtubules) and the FPC in T. brucei. Down-regulation of TbKINX1B by RNA interference in bloodstream forms is lethal, inducing an overall disturbance in the endomembrane network. In procyclic forms, the RNAi knockdown of TbKINX1B leads to a minor phenotype with a small number of cells displaying epimastigote-like morphologies, with a misplaced kinetoplast. Our results characterize TbKINX1B as the first putative kinesin to be localized both at the basal bodies and the FPC with a potential role in transporting cargo along with the microtubule quartet.


[The role of ischemical preconditioning in the development of ischemia-reperfusion hepatic injury in experiment].
The optimal regimen of preliminary ischemic preparation, in which the vessels occlusion causes minimal pathohistological hepatic changes without inhibition of its regeneration capacities, was studied in experiment. The ischemic-reperfusional damage of liver, using hepatoduodenal ligament crossclamping in various regimens, was modeled on 40 rabbits in a randomized experimental investigation. Morphological investigations of the animals liver fragments, taken immediately after ligament crossclamping and on the third postoperative day, were performed. There was established, that severity and reversibility of the hepatic tissue affection have differed, depending on the ischemia duration and reperfusion period. The vessels occlusion regimen with preliminary ischemic preparation was the most safe for hepatic tissue, without rude structural injuries and functional disorders, permitting to recommend it for clinical application as the optimal one while performance of hepatic resection in combination with afferent vascular exclusion.


Effects of Body-Oriented Interventions on Preschoolers' Social-Emotional Competence: A Systematic Review.
A growing body of evidence supports the effectiveness of body-oriented interventions (BOI) in educational contexts, showing positive influences on social-emotional competence. Nevertheless, there is a lack of systematization of the evidence regarding preschool years. This is a two-part systematic review. In this first part, we aim to examine the effects of BOI on preschoolers' social-emotional competence outcomes. Searches were conducted in Pubmed, Scopus, PsycInfo, ERIC, Web of Science, Portal Regional da BVS and CINAHL. English, French and Portuguese language articles published between January 2000 and October 2020, that evaluated the effects of BOI implemented in educational contexts on social-emotional competence of preschool children. Only randomized controlled trials (RCT) or quasi-RCT were included. Two reviewers independently completed data extraction and risk-of-bias assessment. The level of scientific evidence was measured through the Best Evidence Synthesis. Nineteen studies were included. There was strong evidence that BOI do not improve anger/aggression, delay of gratification and altruism. Nevertheless, there was moderate evidence that BOI effectively improve other social-emotional outcomes, such as empathy, social interaction, social independence, general internalizing behaviors, and general externalizing behaviors. The lack of scientific evidence was compromised by the methodological quality of the studies. BOI effectively improve specific social-emotional competences of preschool children. PROSPERO, identifier CRD42020172248.


Temperature- and vacuum-induced framework contraction of Na-ETS-4.
For the first time, reduced pressure to induce a framework contraction of the microporous titanosilicate ETS-4 is used. A vacuum of 10(-2) Torr decreases the temperature of structural contraction from 200 degrees C to near room temperature and presents a potential alternative to the temperature-induced and anion-controlled molecular gate effect. The dimensions and the reversibility of the temperature- and vacuum-induced framework contractions are evaluated by in situ X-ray diffraction experiments. On the basis of these studies, it is revealed that Na-ETS-4 possesses a more rigid framework than Sr-ETS-4, which discloses a way to control the framework flexibility of ETS-4.


The relationship between patient safety and quality improvement in neonatology.
Patient safety and healthcare quality have become foundational components of neonatal care, and hospitals and neonatal intensive care units have developed robust programs and structures committed to improving outcomes through rigorous quality improvement methods. Despite increasingly more sophisticated frameworks for defining and understanding quality, the relationship between patient safety and health care quality is not clearly defined. Safety is often defined as the avoidance of injury and harm, while quality is typically defined as achieving the best possible health care outcomes. Safety can be considered one of multiple domains of quality, and safety can also be considered synonymous with quality. Regardless, both safety and quality are driven by systems of care, and improvement methods should focus on understanding and improving these systems. While many improvement methods will apply to safety goals or quality goals, there are unique aspects of patient safety that require specific tools and approaches. Achieving the safest and highest quality healthcare for our patients and families requires an understanding of the tools needed to improve both safety and quality.


A simple, remote, video based breathing monitor.
Breathing monitors have become the all-important cornerstone of a wide variety of commercial and personal safety applications, ranging from elderly care to baby monitoring. Many such monitors exist in the market, some, with vital signs monitoring capabilities, but none remote. This paper presents a simple, yet efficient, real time method of extracting the subject's breathing sinus rhythm. Points of interest are detected on the subject's body, and the corresponding optical flow is estimated and tracked using the well known Lucas-Kanade algorithm on a frame by frame basis. A generalized likelihood ratio test is then utilized on each of the many interest points to detect which is moving in harmonic fashion. Finally, a spectral estimation algorithm based on Pisarenko harmonic decomposition tracks the harmonic frequency in real time, and a fusion maximum likelihood algorithm optimally estimates the breathing rate using all points considered. The results show a maximal error of 1 BPM between the true breathing rate and the algorithm's calculated rate, based on experiments on two babies and three adults.


Estrogen-dependent depressor response of melatonin via baroreflex afferent function and intensification of PKC-mediated Nav1.9 activation.
Recent studies suggest that melatonin (Mel) plays an important role in the regulation of blood pressure (BP) via the aortic baroreflex pathway. In this study, we investigated the interaction between the baroreflex afferent pathway and Mel-mediated BP regulation in rats under physiological and hypertensive conditions. Mel (0.1, 0.3, and 1.0 mg/mL) was microinjected into the nodose ganglia (NG) of rats. We showed that Mel-induced reduction of mean arterial pressure in female rats was significantly greater than that in male and in ovariectomized rats under physiological condition. Consistently, the expression of Mel receptors (MTNRs) in the NG of female rats was significantly higher than that of males. In L-NAME-induced hypertensive and spontaneously hypertensive rat models, MTNRs were upregulated in males but downregulated in female models. Interestingly, Mel-induced BP reduction was found in male hypertensive models. In whole-cell recording from identified baroreceptor neurons (BRNs) in female rats, we found that Mel (0.1 μM) significantly increased the excitability of a female-specific subpopulation of Ah-type BRNs by increasing the Nav1.9 current density via a PKC-mediated pathway. Similar results were observed in baroreceptive neurons of the nucleus tractus solitarius, showing the facilitation of spontaneous and evoked excitatory post-synaptic currents in Ah-type neurons. Collectively, this study reveals the estrogen-dependent effect of Mel/MTNRs under physiological and hypertensive conditions is mainly mediated by Ah-type BRNs, which may provide new theoretical basis and strategies for the gender-specific anti-hypertensive treatment in clinical practice.


[Rapid response of secondary plasma cell leukemia after carfilzomib and dexamethasone therapy].
An 83-year-old man was admitted to our hospital due to a recurrence of multiple myeloma, accompanied by the appearance of plasma cells in the peripheral blood (PB). Subsequently, he was diagnosed with secondary plasma cell leukemia (sPCL). A chemotherapy regimen of carfilzomib and dexamethasone (Cd) combination therapy was selected, and 15 days later, plasma cells completely disappeared from the PB. Cd therapy was continued, and the free kappa chain levels normalized. Three months later, M-protein could not be detected using serum electrophoresis. This is a valuable report wherein Cd combination therapy was successful in treating sPCL.


[Envenoming by Malayan cobra (Naja naja sputatrix)--case report].
Malayan cobra (Naja naja sputatrix) is the venomous snake of the Elapidae family which involves at least three species of Asian spitting cobras, according to the new taxonomy. This snake occurs naturally in southeastern Asia and in Poland it is kept only in the private breedings. Its venom mainly contains neurotoxins which have paralyzing activities to the nervous system and cardiotoxins which act cytolytically. The present study shows a case of the forty-one-year-old man professionally engaging in venomous reptiles who was bitten in his left ring finger by the Malayan cobra. No general symptoms, especially neurotoxic, were observed in the patient after the snake bite, but there was a significant local tissue injury including necrosis. In the bite site the infection with Morganella morganii developed with consequent phlegmon within the hand and the forearm. Additionally, features of haemolysis and injury of muscles with elevated level of serum creatine phosphokinase (CPK) were present. The local injuries of tissues were treated surgically including the amputation of the bitten finger which has undergone the necrosis. No specific antivenom was used in the treatment.


Biochanin A reduces drug-induced p75NTR expression and enhances cell survival: a new in vitro assay for screening inhibitors of p75NTR expression.
Following spinal cord injury (SCI) or peripheral neuropathy, increased levels of the p75(NTR) death receptor initiate the signal transduction cascade leading to cell death. Investigations of compounds that may ameliorate neuronal cell death have largely used rodent models, which are time consuming, expensive, and cumbersome to perform. Previous studies had demonstrated that steroids, particularly dexamethasone and its analog methylprednisolone sodium succinate, exhibit limited neuroprotective effects against neuronal injury. Significantly, many naturally occurring nonsteroidal plant compounds exhibit structural overlap with steroids. In this report, we present an in vitro cellular screen model to practically examine the efficacy of various phytoestrogens in modulating the ibuprofen-induced expression of p75(NTR) and reduced cell survival of CCFSTTG1 and U87MG cells in a rescue (postinjury) or prevention (preinjury) regimen. We show that the phytoestrogen, biochanin A, and, to a lesser extent, genistein are more effective than dexamethasone at reducing p75(NTR) expression and improving the viability of U87MG and CCFSTTG1 before and after p75(NTR) induction. Furthermore, these studies implicate biochanin A's inactivation of p38-MAPK as a possible contributor to reducing p75(NTR) with associated increased cell survival. This new in vitro assay facilitates a more time-efficient screening of compounds to suppress p75(NTR) expression and increase neuronal cell viability prior to their evaluation in animal models of neurological diseases.


