Acute treatment with diphenyl diselenide inhibits glutamate uptake into rat hippocampal slices and modifies glutamate transporters, SNAP-25, and GFAP immunocontent.
Diphenyl diselenide (PhSe)(2) is a selenium organic compound that has been described to inhibit glutamate binding at synaptic membranes and uptake into cortical slices, but there are no studies about its effects on glutamate transporters and related synaptic proteins. Hippocampal slices from rats treated acutely with (PhSe)(2) (1, 10, and 100 mg/kg, oral route) were evaluated on glutamate uptake, redox state, the immunocontent of glial (glutamate/aspartate transporter [GLAST] and glutamate transporter type I [GLT1]), neuronal (excitatory amino acid carrier 1 [EAAC1]), and vesicular (vesicular glutamate transporter 1 [VGLUT1]) glutamate transporters. Besides, cell viability was evaluated by glial fibrillar acid protein (GFAP) and synaptosomal-associated protein 25 (SNAP-25) immunocontent and 4', 6-diamidino-2-phenylindole (DAPI) and Fluoro Jade C staining. Hippocampal slices from rats treated with (PhSe)(2) exhibited a nondose-dependent inhibition of glutamate uptake (53, 38, and 45%, respectively). All doses increased EAAC1, decreased SNAP-25, did not modify GLT1 immunocontent, and there was no evidence of oxidative stress. (PhSe)(2) (100 mg/kg) increased 32% GLAST, decreased 34% VGLUT1, and 21% GFAP immunocontent. Besides, (PhSe)(2) (100 mg/kg) decreased by 25% GFAP-stained astrocytes and 27% DAPI-stained cells in the CA1 subfield. Our results suggest that the increase of EAAC1 and GLAST immunocontent by (PhSe)(2) might be a compensatory mechanism by surviving cells in order to reduce extracellular glutamate levels, avoiding possible neurotoxic effects. The impairment of glutamate uptake by the highest dose of (PhSe)(2) seems to be related to a decrease on VGLUT1, SNAP-25, and damage to astrocytes. Since there were no signs of oxidative stress, our findings revealed that depending on the dose, acute administration of (PhSe)(2) causes modifications in important synaptic-related proteins and damage to the astrocytes, and these events must be taken into account in its pharmacological properties.


The Predictive Validity of the Danish Psychosocial Work Environment Questionnaire With Regard to Onset of Depressive Disorders and Long-Term Sickness Absence.
To investigate the predictive validity of 32 measures of the Danish Psychosocial Work Environment Questionnaire (DPQ) against two criteria variables: onset of depressive disorders and long-term sickness absence (LTSA). The DPQ was sent to 8958 employed individuals in 14 job groups of which 4340 responded (response rate: 48.4%). Depressive disorders were measured by self-report with a 6-month follow-up. LTSA was measured with a 1-year follow-up in a national register. We analyzed onset of depressive disorders at follow-up using logistic regression models, adjusted for age, sex, and job group, while excluding respondents with depressive disorders at baseline. We analyzed onset of LTSA with Cox regression models, adjusted for age, sex, and job group, while excluding respondents with previous LTSA. The general pattern of the results followed our hypotheses as high job demands, poorly organized working conditions, poor relations to colleagues and superiors, and negative reactions to the work situation predicted onset of depressive disorders at follow-up and onset of LTSA during follow-up. Analyzing onset of depressive disorders and onset of LTSA, we found risk estimates that deviated from unity in most of the investigated associations. Overall, we found higher risk estimates when analyzing onset of depressive disorders compared with onset of LTSA. The analyses provide support for the predictive validity of most DPQ-measures. Results suggest that the DPQ constitutes a useful tool for identifying risk factors for depression and LTSA in the psychosocial work environment.


Abnormal timing in the prenatal ossification of vertebral column and hand in Crouzon syndrome.
We report on a radiographically examined fetus (gestational age 13 weeks) with Crouzon syndrome caused by a mutation in the gene encoding the fibroblast growth factor 2 (FGFR2). We found an approximately 2-week delay in vertebral body and hand ossification with normal vertebral arch ossification, suggesting that regionally delayed skeletal maturation might be a manifestation of FGFR2 mutation syndromes. The findings support other studies indicating that different signaling pathways control skeletal maturation in vertebral bodies and vertebral arches.


Selective cyclooxygenase-2 inhibition does not alter keratinocyte wound responses in the mouse epidermis after abrasion.
The cyclooxygenase isoforms, COX-1 and COX-2, are the rate limiting enzymes in the biosynthesis of prostaglandin E(2), a major prostaglandin involved in epidermal homeostasis and repair. Epidermal injury results in transient hyperplasia and induction of COX-2 expression. The role of COX-2 in this hyperplasia is unknown, however. In this study, we characterized the epidermal expression of COX isozymes following wounding by abrasion in SKH-1 mice using immunohistochemistry, in situ hybridization, and Western analysis. In addition, we evaluated pivotal keratinocyte functions necessary for the reparative hyperplasia, including proliferation by 5-bromo-2'deoxy-uridine labeling and differentiation by the expression of involucrin, keratin 1, and keratin 6. Although COX-1 expression in keratinocytes remained unchanged during wound healing, COX-2 expression was induced coincidentally with keratinocyte proliferation and keratin 6 expression, suggesting a role for COX-2 in epidermal repair. The role of COX-2 was also evaluated using the selective COX-2 inhibitor SC-791 and the traditional COX inhibitors indomethacin and diclofenac. Neither inhibitor altered keratinocyte proliferation or differentiation following abrasion, in contrast to dexamethasone, which delayed these responses. Our results indicated that, although COX-2 expression was coincident with transient epidermal hyperplasia and keratinocyte proliferation/differentiation during the healing of epidermal injury, it does not play a pivotal role in this repair process.


Interaction between Omeprazole and Gliclazide in Relation to CYP2C19 Phenotype.
The antidiabetic drug gliclazide is partly metabolized by CYP2C19, the main enzyme involved in omeprazole metabolism. The aim of the study was to explore the interaction between omeprazole and gliclazide in relation to CYP2C19 phenotype using physiologically based pharmacokinetic (PBPK) modeling approach. Developed PBPK models were verified using in vivo pharmacokinetic profiles obtained from a clinical trial on omeprazole-gliclazide interaction in healthy volunteers, CYP2C19 normal/rapid/ultrarapid metabolizers (NM/RM/UM). In addition, the association of omeprazole cotreatment with gliclazide-induced hypoglycemia was explored in 267 patients with type 2 diabetes (T2D) from the GoDARTS cohort, Scotland. The PBPK simulations predicted 1.4-1.6-fold higher gliclazide area under the curve (AUC) after 5-day treatment with 20 mg omeprazole in all CYP2C19 phenotype groups except in poor metabolizers. The predicted gliclazide AUC increased 2.1 and 2.5-fold in intermediate metabolizers, and 2.6- and 3.8-fold in NM/RM/UM group, after simulated 20-day dosing with 40 mg omeprazole once and twice daily, respectively. The predicted results were corroborated by findings in patients with T2D which demonstrated 3.3-fold higher odds of severe gliclazide-induced hypoglycemia in NM/RM/UM patients concomitantly treated with omeprazole. Our results indicate that omeprazole may increase exposure to gliclazide and thus increase the risk of gliclazide-associated hypoglycemia in the majority of patients.


Antitumor Activity of Lipid-DNA Aptamer Modified T Lymphocytes in Carcinoma.
Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with no current effective therapeutics. One of the main reasons for the low efficacy of PDAC immunotherapy is the limited CD8+ T cell infiltration, without neo antigen present in PDAC. Aptamers represent single-stranded oligonucleotides which bind to specific targets with high specificity. We developed DNA conjugates and prepared diacyl phospholipid-aptamer XQ-2d which has potential for the targeted therapy and diagnosis of PDAC. In this study, flow cytometry and fluorescence microscopy were employed to assess whether the Lipo-XQ-2d probe could anchor on activated T cells to constitute ligands specifically recognizing PDAC PL45 cells. Flow cytometry was employed to determine cytotoxicity in activated T cells. Results showed that the Lipo-XQ-2d probe could be inserted into T cells, and was specifically bound to both T cells and PL45 cells. In addition, the Lipo-XQ-2d probe redirected T cells to kill PL45 cells in vitro and was not toxic to cells. In conclusion, lipid-DNA-aptamer-modified T-lymphocytes might effectively kill PDAC in vitro, supporting the clinical application of T cell adoptive immunotherapy.


Polyampholyte adsorption on a charged sphere.
A theory of the adsorption of polyampholyte chains on a charged spherical particle is developed. It is shown that the equilibrium polymer density profile near an adsorbing particle may be found by balancing the polarization-induced attraction of polyampholytes to the charged spherical particle with the monomer-monomer repulsion. At intermediate values of the particle charge, the polyampholyte chains touching the surface of the particle form a self-similar flowerlike structure. The structure of an adsorbed polyampholyte in the flowerlike conformation is similar to that of a neutral star polymer.


The behavioral activation system and mania.
For over two decades, theorists have suggested that mania relates to heightened sensitivity of the behavioral activation system (BAS). In this article, we review a burgeoning empirical literature on this model, drawing on both cross-sectional and prospective studies. As evidence has emerged for this model, we argue that it is time to consider more specific aspects of BAS sensitivity in this disorder. We review evidence that bipolar disorder relates to an increased willingness to expend effort toward reward and to increases in energy and goal pursuit after an initial reward. We conclude by considering the strengths and weaknesses of this literature, with an eye toward future directions and implications for treatment.


Patient readiness for risk-reduction education and lifestyle change following transient ischemic attack.
Patient readiness for secondary prevention and lifestyle change following transient ischemic attack is not well understood. Understanding patient perspectives about the timing and delivery of secondary prevention education is essential to promote meaningful risk factor reduction in this population. A single, semi-structured, telephone interview was conducted with ten individuals (7 male, 3 female) within three months following a transient ischemic attack. Interviews explored transient ischemic attack experiences and post-event education. Data were analyzed using inductive thematic analysis. Individuals had a variety of experiences with secondary prevention education. Four themes emerged from these experiences including "what the hell happened?", "I mustn't have been quite ready", "what should I be doing?" and "we all see it in different ways." Individual knowledge, personal experience of transient ischemic attack, socio-environmental factors, and the format and content of education influenced patient readiness to receive secondary prevention education and adopt lifestyle changes. Readiness for risk-reduction education and lifestyle change following transient ischemic attack is individual and complex. Logistical factors including the location, time, and cost of education, timing of education delivery, and patient perspectives should be considered in the development and delivery of secondary prevention interventions for these people. Implications for rehabilitation Risk reduction and lifestyle change following transient ischemic attack is vital to prevent recurrent stroke. Patients are ready to receive risk reduction and lifestyle advice approximately one week after their transient ischemic attack. Programs designed to provide risk reduction and lifestyle education should be informed by the unique requirements of this population. Uptake of participation in secondary prevention programs may be maximized by offering flexibility in terms of timing post-event and modes of delivery (e.g. Telehealth).


