Diversity, cultural sensitivity, unequal treatment, and sexual harassment in a school of dental hygiene.
The purpose of this study was to assess the cultural environment in the School of Dental Hygiene at the University of Texas Dental Branch (UTDB) at Houston. A 36-item questionnaire was developed and administered to first- (DH1; n=34) and second-year (DH2, n=33) dental hygiene students. Questions explored satisfaction with diversity and interactions with faculty, staff, patients, and other students relative to gender, ethnicity/race, age, and sexual orientation. Data were analyzed using 2x3 and 2x5 contingency tables to calculate the chi square test statistic. Ninety-one percent of the 67 DH students responded. While the majority of students reported satisfaction with the cultural diversity and their interactions at UTDB at Houston, 76% of the DH2 students and 62% of the DH1 students reported that the curriculum did not prepare them to work with patients whose primary language is not English. Eighty-two percent of DH1 students and 59% of DH2 students reported that the curriculum did not prepare them to work with patients with different sexual orientations and religious backgrounds. The DH2 students reported unequal treatment by faculty of another gender (24%) and ethnicity (21%), and sexual harassment by other students (6%). DH1 reported 6%, 12%, and 0%, respectively. Data indicate that dental hygiene students in the UTDB at Houston dental hygiene program experienced unequal treatment and sexual harassment by either faculty, staff, patients, or other students. To create a more culturally sensitive environment, the students, faculty, and staff could benefit from training on diversity, cross-cultural competence and awareness, and sexual harassment prevention and management. The dental hygiene curriculum should be reviewed for the inclusion of topics related to diversity, cultural competence, and sexual harassment.


Muscle necrosis caused by snake venoms and toxins.
Snake bite is often associated with localised soft tissue necrosis. Less frequently victims may suffer extensive muscle damage leading to rhabdomyolysis and the loss of muscle-specific protein. This review describes the organisation and structure of mammalian skeletal muscle, and its response to myotoxic venoms and to isolated pure myotoxic venom fractions. The clinical reports of muscle damage in man following snake bite are discussed, and the various classes of myotoxic toxins are introduced. Muscle damage caused by the toxins is next described, particular emphasis being placed on the correlation between muscle pathology seen at the light level and the morphological changes seen at the level of the electron microscope. Where known, those subcellular components of the muscle fibre that are especially sensitive to assault, and those components that appear to be spared, are identified. The relevance of the selective sparing of some components to the regenerative capacity of the skeletal muscle is considered.


A mosaic-like distribution of dopamine receptors in rat neostriatum and its relationship to striosomes.
The distribution of dopamine receptors in rat neostriatum was determined by means of light microscopic autoradiography of in vivo labeled binding sites for [3H]N-n-propylnorapomorphine and compared with the distribution of acetylcholinesterase histochemical staining. The distribution of dopamine receptors was non-homogeneous and patches of low receptor density were in register with acetylcholinesterase-poor striosomes. This suggests that the distribution pattern of dopamine receptors is specifically related to various input systems.


Elsholblanosides A-D, Four New Oleuropeic Acid Derivatives Isolated from Elsholtzia blanda and Their Inhibition of NO Production in LPS-activated RAW264.7 Cells.
Phytochemical investigation on the aerial parts of Elsholtzia blanda Benth. afforded four new oleuropeic acid derivatives (1-4), named as elsholblanosides A-D, respectively, together with 11 known compounds (5-15). Their structures were determined based on extensive analyses of HR-ESI-MS, 1D and 2D NMR, and ECD spectra. Compounds 1-4 and 14 showed moderate NO production inhibition in LPS-activated RAW264.7 cells with their IC50 values ranging from 23.2 to 86.33 μM, compared to that of the positive control compound, dexamethasone, IC50 value of 16.9 μM.


Lesch-Nyhan syndrome: a case report.
Lesch-Nyhan syndrome (LNS) is a rare X-linked recessive disorder caused by a mutation in the hypoxanthine phosphoribosyltransferase 1 (HPRT1) gene. This syndrome is characterized by excessive production of uric acid, mental retardation, self-mutilation, choreoathetosis, and spasticity. The most distinctive symptom is compulsive self-mutilation. For patients with LNS, different methods have been tried to reduce self-biting behaviors including restraints, behavioral treatment, medications, deep brain stimulation, tooth extraction and botulinum toxin A injection. In this report, we present a case of LNS undergoing cheiloplasty due to self-mutilation and tooth extraction of the left deciduous maxillary canine.


Design and synthesis of 6-amino-1,4-oxazepane-3,5-dione derivatives as novel broad spectrum anticonvulsants.
Based on the structural estimations of the typical anticonvulsant drugs, a series of 6-amino-1,4-oxazepane-3,5-dione derivatives, novel structures of 7-membered heterocyclic imides, which were hybridized with pharmacophores such as cyclic imide and N-CO-C-N group in their molecule were designed and synthesized. Their anticonvulsant activities were evaluated by the maximal electroshock induced seizure (MES) and subcutaneous pentylenetetrazole (PTZ) tests. Almost all the designed compounds except 1c and 1f showed comparable anticonvulsant activities in at least one of the anticonvulsant tests. Moreover, some of the tested compounds exhibited moderate anticonvulsant activities in both MES and PTZ tests. From these results, 6-amino-1,4-oxazepane-3,5-dione derivatives could be recommended as novel structures of broad spectrum anticonvulsants.


Microfluidic chips as a method for sperm selection improve fertilization rate in couples with fertilization failure.
Sperm quality plays a vital role in successful fertilization and pregnancy. Patients with fertilization failure (total failure or low-fertilization rate) despite having normal semen parameters are a challenging group whose sperm cannot fertilize the oocyte via the intracytoplasmic sperm injection (ICSI) technique. Microfluidics is offered as a new method for proper sperm sorting. This study aimed to evaluate sperm parameters, DNA fragmentation index (DFI), expression of phospholipase C zeta 1 (PLCZ1), and transition nuclear proteins 1 (TNP1) mRNAs in sperm selected by microfluidic sperm sorting (MSS) chip compared with conventional density gradient centrifugation technique in patients with fertilization failure following ICSI. Subsequence fertilization rate and embryo quality were assayed. Normal morphology and total motility were significantly higher, and DFI was significantly lower in sperm selected by the MSS chip in fertilization failure and control groups. The RT-PCR results demonstrated a significant increase in the expression of PLCZ1 and TNP1 genes in sperm of both groups selected by MSS chips compared to the DGC method. In addition, with the selected sperm by MSS chip, an increase in fertilization rate and improvement of embryo quality was obtained. The present study findings show that sperm sorting by the microfluidic method improves fertilization rate in patients with poor fertilization outcomes following ICSI.


Variability on the energy properties of charcoal and charcoal briquettes for barbecue.
In recent years there has been a strong increase in interest in the world of barbecues and outdoor cooking in high-income countries. Referring to FAO data, an exponential growth in imports of charcoal was observed in Europe and North America. Italy is one of the major European consumers and importers. On the market it is possible to find material with different characteristics and origins. However, analysis aimed at ascertaining the quality of the material are poorly performed. This research aimed to analyze the energy properties of charcoal commonly available on the Italian market. Twenty-four bags of charcoal and charcoal briquettes were analyzed. Eighteen samples represent the products most easily found on the market, in stores and on websites. In addition, six samples were supplied directly by the producer/importing company. The samples were grouped according to the continent of origin of the material (Europe, North-Central America and South America). Charcoal briquette samples were included together in a group. Referring to the ISO 17225-1 standard, the moisture content, ash content, heating value, volatile matter and fixed carbon were determined. Except for the moisture content, the results of the tests performed on all parameters show a strong variability both between different groups and within the same group. In detail, the European charcoal samples show characteristics more suitable for their use in barbecues. These have the highest values of fixed carbon and heating value and, at the same time, low values of ash and volatile matter. On the contrary, charcoal briquettes have less suitable characteristics for barbecue. The work also highlighted some gaps in the reference standard relating to laboratory analyses. To ensure careful control of the qualitative characteristics of the products on the market, it is necessary to promote the creation of a quality brand.


Conversion to Roux-en-Y gastric bypass versus one-anastomosis gastric bypass after a failed primary gastric band: a matched nationwide study.
Primary laparoscopic adjustable gastric band (LAGB) has high rates of patients not achieving the desired weight loss, and it remains unclear which bariatric conversion procedure gives better results. To compare weight loss among patients undergoing conversion one-anastomosis gastric bypass (cOAGB) and conversion Roux-en-Y gastric bypass (cRYGB) after a failed LAGB. Nationwide population-based study including all 18 hospitals providing metabolic and bariatric surgery. Patients with a failed primary LAGB who underwent a cRYGB or cOAGB between January 1, 2015, and December 31, 2019, were selected from the Dutch Audit for Treatment of Obesity. The primary outcome was not achieving ≥20% total weight loss (TWL) at 1-year and up to 5-year follow-up. Secondary outcomes included postoperative complications, defined as Clavien-Dindo ≥III within 30 days, and co-morbidity remission. A propensity score matched logistic and Poisson regression model was used to estimate the difference in patients not achieving ≥20% TWL between cRYGB and cOAGB. A total of 615 (78.7%) patients underwent cRYGB, and 166 (21.3%) patients underwent cOAGB, with 163 patients successfully matched. Both groups had similar rates of patients not achieving ≥20% TWL at 1 year (odds ratio [OR] = .64, 95% confidence interval [CI]: .38-1.05). However, a sensitivity analysis showed that patients undergoing cOAGB had lower rates of patients not achieving ≥20% TWL up to 5-year follow-up (rate ratio = .69, 95% CI: .51-.95, P < .05). Patients undergoing cOAGB were less likely to achieve hypertension remission (OR = .22, 95% CI: .07-.66). There were no significant differences between groups in postoperative complications (OR = .39, 95% CI: .07-2.06, P > .05). This matched nationwide study suggests that the cOAGB has similar short-term weight loss outcomes but potentially better long-term weight loss results than cRYGB. Therefore, cOAGB could provide a reliable alternative but needs to be substantiated in future long-term studies.