Bone mineral density in menopausal women with primary hyperparathyroidism before and after parathyroidectomy.
The relationship between osteoporosis and primary hyperparathyroidism (pHPT) has not been definitely established because both diseases occur predominantly in postmenopausal women, and because PTH has a paradoxical effect on bone. We have investigated the prevalence of reduced bone mineral density (BMD) in women with pHPT, its relationship with metabolic parameters, and its course after parathyroidectomy. A prospective observational study was carried out on perimenopausal and postmenopausal women consecutively diagnosed and operated on for pHPT. Demographic data were recorded, as well as, PTH, Ca, calciuria/24h, P, vitamin D, adenoma weight. The BMD was measured at three sites: femoral neck (FN), proximal femur (PF), and lumbar spine (LS). Fifty-two patients were included with a mean age of 61+/-12 years. The prevalence of reduced BMD (< or = 1SD, T-score) was 80%-100% depending on site. Parathyroid hormone was higher in patients with osteoporosis (319+/-181 pg/ml) than in those with osteopenia (230+/-83 pg/ml) or normal BMD (148+/-81 pg/ml;p < 0,04). Twenty-eight patients were investigated 1 year after parathyroidectomy. The BMD improved significantly at all sites, particularly in patients with osteoporosis. Age correlated inversely with BMD increases at the femoral sites (r= -0,47;p = 0,02) but not at the LS. 25-OHD3 plasma levels correlated inversely with BMD increases at PF (r= -0,76; p < 0,0001). In pHPT, there is a high prevalence of BMD abnormalities. No metabolic variables had a definite influence on BMD values but a tendency was observed for lower BMD in severe pHPT. One year after parathyroidectomy, there were significant BMD increases that were more marked at femoral sites, in younger patients, in patients with preoperative osteoporosis, and in those with lower plasma levels of 25-OHD3.


Analysis of phenolic and triterpenoid compounds in licorice and rat plasma by high-performance liquid chromatography diode-array detection, time-of-flight mass spectrometry and quadrupole ion trap mass spectrometry.
High-performance liquid chromatography with diode-array detection (HPLC/DAD), time-of-flight mass spectrometry (HPLC/TOFMS) and quadrupole ion trap mass spectrometry (HPLC/QITMS) were used for separation and identification of several compounds in licorice and rat plasma after oral administration of the herbal extract. Three phenolic compounds and one triterpenoid in licorice extract were unambiguously identified by comparing with the standard compounds. A formula database of known compounds in licorice was established, against which the other 42 compounds were identified effectively based on the accurate extract masses and formulae acquired by HPLC/TOFMS. In order to differentiate the isomers, tandem mass spectrometry was also used. The deduced fragmentation behaviors in QITMS were used to distinguish seven groups of isomers in licorice. By means of the three detectors, 46 compounds in licorice were identified. After oral administration of the extract, 25 compounds in rat plasma were detected and identified by comparing and contrasting the compounds measured in licorice with those in the plasma samples by HPLC/TOFMS. It is concluded that a rapid and effective method based on three analytical techniques was established, which is useful for identification of multiple compounds in licorice in vitro and in vivo. The result should be very useful for the quality control and curative mechanism study of licorice.


Corrigendum to "Genetic and Diet-Induced Obesity Increased Intestinal Tumorigenesis in the Double Mutant Mouse Model Multiple Intestinal Neoplasia X Obese via Disturbed Glucose Regulation and Inflammation".
[This corrects the article DOI: 10.1155/2015/343479.]. In the published paper "Genetic and Diet-Induced Obesity Increased Intestinal Tumorigenesis in the Double Mutant Mouse Model Multiple Intestinal Neoplasia X Obese via Disturbed Glucose Regulation and Inflammation" [1] we mistakenly wrote IL-1β instead of IL-6 in Tables 2 and 3. In addition, IL-6 was not included in the text below the tables stating that it was measured by flow cytometer as was TNFα. The corrected tables are presented here.


Psychosocial Assessment of Candidates for Transplantation (PACT) Score Identifies High Risk Patients in Pediatric Renal Transplantation.
Background: Currently, there is no standardized approach for determining psychosocial readiness in pediatric transplantation. We examined the utility of the Psychosocial Assessment of Candidates for Transplantation (PACT) to identify pediatric kidney transplant recipients at risk for adverse clinical outcomes. Methods: Kidney transplant patients <21-years-old transplanted at Duke University Medical Center between 2005 and 2015 underwent psychosocial assessment by a social worker with either PACT or unstructured interview, which were used to determine transplant candidacy. PACT assessed candidates on a scale of 0 (poor candidate) to 4 (excellent candidate) in areas of social support, psychological health, lifestyle factors, and understanding. Demographics and clinical outcomes were analyzed by presence or absence of PACT and further characterized by high (≥3) and low (≤2) scores. Results: Of 54 pediatric patients, 25 (46.3%) patients underwent pre-transplant evaluation utilizing PACT, while 29 (53.7%) were not evaluated with PACT. Patients assessed with PACT had a significantly lower percentage of acute rejection (16.0 vs. 55.2%, p = 0.007). After adjusting for HLA mismatch, a pre-transplant PACT score was persistently associated with lower odds of acute rejection (Odds Ratio 0.119, 95% Confidence Interval 0.027-0.52, p = 0.005). In PACT subsection analysis, the lack of family availability (OR 0.08, 95% CI 0.01-0.97, p = 0.047) and risk for psychopathology (OR 0.34, 95% CI 0.13-0.87, p = 0.025) were associated with a low PACT score and post-transplant non-adherence. Conclusions: Our study highlights the importance of standardized psychosocial assessments and the potential use of PACT in risk stratifying pre-transplant candidates.


How T cell receptors interact with peptide-MHCs: a multiple steered molecular dynamics study.
The T-cell receptor (TCR) interaction with antigenic peptides (p) presented by the major histocompatibility complex (MHC) molecule is a key determinant of immune response. In addition, TCR-pMHC interactions offer examples of features more generally pertaining to protein-protein recognition: subtle specificity and cross-reactivity. Despite their importance, molecular details determining the TCR-pMHC binding remain unsolved. However, molecular simulation provides the opportunity to investigate some of these aspects. In this study, we perform extensive equilibrium and steered molecular dynamics simulations to study the unbinding of three TCR-pMHC complexes. As a function of the dissociation reaction coordinate, we are able to obtain converged H-bond counts and energy decompositions at different levels of detail, ranging from the full proteins, to separate residues and water molecules, down to single atoms at the interface. Many observed features do not support a previously proposed two-step model for TCR recognition. Our results also provide keys to interpret experimental point-mutation results. We highlight the role of water both in terms of interface resolvation and of water molecules trapped in the bound complex. Importantly, we illustrate how two TCRs with similar reactivity and structures can have essentially different binding strategies.


Improving mass and liquid chromatography based identification of proteins using bayesian scoring.
We present a method for peptide and protein identification based on LC-MS profiling. The method identified peptides at high-throughput without expending the sequencing time necessary for CID spectra based identification. The measurable peptide properties of mass and liquid chromatographic elution conditions are used to characterize and differentiate peptide features, and these peptide features are matched to a reference database from previously acquired and archived LC-MS/MS experiments to generate sequence assignments. The matches are scored according to the probability of an overlap between the peptide feature and the database peptides resulting in a ranked list of possible peptide sequences for each peptide submitted. This method resulted in 6 times more peptide sequence identifications from a single LC-MS analysis of yeast than from shotgun peptide sequencing using LC-MS/MS.


Cellular uptake, retention and bioabsorption of HO-3867, a fluorinated curcumin analog with potential antitumor properties.
Curcumin, a naturally-occurring compound found in the rhizome of Curcuma longa plant, is known for its antitumor activities. However, its clinical efficacy is limited due to poor bioabsorption. A new class of synthetic analogs of curcumin, namely diarylidenylpiperidone (DAP), has been developed with substantially higher anticancer activity than curcumin. However, its cellular uptake and bioabsorption have not been evaluated. In this study we have determined the absorption of a representative DAP compound, HO-3867, using optical and electron paramagnetic resonance spectrometry. The cellular uptake of HO-3867 was measured in a variety of cancer cell lines. HO-3867 was taken in cells within 15 minutes of exposure and its uptake was more than 100-fold higher than curcumin. HO-3867 was also retained in cells in an active form for 72 hours and possibly longer. HO-3867 was substantially cytotoxic to all the cancer cells tested. However, there was no direct correlation between cellular uptake and cytotoxicity suggesting that the cytotoxic mechanisms could be cell-type specific. When administered to rats by intraperitoneal injection, significantly high levels of HO-3867 were found in the liver, kidney, stomach, and blood after 3 hours. Also, significant accumulation of HO-3867 was found in murine tumor xenografts with a dose-dependent inhibition of tumor growth. The results suggest that the curcumin analog has substantially higher bioabsorption when compared to curcumin.


Neuroglial arrangements in the olfactory glomeruli of the hedgehog.
The olfactory glomeruli represent morphological and functional units in which olfactory information is processed in specialized synaptic arrangements established between the central processes of sensory neurons, whose cell bodies are located in the olfactory epithelium, and the terminal (intraglomerular) portions of the dendrites of periglomerular, tufted, and mitral cells. The olfactory glomeruli are surrounded by distinctive glial formations in which the peripheral glia interacts with the central glia. We have studied the morphology and organization of neuroglial cells in the layer of olfactory nerves and the glomerular layer of the olfactory bulb in the insectivorous hedgehog (Erinaceus europaeus) with the electron microscope, Golgi method, and immunohistochemistry by using antibodies to glial fibrillary acidic protein (GFAP) and "rip," a monoclonal antibody that stains oligodendrocytes and their processes in the rat (Friedman et al.: Glia 2:380-390, '89). The peripheral glia is represented by a special category of cells that are closely related to astrocytes and known as sheathing cells. They accompany olfactory axons to their entrance in the glomeruli where they interact with the central glia, represented by astrocytes and oligodendrocytes. The sheathing cells typically display indented nuclei and protoplasmic expansions forming laminar processes wrapping several axons together. Astrocytes surrounding the glomerular neuropil belong to the velate type. They display numerous sheet-like processes enveloping dendritic segments and periglomerular cell bodies. Oligodendrocytes were found surrounding the glomeruli and at the interstices separating different glomeruli. Myelinated dendritic segments and cell bodies were found surrounding the olfactory glomeruli. These myelin coverings probably derive from oligodendrocytes. Together with the astrocytic lamellar expansions, they provide a rigid structural support that contributes to the segregation of group of different cells while remaining relatively isolated from other influences at the periphery of the glomeruli.