Background connectivity between frontal and sensory cortex depends on task state, independent of stimulus modality.
The human brain has the ability to process identical information differently depending on the task. In order to perform a given task, the brain must select and react to the appropriate stimuli while ignoring other irrelevant stimuli. The dynamic nature of environmental stimuli and behavioral intentions requires an equally dynamic set of responses within the brain. Collectively, these responses act to set up and maintain states needed to perform a given task. However, the mechanisms that allow for setting up and maintaining a task state are not fully understood. Prior evidence suggests that one possible mechanism for maintaining a task state may be through altering 'background connectivity,' connectivity that exists independently of the trials of a task. Although previous studies have suggested that background connectivity contributes to a task state, these studies have typically not controlled for stimulus characteristics, or have focused primarily on relationships among areas involved with visual sensory processing. In the present study we examined background connectivity during tasks involving both visual and auditory stimuli. We examined the connectivity profiles of both visual and auditory sensory cortex that allow for selection of task-relevant stimuli, demonstrating the existence of a potentially universal pattern of background connectivity underlying attention to a stimulus. Participants were presented with simultaneous auditory and visual stimuli and were instructed to respond to only one, while ignoring the other. Using functional MRI, we observed task-based modulation of the background connectivity profile for both the auditory and visual cortex to certain brain regions. There was an increase in background connectivity between the task-relevant sensory cortex and control areas in the frontal cortex. This increase in synchrony when receiving the task-relevant stimulus as compared to the task irrelevant stimulus may be maintaining paths for passing information within the cortex. These task-based modulations of connectivity occur independently of stimuli and could be one way the brain sets up and maintains a task state.


Sample cleanup-free determination of mycophenolic acid and its glucuronide in serum and plasma using the novel technology of ultra-performance liquid chromatography-electrospray ionization tandem mass spectrometry.
Mycophenolic acid (MPA) is an immunosuppressant drug which powerfully inhibits lymphocyte proliferation. Since the early 1990s it has been used to prevent rejection in organ transplantation. The requirement of therapeutic drug monitoring shown in previous studies raises the necessity of acquiring accurate and sensitive methods to measure MPA and its major metabolite mycophenolic acid glucuronide (MPAG). The authors developed a sample cleanup-free, rapid, and highly specific method for simultaneous measurement of MPA and MPAG in human plasma and serum using the novel technology of ultra-performance liquid chromatography-electrospray ionization tandem mass spectrometry. MPA- and MPAG-determinations were performed during a 2.0-min run time. Multiple calibration curves for the analysis of MPA and MPAG exhibited consistent linearity and reproducibility in the range of 0.05-100 (r>0.999) mg L(-1) and 4-4000 mg L(-1) (r>0.999), respectively. Limits of Detection were 0.014 mg L(-1) for MPA and 1.85 mg L(-1) for MPAG. Lower Limits of Quantification were 0.05 mg L(-1) for MPA and 2.30 mg L(-1) for MPAG. Interassay imprecision was <10% for both substances. Mean recovery was 103.6% (range 78.1-129.7%) for MPA and 111.1% (range 73.0-139.6%) for MPAG. Agreement was good for MPA and MPAG between the presented method and a validated HPLC-MS/MS method. The Passing-Bablok regression line for MPA and MPAG was HPLC-MS/MS=1.14 UPLC-MS/MS-0.14 [ mg L(-1)], r=0.96, and HPLC-MS/MS=0.77 UPLC-MS/MS+0.50 [ mg L(-1)], r=0.97, respectively. This sample cleanup-free and robust LC-MS/MS assay facilitates the rapid, accurate and simultaneous determination of MPA and MPAG in human body fluids.


[Epidemiology of snake bites in the Republic of Ivory Coast].
A national survey was carried out in Côte d'Ivoire in 1979 in order to evaluate the incidence, morbidity and mortality of snakebites. This unpublished survey has not been renewed to our knowledge. Although 20 odd years have passed since, the survey is not obsolete and can be usefully presented at this congress. We associated a retrospective survey using health centre registers and a prospective survey performed in 7 health centres between 1972 and 1979. The incidence, estimated prospectively for rural areas, exceeded 200 bites for 100,000 inhabitants. This evaluation could be an underestimation because many victims consulted traditional practitioners. Annual morbidity was higher in forest areas (195 envenomations per 100,000 inhabitants) than in the savannah (130 envenomations per 100,000 inhabitants). Conversely, the case fatality rate was higher in the savannah (3.1%) than in forest areas (2%). More than half of the bites involved men aged 15 to 50 years. The risks were significantly higher for farmers, particularly in industrial plantations, where 27% of the total of number of bites involved 1.5% of the population. At the beginning of the 1980s, envenomations could be estimated at over 13,000 per 8 million inhabitants and the number of deaths 200 per annum.


Importance of trehalose biosynthesis for Sinorhizobium meliloti Osmotolerance and nodulation of Alfalfa roots.
The disaccharide trehalose is a well-known osmoprotectant, and trehalose accumulation through de novo biosynthesis is a common response of bacteria to abiotic stress. In this study, we have investigated the role of endogenous trehalose synthesis in the osmotolerance of Sinorhizobium meliloti. Genes coding for three possible trehalose synthesis pathways are present in the genome of S. meliloti 1021: OtsA, TreYZ, and TreS. Among these, OtsA has a major role in trehalose accumulation under all of the conditions tested and is the main system involved in osmoadaptation. Nevertheless, the other two systems are also important for growth in hyperosmotic medium. Genes for the three pathways are transcriptionally responsive to osmotic stress. The presence of at least one functional trehalose biosynthesis pathway is required for optimal competitiveness of S. meliloti to nodulate alfalfa roots.


Clinical pharmaceutical services in retail practice. II. Factors influencing the provision of services.
The second phase of a two-part investigation of factors influencing the development of clinical pharmaceutical services in retail practice is presented. This report focuses on why pharmacists who reported a willingness and competency to perform services in Phase I had not developed such a practice. Transcripts from 11 focus group interviews conducted with pharmacists throughout South Carolina were analyzed by two panels. The first panel summarized subjects' comments regarding the major dimensions: (1) awareness, (2) demand, (3) motivation, (4) requisites, and (5) barriers for delivery of services. The second panel judged the validity of the first panel's analysis. Pharmacists were aware of common clinical services, but had given little thought to unique services oriented to patients' needs. Monetary factors were deemed to be more important than was concluded from the first phase. Pharmacists saw a minimal demand for services, but a great need. Pharmacists also felt the need for more clinical skills, but better systems of delivery also were emphasized. The report concludes with a strategy for promoting clinical services in retail practice.


Risperidone plasma levels, clinical response and side-effects.
Assessment of the relation between oral risperidone dose, serum drug levels and clinical response may provide important information for rational treatment decisions. Inter-individual differences in the liver cytochrome P450 system, especially in the CYP2D6 subsystem, which account for a significant portion of risperidone metabolism, may also influence plasma drug levels and alter clinical response parameters. We thus prospectively investigated risperidone serum concentrations in relation to clinical efficacy and side-effects and genotyped major CYP2D6 polymorphisms to determine their effect upon these parameters. Neuroleptic monotherapy with risperidone was administered to schizophrenia patients in a 6-week open dose clinical trial. Weekly assessments including CGI and PANSS ratings to assess psychopathology; SAS to assess medication side effects; and blood draws to quantify steady state plasma levels of risperidone and 9-OH-risperidone were carried out. In addition, major CYP2D6 polymorphisms including alleles *4, *6 and *14 were genotyped. Eighty-two patients were recruited. Mean oral dose of risperidone was 4.3 +/- 0.9 mg. Mean plasma level of both risperidone and 9-OH-risperidone together ("active moiety") was 41.6 +/- 26.6 ng/ml. Significant improvements in PANSS scales and the various subscales ensued. There was a positive linear correlation between active moiety plasma levels and dose (r = 0.291, p = 0.015) and between risperidone and 9-OH-risperidone levels (r = 0.262; p = 0.016). Nonresponders to pharmacotherapy (PANSS-Improvement < 30%) showed significantly higher active moiety plasma levels (49.9 +/- 30.7 ng/ml) than responders (38.2 +/- 17.0 ng/ml; p = 0.045) without significantly higher oral doses (p = 0.601). Patients with longer illness duration (> or = 3 years) had significantly higher plasma drug levels than those with a shorter course (< 3 years; p = 0.039). Extrapyramidal side effects (EPS) and plasma levels were not correlated (r = 0.028; p = 0.843), but higher plasma levels at week 2 predicted an incidence for EPS (p < 0.050). Accordingly, patients initially receiving higher oral doses of risperidone were significantly more likely to respond with EPS in the trial course. Eight patients (9.8%) were heterozygous carriers of the CYP2D6 allele *4. CYP2D6 polymorphisms did not predict clinical response, but predicted a tendential increase in the plasma risperidone to 9-OH-risperidone ratio (0.5 +/- 0.6 vs. 1.9 +/- 1.8; p = 0.120). The major finding was that responders to risperidone treatment had significantly lower blood levels of risperidone and 9-OH risperidone than patients who did not respond to the treatment despite administration of similar oral doses. The observed CYP2D6 polymorphisms did not contribute to altered clinical efficacy, but affected risperidone to 9-OH-risperidone ratios. Increased plasma levels of the active moiety in patients with longer illness may represent general aging effects. Conversely, the observed higher plasma levels in nonresponders may derive from unaccounted genetic metabolism abnormalities or Phase II metabolism disturbances. Patients initially receiving higher oral risperidone doses were more likely to respond with extrapyramidal side effects which reaffirms the need for careful titration. The high inter-individual variability in risperidone and 9-OH-risperidone metabolization and the relationship between clinical outcome and plasma levels warrants regular plasma level monitoring of both compounds to assess for the clinically relevant active moiety.


The role of SAP97 in synaptic glutamate receptor dynamics.
Proteins of the PSD-95-like membrane-associated guanylate kinase (PSD-MAGUK) family are vital for trafficking AMPA receptors (AMPARs) to synapses, a process necessary for both basal synaptic transmission and forms of synaptic plasticity. Synapse-associated protein 97 (SAP97) exhibits protein interactions, such as direct interaction with the GluA1 AMPAR subunit, and subcellular localization (synaptic, perisynaptic, and dendritic) unique within this protein family. Due in part to the lethality of the germline knockout of SAP97, this protein's role in synaptic transmission and plasticity is poorly understood. We found that overexpression of SAP97 during early development traffics AMPARs and NMDA receptors (NMDARs) to synapses, and that SAP97 rescues the deficits in AMPAR currents normally seen in PSD-93/-95 double-knockout neurons. Mature neurons that have experienced the overexpression of SAP97 throughout development exhibit enhanced AMPAR and NMDAR currents, as well as faster NMDAR current decay kinetics. In loss-of-function experiments using conditional SAP97 gene deletion, we recorded no deficits in glutamatergic transmission or long-term potentiation. These results support the hypothesis that SAP97 is part of the machinery that traffics glutamate receptors and compensates for other PSD-MAGUKs in knockout mouse models. However, due to functional redundancy, other PSD-MAGUKs can presumably compensate when SAP97 is conditionally deleted during development.