Knowledge on leprosy and its management among primary healthcare providers in two districts of Bangladesh.
In 2013, Lepra Bangladesh (a non-government organization) and the National Leprosy Programme of the Directorate General of Health Services under the Ministry of Health and Family Welfare, Bangladesh implemented a 3 years project entitled "2015 and Beyond: Poverty Reduction through Strengthened Health Systems". The aims of this Health System Strengthening (HSS) project were to improve quality of leprosy services through service delivery, capacity development, curriculum development, improved collaboration, coordination, operational research and knowledge sharing to identify and treat leprosy in order to contribute to strengthen existing health systems. We evaluated the changes in knowledge of primary and community level healthcare providers about cardinal signs, course of leprosy treatment, and drug use for paucibacillary (PB) and multibacillary (MB) leprosy cases. We conducted two surveys using purposive sampling technique in two pilot districts: Bogra and Moulvibazar. The first survey was conducted before implementing the HSS project from March to June 2014 among 98 providers. The end-line survey was conducted in November 2015 and included 49 providers. The interview was conducted using the same pre-tested structured questionnaire. Descriptive statistics followed by further analysis was done including proportions, 90% confidence intervals, and p values were calculated for the selected variables. The primary and community level healthcare providers demonstrated significant increases in knowledge on one cardinal sign (definite loss of sensation in a pale -hypopigmented- or reddish skin patch), doses and courses for the adult PB and MB cases and duration of Multi-Drug Therapy (MDT) course at the end line compared to the beginning of the project. All the providers except TB and Leprosy Control Assistants demonstrated statistically significant decreases in knowledge at the end-line compared to the baseline about supportive counseling. HSS activities including training and capacity building of the providers recorded significant increase of knowledge on types of leprosy, one cardinal sign, courses of MDT and drug use for the adult PB and MB cases and use MDT for leprosy treatment among the service providers at the end-line. Any health systems strengthening project should incorporate a capacity building approach within the programme all through.


Community Social Capital and Population Health Outcomes.
While the association between economic connectedness and social mobility has now been documented, the potential linkage between community-level economic connectedness and population health outcomes remains unknown. To examine the association between community social capital measures (defined as economic connectedness, social cohesion, and civic engagement) and population health outcomes (defined across prevalence of diabetes, hypertension, high cholesterol, kidney disease, and obesity). This cross-sectional study included communities defined at the zip code tabulation area (ZCTA) level in all 50 US states. Data were collected from January 2021 to December 2022. Multivariable regression analyses were used to examine the association between population health outcomes and social capital. Adjusted analyses controlled for area demographic variables and county fixed effects. Heterogeneities within the associations based on the racial and ethnic makeup of communities were also examined. In this cross-sectional study of 17 800 ZCTAs, across 50 US states, mean (SD) economic connectedness was 0.88 (0.32), indicating friendship sorting on income; the mean (SD) support ratio was 0.90 (0.10), indicating that 90% of ties were supported by a common friendship tie; and the mean (SD) volunteering rate was 0.08 (0.03), indicating that 8% of individuals within a given community were members of volunteering associations. Mean (SD) ZCTA diabetes prevalence was 10.8% (2.9); mean (SD) high blood pressure prevalence was 33.2% (6.2); mean (SD) high cholesterol prevalence was 32.7% (4.2), mean (SD) kidney disease prevalence was 3.0% (0.7), and mean (SD) obesity prevalence was 33.4% (5.6). Regression analyses found that a 1% increase in community economic connectedness was associated with significant decreases in prevalence of diabetes (-0.63%; 95% CI, -0.67% to -0.60%); hypertension (-0.31%; 95% CI, -0.33% to -0.29%); high cholesterol (-0.14%; 95% CI, -0.15% to -0.12%); kidney disease (-0.48%; 95% CI, -0.50% to -0.46%); and obesity (-0.28%; 95% CI, -0.29% to -0.27%). Second, a 1% increase in the community support ratio was associated with significant increases in prevalence of diabetes (0.21%; 95% CI, 0.16% to 0.26%); high blood pressure (0.16%; 95% CI, 0.13% to 0.19%); high cholesterol (0.16%; 95% CI, 0.13% to 0.19%); kidney disease (0.17%; 95% CI, 0.13% to 0.20%); and obesity (0.08%; 95% CI, 0.06% to 0.10%). Third, a 1% increase in the community volunteering rate was associated with significant increases in prevalence of high blood pressure (0.02%; 95% CI, 0.01% to 0.02%); high cholesterol (0.03%; 95% CI, 0.02% to 0.03%); and kidney disease (0.02%; 95% CI, 0.01% to 0.02%). Additional analyses found that the strength of these associations varied based on the majority racial and ethnic population composition of communities. In this study, higher economic connectedness was significantly associated with better population health outcomes; however, higher community support ratios and volunteering rates were both significantly associated with worse population health. Associations also differed by majority racial and ethnic composition of communities.


A selective fluorescent sensor for detecting lead in living cells.
We present the synthesis, properties, and biological applications of Leadfluor-1 (LF1), a new water-soluble, turn-on fluorescent sensor that is capable of selectively imaging Pb2+ in aqueous solution and in living cells. LF1 combines a fluorescein chromophore and a pseudocrown receptor to provide good selectivity for Pb2+ over a range of biologically and environmentally relevant metal ions in aqueous solution, with sensitivity to parts per billion EPA limits for allowable lead in drinking water. In addition to these attributes, imaging experiments further show that LF1 is the first small-molecule reagent that can be delivered into living cells and report changes in intracellular Pb2+ levels.


Social problems of alcoholics.
A comparison of abstainers and alcoholics showed that the latter were more often involved in social conflicts and breaches of social norms. The breaches of social values were as important as the drinking in society's definition of an alcoholic.


Genetic variation in and covariation between leaf gas exchange, morphology, and development in Polygonum arenastrum, an annual plant.
We present evidence of genetic variation in and covariation between leaf-level gas exchange properties and leaf size among family lines of Polygonum arenastrum. This self-fertilizing annual had previously been shown to vary genetically in developmental phenology and in morphology (size of leaves, internodes, flowers and seeds) (Geber 1990). Significant family differences were found in photosynthetic carbon assimilation rate (A), lcaf conductance to water vapor (g), instantaneous water-use efficiency (WUE), and leaf carbon isotope discrimination (Δ). A strong positive genetic correlation between A and g suggested that there was stomatal limitation on A. In addition, higher g led to relatively greater increases in transpiration, E, than in assimilation, A, so that families with high rates of gas exchange had lower instantaneous WUE and/or higher carbon isotope discrimination values. Leaf size and gas exchange were genetically correlated. In earlier studies leaf size was found to be genetically correlated with developmental phenology (Geber 1990). The pattern that emerges is one in which small-leaved families (which also have small internodes, flowers, and seeds) tend to have high gas exchange rates, low WUE, rapid development to flowering and high early fecundity, but reduced life span and maximum (vegetative and reproductive) yield compared to large-leaved families. We suggest that this pattern may have arisen from selection for contrasting suites of characters adapted to environments differing in season length.


Purification and characterization of a novel thermo-alkali-stable catalase from Thermus brockianus.
A novel thermo-alkali-stable catalase from Thermus brockianus was purified and characterized. The protein was purified from a T. brockianus cell extract in a three-step procedure that resulted in 65-fold purification to a specific activity of 5300 U/mg. The enzyme consisted of four identical subunits of 42.5 kDa as determined by SDS-PAGE and a total molecular mass measured by gel filtration of 178 kDa. The catalase was active over a temperature range from 30 to 94 degrees C and a pH range from 6 to 10, with optimum activity occurring at 90 degrees C and pH 8. At pH 8, the enzyme was extremely stable at elevated temperatures with half-lives of 330 h at 80 degrees C and 3 h at 90 degrees C. The enzyme also demonstrated excellent stability at 70 degrees C and alkaline pH with measured half-lives of 510 h and 360 h at pHs of 9 and 10, respectively. The enzyme had an unusual pyridine hemochrome spectrum and appears to utilize eight molecules of heme c per tetramer rather than protoheme IX present in the majority of catalases studied to date. The absorption spectrum suggested that the heme iron of the catalase was in a 6-coordinate low spin state rather than the typical 5-coordinate high spin state. A K(m) of 35.5 mM and a V(max) of 20.3 mM/min.mg protein for hydrogen peroxide was measured, and the enzyme was not inhibited by hydrogen peroxide at concentrations up to 450 mM. The enzyme was strongly inhibited by cyanide and the traditional catalase inhibitor 3-amino-1,2,4-triazole. The enzyme also showed no peroxidase activity to peroxidase substrates o-dianisidine and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid), a trait of typical monofunctional catalases. However, unlike traditional monofunctional catalases, the T. brockianus catalase was easily reduced by dithionite, a characteristic of catalase-peroxidases. The above properties indicate that this catalase has potential for applications in industrial bleaching processes to remove residual hydrogen peroxide from process streams.


An enzyme-linked immunoassay for nerve growth factor (NGF): a tool for studying regulatory mechanisms involved in NGF production in brain and in peripheral tissues.
A sensitive enzyme-linked immunosorbent assay (ELISA) for nerve growth factor (NGF) has been developed. The sensitivity of this assay (0.1 pg/well) permits the quantification of endogenous immunoreactive NGF in the peripheral nervous system and the CNS. Studies on the regulatory mechanisms involved in NGF production indicate that, in addition to neurally mediated mechanisms, other stimuli, e.g., inflammation, significantly contribute to NGF production.


Paget's disease: a cause of photopenic skeletal defect in indium-111 WBC scintigraphy.
As an incidental finding in an [111In]WBC scan performed in search of an infectious focus, photon deficient areas were found in several skeletal locations, characterized by bone and gallium scintigraphy and confirmed radiographically as sites of active Paget's disease. The literature concerning cold bone defects in the [111In]WBC scintiscan is reviewed. Loss of marrow component in the bone appears to be the underlying mechanism for such an abnormality.


Use of bilevel positive pressure ventilation in patients with bronchiolitis.
This study aims at describing the use of bilevel positive airway pressure (BiPAP) in infants with severe bronchiolitis. The use of BiPAP in infants with bronchiolitis may be associated with a worst outcome. A single-center retrospective study performed from October 2013 to April 2016. All infants from 1 day to 6 months of age admitted in the pediatric intensive care unit (PICU) were included if they had a clinical diagnosis of bronchiolitis and if they required any type of noninvasive ventilation (NIV), including high flow nasal cannula, continuous positive airway pressure and BiPAP at admission in PICU. There was no local written protocol regarding the ventilator management during the study. Overall, 252 infants (median age 45 (26-72) days) were included in the study and 110 infants (44%) were supported by BiPAP at admission. More infants were born preterm in the group of patients supported by BiPAP at admission. No complication related to NIV occurred. Patients in the BiPAP group had a longer duration of noninvasive support as well as a longer PICU length of stay. However, hospital length of stay did not differ according to the type of respiratory support at admission. The use of BiPAP was not associated with endotracheal intubation, however it was associated with increased PICU length of stay and increased duration of NIV.