Paraffin ingestion--the problem.
Paraffin ingestion is the commonest cause of accidental childhood poisoning in South Africa. Children from the lower socio-economic group are affected most. They drink paraffin in the summer months from bottles or intermediate containers, mistaking it for water or cold-drink. The children are predominantly male with a mean age of 24 months. The clinical picture is one of respiratory distress with a hospital case fatality rate of 0.74%. The use of paraffin as a source of household energy in South Africa is on the increase. Based on a modernisation index it would seem that this trend will continue into the next century. It can therefore be expected that the number of cases of paraffin ingestion will steadily increase if no active steps are taken to address the problem. Prevention should entail a wide spectrum of measures, the basis of which should be a child-resistant container. An effective durable, low-cost child-resistant container which is easy to pour from should be made available by petroleum companies and/or entrepreneurs and distributed through their network. This should be combined with health education on the danger of paraffin. Health care workers and administrators should be made more aware of the problem and become involved in health education and prevention. Further research should be undertaken on the effect a change in the colour of paraffin and the use of child-resistant caps would have on the incidence of paraffin ingestion in South Africa.


Application of tumor markers CEA, TPA, and SCC-Ag in patients with low-risk FIGO stage IB and IIA squamous cell carcinoma of the uterine cervix.
The aim of this study was to determine the potential clinical utility of tumor markers carcinoembryonic antigen (CEA), tissue polypeptide antigen (TPA), and squamous cell carcinoma antigen (SCC-Ag) in patients with FIGO stage IB and IIA squamous cell carcinoma of the uterine cervix with low-risk clinicopathologic factors (negative lymph node metastasis, no lymphovascular space involvement, no bulky tumor size, no parametrial invasion, no deep stromal invasion, and well-differentiated cellular histology). A retrospective study was performed on 558 patients with FIGO stage IB-IIA and pathology-proven invasive squamous cell carcinoma of the uterine cervix, treated at the Veterans General Hospital, Taipei, between December 1986 and November 1990. Serum specimens were drawn before operation. A total of 140 assessable patients were enrolled into the study (including 109 stage IB patients and 31 stage IIA patients; all patients had no clinicopathologic risk factors and had at least one tumor marker datum). Survival curves were constructed according to the Kaplan-Meier method and survival curves were compared using the log-rank test. In univariate analysis of survival, CEA, TPA, and SCC-Ag all have roles in the prediction of prognosis. In Cox proportional hazards model using CEA, TPA, and SCC-Ag as covariates, TPA demonstrated the most significant risk factor (P = 0.031). We concluded that preoperative evaluation of serum TPA might be of great value in the prediction of survival of patients without any clinicopathologic risk factors and this special group of patients should be paid much attention in the follow-up period. From this study, preoperative elevation of TPA defines a group of otherwise low-risk invasive cervical cancer patients who are at high risk for recurrence. Adjuvant therapy might be necessary for this special subset of patients. A prospective study with a larger sample should be conducted to prove this particular finding.


Treatment of heredo-degenerative ataxias with amantadine hydrochloride.
Amantadine hydrochloride (AH) was administered (200 mg/day) for more than three months to 17 patients with Friedreich's ataxia (FA) and to 12 patients with olivopontocerebellar atrophies (OPCA) in an open clinical trial. Reaction time (RT) and movement time (MT) with the right and left hand were measured before and after treatment. A striking improvement on both RT and MT was observed in the OPCA group (on seven out of eight measures), whereas in the FA patients improvement was seen only in two out of four MT measures with no improvement in RT. Both groups had low levels of homovanillic acid (HVA) in their cerebrospinal fluid before treatment, relative to their controls. However, improvement with AH was not related to HVA levels.


Larval Density, Sex, and Allocation Hierarchy Affect Life History Trait Covariances in a Bean Beetle.
AbstractLife history theory aims to understand how different environments result in differential investment in fitness-related traits. While trade-offs between traits are expected, many studies show positive or no correlation between pairs of costly traits. One hypothesis that may explain the inconsistency of trade-offs in the literature is that trait investment may occur in a dichotomous hierarchy (the tree model), which allows for differential trait investment weighted by the traits' respective positions within the hierarchy. Previous mathematical models predict different covariances between traits depending on their position on the allocation tree. While hierarchical differential investment is often used to discuss findings in life history theory, the role of an allocation hierarchy in trait covariances has not been directly tested. In turn, this study aims to identify trait covariances between behavioral and morphological phenotypes on different branches of an allocation tree for the bean beetle, Callosobruchus maculatus. While trade-offs between copulatory behaviors and morphology were found for both males and females, only traits at the base and far from each other in the hierarchy negatively covaried. This study empirically shows that trade-offs may be the result of hierarchical investment.


Inspiring hope in our rehabilitation patients, their families, and ourselves.
When confronted with a devastating disability or chronic illness, rehabilitation nurses play a key role in inspiring hope for patients and their families. This article examines strategies nurses can implement in everyday practice: creating an environment of hope in a rehabilitation unit; assisting patients to manage their negative feelings about their disability; relieving chronic neuropathic pain; sustaining patient relationships with staff and family; helping patients to forgive themselves and others; enhancing patient intimacy with others; using literature to promote hope; acknowledging a patient's belief that nothing is impossible; using humor therapeutically; and maintaining hope for the moment. It is the moment-the time we spend with our patients-that is essential. In that moment, we are promoting hope.


Tachykinin receptors in the circular muscle of the guinea-pig ileum.
1. We have studied the mechanical response of circular strips of the guinea-pig ileum to tachykinins and characterized the receptors involved by means of receptor-selective agonists. 2. The strips responded to both substance P (SP) and neurokinin A (NKA), as well as to [Pro9]-SP sulphone (selective NK1-receptor agonist), [beta Ala8]-NKA(4-10) (selective NK2-receptor agonist) and [MePhe7]-neurokinin B (selective NK3-receptor agonist). The ED50s of the various peptides (calculated as the concentration of agonist which produced 50% of the response to 10 microM carbachol) were similar, in the range of 40-200 nM, i.e. no clearcut rank order of potency was evident. 3. The response to a submaximal (10 nM) concentration of SP or NKA was unaffected in the presence of peptidase inhibitors (thiorphan, captopril and bestatin, 1 microM each). 4. The response to the NK1-agonist was totally atropine-resistant, but was reduced (about 30% inhibition) by tetrodotoxin. The response to the NK3-receptor agonist was halved by atropine and abolished by tetrodotoxin. The response to the NK2-agonist was unaffected by either atropine or tetrodotoxin. 5. The response to the selective NK2-agonist was unchanged after desensitization of NK1- or NK3-receptors. 6. The response to the NK2-selective agonist was strongly inhibited by [Tyr5, D-Trp6,8,9, Arg10]-NKA(4-10) (MEN 10,207) a selective NK2-receptor antagonist which did not modify the response to the NK1-selective agonist. 7. Our findings indicate that all the three known types of tachykinin receptors mediate the contractile response of the circular muscle of the guinea-pig ileum to peptides of this family. The response to activation of NK3-receptors is totally neurogenic and partially mediated by endogenous acetylcholine, the response to activation of NK1-receptors is partly neurogenic and largely myogenic and the response to activation of NK2-receptors is totally myogenic.


Systemic amyloidosis with bilateral conjunctival involvement: a case report.
Conjunctival amyloidosis is a very rare condition, generally unilateral, and presents mostly as an isolated condition without systemic compromise. Our purpose is to present a new case of systemic amyloidosis with a bilateral conjunctival involvement. A 66-years-old caucasian female complaining of conjunctival hemorrhage and chemosis in both eyes for the last five years had been discontinuously treated with topical antibiotics and corticosteroids without any evident improvement. She presented with a pink-yellow infiltration in the inferior conjunctiva of both eyes. Conjunctival biopsy under optical microscopy revealed amyloid deposit, confirmed by Congo red staining. Mucosal biopsy from esophagus and rectus confirmed amyloidosis by Congo red stain. Immunohistochemistry of bone marrow biopsy showed an increased number of plasma cells and an over-expression of light chain kappa subunit. She was treated with corticosteroids and lubrication with an improvement of symptoms. Ocular lesions remained stable after a follow-up of 3 years. Conjunctival amyloidosis is a rare entity that may be overlooked, and should be differentiated from chronic conjunctivitis and conjunctival malignancies. Although it presents most frequently as a local process, a systemic involvement should always be ruled out.


Development of a population pharmacokinetic model to describe azithromycin whole-blood and plasma concentrations over time in healthy subjects.
Azithromycin (AZI), a broad-spectrum antibiotic, accumulates in polymorphonuclear cells and peripheral blood mononuclear cells. The distribution of AZI in proinflammatory cells may be important to the anti-inflammatory properties. Previous studies have described plasma AZI pharmacokinetics. The objective of this study was to describe the pharmacokinetics of AZI in whole blood (concentration in whole blood [Cb]) and plasma (concentration in plasma [Cp]) of healthy subjects. In this study, 12 subjects received AZI (500 mg once a day for 3 days). AZI Cb and Cp were quantified in serial samples collected up to 3 weeks after the last dose and analyzed using noncompartmental and compartmental methods. After the last dose, Cb was greater than Cp. Importantly, Cb, but not Cp, was quantifiable in all but one subject at 3 weeks. The blood area under the curve during a 24-h dosing interval (AUC24) was ∼2-fold greater than the plasma AUC24, but simulations suggested that Cb was not at steady state by day 3. Upon exploration of numerous models, an empirical 3-compartment model adequately described Cp and Cb, but Cp was somewhat underestimated. Intercompartmental clearance (CL; likely representing cells) was lower than apparent oral CL (18 versus 118 liters/h). Plasma, peripheral, and cell compartmental volumes were 439 liters, 2,980 liters, and 3,084 liters, respectively. Interindividual variability in CL was low (26.2%), while the volume of distribution variability was high (107%). This is the first report to describe AZI Cb in healthy subjects, the distribution parameters between Cp and Cb, and AZI retention in blood for up to 3 weeks following 3 daily doses. The model can be used to predict Cb from Cp for AZI under various dosing regimens. (This study has been registered at ClinicalTrials.gov under registration no. NCT01026064.).