Revisiting the P-36 oil rig accident 15 years later: from management of incidental and accidental situations to organizational factors.
The accident with the P-36 oil rig in the Campos Basin in Rio de Janeiro State, Brazil, was one of the petroleum industry's worst international disasters. Based on this specific case, the article aims to (a) verify the role of the human dimension in the reliability of highly complex systems, with a focus on the management of incidental and accidental situations with the potential to lead to large-scale accidents. The analysis should help (b) shed light on some of the organizational factors that can increase the risk level in offshore activities, beyond the so-called immediate causes. The methodology involves mainly document research (especially the reports produced by Petrobras, ANP/DPC, and CREA-RJ) and interviews with three professionals that worked on the P-36 rig. The results indicate that the management of incidental and accidental situations in which emergency decisions are made should take advantage of contribution by the workforce, who can identify gaps in the process and discuss them with managers. This involves shared and more flexible decisions and collective analysis of risk situations. The findings also suggest that certain organizational factors contributed to the accident, corroborating domestic and international studies of major accidents and pointing to the need for a shift in the focus adopted by oil companies' management.


Cationic polypeptides modulate in vitro association of low density lipoprotein with arterial proteoglycans, fibroblasts, and arterial tissue.
Polymers of lys (plys) and arg (parg) were found to be efficient inhibitors of the formation of complexes between low density lipoprotein (LDL) and human chondroitin-6-sulfate-rich proteoglycans. Displacement curves indicate that efficiency was dependent on molecular weight. Inclusion of alanine in the polymer up to a 1:1 molar ratio (plys,ala) has a moderate effect on displacing capacity. Poly-L-lys (plys) and poly-L-arg (parg) exhibited similar displacing ability. Inclusion of tryptophan in plys and parg diminished their effect, whereas inclusion of serine in plys,ser (3:1) improved it. Plys (18.3 kD) stimulates LDL binding to human fibroblasts. This may be due to the association of polylysine to LDL, leading to an increase in its positive charge. These more positively charged LDL may have an increased association with the negatively charged region of the apolipoprotein B/E receptor. Perfusion experiments on rabbit aortic segments were used to measure the influx of 125I-LDL into the intima and to study the effect of basic polypeptides. Plys in a 10:1 molar ratio decreased the LDL uptake by approximately 25% when added to the system together with the LDL or in experiments in which the tissue segments were pre-perfused with plys, and LDL was added after elimination of the plys. The results suggest that polycationic polypeptides, due to their strong affinity for sulfated proteoglycans, interfere with the interactions of LDL with components of the arterial extracellular matrix.


N-acetylcysteine is a highly available precursor for cysteine in the neonatal piglet receiving parenteral nutrition.
Cysteine (CYS) is accepted as an indispensable amino acid for infants receiving parenteral nutrition (PN), and CYS is unstable in solution. Thus, developing a method to supply CYS in PN for neonates is needed. N-acetyl-L-cysteine (NAC) is stable in solution and safe for use in humans; therefore, NAC may be a means of supplying parenteral CYS. We determined the bioavailability of NAC in intravenously (IV)-fed piglets randomized to 1 of 4 diet treatments, each supplying 0.3 g/kg/d methionine and either 0.2 g/kg/d CYS (CON), 0 NAC (zeroNAC), 0.13 NAC (lowNAC), or 0.27 g/kg/d NAC (highNAC). Piglets (2 days old; 1.8 kg, n = 20) were surgically implanted with femoral and jugular catheters. On day 3 postsurgery, test diets were initiated and continued until day 8. Piglets were weighed daily. Blood was sampled 6 hours before test diet initiation and at 0, 6, 12, 18, 24, 36, 48, 60, 72, 84, 96, 108, and 120 hours. Urine was collected on ice in 24-hour sample periods. Total mean weight gain was not different between groups; however, average daily gain in the zeroNAC and lowNAC groups declined significantly (p < .05) over the 5-day treatment period. Nitrogen retention was similar between the CON and highNAC groups, both were higher than the lowNAC group, and the zeroNAC treatment produced the lowest nitrogen retention. NAC percent retention was not different between lowNAC and highNAC and was 85.4% and 82.6%, respectively. Plasma NAC was higher in highNAC than lowNAC (p < .05). These data demonstrate that NAC is available as a precursor for CYS to support growth and protein (nitrogen) accretion in piglets administered a parenteral solution.


[Outcomes of surgical treatment of congenital cataract with microphthalmia in infancy].
Objective: To examine the outcomes of surgical treatment for infants with congenital cataract and microphthalmia (CATM). Methods: It was a retrospective case series study. Data of 28 (55 eyes) CATM children who underwent cataract surgery at the Qingdao Eye Hospital of Shandong First Medical University and were followed up for more than 5 years between January 2010 and December 2014 under the age of 6 months. There were 15 male and 13 female children. The age at the time of surgery was (3.2±1.3) months, and the follow-up time was (8.2±1.7) years. The data included the basic information of the children, the ocular biological parameters before and after surgery and intraocular lens (IOL) implantation, and the occurrence of complications. Paired t-tests or Wilcoxon signed rank tests were used to compare groups, and logistic regression analysis was used to identify factors related to IOL implantation, secondary glaucoma, and visual axis opacification (VAO). Results: The mean preoperative axial length was (16.6±1.0) mm, and the mean horizontal corneal diameter was (9.5±0.9) mm. The axial growth rate within 2 years after the first stage of surgery was (1.4±0.8) mm/year. None of the children had an IOL implanted before the age of 2. Sixty percent of the eyes (33/55) received IOL implantation within 2 to 4 years after the first stage of surgery, while the remaining 40% (22/55) did not receive IOL implantation at the last follow-up. The axial growth rate was (0.9±0.7) mm/year within two years after the second stage of surgery. Postoperative secondary glaucoma occurred in 7 eyes (12.7%), and VAO occurred in 15 eyes (27.3%). IOL implantation was associated with preoperative axial length (OR=0.072, P<0.001) and age at the first stage of surgery (OR=7.270, P<0.001), but not with preoperative corneal diameter (P=0.735). The incidence of VAO was associated with preoperative corneal diameter (OR=4.124, P=0.011), but not with age at the first stage of surgery (P=0.489) or preoperative axial length (P=0.489). No factors related to the occurrence of secondary glaucoma were found. The best corrected visual acuity at the last follow-up after IOL implantation was (0.37±0.28) logMAR, which was better than that of children without IOL implantation (0.67±0.19) logMAR (U=49.50, P=0.003). Conclusions: Children with CATM can obtain the opportunity for IOL implantation through early surgery and ultimately achieve good visual outcomes. Properly selecting the timing for implanting IOL can keep the incidence of secondary glaucoma at an acceptable level.


The longitudinal course of adjustment after seizure surgery.
Surgical alleviation of chronic epilepsy can give rise to a process of adjustment as the chronically ill patient learns to become well. This process can manifest clinically as an array of symptoms which we have previously described as the 'burden of normality'. The aim of this study was to explore the longitudinal course of post-operative adjustment by mapping the incidence of symptoms of the burden of normality over a period of 2 years, and examining symptom occurrence relative to seizure outcome. A series of 90 anterior temporal lobectomy (ATL) patients was drawn from our Seizure Surgery Follow-up and Rehabilitation Program. All patients were prospectively assessed using the Austin CEP Interview, which covers symptoms of the burden of normality. In total, 66% of patients reported symptoms at some time within the first 2 years of surgery. Symptoms often emerged by the 3 month review, but were still seen frequently in the second year. At the 24 month review, patients who had been seizure free or experienced auras only within the previous 18 months were significantly more likely to report symptoms compared to patients who had experienced complex partial and/or generalized tonic-clonic seizures (P = 0.03). Surgical alleviation of seizures in chronic epilepsy brings with it the burden of normality. Recognition of this syndrome is essential in maximizing patient outcome.


Kuwaitimycin, effect on synthesis of lipids in Bacillus subtillis cells.
The effects exerted by kuwaitimycin on synthesis of lipids as well as some metabolic activities of Bacillus subtilis were studied. The antibiotic not only arrested the inocrporation of 14C-acetate into the microbial lipids but also altered the fatty acids pattern, contents of i-C 15, a-C 15, i-C 17 and a-C 17 WERE MARKEDLY REDUCED, CONCOMITANT WITH AN INCREASE IN THE CONtents of i-C 14 AND N-C 14. Moreover, the rates of synthesis of phospholipids were decreased by the drug, especially that of phosphatidyl ethanolamine.


A comparative study of multiport versus laparoendoscopic single-site adrenalectomy for benign adrenal tumors.
The safety and feasibility of laparoendoscopic single-site (LESS) adrenalectomy for benign adrenal lesions was proved in early clinical series. However, the advantages of LESS over multiport laparoscopic adrenalectomy still are under investigation. Since October 2009, the authors have prospectively performed LESS retroperitoneal adrenalectomy for 21 consecutive patients with benign adrenal tumors (LESS group). Another 28 patients with benign adrenal tumors were prospectively collected between June 2006 and October 2009 and served as a multiport laparoscopic adrenalectomy group. The patients' demographic data, operating time, estimated blood loss, peri- and postoperative complications, and short-term outcome were collected for further analysis. The demographic data were comparable between the two groups in terms of the patient age, gender, body mass index (BMI), laterality, diagnosis, and resected specimen weight. No major complication or mortality occurred in either group. Neither group had any conversions. No differences were observed between the two groups in terms of intraoperative hemodynamic status or peri- or postoperative complications. The LESS patients had quicker resumption of oral intake (0.18 vs 1 day; p < 0.001), a shorter hospital stay (2 vs 4 days; p < 0.001), and a reduced analgesic requirement postoperatively (0 vs 0.84 mg/kg; p = 0.023) than the multiport laparoscopic patients. The results demonstrate that LESS adrenalectomy is as safe and effective as conventional multiport laparoscopic adrenalectomy for benign adrenal tumors. In addition, LESS adrenalectomy provides short-term convalescence advantages over multiport laparoscopic adrenalectomy.