Primary structure of a glycosylated DNA-binding domain in human plasma fibronectin.
The complete amino acid sequence of a DNA-binding domain isolated from human plasma fibronectin after limited trypsin digestion has been obtained. It contains 132 amino acids and one biantennary glycosyl unit at residue 104, for an estimated Mr of 16,931. The fragment can be purified by a two-step procedure consisting of DNA-affinity chromatography and reverse-phase high performance liquid chromatography. It can also be purified by heparin-affinity chromatography. The domain is unusual in its susceptibility to tryptic-like cleavages even by neutral or aromatic residue-specific proteases. It has no cysteine residues and is predicted to favor a beta-sheet structure by Chou and Fasman analysis. Based on this analysis we have proposed a model which exhibits a clustering of aromatic and basic residues, consistent with similar involvement of basic and aromatic residues in other DNA-binding proteins. The net charge of the domain at neutral pH (+1, without sialic acid) argues against a nonspecific charge interaction with polyanionic macromolecules such as DNA and heparin. Internal sequence repeats occur at intervals of 30, 60, and 90 residues, thus suggesting a maximum size for a repetitive building block which gave rise to this domain.


Kartogenin-loaded hydrogel promotes intervertebral disc repair via protecting MSCs against reactive oxygen species microenvironment by Nrf2/TXNIP/NLRP3 axis.
Intervertebral disc (IVD) degeneration (IDD) and the consequent low back pain present a major medical challenge. Stem cell-based tissue engineering is promising for the treatment of IDD. However, stem cell-based treatment is severely impaired by the increased generation of reactive oxygen species (ROS) in degenerative disc, which can lead to a high level of cell dysfunction and even death. In this study, a kartogenin (KGN)@PLGA-GelMA/PRP composite hydrogel was designed and used as a carrier of ADSCs-based therapies in disc repair. Injectable composite hydrogel act as a carrier for controlled release of KGN and deliver ADSCs to the degenerative disc. The released KGN can stimulate the differentiation of ADSCs into a nucleus pulposus (NP) -like phenotype and boost antioxidant capacity of ADSCs via activating Nrf2/TXNIP/NLRP3 axis. Furthermore, the composite hydrogel combined with ADSCs attenuated the in vivo degeneration of rat IVDs, maintained IVD tissue integrity and accelerated the synthesis of NP-like extracellular matrix. Therefore, the KGN@PLGA-GelMA/PRP composite hydrogel is a promising strategy for stem cell-based therapies of IDD.


Effects of propranolol and swim-training on blood pressure, plasma electrolytes, and vasopressin in spontaneously hypertensive and normotensive rats.
The aim of this work was to study the influence of beta-adrenoreceptor blockade on the adaptation to exercise of one of the hormonal systems (arginine vasopressin) involved in the regulation of blood volume and pressure in spontaneously hypertensive rats (SHR). Systolic blood pressure (SBP) was measured in SHR and WKY rats during 11 wk of swim training. At the end of the training program we determined post-exercise values of plasma arginine-vasopressin (pAVP), osmolality (pOsm), K+ (pK+), Na+ (pNa+), hemoglobin (Hgb), and hematocrit (Hct) in SHR and WKY rats. The following groups were studied: control (C), propranolol treated (PC), swim trained (S), and propranolol-treated and swim-treated (PS). SBP was significantly reduced by swim training or propranolol, bu these beneficial effects on SBP were attenuated when propranolol and swim training were combined. pNa+ and pOsm were significantly reduced by training alone in SHR. This reduction of pNa+ and, consequently, of pOsmol without any modification of other parameters could suggest an Na+ loss. In contrast, the SHR group treated with propranolol alone showed a significant reduction in Hct, suggesting an increased plasma volume without Na+ loss. PS SHR showed a significant reduction of Hgb, Hct, proteins, pNa+, and pOsmol, probably as a consequence of the additive effects of swimming- and propranolol-induced hypervolemia with Na+ loss. The slight and nonsignificant reduction in pAVP observed with either training or propranolol treatment alone became much more pronounced and statistically significant when the 2 treatments were combined. WKY rats showed a much smaller response to exercise and beta-adrenoreceptor blockade than SHR. We conclude that the hypervolemia suggested in PS SHR could be a possible cause of attenuation of the beneficial effects of either swimming or propranolol on SBP.


The impact of metabolic syndrome and endothelial dysfunction on exercise-induced cardiovascular changes.
There is limited information regarding the synergistic or additive effects of metabolic syndrome (MS) and endothelial dysfunction (ED) on cardiovascular disease (CVD). Altered cardiovascular responses to exercise have been shown to predict future cardiovascular events as well as assess autonomic function. The present study evaluated the impact of MS and brachial artery reactivity (a proxy of ED) on peak exercise-induced cardiovascular changes. Individuals (n = 303) undergoing a standard nuclear medicine exercise stress test were assessed for MS. Participants underwent a Forearm Hyperaemic Reactivity test and were considered to have dysfunctional reactivity if their rate of uptake ratio (RUR) was <3.55. Resting and peak blood pressure (BP) and heart rate (HR) were measured. Reactivity was calculated as the difference between peak and resting measures. Analyses, adjusting for age, sex, resting HR, total metabolic equivalents (METs), and a history of major CVD, revealed a main effect of MS (F = 5.51, η(2) = 0.02, P = 0.02) and RUR (F = 6.69, η(2) = 0.02, P = 0.01) on HR reactivity, such that patients with MS and/or poor RUR had reduced HR reactivity. There were no interactive effects of RUR and MS. There were no effects of RUR or MS on systolic BP (SBP) or diastolic BP (DBP) reactivity or rate pressure product (RPP) reactivity. The presence of decreased HR reactivity among participants with MS or poor brachial artery reactivity, combined with the lack of difference in other exercise-induced cardiovascular changes, indicates that these patients may have some degree of parasympathetic dysregulation. Further longitudinal studies are needed to understand the long-term implications of MS and endothelial abnormalities in this context.


Medical computers from the manufacturer's viewpoint.
The recent surge in the scope of computer applications in medical care has brought with it great strides in patient care, but it has also created a variety of concerns to manufacturers of medical software. The spate of product liability suits, with its potentially crippling effects in terms of product development, makes it increasingly vital that manufacturers engage in prospective planning, to anticipate problems and take steps before legal action ensues, so that all parties--the manufacturer, the hospital, and ultimately, the patient--benefit from the availability of new technology. The Food and Drug Administration (FDA) and Congress are similarly grappling with the implications of this new technology, to assure that patient care is not compromised by products that have not yet been fully tested. The tension between the desire to make technology available to the public and the realities of the present regulatory and litigious climate is the key dilemma facing manufacturers of medical software.


Therapeutic targeting of RAS: New hope for drugging the "undruggable".
RAS is the most frequently mutated oncogene in cancer and a critical driver of oncogenesis. Therapeutic targeting of RAS has been a goal of cancer research for more than 30 years due to its essential role in tumor formation and maintenance. Yet the quest to inhibit this challenging foe has been elusive. Although once considered "undruggable", the struggle to directly inhibit RAS has seen recent success with the development of pharmacological agents that specifically target the KRAS(G12C) mutant protein, which include the first direct RAS inhibitor to gain entry to clinical trials. However, the limited applicability of these inhibitors to G12C-mutant tumors demands further efforts to identify more broadly efficacious RAS inhibitors. Understanding allosteric influences on RAS may open new avenues to inhibit RAS. Here, we provide a brief overview of RAS biology and biochemistry, discuss the allosteric regulation of RAS, and summarize the various approaches to develop RAS inhibitors.


Surgical treatment of mature cystic teratomas: A comparison of emergent and elective surgeries.
To compare patient characteristics, imaging and surgical management of mature cystic teratomas (MCTs) according to surgery type - elective versus emergent. The study included surgeries performed between 1990 and 2016, during which histologically verified ovarian MCT material was obtained. The elective management group included surgeries performed at a pre-set date or incidental finding of MCT as part of a different surgery. Emergent surgeries were considered as such if performed as a result of suspected adnexal torsion. One hundred ninety two operations in which MCT was confirmed by histology were included: 136 elective, 56 emergent. The majority (88.5%) of study patients were of reproductive age. Patients in the emergent surgery group were significantly younger (27.5 ± 10.2 vs 36 ± 13.8 years, P < 0.001). Sensitivity for dermoid diagnosis was significantly increased among elective surgery patients (65.2% vs. 47.1%, P = 0.02). Laparoscopy was the preferred surgical mode in both study groups. Adnexal torsion was confirmed in 67.8% of emergent surgeries. Conservative surgery, including cystectomy with or without detorsion, was more commonly performed in emergent surgeries (91% vs. 72.7%, P = 0.006). Bilateral salpingo-oophorectomy with or without total abdominal hysterectomy was more commonly performed in elective surgery patients (22% vs. 3.5%, P = 0.001). Patient parity, mass size and white blood cell count were independently associated with adnexal torsion. Adnexal torsion is common among symptomatic patients with MCT and is related to mass size, patient age, past parity and white blood cell count. Most patients with MCT are of reproductive age and thus are treated with a minimally invasive approach.


Artificial cells delivering itaconic acid induce anti-inflammatory memory-like macrophages to reverse acute liver failure and prevent reinjury.
Hepatic macrophages represent a key cellular component of the liver and are essential for the progression of acute liver failure (ALF). We construct artificial apoptotic cells loaded with itaconic acid (AI-Cells), wherein the compositions of the synthetic plasma membrane and surface topology are rationally engineered. AI-Cells are predominantly localized to the liver and further transport to hepatic macrophages. Intravenous administration of AI-Cells modulates macrophage inflammation to protect the liver from acetaminophen-induced ALF. Mechanistically, AI-Cells act on caspase-1 to suppress NLRP3 inflammasome-mediated cleavage of pro-IL-1β into its active form in macrophages. Notably, AI-Cells specifically induce anti-inflammatory memory-like hepatic macrophages in ALF mice, which prevent constitutive overproduction of IL-1β when liver reinjury occurs. In light of AI-Cells' precise delivery and training of memory-like hepatic macrophages, they offer promising therapeutic potential in reversing ALF by finely controlling inflammatory responses and orchestrating liver homeostasis, which potentially affect the treatment of various types of liver failure.