Predictors of Treatment Access and Initiation Among Diverse, Low-Income Victims of Violence Offered a Trauma-Focused Evidence-Based Psychotherapy.
Many victims of violence may benefit from trauma-focused evidence-based psychotherapies (EBPs), but fail to utilize treatment. The current study investigated factors associated with treatment access and treatment initiation in a low-income, racially and ethnically diverse, urban population of victims of violence who were screened for EBPs. The sample consisted of 941 adults, mean age = 35.87 (SD = 12.8), who were screened for mental health treatment and offered an EBP. Overall, 55.7% of individuals accessed treatment by attending an in-person screening appointment and intake, and 79.0% of the individuals who accessed treatment then initiated treatment by attending the first EBP session. Analysis revealed higher age (odds ratio [OR] = 1.05, 95% confidence interval (CI) = [1.04, 1.09]) and lower expression of posttraumatic stress disorder (PTSD) symptoms predicted higher rates of accessing treatment (OR = 0.20, 95% CI = [0.05, 0.82]). Higher global severity of distress (OR = 3.22, 95% CI = [1.14, 9.10]), poor quality of life in the area of psychological health (OR = 0.90, 95% CI = [0.81, 1.00]), and better quality of life in the area of physical health significantly predicted initiation of treatment (OR = 1.11, 95% CI = [0.998, 1.24]). Findings suggest that low-income, ethnically and racially diverse victims of violence may effectively utilize trauma-focused EBPs offered in a community setting.


Phase II study of KRN8602, 3'-deamino-3'-morpholino-13-deoxo-10-hydroxycarminomycin hydrochloride, MX2 x HCl in patients with metastatic breast cancer.
KRN8602 (3'-deamino-3'-morpholino-13-deoxo-10-hydroxycarminomycin hydrochloride, MX2 x HCl) is a newly developed anthracycline that has been found to be effective against multidrug-resistant tumor cells in vitro and in vivo. In order to clinically confirm these promising preclinical observations, we performed a phase II trial of KRN8602 in patients with anthracycline-resistant metastatic breast cancer. Of 41 patients registered with metastatic breast cancer, 37 were eligible and were given at least two cycles of KRN8602 15 mg/m2 per day at 3-4 week intervals by intravenous bolus injection on days 1, 2, and 3. Of the 37 patients, 6 (16.2%, with a 95% confidence interval of 4.3-28.1%) had a partial response (PR). No complete responses (CRs) were observed. The difference between response rates according to prior history of anthracycline administration was not significant. Myelosuppression was moderately severe, with grade 3 or 4 leukopenia occurring in 65%. Severe nausea/vomiting was observed in 44% of the patients. The results indicate that KRN8602 has modest activity in refractory metastatic breast cancer and is associated with relatively severe toxicity. Furthermore, the preclinical finding that KRN8602 overcomes anthracycline resistance was not reliably reproduced in this clinical phase II trial.


ABCG1 deficiency promotes endothelial apoptosis by endoplasmic reticulum stress-dependent pathway.
The present study was focused on whether ABCG1 deficiency was involved in endothelial apoptosis and its possible mechanism. Human umbilical artery endothelial cells were transfected with ABCG1 siRNA and/or ABCG1 expression plasmid. We observed that silencing of endothelial ABCG1 reduced cholesterol efflux to HDL and increased intracellular lipid content. Moreover, reduction of ABCG1 promoted endothelial apoptosis and expression of endoplasmic reticulum (ER) stress-related molecules GRP78 and CHOP. In contrast, transfection of ABCG1 overexpression plasmid reversed endothelial apoptosis and intracellular lipid accumulation as well as decreased expression of GRP78 and CHOP in ABCG1-deficient endothelial cells. Furthermore, endothelial apoptosis and ER stress-related molecules were induced by repletion of endothelial cells with cholesterol-loaded cyclodextrin, otherwise endothelial apoptotic response and expression of GRP78 and CHOP were suppressed by depletion of cellular cholesterol in ABCG1-deficient endothelial cells. The present results suggest that reduction of ABCG1 induces endothelial apoptosis, which seems associated with intracellular free cholesterol accumulation and subsequent ER stress.


Comparison of diagnostic criteria for common variable immunodeficiency disorder.
Common variable immunodeficiency disorders (CVIDs) are the most frequent symptomatic primary immune deficiency condition in adults. The genetic basis for the condition is not known and no single clinical feature or laboratory test can establish the diagnosis; it has been a diagnosis of exclusion. In areas of uncertainty, diagnostic criteria can provide valuable clinical information. Here, we compare the revised European society of immune deficiencies (ESID) registry (2014) criteria with the diagnostic criteria of Ameratunga et al. (2013) and the original ESID/pan American group for immune deficiency (ESID/PAGID 1999) criteria. The ESID/PAGID (1999) criteria either require absent isohemagglutinins or impaired vaccine responses to establish the diagnosis in patients with primary hypogammaglobulinemia. Although commonly encountered, infective and autoimmune sequelae of CVID were not part of the original ESID/PAGID (1999) criteria. Also excluded were a series of characteristic laboratory and histological abnormalities, which are useful when making the diagnosis. The diagnostic criteria of Ameratunga et al. (2013) for CVID are based on these markers. The revised ESID registry (2014) criteria for CVID require the presence of symptoms as well as laboratory abnormalities to establish the diagnosis. Once validated, criteria for CVID will improve diagnostic precision and will result in more equitable and judicious use of intravenous or subcutaneous immunoglobulin therapy.


Identification and characterization of an exercise-sensitive pool of glucose transporters in skeletal muscle.
Augmentation of glucose transport into skeletal muscle by GLUT4 translocation to the plasma and T-tubule membranes can be mediated independently by insulin and by contraction/exercise. Available data suggest that separable pools of intracellular GLUT4 respond to these two stimuli. To identify and characterize these pools, we fractionated skeletal muscle membranes in a discontinuous sucrose density gradient. Fractions of 32 and 36% sucrose exhibited the highest enrichment of GLUT4 and were independently responsive to insulin and exercise, respectively. The combination of the two stimuli depleted both GLUT4 fractions simultaneously. Both vesicle populations contained the gp160 aminopeptidase, whose expression had previously been shown to be specific to muscle and fat and restricted to GLUT4 vesicles in the latter tissue. In muscle, gp160 translocates exactly as does GLUT4 in response to insulin and exercise. The contraction- and insulin-sensitive GLUT4 pools also contained secretory component-associated membrane protein/glucose transporter vesicle triplet but not GLUT1 and caveolin. Immunoadsorption of the two pools followed by silver staining did not reveal any obvious difference in their major protein components. On the other hand, sedimentational analysis in sucrose velocity gradients revealed that the insulin-sensitive GLUT4 vesicles had a larger sedimentation coefficient than the exercise-sensitive vesicles. Thus, the separation of the two intracellular GLUT4 pools should be useful in dissecting what are likely to be different signal transduction pathways that mediate their translocation to the cell surface.


Contribution of hospital characteristics to the volume-outcome relationship: dislocation and infection following total hip replacement surgery.
Mortality and complication rates after total hip replacement (THR) are inversely associated with the volume of THRs performed at hospitals and by individual surgeons. It is not clear, however, why a higher volume of such procedures is associated with better outcomes. We evaluated the contribution of hospital structural characteristics to the volume-outcome relationship in THR by examining the rates and predictors of postoperative complications. We analyzed data pertaining to 5,211 Medicare patients who underwent primary THR in 1995 or 1996 at 167 hospitals in Colorado, Pennsylvania, and Ohio. Data were derived from several sources, including Medicare Part A and Part B claims, the American Board of Medical Specialties, a hospital survey regarding institution-specific characteristics and structural aspects of the care setting, and the American Hospital Association 1995 Annual Survey. Multivariate models were constructed to determine whether hospital structure or surgeon-associated factors may underlie the relationship between volume of THRs and the occurrence of perioperative orthopedic adverse events, defined as deep wound infection or hip dislocation within 90 days of surgery. Of the patients studied, 2.6% experienced an orthopedic adverse event after THR. Sixty-nine percent fewer events occurred in hospitals where >100 THRs in Medicare patients were performed annually, compared with hospitals where <or=25 THRs were performed. In univariate analyses, several hospital-level factors were associated with a reduced (approximately 50%) risk of adverse events, including private (versus public) ownership, membership in the Council of Teaching Hospitals, presence of any residency training program, availability of a dedicated orthopedic nursing unit, and existence of operating rooms with laminar flow exhaust systems. However, the only hospital-level factor associated with adverse events in multivariate models was the use of laminar flow exhaust systems. When surgeon volume was added to the models, it was the strongest predictor of adverse events, with hospital volume and hospital-level factors having no appreciable association with adverse events. Hospital-level factors were not independent predictors of the association between hospital volume and orthopedic adverse events. The volume of THRs performed by individual surgeons is the most important determinant of orthopedic complications and should be considered in efforts to improve THR outcomes.


Isolation of alkaline phosphatase-positive gingival fibroblasts from patients with chronic inflammatory periodontal disease.
We have reported recently that increased expression of membrane alkaline phosphatase (ALP) activity is a phenotypical characteristic of gingival fibroblasts located in chronic inflammatory periodontal lesions. To understand the cellular properties of these cells, we isolated ALP-positive gingival fibroblasts from patients with adult periodontitis and evaluated their proliferative potential. Using an enzymatic digestion procedure, we prepared gingival cell suspensions containing ALP-positive fibroblasts without affecting their ALP activities. These cell suspensions were then subjected to 1 g sedimentation, followed by allowing cells to adhere to substrata. Using this procedure, 71.9% of isolated cells were ALP-positive. Dissociation of ALP-positive fibroblasts and contamination by non-fibroblastic cells were examined by cytochemical and immunocytochemical analyses. The proliferative capacity of ALP-positive fibroblasts in culture was assessed by monitoring the proportion of ALP-positive cells after repeated subculture passages and by labelling DNA-synthesizing cells with bromodeoxyuridine (BrdU). The proportion of ALP-positive fibroblasts decreased during cell culture passages without an apparent change in the ALP-positive phenotype. The percentage of BrdU-positive cells was significantly lower among ALP-positive than among ALP-negative fibroblasts. These results indicate that ALP-positive fibroblasts in chronic inflammatory periodontal lesions have low growth potential. We suggest that their reduced capacity to grow in vitro reflects a more differentiated state induced under inflammatory conditions in vivo.


Enaminones in heterocyclic synthesis: a novel route to tetrahydropyrimidines, dihydropyridines, triacylbenzenes and naphthofurans under microwave irradiation.
Condensation of phthalimidoacetone (1) with DMFDMA (N,N-Dimethylformamide dimethyl acetal) has afforded enaminone 2. Refluxing 2 with equimolecular amounts of benzaldehyde and urea in acetic acid afforded a mixture of tetrahydropyrimidine 5 and the dihydropyridine 6. Compound 2 undergoes self-condensation on heating in acetic acid or under microwave irradiation in presence of acidic zeolite to give 1,3,5-triacylbenzene 9. Reacting enaminone 11a with naphthoquinone 15 afforded the naphthofuran 18. The possible formation of the aldehyde 19 was excluded based on an HMQC experiment, which revealed that the carbonyl carbon is not linked to any hydrogen.