Action of gonadotropin-releasing hormone II on the baboon ovary.
The content, binding affinity, and bioactivity of chicken II GnRH (GnRH II) and a stable analogue of GnRH II (GnRH II analogue) in the baboon ovary were studied. Although mammalian GnRH is rapidly degraded by baboon ovarian extracts, we designed a GnRH II analogue that is stable to ovarian enzymatic degradation. This analogue binds to the ovarian membranes with high affinity (41 +/- 3 nM), having 20-fold the affinity of a potent mammalian GnRH analogue. The bioactivity of GnRH II and this GnRH II analogue on the regulation of ovarian progesterone release was compared with that for a potent mammalian GnRH analogue using a baboon granulosa cell culture system. Both GnRH II and GnRH II analogue produced significant inhibition of progesterone release from the granulosa cells (P < 0.03 and P < 0.005, respectively), with a greater reduction observed using the GnRH II analogue. After 24 h in culture, this GnRH II analogue produced a 59% +/- 5% inhibition of progesterone with a concentration as low as 1 nM. Maximal inhibition of 75% +/- 1% was attained with 10 nM GnRH II analogue. The endogenous GnRH II content in the baboon ovary was 5-14 pmoles/g protein. The release of endogenous GnRH II from granulosa cells was observed throughout the 48 h in culture. These studies demonstrated the presence of high enzymatic activity for the degradation of mammalian GnRH in the ovary, whereas this GnRH II analogue was stable. High-affinity binding sites for this GnRH II analogue were also found. GnRH II and this GnRH II analogue can regulate progesterone production from baboon granulosa cells, suggesting that GnRH II is a potent regulator of ovarian function.


First-time urea breath tests performed at home by 36,629 patients: a study of Helicobacter pylori prevalence in primary care.
The aim of the current study was (1) to describe the use of a (13) C-urea breath test (UBT) that was performed by patients at their homes as a part of a test-and-treat strategy in primary care and (2) to investigate the prevalence of Helicobacter pylori in patients taking a first-time UBT. The patients performed UBTs at home based on the discretion of the general practitioner and mailed the breath bags to a central laboratory for analysis. Each patient was identified by a unique civil registration number. The study was population-based, and the background population was approximately 700,000 people. From 2003 to 2009, 44,487 UBTs were performed. Of these, 36,629 were first-time UBTs. In total, 726 of 45,213 breath bags received (1.6%) were unable to be analyzed because of errors with the bags. For both women and men who were ≤ 45 years of age, positive H. pylori declined over the time course of the study (women: 19.6% in 2003 to 17.6% in 2009, p < .01; men: 20.7% in 2003 to 16.9% in 2009, p < .001). Patients who were older than 45 years had significantly higher positive H. pylori results than younger patients. A test-and-treat system was possible to implement that allowed patients to perform UBTs at their homes. The results of the first-time UBTs demonstrated that approximately one of five patients who presented with dyspepsia in the clinical setting of Danish primary care was infected with H. pylori.


Severity of Depressive Symptoms and Volume of Superior Temporal Gyrus in People Who Visit a Memory Clinic Unaccompanied.
Depression and cognitive decline are reported to be interrelated. Depression of older adults with memory complaints who seek medical help have not been well documented. This study was carried out to test the hypothesis that a relatively high level of depressive symptoms associated with brain structure is characteristic of people who visited a memory clinic unaccompanied (UA). We retrospectively compared Center for Epidemiologic Studies Depression Scale (CES-D, for evaluation of depressive symptoms) scores of UA subjects (n = 21) with those of people who were accompanied (n = 75). Within each groups, we further examined the association between brain morphology and the CES-D scores using FreeSurfer software. We found that the relatively high CES-D scores of UA subjects were inversely associated with the normalized volumes of bilateral superior temporal gyrus (STG). Our results suggest that depressive symptoms of UA subjects demonstrated by the relatively high levels of CES-D scores were primary, because of the inverse association with the normalized volume of bilateral STG. Thus, focusing on the depressive symptoms may be a suitable approach to satisfy potential medical needs of UA subjects with or without memory impairment.


Analysis of the mechanism of isoniazid-induced developmental toxicity with frog embryo teratogenesis assay: Xenopus (FETAX).
The developmental toxicity of isoniazid (INH) and the metabolites acetylhydrazide (AH) and isonicotinic acid (INA) were examined with the frog embryo teratogenesis assay-Xenopus (FETAX). Late Xenopus laevis blastulae were exposed to INH, AH, and INA for 96 h in two separate static-renewal tests with and without the presence of three differently induced metabolic activation systems (MAS). The MAS consisted of uninduced, Aroclor 1254-induced, and INH-induced rat liver microsomes. Addition of the INH-induced MAS decreased the 96 h LC50 of INH and AH approximately 1.6-fold and 7.9-fold, respectively. The 96 h EC50 (malformation) of INH was virtually unaffected; however, the INH-MAS decreased the teratogenic index (TI) [96 h LC50/96 h EC50 (malformation)] nearly 1.8-fold. The 96 h EC50 (malformation) of AH increased approximately 2.0-fold, decreasing the teratogenic index value 15.8-fold. INA yielded a teratogenic index value of 2.5. Neither the uninduced MAS nor the Aroclor 1254-induced MAS had an effect on any of the compounds tested and none of the MAS affected the developmental toxicity of INA. Results from this study suggest that mixed functional oxidase metabolism may alter the developmental toxicity of INH in vitro by producing a more embryolethal, but less teratogenic metabolite(s) than INH or AH themselves. Results are indicative of the utility and versatility of FETAX in evaluating toxicological mechanisms of teratogenesis in vitro.


Plasmid R16 ArdA protein preferentially targets restriction activity of the type I restriction-modification system EcoKI.
The ArdA antirestriction protein of the IncB plasmid R16 selectively inhibited the restriction activity of EcoKI, leaving significant levels of modification activity under conditions in which restriction was almost completely prevented. The results are consistent with the hypothesis that ArdA functions in bacterial conjugation to allow an unmodified plasmid to evade restriction in the recipient bacterium and yet acquire cognate modification.


MAGE A1-A6 RT-PCR and MAGE A3 and p16 methylation analysis in induced sputum from patients with lung cancer and non-malignant lung diseases.
The melanoma antigen gene (MAGE) A1-A6 RT-PCR system was developed for the detection of lung cancer cells in the sputum. However, we identified MAGE expression in some patients with non-malignant lung diseases. To understand these patterns of MAGE expression, we performed MAGE A3 methylation-specific PCR (MSP) and p16 MSP. We collected 24 biopsy specimens of lung cancer tissue and performed MAGE A1-A6 RT-PCR, MAGE A3 MSP and p16 MSP. RNA and DNA were simultaneously extracted from induced sputum specimens of 133 patients with lung diseases and 30 random sputum specimens of healthy individuals and the 3 molecular analyses were performed. The patients were diagnosed as 65 cases of lung cancer and 68 of benign lung diseases. Positive rates of MAGE A1-A6 RT-PCR, MAGE A3 MSP and p16 MSP were as follows: in lung cancer tissue, 87.5, 58.3 and 70.8%; in the sputum of lung cancer patients, 50.8, 46.2 and 63.1%; benign lung diseases, 10.3, 30.9 and 39.7%; and healthy individuals, 3.3, 6.7 and 3.3%. Of the 40 MAGE-positive cases, 33 were diagnosed with lung cancer and 7 as having benign lung diseases. From the 7 cases of MAGE-positive benign lung diseases, 6 cases showed methylation abnormalities. The MAGE-positive group revealed significantly higher rates of methylation abnormalities. Of the 40 MAGE-positive cases, 39 cases were found to be lung cancer or benign lung diseases with abnormal methylation. Thus, MAGE expression in the sputum suggests the presence of lung cancer cells or pre-cancerous cells.


Explicit general eigenvalue solutions for dielectric slab waveguides.
A formula is developed for dielectric slab waveguides that yields general solutions of the TE eigenmode propagation constants as explicit functions of a composite independent variable involving the guide layer thickness, operating wavelength, and refractive indexes of guide and cladding media. This provides a convenient means for circumventing the transcendental eigenvalue equations. The maximum error is less than 0.6%. A method for deriving the corresponding TM eigenvalues with an accuracy of about 99% or better is shown.


An Effective Route to Dinuclear Niobium and Tantalum Imido Complexes.
Thermal treatment of the trichloro complexes [MCl3(NR)py2] (R = tBu, Xyl; M = Nb, Ta) (Xyl = 2,6-Me2C6H3) under vacuum affords the dinuclear imido species [MCl2(μ-Cl)(NR)py]2 (R = tBu, Xyl; M = Nb 1, 3; Ta 2, 4) with loss of pyridine. Complexes 1-4 can be easily transformed to the mononuclear starting materials [MCl3(NR)py2] (R = tBu, Xyl; M = Nb, Ta) upon reaction with pyridine. While reactions of compounds 1 and 2 with a series of alkylating reagents render the mononuclear peralkylated imido complexes [MR3(NtBu)] (R = Me, CH2Ph, CH2CMe3, CH2CMePh, CH2SiMe3), the analogous treatment with allylmagnesium chloride results in the formation of the dinuclear niobium(IV) derivative [(NtBu)(η3-C3H5)M(μ-C3H5)(μ-Cl)2M(NtBu)py2] (5). Additionally, the treatment of the starting materials 1 and 2 with the organosilicon reductant 1,4-bis(trimethylsilyl)-1,4-diaza-2,5-cyclohexadiene yields the pyridyl-bridged dinuclear derivatives [M2Cl2(μ-Cl)2(NtBu)2py2]2(μ-NC4H4N)2 (M = Nb 6, Ta 7). Controlled hydrolysis reaction of 1 and 2 affords the oxo chlorido-bridged products [MCl(μ-Cl)(NtBu)py]2(μ-O) (M = Nb 8, Ta 9) in a quantitative way, while the treatment of these latter with one more equivalent of pyridine led to complexes [MCl2(NtBu)py2]2(μ-O) (M = Nb 10, Ta 11). Structural study of these dinuclear imido derivatives has been also performed by X-ray crystallography.


Adherence to diabetes control recommendations: impact of nurse telephone calls.
Type 2 diabetes mellitus is increasing in incidence and research has shown that normalization of blood glucose levels can moderate the risk of microvascular and neurological complications. The purpose of this study was to investigate the effect of nurse telephone calls on glycosylated haemoglobin (HbA1c) levels and adherence to diabetes control recommendations. A randomized design with control and experimental groups being assessed pre- and post intervention was used to assess the effectiveness of nurse telephone calls. Twenty patients were randomly assigned to an intervention group and 16 to a control group. The goal of the intervention was to keep blood glucose concentrations close to the normal range (HbA1c < 7%). The intervention was applied to the intervention group for 12 weeks, and consisted of continued education and reinforcement of diet, exercise, medication adjustment recommendations, as well as frequent self-monitoring of blood glucose levels. Telephone intervention was performed twice per week for the first month and then weekly for the second and third month. Participants were requested to write self-management logs including blood glucose levels, diet and an exercise diary. A dietitian analysed the diet diaries and participants were informed about their results by telephone or mail. All medication adjustments were communicated to participants' doctors. The HbA1c and diabetes adherence were measured before and after the intervention. Patients in the intervention group had a mean decrease of 1.2% in HbA1c levels and those in the control group had a mean increase of 0.6% in HbA1c levels. The intervention group had greater diet and blood glucose testing adherence than the control group. These findings indicate that a nurse telephone intervention can improve HbA1c, and diet and blood glucose testing adherence.