Tactile asymbolia.
Agraphesthesia has been attributed to impairment of the ability to detect more rudimentary directionality of lines written on the skin (directional cutaneous kinesthesia). We examined a patient who had a dissociation between preserved perception of line directionality and the loss of graphesthesia for letters and numbers. A man with a metastatic right parietal lesion was tested for the ability to determine the directionality of lines drawn on the palms and forehead and then evaluated for recognition of letters and numbers in these regions. Our patient could identify the directions of lines, letters and numbers drawn on paper. The ability to detect the direction and shape of lines drawn on the skin of the palms and on the forehead was preserved but he had agraphesthesia for numbers and letters in these same locations. The finding of isolated agraphesthesia for letters and numbers may be assigned to damage in the right parietal lobe. It represents a deficit of somatosensory processing that is of a higher order than detection of line directionality. The term "tactile asymbolia" may capture the dissociation. These clinical findings suggest that tactile cortex in humans, like visual cortex, may be hierarchically organized, as has been demonstrated in primates.


Attenuation of Streptococcus suis virulence by the alteration of bacterial surface architecture.
NeuB, a sialic acid synthase catalyzes the last committed step of the de novo biosynthetic pathway of sialic acid, a major element of bacterial surface structure. Here we report a functional NeuB homologue of Streptococcus suis, a zoonotic agent, and systematically address its molecular and immunological role in bacterial virulence. Disruption of neuB led to thinner capsules and more susceptibility to pH, and cps2B inactivation resulted in complete absence of capsular polysaccharides. These two mutants both exhibited increased adhesion and invasion to Hep-2 cells and improved sensibility to phagocytosis. Not only do they retain the capability of inducing the release of host pro-inflammatory cytokines, but also result in the faster secretion of IL-8. Easier cleaning up of the mutant strains in whole blood is consistent with virulence attenuation seen with experimental infections of both mice and SPF-piglets. Therefore we concluded that altered architecture of S. suis surface attenuates its virulence.


Determinants of health in discharge planning for seniors: asking the right questions.
Practitioners are encouraged to consider a shift in their philosophy regarding the manner in which interdisciplinary health care teams ask questions of seniors and their caregivers in the hospital discharge process. By engaging with a discharge framework that encompasses a social-determinants-of-health lens, discharge planning teams can begin to systematically ask questions that move beyond the traditional medical focus on prescriptions, rehabilitation, and treatments. This approach may reveal strengths and also expose health and social inequities that seniors might face upon their arrival home. This information may open a gateway for connecting seniors to social and economic resources that will support them in remaining productive and healthy.


Mitochondria-targeted phenolic antioxidants induce ROS-protective pathways in primary human skin fibroblasts.
Phytochemical antioxidants like gallic and caffeic acid are constituents of the normal human diet that display beneficial health effects, potentially via activating stress response pathways. Using primary human skin fibroblasts (PHSFs) as a model, we here investigated whether such pathways were induced by novel mitochondria-targeted variants of gallic acid (AntiOxBEN2) and caffeic acid (AntiOxCIN4). Both molecules reduced cell viability with similar kinetics and potency (72 h incubation, IC50 ~23 μM). At a relatively high but non-toxic concentration (12.5 μM), AntiOxBEN2 and AntiOxCIN4 increased ROS levels (at 24 h), followed by a decline (at 72 h). Further analysis at the 72 h timepoint demonstrated that AntiOxBEN2 and AntiOxCIN4 did not alter mitochondrial membrane potential (Δψ), but increased cellular glutathione (GSH) levels, mitochondrial NAD(P)H autofluorescence, and mitochondrial superoxide dismutase 2 (SOD2) protein levels. In contrast, cytosolic SOD1 protein levels were not affected. AntiOxBEN2 and AntiOxCIN4 both stimulated the gene expression of Nuclear factor erythroid 2-related factor 2 (NRF2; a master regulator of the cellular antioxidant response toward oxidative stress). AntiOxBEN2 and ANtiOxCIN4 differentially affected the gene expression of the antioxidants Heme oxygenase 1 (HMOX1) and NAD(P)H dehydrogenase (quinone) 1 (NQO1). Both antioxidants did not protect from cell death induced by GSH depletion and AntiOxBEN2 (but not AntiOxCIN4) antagonized hydrogen peroxide-induced cell death. We conclude that AntiOxBEN2 and AntiOxCIN4 increase ROS levels, which stimulates NRF2 expression and, as a consequence, SOD2 and GSH levels. This highlights that AntiOxBEN2 and AntiOxCIN4 can act as prooxidants thereby activating endogenous ROS-protective pathways.


Factor structure for autism spectrum disorders with toddlers using DSM-IV and DSM-5 criteria.
With the publication of the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition, autism spectrum disorders are defined by two symptom clusters (social communication and restricted/repetitive behaviors) instead of the current three clusters. The current study examined the structure of the Baby and Infant Screen for Children with aUtIsm Traits (BISCUIT). First, an exploratory factor analysis was replicated whose results were largely comparable to the previous findings. Then, confirmatory factor analyses compared a two and three factor structure for the BISCUIT. Measures of model fit supported both the two and three factor models relatively well. When directly compared, the three factor model was found to be preferred over the two factor model. Implications are discussed.


Trunk-pelvis coordination during load carriage running.
Understanding the influence of load carriage on trunk-pelvis coordination and its variability has important functional implications for athletes who need to run with load. The aim of this study was to examine the influence of load carriage on trunk-pelvis coordination in running. Thirty healthy adults performed running while wearing a 20% bodyweight backpack, and without load. Vector coding was used to quantify trunk-pelvis segmental coordination and its variability during the stance phase of running. The four coordination patterns were: 1) anti-phase (segments moving in opposite directions), in-phase (segments moving in same directions), trunk-only phase (only trunk movement), and pelvic-only phase (only pelvic movement). For each plane, the percentage of stance phase spent in a specific coordination pattern was quantified. Coordination variability for each plane was averaged over the stance phase. Mixed effects models were used to analyse the effects of load, adjusted for the covariate of sex, on coordination and its variability. Running with load increased trunk-only coordination in the sagittal plane (P < 0.001), increased anti-phase coordination in the frontal plane (P < 0.001), reduced trunk-only phase coordination in axial rotation (P < 0.001), and increased coordination variability in all three planes (Flexion-Extension: P < 0.001; Lateral flexion: P = 0.03; Axial rotation: P < 0.001). Future studies would benefit from investigating how trunk-pelvis coordination and its variability alters candidate end-point variability indices (e.g. COM displacement), and its functional implications in load carriage running.


An example of combined sinoatrial and atrioventricular block.
Combined sinoatrial and atrioventricular block is rare and has been reported in patients on digitalis. We report a case of combined Mobitz type II sinoatrial block and 2:1 atrioventricular block in a patient on no medication who presented with recurrent syncope.


Serum hyaluronic acid in Down's syndrome.
In agreement with previous studies we show an age-related increase in serum levels of hyaluronic acid in healthy individuals. Levels in Down's syndrome persons were slightly higher, especially in those with hypothyroidism. This provides further evidence that the normal ageing process is accelerated in Down's syndrome.


The importance of context information for the spatial specificity of gaze cueing.
In three experiments, we investigated the spatial allocation of attention in response to central gaze cues. In particular, we examined whether the allocation of attentional resources is influenced by context information-that is, the presence or absence of reference objects (i.e., placeholders) in the periphery. On each trial, gaze cues were followed by a target stimulus to which participants had to respond by keypress or by performing a target-directed saccade. Targets were presented either in an empty visual field (Exps. 1 and 2) or in previewed location placeholders (Exp. 3) and appeared at one of either 18 (Exp. 1) or six (Exps. 2 and 3) possible positions. The spatial distribution of attention was determined by comparing response times as a function of the distance between the cued and target positions. Gaze cueing was not specific to the exact cued position, but instead generalized equally to all positions in the cued hemifield, when no context information was provided. However, gaze direction induced a facilitation effect specific to the exact gazed-at position when reference objects were presented. We concluded that the presence of possible objects in the periphery to which gaze cues could refer is a prerequisite for attention shifts being specific to the gazed-at position.


Commercial volumetric MRI reporting tools in multiple sclerosis: a systematic review of the evidence.
MRI is integral to the diagnosis of multiple sclerosis (MS) and is important for clinical prognostication. Quantitative volumetric reporting tools (QReports) can improve the accuracy and objectivity of MRI-based assessments. Several QReports are commercially available; however, validation can be difficult to establish and does not currently follow a common pathway. To aid evidence-based clinical decision-making, we performed a systematic review of commercial QReports for use in MS including technical details and published reports of validation and in-use evaluation. We categorized studies into three types of testing: technical validation, for example, comparison to manual segmentation, clinical validation by clinicians or interpretation of results alongside clinician-rated variables, and in-use evaluation, such as health economic assessment. We identified 10 companies, which provide MS lesion and brain segmentation and volume quantification, and 38 relevant publications. Tools received regulatory approval between 2006 and 2020, contextualize results to normative reference populations, ranging from 620 to 8000 subjects, and require T1- and T2-FLAIR-weighted input sequences for longitudinal assessment of whole-brain volume and lesions. In MS, six QReports provided evidence of technical validation, four companies have conducted clinical validation by correlating results with clinical variables, only one has tested their QReport by clinician end-users, and one has performed a simulated in-use socioeconomic evaluation. We conclude that there is limited evidence in the literature regarding clinical validation and in-use evaluation of commercial MS QReports with a particular lack of clinician end-user testing. Our systematic review provides clinicians and institutions with the available evidence when considering adopting a quantitative reporting tool for MS.


Impact of FcγR variants on the response to alemtuzumab in multiple sclerosis.
Allelic variants of genes encoding for the Fc gamma receptors IIIA and IIA have been associated with the clinical response to cell-depleting antibodies in lymphoma patients. Here, we tested the hypothesis that FCGR3A and FCGR2A high-affinity polymorphisms predict clinical outcomes to alemtuzumab therapy in 85 patients with relapsing-remitting multiple sclerosis. No differences in clinical and MRI-based efficacy parameters, the development of severe infusion-associated reactions and secondary autoimmune diseases during a 2 year follow-up was observed based on FCGR3A or FCGR2A polymorphisms. This study does not support the use of FCGR genetic variants to predict clinical outcomes to alemtuzumab.