An isolate alpha-fetoprotein producing gastric cancer liver metastasis emerged in a patient previously affected by radiation induced liver disease.
We report a case of an isolated hepatic neoplasia which originated in a site of the liver previously affected by radiation induced liver disease (RILD) in a patient resected for gastric cancer and referred to us for high serum alpha-fetoprotein (AFP) levels. This case challenged us in distiguishing, even histologically, between primary liver cancer and AFP producing gastric cancer metastasis. Only a panel of immunohistochemical markers allowed the definitive diagnosis of liver metastasis of endodermal stem cell-derived and AFP producing gastric cancer. We discuss the criteria for a differential diagnosis, as well as the possible link between RILD and emergence of liver neoplasia.


Modulation of cytokine release from human monocytes by drugs used in the therapy of inflammatory bowel diseases.
Cytokines produced in the gut mucosa play an important role in the pathogenesis of inflammatory bowel diseases (IBD). To determine whether drugs used in the treatment of these diseases modulate cytokine synthesis, we investigated their effects on endotoxin-induced tumour necrosis factor (TNF)-alpha, interleukin (IL)-1 beta and IL-6 release by elutriation-purified human monocytes in vitro. Drugs tested were dexamethasone, 5-aminosalicylic acid, sulphapyridine and zileuton (a 5-lipoxygenase inhibitor). Monocytes were isolated and stimulated with endotoxin, and TNF, IL-1 and IL-6 levels were determined using an enzyme-linked immunosorbent assay. Monocyte stimulation with endotoxin resulted in an average TNF release of 2464 +/- 64 pg/10(6) cells, IL-1 release of 616 +/- 47 pg/10(6) cells and IL-6 release of 2259 +/- 148 pg/10(6) cells. Addition of dexamethasone resulted in a reduction of TNF, IL-1 and IL-6 release to below background levels. Sulphapyridine significantly reduced TNF and induced IL-1 release in a dose-dependent fashion, but had no significant effect on IL-6 release. 5-Aminosalicylic acid did not modulate IL-6 synthesis, but significantly reduced IL-1 and enhanced TNF synthesis. Zileuton reduced TNF and IL-6 release, but enhanced IL-1 release. We conclude that these anti-inflammatory drugs are able to modulate cytokine release by human monocytes. Further studies are needed to determine whether these effects are related to their therapeutic efficacy in IBD.


Cellular events involved in hormonal control of receptor-mediated endocytosis: regulation occurs at multiple sites in the low density lipoprotein pathway, including steps beyond the receptor.
We used biochemical and quantitative structural approaches to analyze hormonal regulation of receptor-mediated endocytosis of human low density lipoprotein (LDL) by differentiating rat granulosa cells in culture. We studied uptake and metabolism of 125I-labeled LDL and distribution of gold-labeled LDL in nontreated and FSH- or FSH/androstenedione-treated granulosa cells. FSH and androstenedione worked together to enlarge the segment of the granulosa cell population capable of accumulating LDL and to increase the number of LDL receptors at the cell surface. More importantly, FSH affected postreceptor aspects of the LDL pathway, including 1) accelerating the apparent rate of LDL internalization, and 2) decreasing the time needed for LDL to reach lysosomes. In both cases we eliminated the possibility that the observed effects merely reflected differences in receptor numbers between hormone-treated and nontreated cells. FSH also increased the number of both gold-labeled lysosomes per cellular profile and gold particles per lysosome. In all, FSH expanded the capacity of the LDL pathway to accommodate more intracellular ligand by augmenting the numbers of organelles participating in the endocytic process. However, it did not affect cell size, sizes of individual organelles comprising the LDL pathway, or numbers of gold particles per organelle (except lysosomes). Our findings indicate that hormonal regulation of the LDL pathway extends beyond simply causing expression of cell surface LDL receptors to encompass postreceptor events, including enhancing the apparent rates at which ligand is internalized and transported to lysosomes.


Tissue miR-200c-3p and circulating miR-1290 as potential prognostic biomarkers for colorectal cancer.
Epithelial-mesenchymal transition (EMT)-related cancers generally elicit low immune responses. EMT is regulated by several microRNAs (miRNAs) in cancers. Thus, this study aimed to evaluate the prognostic potential of EMT-related miRNAs as biomarkers in colorectal cancer (CRC). Formalin-fixed paraffin-embedded tumor and normal tissue and plasma samples were obtained from 65 patients with pathologically confirmed CRC. In addition, plasma samples were obtained from 30 healthy volunteers. Immunohistochemical staining for E-cadherin, ZEB1, PD-1, PD-L1, CD3, CD4, CD8, Foxp3, and CD68 was conducted on tissue samples. Droplet digital polymerase chain reaction (ddPCR) analysis was performed to evaluate miR-21-5p, 34a-5p, 138-5p, 200a-3p, 200b-5p, 200c-3p, 630, 1246, and 1290 expression in tissue samples and miR-630, 1246, and 1290 expression in plasma samples. miR-21-5p, 34a-5p, 630, 1246, and 1290 expression was higher in tumor tissues than in normal tissues (P < 0.05). EMT was significantly associated with reduced tumor-infiltrating T cells. Moreover, miR-21-5p, miR-34a-5p, miR-200a-3p, and miR-200c-3p expression was negatively correlated with T cell density (P < 0.05). High tissue levels of miR-200c-3p were associated with poor overall survival (OS) (P < 0.001). CRC patients with the EMT phenotype had poor OS; however, PD-L1 positivity and abundant PD-1 positive immune cells were correlated with better OS (P < 0.05). miR-1246 and miR-1290 levels were significantly higher in the plasma of patients with CRC than in the plasma of healthy controls (P < 0.05). High plasma levels of miR-1290 were correlated with advanced stage and poor OS (P < 0.05). The tissue expression of miR-200c-3p and plasma levels of miR-1290 measured by ddPCR indicate their potential as prognostic biomarkers for CRC.


Paying a high price for low costs: why there should be no legal constraints on the profits that can be made on drugs for tropical diseases.
This paper deals with the question of how to price drugs for tropical diseases. The thesis defended in the paper is: (i) there should be no legal constraints on the profits pharmaceutical companies can make on their products for tropical diseases. In essence, (i) expresses the idea that drugs for tropical diseases should be treated as any other product on the free market and that the producers of these drugs should be allowed to sell their products at whatever price the market can bear. The main argument in favour of (i) is first outlined. Five common arguments against (i) are thereafter discussed, and it is argued that all of these fail in their intended purpose.


Health system governance in strengthening International Health Regulations (IHR) compliance in Myanmar.
The International Health Regulations 2005 (IHR) is a legally binding framework which requires 196 WHO Member States to take actions to prevent, protect against, control and provide public health response to the international spread of disease. Improving IHR compliance provides grounds for better health system strengthening, which is key to moving countries closer towards Universal Health Coverage. Multisectoral, collaborative working within and across sectors is fundamental to improving IHR (2005) compliance, and for that, governance is the best lever of the health system. This paper highlights the importance of the relationship between governance and IHR in the context of Sustainable Development Goals (SDGs) which follow the fundamental principle of interdependence; SDGs interlink with one another. We consider governance (SDG 16) and how it influences the IHR capacity of SDG 3 (health and well-being for all at all ages). This paper considers the successes of the Myanmar Ministry of Health and Sports thus far in improving IHR compliance and highlights that an even greater focus on health system governance would lead to more sustainable outcomes. Nurturing an institutional culture with enforced rules, which are conducive for improved accountability through inclusive participation would further improve Myanmar IHR strengthening efforts. Without those principles of good governance, the developed IHR capacities cannot be sustained or owned by Myanmar people. This has now become even more urgent given the current COVID-19 pandemic.


Improved Efficiency and Stability of Red Phosphorescent Organic Light-Emitting Diodes via Selective Deuteration.
The secondary kinetic isotope effects (KIEs) of red phosphorescent Ir(III) complexes and the corresponding devices have been investigated. The selective deuterated red emitters show negligible influence on the luminescent spectra, but have positive effects on the quantum efficiencies and stabilities in the devices. As secondary KIEs predicted, the photolysis coinciding with the electrolysis of the deuterated complexes in the devices, measured via decreasing of luminescent intensity, are reduced in rate. An about 33% increase of the device working lifetime could be readily obtained with the strategy of selective deuteration on the emitter complexes. The findings demonstrate the importance of the isotopic effect on the performance improvement of organic light emitting devices and will also trigger the study on organic optoelectronic materials via isotopic tools.


Pharmacology of descending control systems.
In the cat there is no convincing evidence that a particular compound mediates a supraspinal control of spinal transmission of nociceptive information. There is good evidence that opioid peptides are released segmentally in response to nociceptive input to the spinal cord and that this acts to inhibit motoneurons and to reduce transmission of nociceptive information to supraspinal areas. In the cat there is no evidence that stimulation at supraspinal sites producing analgesia results in a spinal release of opioid peptides. In the rat evidence for the latter has been obtained but there are no data from other species. Tonically present supraspinal inhibition of spinal transmission of nociceptive information in the cat does not involve opioid peptides. Indirect evidence favours a role for 5-hydroxytryptamine and noradrenaline in supraspinal control of spinal processing of nociceptive transmission. Peripheral antagonists of 5-HT have reduced spinal inhibition from stimulation at supraspinal sites but the site of action is unknown. Progress with noradrenaline involvement has been hindered by lack of a suitable antagonist. Although the amino acids, glycine and GABA are involved in segmental inhibition of transmission of nociceptive information, no convincing evidence has indicated their involvement in supraspinal controls.