Can a single session of a community-based group exercise program combining step aerobics and bodyweight resistance exercise acutely reduce blood pressure?
This study aimed to analyze the acute effects of a single session of a community-based group exercise program combining step aerobics and bodyweight resistance exercise on blood pressure in healthy young adult women. Twenty-three healthy young adult women (aged 31.57 ± 7.87 years) participated in two experimental sessions (exercise and control) in a crossover study design. Blood pressure was monitored before, immediately after and at 10, 20 and 30 min of recovery. The exercise session consisted of four phases: 1) a warm-up (5 min of dance aerobics); 2) aerobic exercise training (30 min of step aerobics); 3) resistance exercise training (six sets of 12 repetitions of three bodyweight exercises in a circuit mode, 10 min); and 4) a cool-down (5 min of breathing and flexibility exercises); totaling 50 min of duration. Systolic blood pressure after exercise was significantly lower compared to control at the 10th min (-10.83 ± 2.13 vs. -2.6 ± 2.13 mmHg; p = 0.009), 20th min (-11.26 ± 2.13 vs. -3.04 ± 2.13 mmHg; p = 0.009) and 30th min of recovery (-10.87 ± 2.39 vs. -0.48 ± 2.39 mmHg; p = 0.004). A single session of a community-based group exercise program combining step aerobics and bodyweight resistance exercise was effective in inducing significant post-exercise hypotension in healthy young adult women. This type of low-cost exercise interventions may have an important role in the prevention of cardiovascular diseases and in community health promotion.


Early gastric cancer with signet ring cell histology remained unresected for 53 months.
The natural course of untreated patients with signet ring cell carcinoma of the stomach remains poorly understood while assumptions have been made to distinguish it from other types of gastric cancer. A 74-year-old Korean woman was diagnosed with early gastric cancer with signet ring cell histology and refused surgery. A satellite lesion was identified 46 months after the initial diagnosis. The patient finally agreed to undergo distal subtotal gastrectomy 53 months following the initial diagnosis. Postoperative histological examination of both lesions confirmed signet ring cell carcinoma associated with submucosal invasion. There was no evidence of lymph node metastasis.


Regulation of alternative pre-mRNA splicing by a novel repeated hexanucleotide element.
The alternatively spliced exon EIIIB is regulated in a cell type-specific manner in the rat fibronectin gene. Splicing of EIIIB into fibronectin mRNA is dependent on sequences in the intron immediately downstream of EIIIB. We show that a short, highly repeated TGCATG motif in this intron is important for cell type-specific recognition of EIIIB as an exon. This motif enhances usage of the EIIIB 5' splice site; furthermore, this repeated TGCATG sequence can activate an alternatively spliced exon in the unrelated rat preprotachykinin pre-mRNA. Interestingly, this sequence can also be found within cis-acting elements identified previously in other alternatively spliced genes. This short repeated TGCATG motif is therefore a cell type-specific element that, in addition to controlling fibronectin alternative splicing, may participate in the regulation of other alternative RNA processing events.


Gastrointestinal Gas and Abdominal Fat Quantity Measured by Three-Dimensional Abdominal Computed Tomography in Patients with Functional Bloating.
The aim of this study was to assess whether increased intestinal gas or fat content in the abdominal cavity is related to abdominal bloating, using three-dimensional abdominal computed tomography scan. Twenty-nine healthy individuals without abdominal bloating and organic disease (15 women; mean age, 49 years; range of age, 23-73 years) and 30 patients with chronic recurrent abdominal bloating-diagnosed with functional bloating (10 women; mean age, 53 years; range of age, 35-75 years) - participated in this study. The mean values of measured parameters were compared using independent sample t-test. The mean volume of total colon gas in bloated patients was similar to that in control subjects. The distribution of intra-abdominal gas was also similar between the two groups. However, the amount of gas in the transverse colon tended to be significantly higher in patients with bloating than in controls (p=0.06). Body mass index was similar between the two groups (23.4±3.2 kg/m2 and 22.3±3.1 kg/m2, respectively). Moreover, no significant differences with respect to circumferential area, subcutaneous fat, visceral fat area, and total fat area were found between the two groups. Bloating might not just be the result of gastrointestinal gas or intra-abdominal fat. Other contributing factors, such as localized abnormality in gas distribution and visceral hypersensitivity, may be involved.


Electrorheology of nanofiber suspensions.
Electrorheological (ER) fluid, which can be transformed rapidly from a fluid-like state to a solid-like state under an external electric field, is considered to be one of the most important smart fluids. However, conventional ER fluids based on microparticles are subjected to challenges in practical applications due to the lack of versatile performances. Recent researches of using nanoparticles as the dispersal phase have led to new interest in the development of non-conventional ER fluids with improved performances. In this review, we especially focus on the recent researches on electrorheology of various nanofiber-based suspensions, including inorganic, organic, and inorganic/organic composite nanofibers. Our goal is to highlight the advantages of using anisotropic nanostructured materials as dispersal phases to improve ER performances.


Attorney attitudes regarding behaviors associated with child sexual abuse.
There appears to be a good deal of disagreement between professionals as to what constitutes child abuse. Attorneys as a group have been found to judge behaviors associated with child abuse more leniently than other abuse professionals. However, no one has discriminated between defense and prosecuting attorneys in these areas. It was hypothesized that because of divergent roles in child sexual abuse cases attitudes toward adult-child behaviors associated with sexual abuse would differ among attorney groups. Two prosecuting and two defense attorneys from every county in the state of Indiana were sent questionnaires. Participants were asked to indicate if a behavior was acceptable, inappropriate, or sexual abuse if it occurred on one or on multiple occasions. Prosecutors had more severe judgements than the defense attorneys on 32 of the 42 behaviors. They were more likely to indicate that a behavior was inappropriate or abuse. Cognitive dissonance theory is proposed as a possible explanation for these findings.


Ideal body weight in children.
There is no clear consensus on the correct definition of ideal body weight (IBW) in children or on the best method used to calculate IBW. There are at least 3 ways of obtaining IBW in children. They are (1) the McLaren method, (2) the Moore method, and (3) the body mass index method. In children under the age of 8 years, all of these methods provide relatively similar results across all percentiles. In older children, especially at the lowest and highest percentiles, the different methods provide widely disparate results for IBW. It is important to be consistent in the method used as the different methods will provide different results for IBW.


Comparison of the Bioactive Components in Two Seeds of Ziziphus Species by Different Analytical Approaches Combined with Chemometrics.
The Ziziphus species are considered to be the medicine and food dual purposes plants. Among them, the seed of Ziziphus jujuba var. spinosa (ZS) has traditionally been used as an ethnomedicine in Asian countries for thousands years. Owing to the significant benefits for human health, the demand for ZS increased year by year, and the wild resources have become increasingly scarce, which resulted in a shortage of market supply for ZS and product adulteration by substituting ZS with the seeds of Z. mauritiana Lam. (ZM). However, whether the bioactivity of ZM is similar to ZS has not been fully confirmed till now. Thus, to provide potential information for evaluating the similarity of the health promoting activities between these two Ziziphus seeds, their chemical profiles, including triterpenoids, flavonoids, nucleosides, free amino acids and fatty acids were compared using high-performance liquid chromatography coupled with evaporative light scattering detection (HPLC-ELSD), ultra-high performance liquid chromatography coupled with triple-quadrupole mass spectrometry (UHPLC-TQ MS), and gas chromatography coupled with mass spectrometry (GC-MS) methods. Furthermore, a more holistic investigation was performed with multivariate principle component analysis and orthogonal projections to latent structures-discriminant analysis analyses to explore the relative variability between the seeds of two species. The results showed that a significant difference exists between ZS and ZM, and ZS was more rich in saponins, polyunsaturated fatty acids and some amino acids, whereas ZM was particularly rich in saturated fatty acids and flavonoids. The above results suggested the bioactivities of ZM for human health may not be similar to ZS owing to their difference in chemical profiles. These results would also be helpful for distinguishing the ZM from ZS with the chemical markers obtained from the study, and set a scientific foundation for establishing the quality control method of ZS.


Effects of simvastatin on the expression of inducible nitric oxide synthase and brain-derived neurotrophic factor in a lipopolysaccharide-induced rat model of Parkinson disease.
To investigate the effects of simvastatin on the expression of inducible nitric oxide synthase (iNOS) and brain-derived neurotrophic factor (BDNF) in the substantia nigra in a lipopolysaccharide (LPS)-induced rat model of Parkinson disease (PD), and to study the mechanisms underlying the neuroprotective effects of simvastatin in PD. The LPS-PD model was established by injection of LPS (5 mg/mL, 2.0 μL) into the right substantia nigra compacta (SNC). Rats in the sham-operated group received saline. The simvastatin treatment group was intraperitoneally administered simvastatin (5 mg/kg, 2.0 μL) at 1 h before, and daily for 14 days after surgery, while the sham-operated and LPS-model groups received saline. Iba-1-positive cells and tyrosine hydroxylase (TH), as well as iNOS and BDNF in the SNC were detected by immunohistochemistry and Western blotting, respectively. The effect of simvastatin in the PD model was also examined in behavioral tests. The LPS-model group exhibited typical animal PD behaviors. Compared with the control group, the LPS-model group exhibited a decreased number of DA neurons (p < 0.01) in the SNC, as well as increases in the Iba-1-positive cell number and iNOS expression (p < 0.05), while BDNF expression was downregulated (p < 0.01). These effects were inhibited by simvastatin treatment (p < 0.05). Simvastatin mediates a protective effect on dopaminergic neurons in the SNC in the LPS-PD model, possibly by promoting neuronal repair and regeneration, and by inhibiting oxidative stress, thus improving substantia nigra function.


Indium-111-labelled human platelets: a method for use in severe thrombocytopenia.
We describe and evaluate a simple method for labelling autologous human platelets with Indium-111-oxine in patients with severe thrombocytopenia. Twenty patients with immune thrombocytopenia and platelet counts ranging from 5 to 119 X 10(9)/1 were investigated. Platelets were isolated from blood by differential centrifugation, residual platelets were repeatedly washed from the red cell layer and buffy coat and labelled with In 111 in saline. A mean of 55% +/- 21 of platelets were harvested from the blood, labelled with 49% +/- 24 efficiency and 15.8 X 10(8) labelled platelets reinjected to the patients. Contamination of the platelets with red cells and plasma was low. The labelled platelets were viable as assessed by in vitro aggregation, recovery in the circulation and mean survival time. This method permits quantitative platelet imaging with autologous labelled platelets in patients with severe thrombocytopenia.