Theoretical model of interactions between ligand-binding sites in a dimeric protein and its application for the analysis of thiamine diphosphate binding to yeast transketolase.
The binding of thiamin diphosphate (ThDP) to yeast dimeric apotransketolase (apoTK) is accompanied by the appearance of a band in the absorption spectrum with maximum at 320 nm. The saturation function has been analyzed using a scheme that involves binding of ThDP to each subunit followed by the conformational transition of this subunit. It is assumed that the binding of ThDP to one subunit may affect the conformational transition of the other subunit. Rigorous mathematical expressions describing the dependence of the optical absorption on the total concentration of ThDP are first developed. Equilibrium constants and corresponding rate constants for the binding of ThDP to apoTK have been estimated. The negative cooperativity in the ThDP binding has been characterized by the function reflecting the dependence of the conformational change on the saturation of apoTK by ThDP.


[Ileocecal tuberculosis as rare differential diagnosis of lower abdominal tumor].
Tuberculosis is extremely rare in Germany today. Diagnosis of extrapulmonary tuberculosis has proved to be particularly difficult and a correct diagnosis can take months. The danger of fatality is high. In the case of a 29 year old male paraplegic patient suffering from enteral tuberculosis, diagnosis was possible only after several weeks of onward observation, extreme physical degeneration and finally, a laparotomy.


β-Galactosidase.
β-galactosidase is used as a reporter for the quantitative analysis of gene expression. It is also used as a histochemical marker. This introduction briefly reviews the enzymatic reactions catalyzed by β-galactosidase and methods for assaying β-galactosidase activity.


Maritime route and vessel tracklet dataset for vessel-to-route association.
With an ever-increasing number of vessels at sea, the modelling, analysis and visualisation of maritime traffic are of paramount importance to support the monitoring tasks of maritime stakeholders. Sensors have been developed in this respect to track vessels and capture the maritime traffic at the global scale. The Automatic Identification System (AIS) is transmitting maritime positional and nominative information at highest frequency rate, making it a valuable source for maritime traffic modelling. From an original AIS dataset covering the area of Brest, France, we extracted a set of 17 maritime routes, connecting ports in this area. Two different representations for the routes are provided: (1) clusters of AIS contacts, and (2) route prototypes, representing the nominal trajectory of the vessels following the route. Additionally, a set of tracklets (built by five consecutive AIS contacts from the same vessel trajectory) has been extracted from the set of routes and the original dataset, and labelled either with the route name to which they belong or as off-route tracklets. This dataset provides thus some ground truth on the routes followed by vessels and is aimed at testing and validating vessel-to-route or track-to-route association algorithms.


On the solvent-extraction of acetylcholine receptor.
Chloroform/methanol rechromatography on Sephadex LH-20 of fractions isolated from organic solvent extracts of E. electricus electric organs exhibited alterations in elution point compared to the original chromatography. Additionally, 3H decamethonium bromide did not coelute with any of the observed fractions. It is concluded that as presently described the organic solvent isolation procedure for the cholinergic receptor exhibits undesirable characteristics.


Child abuse and epigenetic mechanisms of disease risk.
Child abuse is highly prevalent and associated with increased risk for a range of health problems, including cancer, cardiovascular disease, diabetes, psychiatric disorders, and other health problems. Little is currently known about the mechanism by which early adversity confers risk for health problems later in life. To determine if there are epigenetic differences associated with child maltreatment that may help explain association between adverse childhood experiences and later health problems. As part of a study examining genetic and environmental factors associated with depression, saliva DNA specimens were collected on 96 maltreated children removed from their parents due to abuse or neglect and 96 demographically matched control children between 2003 and 2010. In 2011, the Illumina 450K BeadChip was used on stored DNA specimens and analyzed to examine whole-genome methylation differences between maltreated and control children. After controlling for multiple comparisons, maltreated and control children had significantly different methylation values at 2868 CpG sites (p<5.0 × 10(-7), all sites; average methylation difference per site=17%; range=1%-62%). The gene set contained numerous markers of diseases and biological processes related to the health problems associated with early childhood adversity. Although replication is required, this study suggests that epigenetic mechanisms may be associated with risk for health problems later in life in maltreated children. This study lays the groundwork for future studies examining health and methylation measures to further characterize the role of epigenetic mechanisms in conferring risk for medical problems in individuals with histories of early adversity.


Theoretical prediction of dental composites yield stress and flexural modulus based on filler volume ratio.
A costly advantageous approach in composites development process is to limit experimental tests by predicting mechanical properties with respect to their filler ratio. Models exist for other fields than dentistry. They have been compared to 3-point bending test experimental results for yield stress, flexural modulus and flexural strength. Five formulations of the same experimental material were made. They were composed of an organic matrix and different ratios of silanated barium glass particles. The samples were stored in distilled water for 24h at 37°C prior to the 3-point bending test. The Turcsányi model for yield stress was notably investigated, and SEM was used to complete data analysis. The yield stress showed reproducible results and a good fit with Turcsányi model with respect to filler ratio. The flexural modulus data are not scattered but did not fit with the existing models. No trend could emerge for flexural strength and strain because of scattering; these properties are more unpredictable. The SEM observations of fracture areas confirm a good matrix-filler interface quality. SEM pictures validated the numerical parameter obtained from Turcsányi model. The latter therefore seems to be applicable to dental composites. Firstly, it enables to predict the evolution of the material yield stress without testing all filler ratios. Secondly, this model provides a good way to get micro-information on the matrix-filler interface from macroscopic tests. The discrepancy between flexural modulus results and theory highlighted the necessity to include an "interface quality" parameter in accurate predictive models.


Stem-cell-derived products: an FDA update.
The therapeutic potential of products derived from stem cells of various types has prompted increasing research and development and public attention. Initiation of human clinical trials in the not-too-distant future is now a realistic possibility. It is, therefore, important to weigh the potential benefits against known, theoretical and totally unsuspected risks in light of current knowledge to ensure that subjects participating in these trials are afforded the most reasonable balance possible between potential risks and potential benefits. There are no apparent differences in fundamental, qualitative biological characteristics between stem-cell-derived products and other cellular therapies regulated by the United States Food and Drug Administration (FDA). Existing authorities can, therefore, be applied. Nevertheless, these products do have properties that require careful evaluation.


The impact of COVID-19 on paediatric emergency department visits. A one-year retrospective study.
The number of paediatric emergency department (ED) visits and hospital admissions was recorded in a tertiary referral centre during the first year of the COVID-19, March 2020-February 2021, and compared with those of the preceding year. The number of visits and admissions and the reason of visit and admission were prospectively recorded from 15,087 patients' files. A substantial decline in the total number of visits and increase in the admission rate were documented during the COVID-19 year compared to the preceding year (10691 vs 4396 patients, 22.59% vs 18.15% (OR: 1.316, CI 95%: 1.208-2.242, p < 0.0001), respectively). Fever and/or respiratory symptoms were the commonest reported symptoms in both periods. Possible explanations include: (i) restricted overall infection transmission due to confinement and self-protective measures, (ii) avoidance of unnecessary hospital visits in the absence of severe symptoms and (iii) reduced or delayed access to medical care due to parental fear of children's exposure to COVID-19. This study is the first worldwide to investigate the impact of COVID-19 on ED visits and admissions throughout the whole year of the pandemic, and to highlight the need for re-evaluation of future protective strategies to infections, adjustment of health-care systems and parental education so that medical care in a health-care setting is sought in a more appropriate manner. A significant decline in paediatric ED visits and increase in the admission rate was observed during the first year of COVID-19 in a tertiary referral centre, possibly due to reduced overall infection transmission, limited ED overuse, but also ED underuse due to parental fear of children's exposure to SARS-CoV-2. COVID-19 may serve as an opportunity for societies to re-evaluate future strategies to infections, adjust health-care systems accordingly, and reinforce parents to seek medical care more appropriately. Although the incidence of critical illness in children due to COVID-19 and in general is low, special attention should be devoted to identifying children at risk early.


Effects of individual and neighborhood social risks on diabetes pay-for-performance program under a single-payer health system.
Enrollment in and adherence to a diabetes pay-for-performance (P4P) program can lead to desirable processes and outcomes of diabetes care. However, knowledge is limited on the potential exclusion of patients with individual or neighborhood social risks or interruption of services in the disease-specific P4P program without mandatory participation under a single-payer health system. To investigate the impact of individual and neighborhood social risks on exclusion from and adherence to the diabetes P4P program of patients with type 2 diabetes (T2D) in Taiwan. This study used data from Taiwan's 2009-2017 population-based National Health Insurance Research Database, 2010 Population and Housing Census, and 2010 Income Tax Statistics. A retrospective cohort study was conducted, and study populations were identified from 2012 to 2014. The first cohort comprised 183,806 patients with newly diagnosed T2D, who had undergone follow up for 1 year; the second cohort consisted of 78,602 P4P patients who had undergone follow up for 2 years after P4P enrollment. Binary logistic regression models were used to examine the associations of social risks with exclusion from and adherence to the diabetes P4P program. T2D patients with higher individual social risks were more likely to be excluded from the P4P program, but those with higher neighborhood-level social risks were slightly less likely to be excluded. T2D patients with the higher individual- or neighborhood-level social risks showed less likelihood of adhering to the program, and the person-level coefficient was stronger in magnitude than the neighborhood-level one. Our results indicate the importance of individual social risk adjustment and special financial incentives in disease-specific P4P programs. Strategies for improving program adherence should consider individual and neighborhood social risks.