Pharmacokinetics and bioequivalence evaluation of cyclobenzaprine tablets.
The purpose of this study was to investigate cyclobenzaprine pharmacokinetics and to evaluate bioequivalence between two different tablet formulations containing the drug. An open, randomized, crossover, single-dose, two-period, and two-sequence design was employed. Tablets were administered to 23 healthy subjects after an overnight fasting and blood samples were collected up to 240 hours after drug administration. Plasma cyclobenzaprine was quantified by means of an LC-MS/MS method. Pharmacokinetic parameters related to absorption, distribution, and elimination were calculated. Cyclobenzaprine plasma profiles for the reference and test products were similar, as well as absorption pharmacokinetic parameters AUC (reference: 199.4 ng ∗ h/mL; test: 201.6 ng ∗ h/mL), Cmax (reference: 7.0 ng/mL; test: 7.2 ng/mL), and T(max) (reference: 4.5 h; test: 4.6 h). Bioequivalence was evaluated by means of 90% confidence intervals for the ratio of AUC (93%-111%) and C(max) (93%-112%) values for test and reference products, which were within the 80%-125% interval proposed by FDA. Cyclobenzaprine pharmacokinetics can be described by a multicompartment open model with an average rapid elimination half-life (t(1/2)β) of 3.1 hours and an average terminal elimination half-life (t(1/2)γ) of 31.9 hours.


Positive Correlation Between LTA Expression and Overall Immune Activity Suggests an Increased Probability of Survival in Uterine Corpus Endometrial Carcinoma.
Mounting evidence indicates that immune status plays a crucial role in tumor progress and metastasis, while there are no effective and easily assayed biomarkers to reflect it in uterine corpus endometrial carcinoma (UCEC) patients. Here, we attempted to identify the potential biomarkers that were differentially expressed between normal and tumor tissues and involved in prognosis and immune microenvironment of UCEC patients. RNA-seq data with relevant clinical information were obtained from The Cancer Genome Atlas (TCGA). ssGSEA algorithm was applied to calculate the enrichment scores of every tumor infiltration lymphocyte (TIL) set in each sample, and patients were then divided into three clusters using multiple R packages. Cox analysis, ESTIMATE, and CIBERSORT were utilized to determine the differentially expressed immune-related genes (DEIGs) with overall survival, and to explore their roles in prognosis, immune microenvironment, and immunotherapeutic response. The TIMER and TISIDB databases were utilized to predict the effectiveness of immunotherapy in UCEC patients. LTA was finally identified to be significantly upregulated in tumor tissues and closely associated with prognosis and immunological status, which was then verified in GSE17025. In multivariate analysis, the hazard ratio of LTA was 0.42 with 95% CI (0.22-0.80) (p = 0.008). Patients with high LTA expression had better survival and apparently immune-activated phenotypes, such as more tumor mutation burden (TMB), stronger immune cell infiltrations, higher expression of immunosuppressive points, and higher immunophenoscore, meaning they had an immunotherapeutic advantage over those with low LTA expression. TIMER and TISIDB indicated that LTA was highly expressed in UCEC, and its expression was negatively correlated with stages and positively related to prognosis. Additionally, we found that LTA ectopic expression weakened the proliferation ability of RL95-2 cells. All these findings indicated that LTA could act as a novel and easily assayed biomarker to predict immunological status and clinical outcomes and even as an antioncogene to explore UCEC in depth.


Career options in colon and rectal surgery.
As the field of colon and rectal surgery has expanded and diversified, so has the multitude of opportunities available to the prospective colon and rectal surgery graduate. Although this may initially appear exciting, these decisions may eventually become daunting and even paralyzing. However, prior to making a decision, candidates must first make an honest assessment of their goals, abilities, and priorities. This article briefly outlines some of these challenging choices and helps lay the groundwork for a successful decision process.


Negotiating the transition to middle school: the role of self-regulatory processes.
The present research examined the role of maladaptive self-regulatory beliefs as vulnerability factors for academic and emotional difficulties during the transition to middle school. A short-term longitudinal design was employed to follow two groups of early adolescents: 187 adolescents who experienced a school transition between the fifth and sixth grades, and 142 adolescents who did not experience a school transition between the fifth and sixth grades. Adolescents completed measures of perceptions of academic control and importance of academic success, experience of chronic academic strain, daily school hassles, and depressive symptoms. Teachers reported on students' academic engagement, including levels of helpless behavior, effort, and academic performance. Consistent with the proposed model of self-regulation, maladaptive self-regulatory beliefs (i.e., decreased perceptions of academic control and importance) predicted individual differences in perceived school-related stress and depressive symptoms over the course of the middle school transition, but were not associated with academic and emotional difficulties in adolescents who remained in a stable school environment. Moreover, a self-regulatory sequence was identified proceeding from maladaptive self-regulatory beliefs, to academic disengagement, to enhanced perceptions of school-related stress, to depressive symptoms. This study bridges prior theory and research concerning the psychological impact of normative developmental transitions, the developmental context of depression, and the associations among self-regulatory beliefs, achievement-related behavior, and emotional experience.


Developmentally Regulated Rebound Depolarization Enhances Spike Timing Precision in Auditory Midbrain Neurons.
The inferior colliculus (IC) is an auditory midbrain structure involved in processing biologically important temporal features of sounds. The responses of IC neurons to these temporal features reflect an interaction of synaptic inputs and neuronal biophysical properties. One striking biophysical property of IC neurons is the rebound depolarization produced following membrane hyperpolarization. To understand how the rebound depolarization is involved in spike timing, we made whole-cell patch clamp recordings from IC neurons in brain slices of P9-21 rats. We found that the percentage of rebound neurons was developmentally regulated. The precision of the timing of the first spike on the rebound increased when the neuron was repetitively injected with a depolarizing current following membrane hyperpolarization. The average jitter of the first spikes was only 0.5 ms. The selective T-type Ca2+ channel antagonist, mibefradil, significantly increased the jitter of the first spike of neurons in response to repetitive depolarization following membrane hyperpolarization. Furthermore, the rebound was potentiated by one to two preceding rebounds within a few hundred milliseconds. The first spike generated on the potentiated rebound was more precise than that on the non-potentiated rebound. With the addition of a calcium chelator, BAPTA, into the cell, the rebound potentiation no longer occurred, and the precision of the first spike on the rebound was not improved. These results suggest that the postinhibitory rebound mediated by T-type Ca2+ channel promotes spike timing precision in IC neurons. The rebound potentiation and precise spikes may be induced by increases in intracellular calcium levels.


Pilot Study on the Forehead Skin Microbiome and Short Chain Fatty Acids Depending on the SC Functional Index in Korean Cohorts.
Dry skin is one of the indicators of a compromised skin barrier. An intact skin barrier is not only important to reserve the hydration within the epidermal tissue but also to protect our skin from environmental stressors and inhibit pathogen invasion; damage to the skin barrier may lead to inflammatory skin diseases. Some microbial metabolites such as short chain fatty acids may inhibit or destroy harmful bacteria and regulate the host immune system. The impact of the skin microbiome and short chain fatty acids on skin barrier function was studied in two groups of 75 participants each. The cohort was equally divided in dry and moist skin types, based on stratum corneum (SC) functionality index (SCFI), reflecting the ratio of transepidermal water loss (TEWL). A dry group represents a low SCFI and a moist group a high SCFI. Compared with the dry skin group, propionate and Cutibacterium levels (previously known as Propionibacterium acnes) were significantly higher (p < 0.001) in the moist group. Levels of Cutibacterium were negatively correlated with those of Staphylococcus (p < 0.0001) in both dry and moist groups. The moist group also had a significantly higher propionate concentration (p < 0.001). This study showed that the microbial community and short chain fatty acid concentration may be considered as significant determinants of the SCFI of the skin.


The survey of healthcare software in Yugoslavia.
The aim of this study is to identify vendors of software packages applicable to health care system as well as to evaluate software packages offered to the health sector by a variety of sources, namely state owned software development companies, privately operated software development companies as well as sole traders. The approach undertaken was to preselect the potential suppliers via an initial targeted interview. Subsequently a questionnaire, consisting of 23 questions, was addressed to the selected vendors and suppliers. The response rate to the questionnaire was 58%. Investigation of 113 has revealed the non government software suppliers clearly lead in copyright ownership, IBM compatible personal computers were the platform of choice whereas majority of code was written utilising languages capable of supporting relational data base queries. The final outcome of the above study is a database of software packages and applications available to the health sector offering the health professionals and institutions guide lines and support in developing information systems, relevant subsystems and modules.


Hemiconvulsion-hemiplegia-epilepsy Syndrome: A Case Series.
Hemiconvulsion-hemiplegia-epilepsy (HHE) syndrome is an uncommon outcome of prolonged focal status epilepticus in childhood. We present four cases with age between 6 months and 3 years diagnosed with HHE syndrome. Two patients were lost to follow-up; other two cases had severe developmental delay and refractory epilepsy. An early diagnosis, a good seizure control, and a better understanding of the underlying mechanisms of HHE are needed to improve the outcome of this condition.


