Uncoupling histogenesis from morphogenesis in the vertebrate embryo by collapse of the transneural tube potential.
We have shown that unidirectional pumping of Na+ out of the neural tube's luminal fluids in amphibian embryos produces a large potential difference (40-90 mV, lumen negative to the abluminal surface). This transneural tube potential (TNTP) is analogous to the Na+ dependent transepithelial potential (TEP) that exists across surface ectoderm. This TEP is retained in ectoderm after it is internalized when the neural folds fuse to form the neural tube. The TNTP can be markedly reduced for several hours by injection of the Na+ channel blockers amiloride or benzamil into the lumen by iontophoresis through microelectrodes. Here we describe the effect of TNTP modification on developmental anatomy. Axolotl embryos possessing a fused and closed neural tube (stage 21-23) were injected with either amiloride or benzamil and allowed to continue development for 36-52 hr. These were compared to control embryos injected with vehicle alone, or to embryos in which amiloride or benzamil was iontophoresed just beneath surface ectoderm. All embryos in which the TNTP was reduced were grossly defective. These were characterized by a disaggregation of the cells comprising the structures that had already begun to form (otic primordia, brain, spinal cord, notochord) as well as a failure in the development of new structures. Remarkably, some of these embryos displayed continuing development of external form in the complete absence of concomitant internal histogenesis. We discuss the ways in which a large endogenous voltage gradient associated with an epithelial potential difference (the TNTP) may be required both for the structural integrity of the early neuroepithelium, and a prerequisite for normal morphogenesis.


Improving survivorship care for patients with colorectal cancer.
The consequences of cancer and its treatment are substantial. The aging population and recent advances in detection and treatment of cancer are expected to augment the burgeoning cohort of cancer survivors. During the transition to off-treatment status, patients may experience heightened needs coupled with significant decrements, if not dissolution, in quality of care during this critical period of re-entry. A basic source of this problem is the lack of communication and coordination of care during this transition. Treatment summaries and survivorship care plans have been proposed as potential solutions to improve quality of care for cancer survivors. Patients with colorectal cancer provide an ideal population within which to begin to empirically examine their clinical utility. Potential benefits and promising research methodology are proposed, including adoption of a treatment summary (brief synopsis of cancer care received) and a survivorship care plan (recommendations for follow-up care). The status of the evidence base is reviewed. To date, treatment summaries and survivorship care plans remain largely untried and untested in adult oncology despite their promise to improve patient outcomes and quality of life. The implementation of treatment summaries and survivorship care plans rests on the provision of strong evidence of efficacy and feasibility in the context of follow-up care for cancer survivors. Qualitative, observational, and interventional research should be initiated in order to identify benefits to patients and survivors by the enhancement of survivorship care planning.


Recall of Point-of-Sale Marketing Predicts Cigar and E-Cigarette Use Among Texas Youth.
While research has documented associations between recall of point-of-sale (POS) tobacco marketing and youth tobacco use, much of the research is cross-sectional and focused on cigarettes. The present longitudinal study examined recall of tobacco marketing at the POS and multiple types of tobacco use 6 months later. The Texas Adolescent Tobacco Advertising and Marketing Surveillance System (TATAMS) is a large-scale, representative study of 6th, 8th, and 10th graders in 79 middle and high schools in five counties in Texas. Weighted logistic regression examined associations between recall of tobacco advertisements and products on display at baseline and ever use, current use, and susceptibility to use for cigarette, e-cigarette, cigar, and smokeless products 6 months later. Students' recall of signs marketing e-cigarettes at baseline predicted ever e-cigarette use and increased susceptibility to use e-cigarettes at follow-up, across all store types. Recall of e-cigarette displays only predicted susceptibility to use e-cigarettes at follow-up, across all store types. Both recall of signs marketing cigars and cigar product displays predicted current and ever cigar smoking and increased susceptibility to smoking cigars at follow-up, across all store types. Recall of cigarette and smokeless product marketing and displays was not associated with tobacco use measures. The POS environment continues to be an important influence on youth tobacco use. Restrictions on POS marketing, particularly around schools, are warranted. Cross-sectional studies have shown that exposure to POS cigarette marketing is associated with use of cigarettes among youth, though longitudinal evidence of the same is sparse and mixed. Cross-sectional studies have found that recall of cigars, smokeless product, and e-cigarette tobacco marketing at POS is associated with curiosity about tobacco use or intentions to use tobacco among youth, but limited longitudinal research has been conducted. Findings from the present longitudinal study suggest that recall of tobacco marketing at retail POS predicts ever use of e-cigarettes and cigars, current use of cigars, and susceptibility to cigar and e-cigarette use among youth.