Transcriptome analysis of candidate genes and signaling pathways associated with light-induced brown film formation in Lentinula edodes.
High-throughput Illumina RNA-seq was used for deep sequencing analysis of the transcriptome of poly(A)+ RNA from mycelium grown under three different conditions: 30 days darkness (sample 118), 80 days darkness (313W), and 30 days darkness followed by 50 days in the light (313C), in order to gain insight into the molecular mechanisms underlying the process of light-induced brown film (BF) formation in the edible mushroom, Lentinula edodes. Of the three growth conditions, BF formation occurred in 313C samples only. Approximately 159.23 million reads were obtained, trimmed, and de novo assembled into 31,511 contigs with an average length of 1,746 bp and an N 50 of 2,480 bp. Based on sequence orientations determined by a BLASTX search against the NR, Swiss-Prot, COG, and KEGG databases, 24,246 (76.9 %) contigs were assigned putative descriptions. Comparison of 313C/118 and 313C/313W expression profiles revealed 3,958 and 5,651 significantly differentially expressed contigs (DECs), respectively. Annotation using the COG database revealed that candidate genes for light-induced BF formation encoded proteins linked to light reception (e.g., WC-1, WC-2, phytochrome), light signal transduction pathways (e.g., two-component phosphorelay system, mitogen-activated protein kinase pathway), and pigment formation (e.g., polyketide synthase, O-methyltransferase, laccase, P450 monooxygenase, oxidoreductase). Several DECs were validated using quantitative real-time polymerase chain reaction. Our report is the first to identify genes associated with light-induced BF formation in L. edodes and represents a valuable resource for future genomic studies on this commercially important mushroom.


Toward more rational nerve conduction interpretations: the effect of height.
One hundred four normal subjects ranging in age from 17 to 77 years and in height from 115 to 203 cm underwent nerve conduction studies of sural, peroneal, tibial, and median nerves. Foot temperature was measured in each patient. A strong inverse correlation was found between height and sural (r = -0.7104), peroneal (r = -0.6842), and tibial (r = -0.5044) conduction velocities. These correlations were significant at the P less than 0.001 level. Median conduction velocity was not correlated with height. Height was correlated with the distal latencies of all nerves studied (sural r = 0.6518, peroneal r = 0.4583, tibial r = 0.7217, median r = 0.5440). These correlations were significant at the P less than 0.001 level. Age was inversely correlated with both tibial (r = -0.4071) and median (r = -0.3464) nerve conduction velocities but not with sural and peroneal conductions. There were no correlations between distal latencies and age. If the variation in conduction velocity accounted for by the linear relationship with height was removed, then age would be inversely correlated to all conduction velocity measurements with the exception of the sural. Temperature is inversely correlated with the sural (r = -0.2233), peroneal (r = -0.2102), and tibial (r = -0.2710) distal latencies. In all instances, the effects of age and temperature were minor determinants when compared with the effects of height. Diagnostic conclusions made from nerve conduction data without correcting for height may be invalid in patients taller and shorter than normal.(ABSTRACT TRUNCATED AT 250 WORDS)


A CCAAT DNA binding factor consisting of two different components that are both required for DNA binding.
A CCAAT-binding activity present in nuclear extracts of rat liver and NIH 3T3 fibroblasts was purified using, as assay, DNA binding to a segment of the mouse alpha 2(I) collagen promoter. The activity consists of two components, designated factors A and B, which are separated by ion exchange chromatography on either Mono Q or Mono S columns. Factor A is heat-sensitive, whereas factor B is heat-resistant. Both factors are required for DNA binding and both are present in the DNA protein complex. The A + B complex was extensively purified by heparin-agarose and sequence-specific affinity chromatography. The Mr of factor A is 39,000, whereas the Mr of factor B is 41,000 as determined by renaturation of a highly purified preparation after sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Competition experiments indicate that this CCAAT-binding complex has a DNA sequence specificity that is different from those of other CCAAT-binding proteins.


Rv2358 and FurB: two transcriptional regulators from Mycobacterium tuberculosis which respond to zinc.
In a previous work, we demonstrated that the Mycobacterium tuberculosis Rv2358-furB operon is induced by zinc. In this study, the orthologous genes from Mycobacterium smegmatis mc(2)155 were inactivated and mutants analyzed. Rv2358 protein was purified and found to bind upstream of the Rv2358 gene. Binding was inhibited by Zn(2+) ions.


Determinants of fruit and seed set in Pavonia dasypetala (Malvaceae).
Female reproductive success (fruit and seed set) in Pavonia dasypetala (Malvaceae) was only weakly related to pollinator attentiveness (number of pollinator visits and number of pollen grains deposited on stigmas). This result has implications for field studies of pollination: observational measures of pollinator attentiveness do not necessarily provide an, accurate basis for inferring reproductive success. Further, these results indicate that, although pollination is essential for seed set in this species, reproduction is not limited by pollination. Many flowers that were visited numerous times by hummingbirds and that received pollen in excess of the number of ovules per flower failed to produce fruits. If pollen is limiting, it is pollen quality rather than quantity that is inadequate. Patterns of reproduction in this species were as predicted if resource availability limits seed set (Stephenson 1981): (1) among mature fruits there was an excess of fruits with full seed set (4 or 5 seeds) and (2) probability of fruit, set decreased over the reproductive season. However, resource availability was not the only determinant of seed set in this species: there was also variation among individuals that seems unrelated to either pollen or resource availability. Reproductive success thus appears to be determined by several factors and cannot be described as simply pollen or resource limited.


Drug Interactions with Lithium: An Update.
Lithium has been used for the management of psychiatric illnesses for over 50 years and it continues to be regarded as a first-line agent for the treatment and prevention of bipolar disorder. Lithium possesses a narrow therapeutic index and comparatively minor alterations in plasma concentrations can have significant clinical sequelae. Several drug classes have been implicated in the development of lithium toxicity over the years, including diuretics and non-steroidal anti-inflammatory compounds, but much of the anecdotal and experimental evidence supporting these interactions is dated, and many newer medications and medication classes have been introduced during the intervening years. This review is intended to provide an update on the accumulated evidence documenting potential interactions with lithium, with a focus on pharmacokinetic insights gained within the last two decades. The clinical relevance and ramifications of these interactions are discussed.


Testosterone and 17-methyltestosterone from hyodeoxycholic acid.
The preparation of the title compounds from hyodeoxycholic acid is described. A modified Oppenauer oxidation using alumina in place of conventional alkoxide catalyst is outlined.


A method for discovering transmembrane beta-barrel proteins in Gram-negative bacterial proteomes.
Transmembrane beta-barrel (TMB) proteins play pivotal roles in many aspects of bacterial functions. This paper presents a k-nearest neighbor (K-NN) method for discriminating TMB and non-TMB proteins. We start with a method that makes predictions based on a distance computed from residue composition and gradually improve the prediction performance by including homologous sequences and searching for a set of residues and di-peptides for calculating the distance. The final method achieves an accuracy of 97.1%, with 0.876 MCC, 86.4% sensitivity and 98.8% specificity. A web server based on the proposed method is available at http://yanbioinformatics.cs.usu.edu:8080/TMBKNNsubmit.


The role of enteric dysbacteriosis and modulation of gut microbiota in the treatment of inflammatory bowel disease.
The incidence of inflammatory bowel disease (IBD) is globally increasing. This disorder seriously affects the quality of life in patients. Interestingly, studies have detected that the intestinal flora imbalance is a critical factor in the progression of IBD. One potential treatment strategy for IBD involves regulating the composition and function of the intestinal flora. To date, a multitude of experiments have confirmed the relationship between intestinal flora, immune regulation, and anti-inflammation. The intestinal flora can reduce intestinal inflammation by regulating immunity and increasing the secretion of metabolic short-chain fatty acids. In this review, we discuss the composition and function of the intestinal flora, the relationship between the intestinal flora and the host, the role of intestinal flora disorders in IBD, and the progress in IBD treatment. Combining the regulation of the intestinal flora with probiotics treatment is considered a promising strategy for substantially improving the treatment of IBD.


[Light microscopic and histochemical findings on the mouse lung after neutron and 60 cobalt gamma-irradiation].
The morphological changes on lungs of thorax irradiated mice, receiving a single dose of fast neutron and 60 cobalt radiation were investigated. Lungs were studied by histological and histochemical methods 2 weeks up to 10 months. Harvest changes were found after a time of 4-8 weeks. With histochemical methods more detailed damages are seen in contrast to routine histology. Two weeks post irradiation disturbances of phospholipid synthesis in alveolar epithelium cells of type II (AEC II) are found. Impairment of capillary endothelial cells are indicated by decreased activity of adenosine triphosphatase. Increased activity of beta-glucuronidase is seen in damaged bronchial epithelium.


Caesium adsorption on a zeolitic imidazolate framework (ZIF-8) functionalized by ferrocyanide.
137Cs is one of the most hazardous radionuclides in nuclear waste owing to its toxicity. Developing an adsorbent for Cs+ with a high capacity and selectivity is a challenging task. A metal-organic framework (MOF) is a material with a high surface area that has been widely applied in wastewater treatment. Exploiting the affinity between ferrocyanide (FC) and Cs+, zeolitic imidazolate framework-8 (ZIF-8) was chemically functionalized with FC, ZIF-8-FC to selectively capture Cs+. After functionalization, ZIF-8-FC has a hollow morphology and small FC related crystals, which might result in better migration of Cs+ inside ZIF-8-FC. This synergistic effect was proven by the Qmax of ZIF-8-FC, 422.42 mg g-1, which is 15.9 times higher than that of ZIF-8. Additionally, ZIF-8-FC retained its good adsorption performance within a pH range of 3-11 and an excellent Cs+ selectivity even in artificial seawater conditions. The structure of ZIF-8-FC after adsorption proves its stability. Furthermore, the thermodynamic adsorption implied that higher temperatures are more favorable for Cs+ uptake. This work demonstrates the remarkable adsorption and selectivity of ZIF-8-FC, which make it a promising candidate for remediation of radioactive Cs+.


Anti-inflammatory cytokines IL-35 and IL-10 block atherogenic lysophosphatidylcholine-induced, mitochondrial ROS-mediated innate immune activation, but spare innate immune memory signature in endothelial cells.
It has been shown that anti-inflammatory cytokines interleukin-35 (IL-35) and IL-10 could inhibit acute endothelial cell (EC) activation, however, it remains unknown if and by what pathways IL-35 and IL-10 could block atherogenic lipid lysophosphatidylcholine (LPC)-induced sustained EC activation; and if mitochondrial reactive oxygen species (mtROS) can differentiate mediation of EC activation from trained immunity (innate immune memory). Using RNA sequencing analyses, biochemical assays, as well as database mining approaches, we compared the effects of IL-35 and IL-10 in LPC-treated human aortic ECs (HAECs). Principal component analysis revealed that both IL-35 and IL-10 could similarly and partially reverse global transcriptome changes induced by LPC. Gene set enrichment analyses showed that while IL-35 and IL-10 could both block acute EC activation, characterized by upregulation of cytokines/chemokines and adhesion molecules, IL-35 is more potent than IL-10 in suppressing innate immune signatures upregulated by LPC. Surprisingly, LPC did not induce the expression of trained tolerance itaconate pathway enzymes but induced trained immunity enzyme expressions; and neither IL-35 nor IL-10 was found to affect LPC-induced trained immunity gene signatures. Mechanistically, IL-35 and IL-10 could suppress mtROS, which partially mediate LPC-induced EC activation and innate immune response. Therefore, anti-inflammatory cytokines could reverse mtROS-mediated acute and innate immune trans-differentiation responses in HAECs, but it could spare metabolic reprogramming and trained immunity signatures, which may not fully depend on mtROS. Our characterizations of anti-inflammatory cytokines in blocking mtROS-mediated acute and prolonged EC activation, and sparing trained immunity are significant for designing novel strategies for treating cardiovascular diseases, other inflammatory diseases, and cancers.