Genotoxicity of 1,3-butadiene and its epoxy intermediates.
Current risk assessments of 1,3-butadiene (BD*) are complicated by limited evidence of its carcinogenicity in humans. Hence, there is a critical need to identify early events and factors that account for the heightened sensitivity of mice to BD-induced carcinogenesis and to deter-mine which animal model, mouse or rat, is the more useful surrogate of potency for predicting health effects in BD-exposed humans. HEI sponsored an earlier investigation of mutagenic responses in mice and rats exposed to BD, or to the racemic mixture of 1,2-epoxy-3-butene (BDO) or of 1,2,3,4-diepoxybutane (BDO2; Walker and Meng 2000). In that study, our research team demonstrated (1) that the frequency of mutations in the hypoxanthine-guanine phosphoribosyl transferase (Hprt) gene of splenic T cells from BD-exposed mice and rats could be correlated with the species-related differences in cancer susceptibility; (2) that mutagenic-potency and mutagenic-specificity data from mice and rats exposed to BD or its individual epoxy intermediates could provide useful information about the BD metabolites responsible for mutations in each species; and (3) that our novel approach to measuring the mutagenic potency of a given chemical exposure as the change in Hprt mutant frequencies (Mfs) over time was valuable for estimating species-specific differences in mutagenic responses to BD exposure and for predicting the effect of BD metabolites in each species. To gain additional mode-of-action information that can be used to inform studies of human responses to BD exposure, experiments in the current investigation tested a new set of five hypotheses about species-specific patterns in the mutagenic effects in rodents of exposure to BD and BD metabolites: 1. Repeated BD exposures at low levels that approach the occupational exposure limit for BD workers (set by the U.S. Occupational Safety and Health Administration) are mutagenic in female mice. 2. The differences in mutagenic responses of the Hprt gene to BD in similarly exposed rodents of a given species (reported in various earlier studies) are primarily associated with age-related thymus activity and trafficking of T cells and with sex-related differences in BD metabolism. 3. The mutagenic potency of the stereochemical forms of BD's epoxy intermediates plays a significant role in the species-related mutagenicity of BD. 4. The hydrolysis-detoxification pathway of BD through 1,2-dihydroxy-3-butene (BD-diol) is a major contributor to mutagenicity at high-level BD exposures in mice and rats. 5. Significant and informative species-specific differences in mutation spectra can be identified by examining both large- and small-scale genetic alterations in the Hprt gene of BD-exposed mice and rats. The first four hypotheses were tested by exposing mice and rats to BD, meso-BDO2, or BD-diol and measuring Hprt Mfs as the primary biomarker. For this, we used the T-cell-cloning assay of lymphocytes isolated from the spleens of exposed and control (sham-exposed) mice and rats. The first hypothesis was tested by exposing female B6C3F1 mice (4 to 5 weeks of age) by inhalation for 2 weeks (6 hours/day, 5 days/week) to 0 or 3 ppm BD. Hprt Mfs were measured at the time of peak mutagenic response after exposure for this age of mice. We then compared the resulting data to those from mutagenicity studies with mice of the same age that had been exposed in a similar protocol to higher levels of BD (Walker and Meng 2000). In mice exposed to 3 ppm BD (n = 27), there was a significant 1.6-fold increase over the mean background Hprt Mf in control animals (n = 24, P = 0.004). Calculating the efficiency of Hprt mutant induction, by dividing induced Hprt Mfs by the respective BD exposure levels, demonstrated that the mutagenic potency of 3 ppm BD was twice that of 20 ppm BD and almost 20 times that of 625 or 1250 ppm BD in exposed female mice. Sample-size calculations based on the Hprt Mf data from this experiment demonstrated the feasibility of conducting a future experiment to find out whether induced Mfs at even lower exposure levels (between 0.1 and 1.0 ppm BD) fit the supralinear exposure-response curve found with exposures between 3.0 and 62.5 ppm BD, or whether they deviate from the curve as Mf values approach the background levels found in control animals. The second hypothesis was tested by estimating mutagenic potency for female mice exposed by inhalation for 2 weeks to 0 or 1250 ppm BD at 8 weeks of age and comparing this estimate to that reported for female mice exposed to BD in a similar protocol at 4 to 5 weeks of age (Walker and Meng 2000). For these two age groups, the shapes of the mutant splenic T-cell manifestation curves were different, but the mutagenic burden was statistically the same. These results support our contention that the disparity in responses reported in earlier Hprt-mutation studies of BD-exposed rodents is related more to age-related T-cell kinetics than to age-specific differences in the metabolism of BD. The third hypothesis was tested by estimating mutagenic potency for female mice and rats (4 to 5 weeks of age) exposed by inhalation to 2 or 4 ppm meso-BDO2 and comparing these estimates to those previously obtained for female mice and rats of the same age and exposed in a similar protocol to (+/-)-BDO2 (Meng et al. 1999b; Walker and Meng 2000). These exposures to stereospecific forms of BDO2 caused equivalent mutagenic effects in each species. This suggests that the small differences in the mutagenic potency of the individual stereoisomers of BDO2 appear to be of less consequence in characterizing the sources of BD-induced mutagenicity than the much larger differences between the mutagenic potencies of BDO2 and the other two BD epoxides (BDO and 1,2-dihydroxy-3,4-epoxybutane [BDO-diol]). The fourth hypothesis was tested in several experiments. First, female and male mice and rats (4 to 5 weeks of age) were exposed by nose only for 6 hours to 0, 62.5, 200, 625, or 1250 ppm BD or to 0, 6, 18, 24, or 36 ppm BD-diol primarily to establish BD and BD-diol exposure levels that would yield similar plasma concentrations of BD-diol. Second, animals were exposed in inhalation chambers for 4 weeks to 0, 6, 18, or 36 ppm BD-diol to determine the mutagenic potency estimates for these exposure levels and to compare these estimates with those reported for BD-exposed female mice and rats (Walker and Meng 2000) in which similar blood levels of BD-diol had been achieved. Measurements of plasma concentrations of BD-diol (via a gas chromatography and mass spectrometry [GC/MS] method developed for this purpose) showed these results: First, BD-diol accumulated in a sublinear manner during a single 6-hour exposure to more than 200 ppm BD. Second, BD-diol accumulated in a linear manner during single (6-hour) or repeated (4-week) exposure to 6 or 18 ppm BD and in a sublinear manner with increasing levels of BD-diol exposure. Third, exposure of female mice and rats to 18 ppm BD-diol produced plasma concentrations equivalent to those produced by exposure to 200 ppm BD (exposure to 36 ppm BD-diol produced plasma concentrations of about 25% of those produced by exposure to 625 ppm BD). In general, 4-week exposure to 18 or 36 ppm BD-diol was significantly mutagenic in female and male mice and rats. The differences in mutagenic responses between the species and sexes were not remarkable, except that the mutagenic effects were greatest in female mice. The substantial differences in the exposure-related accumulation of BD-diol in plasma after rodents were exposed to more than 200 ppm BD compared with the relatively small differences in the mutagenic responses to direct exposures to 6, 18, or 36 ppm BD-diol in female mice provided evidence that the contribution of BD-diol-derived metabolites to the overall mutagenicity of BD has a narrow range of effect that is confined to relatively high-level BD exposures in mice and rats. This conclusion was supported by the results of parallel analyses of adducts in mice and rats concurrently exposed to BD-diol (Powley et al. 2005b), which showed that the exposure-response curves for the formation of N-(2,3,4-trihydroxybutyl)valine (THB-Val) in hemoglobin, formation of N7-(2,3,4-trihydroxybutyl)guanine (THB-Gua) in DNA, and induction of Hprt mutations in exposed rodents were remarkably similar in shape (i.e., supralinear). Combined, these data suggest that trihydroxybutyl (THB) adducts are good quantitative indicators of BD-induced mutagenicity and that BD-diol-derived BDO-diol (the major source of the adducts) might be largely responsible for mutagenicity in rodents exposed to BD-diol or to hight levels of BD. The mutagenic-potency studies of meso-BDO2 and BD-diol reported here, combined with our earlier studies of BD, (+/-) BDO, and(+/-)-BDO2 (Walker and Meng 2000), revealed important trends in species-specific mutagenic responses that distinguish the relative degree to which the epoxy intermediates contribute to mutation induction in rodents at selected levels of BD exposures. These data as a whole suggest that , in mice, BDO2 largely causes mutations at exposures less than 62.5 ppm BD and that BD-diol-derived metabolites add to these mutagenic effects at higher BD exposures. In rats, it appears that the BD-diol pathway might account for nearly all the mutagenicity at the hight-level BD exposures where significant increases in Hprt Mfs are found and cancers are induced. Additional exposure-response studies of hemoglobin and DNA adducts specifics to BDO2, BDO-diol, and other reactive intermediates are needed to determine more definitively the relative contribution of each metabolite to the DNA alkylation and mutation patterns induced by BD exposure in mice and rats. For the fifth hypothesis, a multiplex polymerase chain reaction (PCR) procedure for the analysis of genomic DNA mutations in the Hprt gene of mice was developed. (ABSTRACT TRUNCATED)


Negotiated Management Strategies for Bovine Tuberculosis: Enhancing Risk Mitigation in Michigan and the UK.
Bovine tuberculosis (bTB) is an epidemiologically, politically, and socially complex disease. Across multiple international contexts, policy makers have struggled to balance the competing demands of wildlife and agricultural interests in their efforts to create workable and effective disease management strategies. This paper draws comparative lessons between the cases of Michigan in the USA and the UK to exemplify some of the challenges of developing an effective strategy for the long-term control of endemic disease, particularly reflecting on efforts to "responsibilise" cattle producers and engage them in proactive activities to mitigate transmission risks on their own farms. Using qualitative data derived from 22 stakeholder interviews, it is argued that the management of bTB in Michigan has important lessons for the UK on the role of human dimensions in influencing the direction of disease control. The management of endemic bTB relies on the actions of individuals to minimise risk and, in contrast to the predominantly voluntary approach pursued in the UK, Michigan has shifted the emphasis towards obtaining producer support for wildlife risk mitigation and biosecurity via a mix of regulatory, fiscal, and social interventions. Whilst the scale of the bTB challenge differs between these two contexts, analysis of the different ideological bases for selecting management approaches offers interesting insights on the role of negotiated outcomes in attempts to adaptively manage a disease that is characterised by complexity and uncertainty.


Hamstring weakness after surgery for anterior cruciate injury.
The purpose of this study was to measure the effects of surgery and immobilization on the isometric strength of the hamstrings. Fifteen male volunteers were measured for isometric hamstring torque prior to surgery for correction of anterior cruciate ligament (ACL) insufficiency. After surgery the subjects were casted for 6 weeks and did not perform exercises specific to the hamstrings. Subjects were retested immediately after cast removal and the hamstring output was compared to the preoperative hamstring output. A 43% decrease in hamstring torque was noted which is statistically significant (p < 0.001). It is suggested that exercise of the hamstring, a muscle group of great importance to the ACL-injured knee, during immobilization may be helpful in limiting hamstring strength loss during the immobilization period. J Orthop Sports Phys Ther 1986;7(6):310-313.


Characteristics of tasks utilized for evaluation of judgment errors in the elderly.
[Purpose] The present study compared assessments utilized to evaluate judgment errors in the elderly. [Subjects and Methods] A total of 94 community-dwelling elderly participants in an examination of physical fitness for health promotion and health guidance in a rural area in Japan were included. Spatially and temporally predictive tasks were used to evaluate judgment errors. Distances measured on the Functional Reach and upward reaching tests were used to assess spatial prediction, and times measured on the Timed Up and Go test and Standardized Walking Obstacle Course were used to assess temporal prediction. Differences between the self-predicted values and actual results were deemed judgment errors. [Results] Significant differences were observed between self-predicted abilities and the patients' performances. Participants underestimated their abilities in spatially predictive tasks and overestimated them in temporally predictive tasks. On comparing the four tasks, there were significant differences in judgment error ratios between them. Statistical analysis indicated a significant difference in the judgment error ratio for the Standardized Walking Obstacle Course correlated with a history of falls. [Conclusion] Judgment errors were identified using both spatially and temporally predictive tasks. A temporally predictive task like the Standardized Walking Obstacle Course might better evaluate judgment errors in the elderly.