Current Predictive Indices and Nomograms To Enable Personalization of Radiation Therapy for Patients With Secondary Malignant Neoplasms of the Central Nervous System: A Review.
The proper treatment of brain metastases continues to be a challenge for oncologists given the variability of individual patients' prognoses and the variety of treatment options available to address brain metasteses. There have been efforts since the 1990s to develop prognostic indices and nomograms to help clinicians determine the best approach for individuals with secondary malignant neoplasms of the central nervous system. A literature search was performed to identify the existing prognostic tools published between January 1995 and January 2017. While there have been several reported indices, many are limited by the number of patients analyzed or lack of generalizability. The most robust prognostic tools available are the Disease Specific Graded Prognostic Assessment and the Barnholtz-Sloan nomogram, both of which have online tools available to help clinicians. While these tools are helpful in stratifying different patients' outcomes, they are limited by their retrospective nature and likely underestimate survival in the modern era, where there is a rapidly growing arsenal of systemic agents available to patients with metastatic disease.


Histopathologic features predictive of perivascular deposition of IgA on direct immunofluorescence in cases of leukocytoclastic vasculitis: A retrospective study of 112 specimens.
IgA vasculitis is a small-vessel vasculitis subtype with increased risk of systemic involvement. We aimed to investigate if any light-microscopic features can predict the presence of perivascular granular IgA deposits on direct immunofluorescence (DIF) microscopy. We performed a retrospective search of cutaneous pathology reports from our internal and consultation practice (January 1, 2010-October 5, 2021) with a diagnosis of leukocytoclastic vasculitis and accompanying DIF. A blinded dermatopathologist reviewed standard microscopy slides for predetermined histopathological features. Fifty-six biopsies (48 patients) and 56 biopsies (42 patients) met inclusion criteria for IgA+ and IgA-, respectively. The presence of eosinophils and mid and deep dermal inflammation were statistically more associated with IgA- (41/56 [73.2%] and 31/56 [55.4%], respectively) than IgA+ cases (28/56 [50.0%] and 14/56 [25.0%]; p = 0.049 and 0.006, respectively, chi-squared test). Other microscopic criteria recorded were not significantly different between the two groups (p > 0.05, chi-squared and Fisher's exact tests). In this retrospective study of 112 cases, we found that while the absence of eosinophils and absence of mid- and deep inflammation were correlated with increased likelihood of IgA perivascular deposition on DIF, no other histopathological features on light microscopy tested could reliably predict the presence of IgA perivascular deposition on DIF. Therefore, DIF remains a necessary component for the accurate diagnosis of cutaneous IgA vasculitis.


Effects of Blank Quality on Press-Formed PEKK/Carbon Composite Parts.
The causes of delamination and porosities during press forming of pre-consolidated flat laminates (blanks) made of carbon fiber-reinforced poly(ether ketone ketone) (PEKK) were addressed in this study. In particular, the quality of the blank laminate was investigated before and after infrared heating. The consolidation quality was evaluated by thickness measurements, non-destructive inspection (NDI), and optical microscopy. The experimental results confirmed that deconsolidation phenomena can be related to residual stresses formed during blank forming in an autoclave, then released during infrared heating (IR) of the blank, determining most of the defects in IR heated blanks. These defects, generated at the pre-heating stage, were not fully removed in the consolidation stage of the press forming process. An annealing treatment, performed on autoclave-consolidated blanks above the glass transition temperature of the matrix, was proposed to reduce the formation of defects during IR heating. The stress relaxation phenomena during annealing were modelled using a simple viscoelastic model.


Occam's razor cuts out the mind-body dichotomy.
Psychiatric symptoms are among the most common manifestations of endocrine disorders. We present a case of Schmidt's syndrome, or polyglandular type II failure. Due to a florid psychiatric presentation, the initial endocrine diagnosis was missed, and a diagnosis of a nonorganic psychotic illness was made. This impacted on the treatment and appropriate placement of the patient. This case is presented to illustrate the importance of the organic work-up and follow-up on abnormal laboratory results in patients with dementia. In the elderly, a new onset of psychosis is usually associated with an organic cause. Furthermore, the presence of either a fixed or intermittent change in cognitive function suggests a strong likelihood of organicity. These features were present, but not noted, leading to management problems that are described here to illustrate the need for careful clinical scrutiny.


Multiple instance learning of Calmodulin binding sites.
Calmodulin (CaM) is a ubiquitously conserved protein that acts as a calcium sensor, and interacts with a large number of proteins. Detection of CaM binding proteins and their interaction sites experimentally requires a significant effort, so accurate methods for their prediction are important. We present a novel algorithm (MI-1 SVM) for binding site prediction and evaluate its performance on a set of CaM-binding proteins extracted from the Calmodulin Target Database. Our approach directly models the problem of binding site prediction as a large-margin classification problem, and is able to take into account uncertainty in binding site location. We show that the proposed algorithm performs better than the standard SVM formulation, and illustrate its ability to recover known CaM binding motifs. A highly accurate cascaded classification approach using the proposed binding site prediction method to predict CaM binding proteins in Arabidopsis thaliana is also presented. Matlab code for training MI-1 SVM and the cascaded classification approach is available on request. email@example.com or email@example.com.


CD95 antigen mutations in hematopoietic malignancies.
The CD95 receptor, also known as Fas/Apo-1, is a member of the Tumor Necrosis Factor receptor (TNF-R) family of death receptors. Apoptosis mediated by CD95 plays a central role in maintaining homeostasis of the immune system. Dysregulation of the CD95 apoptotic pathway has been proposed as a mechanism of oncogenesis by providing a survival advantage to potentially malignant cells. This extended lifespan could allow the accumulation of further mutations leading to malignant transformation. Several mechanisms of resistance to CD95 mediated apoptosis have been identified, including reduced surface expression of the receptor, overexpression of anti-apoptotic molecules, and loss of function mutations. This review will focus on the potential role of the CD95-CD95 ligand system in the pathogenesis of hematological malignancies, with particular emphasis on recent work from our laboratory examining the expression of CD95 in B cell lymphomas. We demonstrate that CD95 mutations occur at low frequency in NHL tumors, however, surface expression of the CD95 protein varies with the subtype of lymphoma. Loss of surface CD95 is more likely to occur in lymphomas of aggressive histology, and is unrelated to the detection of CD95 mutations.


[Possibilities of remission of acute lymphoblastic leukemia in adults: retrospective study of 51 patients subjected to a "total therapy" protocol in the period 1969-1983].
Between 1969 and 1983, 51 (35 men and 16 women) new cases of acute lymphoblastic leukemia (ALL) were diagnosed in patients aged 15 to 85 years (mean 21 yrs.). All patients received a "total therapy" which included: 1st induction (PRD, VCR, DBR, and/or L-ASN); 2nd, Central Nervous System profilaxis (craneal TCT and/or intrathecal MTx); 3rd, maintenance (6MP and MTx) and 4th, reinductions every 3 months (PRD, VCR, and DRB). This treatment lasted for at least 3 years. Complete Remission (CR) was achieved in 45 patients (88.2%): 3 of these patients were referred to other centers to continue treatment, 1 patient developed an early "metamorphosis" to hemophagocytic hystiocytosis and another patient developed a late chronic granulocytic leukemia (Ph +) dying a few months later after an acute myeloblastic worsening. During treatment 16 patients relapsed (9 in bone marrow and 7 in Central Nervous System). Treatment was discontinued in 24 patients with complete remission of which 5 relapsed in bone marrow 17 to 61 months after treatment). In one of the latter (ALL Ph +) an allogenic bone marrow transplant was performed and CR was achieved and maintained 46 months later. The post diagnosis acutarial curve of the 51 patients gave a mean survival of 6 years with a plateau at 43% of the patients after 11 years. The duration of the first uninterrupted CR was of 6.5 years and a plateau was reached at 46% of the patients after 10.5 years. At the present time, 20 patients are in CR (46 to 129 months) without treatment.(ABSTRACT TRUNCATED AT 250 WORDS)


Multi-Responsive Supramolecular Gels Based on Charge Transfer Interactions.
We report the co-assembly of aromatic donor (D) and acceptor (A) molecules into purple sponge-like supramolecular gels through susceptible charge transfer interactions with the aid of solvophobic interactions. The gel remained intact with the addition of up to 23 % (v/v) of nonpolar good solvents, such as toluene and xylene, but dissociated in the presence of <2 % (v/v) of polar solvents, such as tetrahydrofuran, ethyl acetate, and alcohols, with highly distinguishable changes of color. Notably, the gel dissolved within 1 min and the solution turned blue when 0.1 % (v/v) of methanol was added. The response to trifluoroacetic acid was extremely sensitive (i.e., the gel vanished immediately in the presence of 2 equivalents of trifluoroacetic acid), and the subsequent addition of trimethylamine could recover the purple gel. The multiple and visible response thus render the D-A gels as a potential detector for sensing complex chemical environments.


Efficacy and safety of Mydriatic Microdrops for Retinopathy Of Prematurity Screening (MyMiROPS): study protocol for a non-inferiority crossover randomized controlled trial.
Retinopathy of prematurity (ROP) eye examination screening presupposes adequate mydriasis for an informative fundoscopy of preterm infants at risk, on a weekly basis. Systemic absorption of the instilled mydriatic regimens has been associated with various adverse events in this fragile population. This report aims to present the fully developed protocol of a full-scale trial for testing the hypothesis that the reduced mydriatic drop volume achieves adequate mydriasis while minimizing systemic adverse events. A non-inferiority crossover randomized controlled trial will be performed to study the efficacy and safety of combined phenylephrine 1.67% and tropicamide 0.33% microdrops compared with standard drops in a total of 93 preterm infants requiring ROP screening. Primary outcome will be the pupil diameter at 45 (T45) min after instillation. Pupil diameter at T90 and T120 will constitute secondary efficacy endpoints. Mixed-effects linear regression models will be developed, and the 95% confidence interval approach will be used for assessing non-inferiority. Whole blood samples will be analyzed using hydrophilic liquid chromatography-tandem mass spectrometry method (HILIC-MS/MS), for gathering pharmacokinetic (PK) data on the instilled phenylephrine, at nine specific time points within 3 h from mydriasis. Pooled PK data will be used due to ethical restrictions on having a full PK profile per infant. Heart rate, oxygen saturation, blood pressure measurements, and 48-h adverse events will also be recorded. This protocol is designed for a study powered to assess non-inferiority of microdrops compared with standard dilating drops. If our hypothesis is confirmed, microdrops may become a useful tool in ROP screening. ClinicalTrials.gov NCT05043077 . Registered on 2 September 2021.