[Double-chamber right ventricle, aortic subvalvular stenosis and interventricular septal defect. Apropos of 12 cases].
The authors report 12 cases of double-chamber right ventricle associated with discrete subaortic stenosis and ventricle septal defect. The statistics derived from 3,292 surgical reports of congenital heart diseases operated on at the Marie-Lannelongue Surgical Center over an 8 years period show that this association is 7 times more frequent than the law of chance. Twenty-two per cent of double-chamber right ventricles had an associated discrete subaortic stenosis and, in 9% of cases of subaortic stenosis a double-chamber right ventricle was observed. The cause of this malformation could be a developmental defect of the primitive interampullar ring.


Structural characterization of stripe rust progress in wheat crops sown at different planting dates.
An advanced insight into characterizing stripe rust progress curves is required to improve accuracy and efficiency of future research for disease measurement and estimation purposes. The rate of stripe rust increase in wheat crops is highly variable, resulting in variations and uncertainties in evaluating disease progress over time. This variability was described by fitting standard curves to disease severity data collected over a four-season experiment to identify effective disease curve elements in Iranian wheat cultivars planted at different dates. Gaussian curves appeared to be the best fitted models for all four growing seasons. Three Gaussian parameters in combination with the area under the disease progress curve (AUDPC), disease onset time, maximum disease incidence and severity were then considered to describe the rate of disease increase. Based on H-tests of Kruskal-Wallis one-way analysis of variance, cultivar and planting date significantly affected AUDPC, maximum disease incidence and severity. There were significant correlations between continuous disease descriptors. Then, significant associations were determined between AUDPC, disease onset time, Gaussian parameters, maximum disease incidence and severity according to factor analysis. With these novel findings, we should be aware of descriptive value of wheat-stripe-rust progress variables. Such information will assist with stripe rust measurements for wheat breeding programs, yield loss estimation, development of disease control strategy, and epidemiological studies.


Angiotensin-converting enzyme inhibitor related angioedema and the anaesthetist.
Angioedema of the face and neck is an uncommon but potentially life-threatening complication of angiotensin-converting enzyme (ACE) inhibitor therapy. This condition is of particular concern to the anaesthetist as it can rapidly progress to upper airway obstruction. We describe the presentation and management of five cases of ACE inhibitor related angioedema, all of which were associated with significant upper airway obstruction.


Metabotropic glutamate type 1alpha receptor localizes in low-density caveolin-rich plasma membrane fractions.
Recent evidence suggest that many G protein-coupled receptors (GPCR) and signalling molecules localize in microdomains of the plasma membrane. In this study, flotation gradient analysis in the absence of detergents demonstrated the presence of the metabotropic glutamate receptor type 1alpha (mGlu1alpha) in low-density caveolin-enriched membrane fractions (CEMF) in permanently transfected BHK cells. BHK-1alpha cells exhibit a similar pattern of staining for caveolin-1 and caveolin-2, and these two proteins show a high degree of co-localization with mGlu1alpha receptor as demonstrated by immunogold and confocal laser microscopy. The presence of mGlu1alpha in CEMF was also demonstrated by co-immunoprecipitation of mGlu1alpha receptor using antibodies against caveolin proteins. Activation of the mGlu1alpha receptor by agonist increased extracellular signal-regulated kinases phosphorylation in CEMF and not in high-density membrane fractions (HDMF), suggesting that mGlu1alpha receptor-mediated signal transduction could occur in caveolae-like domains. Overall, these results clearly show a molecular and functional association of mGlu1alpha receptor with caveolins.


A Small-Molecule Inhibitor Targeting TRIP13 Suppresses Multiple Myeloma Progression.
The AAA-ATPase TRIP13 drives multiple myeloma progression. Here, we present the crystal structure of wild-type human TRIP13 at a resolution of 2.6 Å. A small-molecule inhibitor targeting TRIP13 was identified on the basis of the crystal structure. The inhibitor, designated DCZ0415, was confirmed to bind TRIP13 using pull-down, nuclear magnetic resonance spectroscopy, and surface plasmon resonance-binding assays. DCZ0415 induced antimyeloma activity in vitro, in vivo, and in primary cells derived from drug-resistant patients with myeloma. The inhibitor impaired nonhomologous end joining repair and inhibited NF-κB activity. Moreover, combining DCZ0415 with the multiple myeloma chemotherapeutic melphalan or the HDAC inhibitor panobinostat induced synergistic antimyeloma activity. Therefore, targeting TRIP13 may be an effective therapeutic strategy for multiple myeloma, particularly refractory or relapsed multiple myeloma. SIGNIFICANCE: These findings identify TRIP13 as a potentially new therapeutic target in multiple myeloma.


The origins of behavioral genetics.
The passing of Seymour Benzer has inspired various retrospectives on his scientific career, and much attention has been paid to his inauguration of single-gene mutant studies of behavior in the fruitfly Drosophila melanogaster. Studies of genes and behavior actually go back to the beginnings of genetics. The end of the era marked by Benzer's life offers a good opportunity to look back at the origins of the field he influenced so profoundly.


Collinearity tolerance of cells in areas 17 and 18 of the cat's visual cortex: relative sensitivity to straight lines and chevrons.
Collinearity tolerance and length dependence of orientation tuning were compared in cells recorded from areas 17 and 18 of the lightly anaesthetised cat's visual cortex. Orientation tuning and interaction between receptive field halves of the same cells are reported in the preceding paper and elsewhere (Hammond and Andrews, 1978a, b). In confirmation of previous work, increase in stimulus length was associated with sharper orientation tuning in all simple and hypercomplex cells, and in most complex cells even in the absence of length summation. Cells in areas 17 and 18 were more sharply tuned for chevrons was noticeably skewed compared with tuning for straight lines. In area 17, the best response was always obtained with a straight line of optimal orientation. The two halves of the receptive fields of some cells in area 18 had dissimilar preferred orientations. Even in cells whose receptive field halves were similarly tuned, broadly tuned, or apparently untuned for orientation, simultaneous stimulation of both halves of the receptive field led to substantial sharpening of tuning. In cells with dissimilarly tuned half fields, the skew in chevron tuning was predictable from the orientation tuning of each half of the receptive field. Two area 18 cells responded consistently better to a chevron stimulus than to a straight line of any orientation.


Optimization of n-butanol synthesis in Lactobacillus brevis via the functional expression of thl, hbd, crt and ter.
N-butanol is an important chemical and can be naturally synthesized by Clostridium species; however, the poor n-butanol tolerance of Clostridium impedes the further improvement in titer. In this study, Lactobacillus brevis, which possesses a higher butanol tolerance, was selected as host for heterologous butanol production. The Clostridium acetobutylicum genes thl, hbd, and crt which encode thiolase, β-hydroxybutyryl-CoA dehydrogenase, and crotonase, and the Treponema denticola gene ter, which encodes trans-enoyl-CoA reductase were cloned into a single plasmid to express the butanol synthesis pathway in L. brevis. A titer of 40 mg/L n-butanol was initially achieved with plasmid pLY15-opt, in which all pathway genes are codon-optimized. A titer of 450 mg/L of n-butanol was then synthesized when ter was further overexpressed in this pathway. The role of metabolic flux was reinforced with pLY15, in which only the ter gene was codon-optimized, which greatly increased the n-butanol titer to 817 mg/L. Our strategy significantly improved n-butanol synthesis in L. brevis and the final titer is the highest achieved amongst butanol-tolerant lactic acid bacteria.


Oxidative DNA damage induced by iron chloride in the larvae of the lace coral Pocillopora damicornis.
Biochemical and molecular biomarkers tools are utilized as early warning signatures of contaminant exposure to target and non-target organisms. The objective of this study was to investigate the sublethal effects of iron chloride to the larvae of the lace coral Pocillopora damicornis by measuring a suit of oxidative-stress biomarkers. The larvae were exposed to a range of sublethal concentrations of iron chloride (0.01, 0.1, 1, 10, and 100 ppm) for seven days. With reference to oxidative stress biomarkers, the no-observed effect concentration (NOEC) and the lowest observed effect concentration (LOEC) of iron chloride were observed to be 0.01 and 100 ppm respectively. At the end of the seventh day the antioxidant status of the larvae was evaluated by the levels of glutathione (GSH), glutathione peroxidase (GPX), glutathione reductase (GR), and glutathione-S-transferase (GST), in both experimental and control groups. For the quantification of cellular oxidative damage, lipid peroxidation (LPO) activity was determined in the same and the extent of DNA damage was assessed by the expression of DNA apurinic/apyrimidinic (AP) sites. Iron chloride exhibited a concentration-dependent inhibition of GSH and GPX and induction of GR, GST, LPO, and DNA-AP sites in the P. damicornis larvae when compared to the control group. The oxidative stress biomarkers of the larvae exposed to 0.1, 1, and 10 ppm of iron chloride did not show any significant overall differences when compared to the control group. However the activities of LPO, GSH, GPX, GR, GST and DNA-AP in the larval group exposed to 100 ppm of iron chloride exhibited statistically significant (P=0.002, 0.003, 0.002, 0.002, 0.005 and 0.007) differences when compared to the control group. The research results indicated that iron chloride in concentrations at the 100 ppm level caused oxidative stress in the P. damicornis larvae.