Tuberculosis control priorities defined by using cost-effectiveness and burden of disease.
To define TB control priorities using cost-effectiveness and burden of disease. An assumed cohort of 2,000 cases was set up based on age-specific incidence of 794 newly registered smear-positive cases in Beijing in 1994. Prognostic trees and model diagrams of infectivity with natural history and DOTS intervention were constructed based on the epidemiological parameters. DOTS reduced 89.19% of YLL, 78.90% of YLD, and 99.98% of infectivity BOD. One DALY could be saved with 45.70 Yuan by DOTS with 3% discount. Sensitivity analysis showed that discount had effect on CER. Weight of age was insensitive to CER. The higher the DOTS cured rate, the more the cost-effectiveness. DOTS is a good cost-effectiveness TB control strategy. Cost-effectiveness and burden of disease can be used to define TB control priorities.


Focal therapy for localized prostate cancer - Current status.
Focal therapy (FT) has recently gained popularity for the treatment of localized prostate cancer (PCa). FT achieves cancer control by targeting the lesions or the regions of the cancer and avoids damage to the surrounding tissues thus minimizing side effects which are common to the radical treatment, such as urinary continence and sexual function, and bowel-related side effects. Various ablative methods are used to deliver energy to the cancerous tissue. We review the different modalities of treatment and the current state of FT for PCa.


Medullary thymic epithelial stem cells: role in thymic epithelial cell maintenance and thymic involution.
The thymus consists of two distinct anatomical regions, the cortex and the medulla; medullary thymic epithelial cells (mTECs) play a crucial role in establishing central T-cell tolerance for self-antigens. Although the understanding of mTEC development in thymic organogenesis as well as the regulation of their differentiation and maturation has improved, the mechanisms of postnatal maintenance remain poorly understood. This issue has a central importance in immune homeostasis and physiological thymic involution as well as autoimmune disorders in various clinicopathological settings. Recently, several reports have demonstrated the existence of TEC stem or progenitor cells in the postnatal thymus, which are either bipotent or unipotent. We identified stem cells specified for mTEC-lineage that are generated in the thymic ontogeny and may sustain mTEC regeneration and lifelong central T-cell self-tolerance. This finding suggested that the thymic medulla is maintained autonomously by its own stem cells. Although several issues, including the relationship with other putative TEC stem/progenitors, remain unclear, further examination of mTEC stem cells (mTECSCs) and their regulatory mechanisms may contribute to the understanding of postnatal immune homeostasis. Possible relationships between decline of mTECSC activity and early thymic involution as well as various autoimmune disorders are discussed.


An interpretation of some whole plant water transport phenomena.
A treatment of water flow into and through plants to the evaporating surface of the leaves is presented. The model is driven by evaporation from the cell wall matrix of the leaves. The adsorptive and pressure components of the cell wall matric potential are analyzed and the continuity between the pressure component and the liquid tension in the xylem established. Continuity of these potential components allows linking of a root transport function, driven by the tension in the xylem, to the leaf water potential. The root component of the overall model allows for the solvent-solute interactions characteristic of a membrane-bound system and discussion of the interactions of environmental variables such as root temperature and soil water potentials. A partition function is developed from data in the literature which describes how water absorbed by the plant might be divided between transpiration and leaf growth over a range of leaf water potentials.Relationships between the overall system conductance and the conductance coefficients of the various plant parts (roots, xylem, leaf matrix) are established and the influence of each of these discussed.The whole plant flow model coupled to the partition function is used to simulate several possible relationships between leaf water potential and transpiration rate. The effects of changing some of the partition function coefficients, as well as the root medium water potential on these simulations is illustrated.In addition to the general usefulness of the model and its ability to describe a wide range of situations, we conclude that the relationships used, dealing with bulk fluid flow, diffusion, and solute transport, are adequate to describe the system and that analogically based theoretical systems, such as the Ohm's law analogy, probably ought to be abandoned for this purpose.