[In vitro parameters for understanding the immunocompetence of chickens of different lineage. 1. The cytotoxicity of avian whole blood against Saccharomyces cells].
A cytotoxicity test was performed as a parameter for the nonspecific defense capacity in chickens using blood and saccharomyces cells (SCT). The test has the special merit of frequent repetitions of the results by two parallel test arrangements. The results of individual animals were not altered during a period of 14 days, as well as relatively not being affected by actual day fluctuation as long as environmental changes or antigenic changes do not appear. The cytotoxic activity is due to cellular defense mechanisms, especially concerning the activity of granulocytes, thrombocytes and monocytes but not lymphocytes and erythrocytes. The lysozyme contents of plasma show a very space cytotoxic activity against saccharomyces cells.


High-resolution remote sensing-based spatial modeling for the prediction of potential risk areas of schistosomiasis in the Dongting Lake area, China.
The geographical distribution of snail (i.e., the intermediate host of schistosomiasis) is consistent with that of endemic areas. The suitable snail habitus requires necessary environmental conditions for snail population. The high-resolution remote sensing provides an important tool for the spatio-temporal analysis of disease monitoring and prediction. This study conducted a typical schistosomiasis epidemic area in the marshland and lake regions along the Yangtze River, Yueyang City, Hunan Province of China. And three types of environmental factors, i.e., NDVI, soil moisture, and shortest distance to water body, associated with the geographical distribution of snail population, were extracted from the high-resolution remoting sensing data. The predicted distribution of snail habitus from the high-resolution environmental factors were compared with the data of annual program of snail survey. The results have shown that the application of high-resolution remote sensing can improve the accuracy of the modeled and predicted the potential risk areas of schistosomiasis, and may become an important tool for the ongoing national schistosomiasis control program.


Protective effect of Tongdu Tiaoshen acupuncture combined with Xiaoxuming decoction on dopaminergic neurons in Parkinson's disease model.
To explore the possible mechanism of Tongdu Tiaoshen acupuncture combined with Xiaoxuming decoction (, XXMD) in the treatment of Parkinson's disease (PD). C57BL/6 mice were randomly divided into eight groups ( 12), including blank group, model group, medication group, acupuncture group, high-dose XXMD group (XXMD-H), low-dose XXMD group (XXMD-L), acupuncture combined with high-dose XXMD group (A+H), and acupuncture combined with low-dose XXMD group (A+L). After treatment for 6 weeks, dopamine (DA) neurons and the pathological changes of tyrosine hydroxylase (TH) positive cells were observed. The enzyme-linked immunosorbent assay (ELISA) was used to measure the content of DA and the level of interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-10 (IL-10) and tumor necrosis factor alpha (TNF-α). The mRNA level of PINK1 and Parkin and the protein expression of Nix, PINK1 and Parkin in the substantia nigra were also detected. Combination treatment effectively ameliorated the symptoms of PD. Compared with model group, combined treatment significantly up-regulated the protein expression of Nix, Parkin and PINK1 and the mRNA levels of PINK1 and Parkin in the substantia nigra (<0.0001, <0.001, <0.01 or <0.05). Furthermore, the levels of pro-inflammation cytokines were obviously decreased after combination therapy, while IL-10 content was increased remarkably (<0.01). Compared with each treatment alone, combination therapy improved the pathological damage of DA neurons of PD mice more effectively. The possible mechanism may be attributed to the up-regulated level of mitochondrial autophagy and improved mitochondrial function. These results provide fresh insight into the mechanism of co-treatment with Tongdu Tiaoshen acupuncture and XXMD for PD.


Impact of bone quality, implant type, and implantation site preparation on insertion torques of mini-implants used for orthodontic anchorage.
Mini-implants are widely used as skeletal anchorage in orthodontics. To reduce implant loss rate, sufficient primary stability is required. This study quantitatively analysed the impact of bone quality and pre-drilling diameter on the insertion torque of five different mini-implants. Twenty pig bone segments were dissected and embedded in resin. The insertion torques of two different mini-implant types (Tomas Pin, Dentaurum, Germany, 8 and 10 mm; and Dual Top, Jeil, Korea, 1.6 mm × 8 and 10 mm plus 2 mm×10 mm) were measured. After preparation of the implant sites using pilot drill diameters 1.0, 1.1, 1.2 and 1.3mm, 30 implants were inserted into each bone segment. Five reference implants were inserted into each segment for comparison. Micro CT evaluated bone compacta thickness. Insertion moments of orthodontic mini-implants, and hence primary stability, varied strongly depending on compacta thickness, implant design, and pre-drilling at the implant site. The Dual Top consistently showed higher primary stability than the Tomas Pin. Insertion moments higher than 230 Nmm resulted in fractures in some cases. Compacta thickness, implant design and preparation of implant site affect the insertion torque of mini-implants for orthodontic anchorage. To avoid fractures and high bone stresses, optimum pre-drilling diameters should be chosen.


Methamphetamine and cocaine use among Mexican migrants in California: the California-Mexico Epidemiological Surveillance Pilot.
Methamphetamine and cocaine use have been associated with a vulnerability to HIV infection among men who have sex with men and among men who have sex with women but not specifically among Mexican migrants in the United States. The California-Mexico Epidemiological Surveillance Pilot was a venue-based targeted survey of male and female Mexican migrants living in rural and urban areas in California. Among men (n = 985), the percentage of methamphetamine/cocaine use in the past year was 21% overall, 20% in male work venues, 19% in community venues, and 25% in high-risk behavior venues. Among women, 17% reported methamphetamine/cocaine use in high-risk behavior venues. Among men, methamphetamine/cocaine use was significantly associated with age less than 35 years, having multiple sex partners, depressive symptoms, alcohol use, sexually transmitted infections (including HIV), and higher acculturation. Prevention interventions in this population should be targeted to specific migrant sites and should address alcohol, methamphetamine, and cocaine use in the context of underlying psychosocial and environmental factors.


The kappa-carrageenase of P. carrageenovora features a tunnel-shaped active site: a novel insight in the evolution of Clan-B glycoside hydrolases.
kappa-carrageenans are gel-forming, sulfated 1,3-alpha-1,4-beta-galactans from the cell walls of marine red algae. The kappa-carrageenase from the marine, gram-negative bacterium Pseudoalteromonas carrageenovora degrades kappa-carrageenan both in solution and in solid state by an endoprocessive mechanism. This beta-galactanase belongs to the clan-B of glycoside hydrolases. The structure of P. carrageenovora kappa-carrageenase has been solved to 1.54 A resolution by the multiwavelength anomalous diffraction (MAD) method, using a seleno-methionine-substituted form of the enzyme. The enzyme folds into a curved beta sandwich, with a tunnel-like active site cavity. Another remarkable characteristic is the presence of an arginine residue at subsite -1. The crystal structure of P. carrageenovora kappa-carrageenase is the first three-dimensional structure of a carrageenase. Its tunnel-shaped active site, the first to be reported for enzymes other than cellulases, suggests that such tunnels are associated with the degradation of solid polysaccharides. Clan-B glycoside hydrolases fall into two subgroups, one with catalytic machinery held by an ancestral beta bulge, and the other in which it is held by a regular beta strand. At subsite -1, all of these hydrolases exhibit an aromatic amino acid that interacts with the hexopyranose ring of the monosaccharide undergoing catalysis. In addition, in kappa-carrageenases, an arginine residue recognizes the sulfate-ester substituents of the beta-linked kappa-carrageenan monomers. It also appears that, in addition to the nucleophile and acid/base catalysts, two other amino acids are involved with the catalytic cycle, accelerating the deglycosylation step.


Effects of stimulant medications on the EEG of children with attention-deficit/hyperactivity disorder.
Stimulant medications are the most commonly used treatments for attention deficit/hyperactivity disorder (ADHD) in North America and Australia, although it is still not entirely known how these medications work. This study aimed to investigate the effects of stimulant medications on the EEG of children with the Combined subtype of ADHD. An initial EEG was recorded during an eyes-closed resting condition and Fourier transformed to provide absolute and relative power estimates for the delta, theta, alpha and beta bands. Theta/alpha and theta/beta ratios were also calculated. Subjects were placed on a 6-month trial of a stimulant and a second EEG was recorded at the end of the trial. The ADHD group had significantly greater absolute delta and theta, less posterior absolute beta, more relative theta, and less relative alpha than the control group, which is typical of EEG studies of children with ADHD. The use of stimulant medications resulted in normalisation of the EEG, primarily evident in changes in the theta and beta bands. These results suggest that stimulants act to increase cortical arousal in children with ADHD, normalising their brain activity.


An assay for O6-alkylguanine-DNA alkyltransferase based on restriction endonuclease inhibition and magnetic bead separation of products.
We describe an improved, rapid and cost effective assay for measuring O6-alkylguanine-DNA alkyltransferase (AGT) levels in large numbers of small biological samples. The assay is based on the use of a synthetic O6-methylguanine oligonucleotide bound to magnetic beads via a biotin-streptavidin linkage and bound to its complement. A 35S label is incorporated into the free end of the duplex. The basis of the assay lies in the observation that the restriction enzyme PvuII will not cleave the bead-bound duplex oligonucleotide having an O6-methylguanine within the restriction sequence. However, on removal of the methyl group by AGT present in cell extracts prior to incubation with PvuII, the 35S-labelled oligonucleotide is cleaved by the restriction enzyme, releasing a 35S-labelled 8 bp fragment. Due to the stoichiometric nature of the AGT reaction, quantitation of AGT is easily achieved by counting an aliquot of the supernatant after pelleting the unrestricted bead complexes with a magnet. AGT levels measured in certain cell lines and human lymphocytes by the reported assay are comparable to other methods. The assay can be performed in basic laboratories and allows for the rapid processing of many samples simultaneously, which could prove useful in clinical and epidemiological studies.


Expression, crystallization and preliminary diffraction studies of the Pseudomonas putida cytochrome P450cam operon repressor CamR.
The Pseudomonas putida cam repressor (CamR) is a homodimeric protein that binds to the camO DNA operator to inhibit the transcription of the cytochrome P450cam operon camDCAB. CamR has two functional domains: a regulatory domain and a DNA-binding domain. The binding of the inducer D-camphor to the regulatory domain renders the DNA-binding domain unable to bind camO. Native CamR and its selenomethionyl derivative have been overproduced in Escherichia coli and purified. Native CamR was crystallized under the following conditions: (i) 12-14% PEG 4000, 50 mM Na PIPES, 0.1 M KCl, 1% glycerol pH 7.3 at 288 K with and without camphor and (ii) 1.6 M P(i), 50 mM Na PIPES, 2 mM camphor pH 6.7 at 278 K. The selenomethionyl derivative CamR did not crystallize under either of these conditions, but did crystallize using 12.5% PEG MME 550, 25 mM Na PIPES, 2.5 mM MgCl2 pH 7.3 at 298 K. Preliminary X-ray diffraction studies revealed the space group to be orthorhombic (P2(1)2(1)2), with unit-cell parameters a = 48.0, b = 73.3, c = 105.7 A. Native and selenomethionyl derivative data sets were collected to 3 A resolution at SPring-8 and the Photon Factory.