[Human immunoglobulins, adverse drug reaction, prevention].
Adverse drug reactions occur during 10% of immunoglobulin treatment. Risk factor of adverse drug reactions have been identified. Simple measures during prescription, administration and supervision of immunoglobulin treatment should prevent most of serious and non-serious adverse drug reactions. Patients with risk factor of adverse drug reactions may be identified. Hydration before and during immunoglobulin treatment is recommended. Low dose of immunoglobulin and slow rate of infusion associated with hydration should prevent many adverse drug reactions. Anyway follow-up of tolerance during infusion is necessary. Changing immunoglobulin preparation does not prevent adverse drug reactions although measures of safe prescription and administration do. Careful prescription, administration and supervision of immunoglobulin therapy should prevent most of immunoglobulin-related adverse drug reactions.


Multi-tissue to whole plant metabolic modelling.
Genome-scale metabolic models have been successfully applied to study the metabolism of multiple plant species in the past decade. While most existing genome-scale modelling studies have focussed on studying the metabolic behaviour of individual plant metabolic systems, there is an increasing focus on combining models of multiple tissues or organs to produce multi-tissue models that allow the investigation of metabolic interactions between tissues and organs. Multi-tissue metabolic models were constructed for multiple plants including Arabidopsis, barley, soybean and Setaria. These models were applied to study various aspects of plant physiology including the division of labour between organs, source and sink tissue relationship, growth of different tissues and organs and charge and proton balancing. In this review, we outline the process of constructing multi-tissue genome-scale metabolic models, discuss the strengths and challenges in using multi-tissue models, review the current status of plant multi-tissue and whole plant metabolic models and explore the approaches for integrating genome-scale metabolic models into multi-scale plant models.


Limbal autograft and allograft transplantations in patients with corneal burns.
To investigate and compare the surgical outcomes of limbal autograft and limbal allograft transplantations in patients with corneal burns. In total, 20 patients (n=22 eyes) with chemical burn and two patients (n=2 eyes) with thermal burn were included in this study. Limbal autograft or limbal allograft transplantation surgery was performed in all patients. HLA-typing was tested before allograft surgeries. Limbal allografting was performed in all eyes using donor tissue from live relatives. Systemic cyclosporine A was administered for immunosuppression. The corneal surface was successfully reconstructed in all eyes (100%) after limbal autografting, two eyes required additional amniotic membrane transplantation and one eye required allografting. The mean follow-up period for limbal autografts was 13.9 +/- 7.0 months. Limbal allografting failed to reduce corneal vascularity and opacification in five (55.6%) eyes and was successful only in four (44.4%) eyes (mean follow-up 16.2 +/- 11.2 months) (P=0.002). In all, 15 eyes undergoing limbal autografting completed re-epithelialization of the cornea at a mean of 35.6 +/- 60.2 days. The mean epithelial healing time in nine eyes undergoing limbal allografting was 13.0 +/- 7.3 days (P=0.525). After limbal autografting, functional vision (> or =1/10) was attained in 12 (80%) eyes. Only one eye (11.1%) achieved functional vision after limbal allografting (P=0.036). Penetrating keratoplasty was performed in three patients following limbal allografting. No cyclosporine-associated side effects were observed. Limbal autograft transplantation is an effective and safe procedure for unilateral corneal burns. It seems that limbal allograft transplantation is better combined with penetrating keratoplasty for a better visual outcome and higher graft survival rate. Systemic immunosuppression seems to be necessary for limbal allografts even in the presence of HLA-matched donor tissues.


Compatibility and stability of dexamethasone sodium phosphate and ketamine hydrochloride subcutaneous infusions in polypropylene syringes.
The stability of ketamine hydrochloride injection and dexamethasone sodium phosphate injection, when mixed and stored in polypropylene syringes, was studied. Formulations containing ketamine hydrochloride (50 mg or 600 mg) and dexamethasone sodium phosphate (1 mg) in 0.9% sodium chloride injection (to 14 ml) were prepared and stored at 4 degrees C, 23 degrees C, and 37 degrees C, under normal fluorescent light conditions, for 192 hours. The concentrations of the drugs were determined at 0, 2, 4, 8, 24, 48, 96, and 192 hours using a validated high-pressure liquid chromatography method. The pH, color, and visible particles of each solution were also assessed at each time point. All formulations tested maintained more than 98% of the initial concentrations of both drugs, and no degradation products were detected. The solutions remained clear and colorless and the pH varied within 0.05 units throughout 192 hours. The results indicate that, at the concentrations studied, combinations of ketamine hydrochloride and dexamethasone sodium phosphate in 0.9% sodium chloride injection were physically and chemically stable for at least 192 hours (8 days) when stored in polypropylene syringes.


Immune-modulation by 7, 8-diacetoxy-4-methylthiocoumarin in total body-irradiated mice: Implications for the mitigation of radiation-induced hematopoietic injury.
Development of novel medical countermeasures (MCMs) against acute radiation syndrome (ARS) and the associated lethality involves protection from and/or mitigation of radiation-induced hematopoietic injury, a critical clinical component of ARS. We earlier identified the molecule 7,8-diacetoxy-4-methylthiocoumarin (DAMTC) as a potent mitigator of hematopoietic injury and mortality in C57BL/6 mice when administered 24 h following total body irradiation (TBI). In the present study, we investigated mechanisms and functional relevance of immune modulation by DAMTC during the mitigation of hematopoietic injury. C57BL/6 mice were subjected to TBI doses of 3 and 7.6Gy; administered DAMTC intra-peritoneally 24 h post TBI. Isolation, characterization, intra-cellular cytokine analysis of myeloid cells from bone marrow and spleen accompanied by flow cytometric determination and characterization of B-lymphocytes, serum isolation from peripheral blood and cytokine analysis. Results showed that DAMTC induced stimulation of pro-inflammatory myeloid subsets in the bone marrow and spleen of TBI mice. Further, it promoted a favorable transition from Th2 to Th1 immunity, triggered humoral immunity, and activated an intricately balanced inflammatory response that appear to contribute to immune-modulation. Thus, the present study shows that immune-modulation maybe one of the contributing factors for the mitigation of hematopoietic injury by DAMTC and underscores its efficacy as a potent mitigator of hematopoietic injury that merits to be developed further as a novel MCM to combat H-ARS.


A mutation in the human neurofilament M gene in Parkinson's disease that suggests a role for the cytoskeleton in neuronal degeneration.
Parkinson's disease (PD) is a common neurodegenerative movement disorder characterized by the destruction of dopaminergic neurons of the substantia nigra. We have identified a new mutation (Gly336Ser) in the medium neurofilament subunit in a patient of French-Canadian origin with early onset severe PD. This finding suggests, for the first time, that aberrations in neuronal molecules involved in the cytoskeleton could lead to the development of the pathology seen in PD.


Effects of music therapy on pain, anxiety, and vital signs in patients after thoracic surgery.
To examine the effectiveness of music listening on pain, anxiety, and vital signs among patients after thoracic surgery in China. A randomized controlled clinical trial was conducted in the thoracic surgery department of two tertiary hospitals in Wuhan, China. 112 patients were recruited and randomly assigned to either experimental (n=56) or control (n=56) group respectively. The experimental group received standard care and a 30-min soft music intervention for 3 days, while the control group received only standard care. Measures include pain, anxiety, vital signs (blood pressure, heart rate and respiratory rate), patient controlled analgesia, and diclofenac sodium suppository use. The experimental group showed statistically significant decrease in pain, anxiety, systolic blood pressure and heart rate over time compared to the control group, but no significant difference were identified in diastolic blood pressure, respiratory rate, patient controlled analgesia and diclofenac sodium suppository use. The findings provide further evidence to support the practice of music therapy to reduce postoperative pain and anxiety, and lower systolic blood pressure and heart rate in patients after thoracic surgery in China.


Distribution of choline acetyltransferase immunopositive structures in the rat brainstem.
The distribution of neurons, fibers and terminal fields in rat brainstem displaying positive immunoreactivity to a polyclonal antiserum to human placental choline acetyltransferase (ChAT) is described. The antiserum was used at the high dilution of 1:10,000 and was coupled with a sensitive detection system using the nickel ammonium sulfate intensification method. In addition to previously described ChAT immunopositive groups of large cells in the cranial motor nuclei, and the parabrachial and reticular complexes, many small or medium size, weakly immunopositive neurons were identified. Some of these appeared in structures in the region of the fourth ventricle, including the area postrema. Others were in structures associated with the superior olivary complex, including the lateral superior olive, and the medioventral, lateroventral and superior periolivary nuclei. Scattered, weakly positive cells were seen in numerous other structures, including the ventral tegmental area of Tsai, central gray, superior colliculus, spinal nucleus of nerve 5, dorsal cochlear nucleus and non-motor regions of the spinal cord. The prominent ascending fiber tract of the laterodorsal tegmental pathway was traceable from the parabrachial area to the subgeniculate region of the thalamus. Prominent terminal fields were seen in a number of brainstem structures, including the superior colliculus, pontine nuclei, anterior pretectal nucleus, interpeduncular nucleus and spinal nucleus of nerve 5. The association of small ChAT positive cells and terminal fields with many sensory structures suggests a significant cholinergic participation in the physiology of sensory function.


Optimized verification method for detection of an albumin-sulfur mustard adduct at Cys(34) using a hybrid quadrupole time-of-flight tandem mass spectrometer after direct plasma proteolysis.
The vesicant sulfur mustard (SM) is a banned chemical warfare agent that is controlled by the Organisation for the Prohibition of Chemical Weapons (OPCW). Bioanalytical procedures are mandatory for proving an alleged use and incorporation of SM into the body. We herein present the development and application of a novel optimized procedure suitable for qualitative verification analysis of plasma targeting the SM-adduct of human serum albumin (HSA) alkylated at the cysteine(34) residue. Diluted human plasma is directly mixed with pronase in an ultrafiltration device (10kDa cut-off) for proteolysis (4h, 37°C). Following ultrafiltration the filtrate is diluted and analyzed by microbore liquid chromatography-electrospray ionization high resolution tandem-mass spectrometry (μLC-ESI HR MS/MS) targeting the alkylated dipeptide hydroxyethylthioethyl-CysPro (HETE-CP). A hybrid quadrupole time-of-flight mass spectrometer provided high mass spectrometric resolution in the MS/MS mode enabling highest selectivity and sensitivity (lower limit of detection corresponding to 9.8nM SM in plasma). Kinetics of HETE-CP formation from heparin-, citrate-, and EDTA-plasma as well as serum are presented and the influence of different EDTA and pronase concentrations was characterized. The novel procedure was applied to plasma samples provided by the OPCW as well as to patientś plasma derived from real cases of SM-poisoning.