Sacral nerve stimulation for faecal incontinence: results from a single centre over a 10-year period.
Sacral nerve stimulation (SNS) is considered a first-line surgical treatment option for faecal incontinence. There is little information on long-term results. The results of SNS for faecal incontinence performed at a single centre over a 10-year period are reported. A cohort analysis of consecutive patients treated with SNS for faecal incontinence over a 10-year period was carried out. Data were collected prospectively using bowel habit diaries and St Mark's and Cleveland Clinic incontinence scores. Treatment success was defined as a >50% reduction in episodes of faecal incontinence compared with baseline. Temporary SNS was performed in 118 patients, and 91 (77%) were considered suitable for chronic stimulation. The median period of follow up was 22 (1-138) months. Seventy patients were followed for 1 year with success in 63 (90%). Of 18 patients followed for 5 years, 15 (83%) reported continued success, 11 (61%) maintained full efficacy, 4 (22%) reported some loss, and 3 (17%) reported complete loss. Three patients with a 10-year follow up had no loss in efficacy. Overall, complete loss of efficacy was observed in 14 (16%) patients at a median of 11.5 months following implantation. A further 5 (6%) patients showed deterioration with time. In 9 (47%), no reason for the deterioration in symptoms could be identified. SNS can be effective for up to 10 years. Some patients experience deterioration in symptoms over time. The reasons for this are often not evident.


Identification of a Recently Dominant Sublineage in Salmonella 4,[5],12:i:- Sequence Type 34 Isolated From Food Animals in Japan.
Salmonella enterica subsp. enterica serovar Typhimurium sequence type 34 (ST34) and its monophasic variant (Salmonella 4,[5],12:i:-) are among the most frequently isolated clones from both humans and animals worldwide. Our previous study demonstrated that Salmonella Typhimurium/4,[5],12:i:- strains isolated in Japan could be classified into nine clades and that clade 9 consisted of ST34 strains. In Japan, ST34/clade 9 was first found in the 1990s and has become predominant among food animals in recent years. In the present study, we analyzed the whole genome-based phylogenetic relationships and temporal information of 214 Salmonella Typhimurium/4,[5],12:i:- ST34/clade 9 strains isolated from 1998 to 2017 in Japan. The 214 strains were classified into two sublineages: the newly identified clade 9-2 diverged from clade 9 in the early 2000s and has predominated in recent years. Clonally expanding subclades in clades 9-1 or 9-2 lacked Gifsy-1 or HP1 prophages, respectively, and some strains in these subclades acquired plasmids encoding antimicrobial resistance genes. Additional genome reduction around the fljB gene encoding the phase 2-H antigen was generated by an IS26-mediated deletion adjacent to the transposon in clade 9-2. Although most of the clade 9 strains were isolated from cattle in Japan, the clonally expanding subclades in clade 9-2 (i.e., all and 24% strains of subclades 9-2a and 9-2b, respectively) were isolated from swine. The spread of clade 9 in recent years among food animals in Japan was responsible for the emergence of multiple host-adapted sublineages involving the clonally expanding subclades generated by mobile genetic element-mediated microevolution.