Fournier's gangrene: our experience in 5 years, bibliographic review and assessment of the Fournier's gangrene severity index.
Fournier's gangrene is a devastating infection, which includes the genital, perineal and/or perianal regions. It is potentially fatal, and affects any age and gender. The severity index for Fournier's gangrene has been described; it is useful for evaluating the prognosis of these patients. Our goal is to report our experience with this disease over the past 5 years and evaluate the index in retrospect. We analyzed medical records of patients with Fournier gangrene over the last 5 years at the University Hospital "Dr. José E. González". We reviewed 50 cases, male gender was predominant (96%), mean age 47.5 years, diabetes mellitus was found in 80%, neurogenic bladder in 10%, 2% HIV positive. The most frequent sites of origin of infection were scrotum (52%) and perineum (38%), the most common pathogen E. coli and Enterococcus faecalis (48 and 28% respectively). The death rate was 12%. The average severity index was 5.64. In our hospital, Fournier's gangrene is rare. Nevertheless, there is a rapid diagnosis protocol and therapeutic management is performed immediately. Until now, the immediate surgical treatment and early initiation of antibiotic therapy remains the best therapeutic option. There is a relationship between the index of severity and patient survival, which may become a useful parameter in evaluating these patients.


[Amiodarone treatment and visual prognosis].
Amiodarone is currently regarded as the most effective antiarrhythmic drug available for the treatment of tachyarrhythmias. Up to now, no recommendations exist concerning ophthalmological follow-up examinations at regular intervals of patients treated with amiodarone. We examined six patients with a mean age of 71.7 years (five men, one woman) who were treated with amiodarone. One patient had no visual disturbances and a second patient had no permanent change of the optic nerve because treatment with amiodarone was discontinued in time. In one patient an abnormal blue colour vision was noticed. Swelling of the optic disc completely disappeared in five patients after discontinuing the drug. One patient revealed a posterior ischaemic optic neuropathy (PION). In two patients a unilateral change of the optic disc occurred. In three patients a severe irreversible lesion of the optic nerve was found at follow-up examination. An insidious visual loss can occur with amiodarone treatment. A swelling of the optic disc without visual deterioration can occur as the first sign of a defect of the optic nerve. An abnormal blue colour vision can also be detected. After discontinuation of amiodarone either a visual improvement or a permanent deterioration may result. We recommend that every patient being treated with amiodarone should be observed by opthalmoscopy and colour vision examination at regular intervals (approximately every 3 months). Treatment with amiodarone should be discontinued after exclusion of life-threatening situations by a cardiologist, as soon as the first changes of the optic disc occur.


hACE2-Induced Allosteric Activation in SARS-CoV versus SARS-CoV-2 Spike Assemblies Revealed by Structural Dynamics.
SARS-CoV and SARS-CoV-2 cell entry begins when spike glycoprotein (S) docks with the human ACE2 (hACE2) receptor. While the two coronaviruses share a common receptor and architecture of S, they exhibit differences in interactions with hACE2 as well as differences in proteolytic processing of S that trigger the fusion machine. Understanding how those differences impact S activation is key to understand its function and viral pathogenesis. Here, we investigate hACE2-induced activation in SARS-CoV and SARS-CoV-2 S using hydrogen/deuterium-exchange mass spectrometry (HDX-MS). HDX-MS revealed differences in dynamics in unbound S, including open/closed conformational switching and D614G-induced S stability. Upon hACE2 binding, notable differences in transduction of allosteric changes were observed extending from the receptor binding domain to regions proximal to proteolytic cleavage sites and the fusion peptide. Furthermore, we report that dimeric hACE2, the native oligomeric form of the receptor, does not lead to any more pronounced structural effect in S compared to saturated monomeric hACE2 binding. These experiments provide mechanistic insights into receptor-induced activation of Sarbecovirus spike proteins.


Practical hints for hemostasis in laparoscopic surgery.
With the developments achieved in recent years in laparoscopic surgery, the field has acquired a host of new techniques to achieve haemostasis, allowing the surgeon to tackle complex procedures. These techniques include physical modalities (as simple as compression or suturing and as sophisticated as endovascular staples), thermal modalities (such as bipolar coagulation, laser or ultrasonic dissectors), and topical sealants (e.g. Fibrin glue or gelatine matrix). It is up to the laparoscopic surgeon to be familiar with all these different modalities and their proper use and limitations. It should also be kept in mind that the best approach to haemostasis in laparoscopy is prevention by thorough case preparation and meticulous dissection technique. We herein expose an overview of the available techniques to achieve haemostatic control in laparoscopic surgery in the emergency as well as the elective setting. Representative surgeries are used for illustrative purposes to describe special manoeuvres.


Effects of Shugan-Jianpi Recipe on the Expression of the p38 MAPK/NF-κB Signaling Pathway in the Hepatocytes of NAFLD Rats.
Background: In traditional Chinese medicine, the Shugan-Jianpi recipe is often used in the treatment of nonalcoholic fatty liver disease (NAFLD). This study aimed to explore the mechanism of the Shugan-Jianpi recipe in relation to rats with NAFLD induced by a high-fat diet. Methods: Rats were randomly divided into eight groups: normal group (NG), model group (MG), low-dose Chaihu⁻Shugan⁻San group (L-CG), high-dose Chaihu⁻Shugan⁻San group (H-CG), low-dose Shenling⁻Baizhu⁻San group (L-SG), high-dose Shenling⁻Baizhu⁻San group (H-SG), low dose of integrated-recipes group (L-IG), and high dose of integrated-recipes group (H-IG). After 26 weeks, a lipid profile, aspartate, and alanine aminotransferases in serum were detected. The serum levels of inflammatory factors including interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha (TNF-α) were analyzed using the enzyme linked immunosorbent assay (ELISA) method. Hepatic pathological changes were observed with hematoxylin-eosin (HE) and oil red O staining. The expression of the p38 mitogen-activated protein kinases (MAPK)/nuclear factor-κB (NF-κB) pathway was detected by quantitative real-time PCR and Western blotting. Results: A pathological section revealed that NAFLD rats have been successfully reproduced. Compared with the model group, each treatment group had different degrees of improvement. The Shugan-Jianpi recipe can inhibit the serum levels of IL-1β, IL-6, and TNF-α in NAFLD rats. The expression of mRNA and a protein related to the p38 MAPK/NF-κB signaling pathway were markedly decreased as a result of the Shugan-Jianpi recipe. Conclusions: The Shugan-Jianpi recipe could attenuate NAFLD progression, and its mechanism may be related to the suppression of the p38 MAPK/NF-κB signaling pathway in hepatocytes.


The implications of management by walking about: a case study of a German hospital.
The purpose of this article is to report on case study research conducted in a German hospital and describe the implications that the "Management by walking about" approach had on healthcare employees. "Management by walking about" is widely seen as one of the favoured procedures for increasing employee commitment and shared understanding as well as supporting high trust work relations. This case study set out to examine the actual labour processes and the concrete experiences of healthcare employees behind the "Management by walking about" approach in a German hospital. This was achieved by means of a six month field study of day-to-day life in the hospital's nursing division. In this case study, the popular initiative of "Management by walking about" was used as a means of managerial control and, as such, the internal promotion of soaring values and path-finding visions was met with both scepticism and cynicism. Pre-commitment and motivation levels were high among healthcare employees, they were passionate about their healthcare work and they actively engaged in open communication and organisational development. But all this had little to do with "Management by walking about", and its implications raise questions about its influence on high trust work relations more generally. The paper concludes that a more critical analysis is necessary to challenge the way in which "Management by walking about" is examined by healthcare management academics and practitioners.


The Future of Women and Heart Disease in a Pandemic Era: Let's Learn from the Past.
When the pandemic started in February, about 5 million women were running businesses. Just 2 months later, 25% of those businesses closed. Approximately 2.5 million women have lost their jobs or dropped out of the workforce since the pandemic, but that is just the start of the impact on women. Women have been disproportionately affected by the pandemic, as the brunt of homelife has fallen on them, and the psychosocial impact will inevitably have a physical impact. The pandemic has revealed the gender inequality that exists from the socioeconomic perspective, but soon we will see the impact from the medical perspective. Predictably, we know that the impact of stress and lack of self-care that women have had to endure heightens heart disease, already the number one killer of all women. Heart disease is 80% preventable based on the major risk factors: high cholesterol, high blood pressure, elevated sugar, obesity, smoking, sedentary lifestyle, and poor diet. But the psychological risk factors drive up biomarkers and the root causes of manifesting disease. Historically, women have been less diagnosed and treated, and less likely to receive lifesaving care in a timely fashion. The pandemic is sure to amplify these issues. Without mitigation and prevention, women's hearts will suffer. We need to be aware of this now to prepare for the future potential of a significant increase in the incidence of women and heart disease.


Toxicity of anticholinesterases: interactions of pyridostigmine and physostigmine with soman.
This investigation was conducted to assess the potential of carbamate pretreatment to exacerbate the ill effects of low doses of soman. Ambulatory Activity in a photocell cage (AA) and performance time on an accelerating rotarod (ARR) were used to test for interactions between pyridostigmine or physostigmine and soman. ED50s (i.e., dosages sufficient to reduce ARR time and AA to 50% of control level) of each carbamate (IM) and soman (SC) were determined. The ED50 values (mg/kg) in the ARR test were 3.2, 0.21, and 0.072 for pyridostigmine, physostigmine and soman, respectively, while in the AA test the corresponding values were 1.8, 0.072 and 0.060. The matrix of 16 combinations of 0, 1, 2/3, and 1/3 ED50 each of carbamate and soman was studied in each test system, as well as the effect of behavioral deficit free (BDF) dosages of each carbamate on the ED50s of soman. In both the AA and ARR tests the matrix of combinations of pyridostigmine and soman indicated an additive effect. In contrast, physostigmine produced one instance of potentiation in each test system and anatagonism in two combinations in the AA procedure. A BDF dosage of each carbamate (0.056 mg/kg of pyridostigmine and 0.026 mg/kg of physostigmine) gave no evidence of adding to the deficit in AA induced by soman. In the ARR test, the ED50 of soman was lower by 11% with pyridostigmine pretreatment and by 14% with physostigmine; the latter just reached statistical significance (p less than 0.05). Although additivity was most often found at higher dosages of pyridostigmine and physostigmine, at the BDF dosages little or no adverse interaction was found between Pyridostigmine or Physostigmine and low levels of soman.