A large waterborne gastroenteritis outbreak in central Greece, March 2012: challenges for the investigation and management.
In March 2012, there was an unusual increase of gastroenteritis cases in a district with 37,264 inhabitants in central Greece. It was estimated that more than 3600 people developed symptoms. A 1:1 case-control study showed that consumption of tap water was a risk factor for acquiring infection [odds ratio (OR) 2.18, 95% confidence interval (CI) 1.11-4.28]. Descriptive data, low gastroenteritis incidence in adjacent areas with different water supply systems, and water-quality data further supported the hypothesis of a waterborne outbreak. Thirty-eight stool samples were positive for rotavirus. Bacterial indicators of recent faecal contamination were detected in samples from the water source and ice cubes from a local production enterprise. Molecular epidemiology of rotavirus strains, apart from the common strain, G3[P8], identified the unusual G/P combination G2P[8]. Water sanitation measures contributed to the control of the outbreak. This outbreak demonstrated the need for the cooperation of laboratories with different expertise and the importance of early notification of waterborne gastroenteritis outbreaks.


Maraviroc concentrations in cerebrospinal fluid in HIV-infected patients.
To determine maraviroc (MVC) concentrations in cerebrospinal fluid (CSF) in HIV-infected patients. Twelve CCR5+ HIV-1 adult antiretroviral-experienced patients receiving MVC-containing regimens for at least 1 month were enrolled. Both CSF and blood samples were taken around 12 hours after the last MVC dose. liquid chromatography tandem mass spectrometry was used to determine MVC concentrations, and HIV-1 viral load was determined by real-time polymerase chain reaction, (LOD, 40 copies/mL). Twelve blood and 12 CSF samples were collected. Median CD4 count was 281(120-759) cells per microliter, and median HIV-1 viral load was <40 copies per milliliter. Median time on MVC was 13.5 weeks (4-60). Nucleoside analogues (tenofovir/didanosine) were given in only 1 case. Median MVC concentrations in plasma were 124.75 (7.3-517) ng/mL. In all except one, CSF sample-receiving an erroneous MVC dose while taking concomitantly nevirapine-MVC concentrations [2.58 (<0.5-7.22) ng/mL] were within the EC(90) range (0.06-10.70). Median MVC CSF: plasma ratio was 0.022 (0.004-0.17), and when the free MVC plasma concentration was used, 0.094 (2.58-27.44). CSF viral load was <40 copies per milliliter in all 9 patients with undetectable plasma viral load. MVC achieves concentrations within the EC(90) range in CSF. All patients with undetectable plasma viral load although receiving nucleoside-sparing regimens including new drugs showed viral suppression in CSF.


Two cases of feline paraneoplastic alopecia associated with a neuroendocrine pancreatic neoplasia and a hepatosplenic plasma cell tumour.
Feline paraneoplastic alopecia (FPA) is a rare condition listed among the cutaneous paraneoplastic syndromes, which occurs in association with pancreatic carcinoma, cholangiocarcinoma, hepatocellular carcinoma and metastatic intestinal carcinoma. To describe the clinicopathological findings of paraneoplastic alopecia in two cats each with an uncommon tumour not previously reported in association with FPA. Paraneoplastic alopecia was associated with neuroendocrine pancreatic neoplasia in a Persian cat and with a hepatosplenic plasma cell tumour in a domestic short hair cat. FPA was suspected based on age, rapid onset of clinical signs, ventral distribution of alopecia, shiny appearance of the skin and telogenization/miniaturization of the follicles on histopathology. The nature of the tumours was determined through cytology, postmortem, histopathological and immunohistochemical examination, and capillary immunoelectrophoresis. A causative association between the skin lesions and the tumour was suggested by clinical and histopathological features shared with previously published cases. Pancreatic neuroendocrine and plasma cell tumour should be considered as differential diagnoses when evaluating FPA.


Influence of porcine liver esterase on the color of dental resin composites by CIEDE2000 system.
The objectives of this study were to evaluate the changes in color and color coordinates of dental resin composites after immersion in porcine liver esterase (PLE, 400 mU/mL; a substitute for salivary hydrolase) with CIEDE2000 color system, and to compare those with CIELAB color system. Color of resin composites was measured after immersion in PBS (phosphate buffered saline; control) or PLE up to nine weeks. Color difference (delta E00) and changes in lightness (L'), red-green parameter (a'), yellow-blue parameter (b'), and chroma (C') with CIEDE2000 system were compared. Correlation in the changes of color with CIEDE2000 and CIELAB systems was determined. Delta E00 values after a 9-week immersion in PLE were 0.7-2.8, which were not higher than those in PBS except for a few cases. Changes in b' and C' values after a 9-week immersion in PLE were generally lower than those in PBS, and were in the range of -4.0 to -0.1 and -4.0 to -0.1, respectively. Therefore, the influence of porcine liver esterase on the changes of color and color coordinates was negligible with CIEDE2000 color system. There was a significant correlation between color differences (delta E00 vs deltaE*ab) with CIEDE2000 and CIELAB systems [correlation coefficient (r) = 0.95, p < 0.01].


A petunia ethylene-responsive element binding factor, PhERF2, plays an important role in antiviral RNA silencing.
Virus-induced RNA silencing is involved in plant antiviral defense and requires key enzyme components, including RNA-dependent RNA polymerases (RDRs), Dicer-like RNase III enzymes (DCLs), and Argonaute proteins (AGOs). However, the transcriptional regulation of these critical components is largely unknown. In petunia (Petunia hybrida), an ethylene-responsive element binding factor, PhERF2, is induced by Tobacco rattle virus (TRV) infection. Inclusion of a PhERF2 fragment in a TRV silencing construct containing reporter fragments of phytoene desaturase (PDS) or chalcone synthase (CHS) substantially impaired silencing efficiency of both the PDS and CHS reporters. Silencing was also impaired in PhERF2- RNAi lines, where TRV-PhPDS infection did not show the expected silencing phenotype (photobleaching). In contrast, photobleaching in response to infiltration with the TRV-PhPDS construct was enhanced in plants overexpressing PhERF2 Transcript abundance of the RNA silencing-related genes RDR2, RDR6, DCL2, and AGO2 was lower in PhERF2-silenced plants but higher in PhERF2-overexpressing plants. Moreover, PhERF2-silenced lines showed higher susceptibility to Cucumber mosaic virus (CMV) than wild-type (WT) plants, while plants overexpressing PhERF2 exhibited increased resistance. Interestingly, growth and development of PhERF2-RNAi lines were substantially slower, whereas the overexpressing lines were more vigorous than the controls. Taken together, our results indicate that PhERF2 functions as a positive regulator in antiviral RNA silencing.


Realization of subwavelength guiding utilizing coupled wedge plasmon polaritons in splitted groove waveguides.
A detailed numerical study of propagation characteristics of a coupled wedge plasmon polariton (CWPP) in splitted groove waveguide (SGW) formed with two metal wedges is performed by using the finite element method (FEM). It is shown that the SGW structure could confine CWPP modes tightly to the nano-gap region between the wedge tips, operating in a much broad bandwidth. The effect of the glass substrate, wedge roundness, gap width, groove wedge angle, and groove depth are also investigated. Particularly, our SGWs are found to be quite robust against groove depth reduction, which could be beneficial to minimize the waveguide structure dimensions. Feasibility of using such SGWs for the design of efficient subwavelength plasmonic elements is also discussed on the nanoscale whispering gallery resonators as an example.


A simple and effective approach to the synthesis of isoquinoline derivatives under solvent-free conditions.
An efficient synthesis of dialkyl pyrrolo[2,1-a]isoquinoline-2,3-dicarboxylates, pyrrolo[1,2-a]quinoline-1,2- dicarboxylates and indolizines is described via one-pot reactions of isoquinoline, quinoline or pyridine and phenacyl bromids with dialkyl acetylenedicarboxylates or diaryloylacetylene under solvent-free conditions at 50°C. The mild reaction conditions and high yields of the products exhibit the good synthetic advantage of these methods.


Schedule-dependent synergism of vinorelbine and 5-fluorouracil/UFT against non-small cell lung cancer.
Elderly patients with advanced non-small cell lung cancer (NSCLC) require chemotherapy that is effective and minimally toxic. We evaluated the activity of a combination of vinorelbine and 5-fluorouracil (5-FU)/UFT (a fixed combination of tegafur and uracil) in vitro and in vivo to establish a rationale for clinical use. The cytotoxic activities of various combinations of vinorelbine and 5-FU, the active metabolite of tegafur, were analyzed by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazlium bromide (MTT) assay and isobologram technique in vitro, using 3 NSCLC cell lines (A549, PC14, and Ma10). Sequential exposure to vinorelbine followed by 5-FU showed additive or synergistic activity against all 3 NSCLC cell lines tested. The reverse sequence showed no synergism. Antitumor activity and survival prolongation after treatment with different combinations of vinorelbine and UFT were evaluated in nude mice bearing PC14 xenografts. Treatment with vinorelbine before UFT was associated with higher antitumor activity, less toxicity, and longer survival than the reverse sequence. To clarify the underlying mechanism by which the combination exerts the synergistic effects, the expression of thymidylate synthase (TS) was assessed by Western blot analysis in vitro and by immunohistochemical analysis in an animal model. Vinorelbine suppressed the 5-FU-induced increase in TS protein in A549 cells. In PC14 tumor tissues of animal models, TS expression in cancer cells was suppressed by vinorelbine. Our data suggest that treatment with vinorelbine injection before oral UFT may have synergistic activity against NSCLC. This synergistic activity may be attributed to increased chemosensitivity to UFT caused by vinorelbine-induced suppression of TS.


Impediments to mental health treatment as predictors of mental health symptoms following combat.
This longitudinal study examined whether impediments to mental health treatment would predict changes in mental health symptoms (posttraumatic stress disorder [PTSD] and depression) in the months following soldiers returning from combat. Three-hundred ten combat veterans completed measures of impediments to treatment and measures of PTSD and depression symptoms at 2, 3, and 4 months following a 15-month combat deployment. Structural equation modeling revealed that greater impediments (a latent variable indexed by stigma, practical barriers, and negative treatment attitudes) at 2 months predicted increased PTSD and depression symptoms from 2-3 months (β = .14) and greater impediments at 3 months predicted increased symptoms from 3-4 months (β = .26). In contrast, evidence was not obtained for the opposite causal direction of symptoms predicting higher levels of impediments at the different periods. Possible mechanisms for the predictive effects of impediments are discussed.