Complex segregation analysis of familial amyloidosis in Oriental shorthair cats.
Amyloidosis in Siamese/Oriental cats is a lethal condition with variable age of clinical onset. There is no sex predisposition and clinical signs of disease usually become apparent by 1-7 years of age. In the terminal stages, the liver is enlarged and pale, and contains parenchymal hemorrhages. In the present study, pedigree data from 17 cats with clinical signs consistent with amyloidosis underwent genetic analysis. Necropsy and histopathological data were available for 10 of the 17 cats. Necropsy findings included pale, fragile and enlarged livers with capsular ruptures and parenchymal hemorrhages, and sanguineous effusions in the abdominal cavity. Congo red staining with birefringence confirmed systemic amyloidosis mostly involving the liver and thyroid gland. In four of the 10 cases, protein deposits were classified as amyloid A protein (AA-amyloid) by immunostaining. Pedigree data for all 17 affected cats indicated a familial trait. Animal threshold model analysis demonstrated that the heritability for amyloidosis was 0.56 ± 0.09 (standard error). Complex segregation analysis was used for statistical comparisons among models to determine environmental or sex dependent effects, and Mendelian, polygenic, or mixed Mendelian and polygenic inheritance patterns. A mixed model with a Mendelian and polygenic component provided the best fit to the data and thus was most likely. All other models of inheritance were rejected due to their insufficient ability to explain segregation of amyloidosis. In conclusion, we found evidence for a complex genetic basis for amyloidosis in Oriental shorthair cats.


Patients with antibodies to both PmScl and dsDNA.
To determine the significance of dsDNA antibodies in patients with antibodies to PmScl. All patients testing positive for PmScl and/or dsDNA antibodies at an academic medical center between 1977 and 2002 were identified. Charts for the PmScl-positive patients were reviewed for manifestations of lupus, scleroderma, or polymyositis/dermatomyositis. Patients with antibodies to dsDNA were matched to each of the double-positive PmScl+/dsDNA+ patients on the basis of sex, race, age, and date of autoantibody testing. Standard classification criteria for lupus, scleroderma, and myositis were used (excluding dsDNA, PmScl, or antinuclear antibodies as criteria), and the number of subjects meeting classification criteria was recorded. Records were available for 38 out of 47 patients who were identified as PmScl-positive. The prevalence of dsDNA antibodies in this group was 42% (16/38). Patients with PmScl and dsDNA antibodies had a higher prevalence of systemic lupus erythematosus (8/16 vs 2/22; p = 0.008) and a lower rate of scleroderma or myositis (1/16 vs 9/22; p = 0.025) than dsDNA-negative patients with PmScl antibodies. The prevalence of systemic lupus erythematosus, myositis, and scleroderma in patients with PmScl and dsDNA antibodies was not different from the prevalences of these diseases in a matched cohort of patients who were dsDNA-positive. Antibodies to PmScl are associated with scleroderma and myositis when dsDNA antibodies are not present. In the presence of dsDNA antibodies, PmScl antibodies do not appear to have clinical relevance.


[Fetal megalosomia: clinical and prognostic value of main risk factors].
Fetal megalosomia associates with an increased risk of maternal and perinatal pathology. However it is right to make a clear distinction between "physiologic" megalosomia, expression of a high genetic potential of growth from the fetus, and megalosomia referable to any maternal pathology. While the first one entails problems of obstetric management at the most, the second one compels to take measures in order to reduce its incidence. A sample of 45 fetuses with megalosomia was studied retrospectively and compared with a standard sample, randomly selected among the fetuses, term delivered, who in the same period considered (January 1990-January 1994) weighed less than 4 kg at birth. This was done in order to verify which of the risk factors of fetal megalosomia reported in the medical literature affects the most the people who address our Institute. Important risk factors resulted, besides maternal height and postdatism, pre-gestational overweight and obesity. The prognostic significance of the factors, such as advanced maternal age, multiparity, male sex of the unborn child, excessive maternal weight gain during pregnancy, previous megalosomia, was of more difficult interpretation. In our experience, gestational diabetes didn't play the role, universally recognized to it, of the most important risk factor of fetal megalosomia.


The mismatch repair-dependent DNA damage response: Mechanisms and implications.
An important role for the DNA mismatch repair (MMR) pathway in maintaining genomic stability is embodied in its conservation through evolution and the link between loss of MMR function and tumorigenesis. The latter is evident as inheritance of mutations within the major MMR genes give rise to the cancer predisposition condition, Lynch syndrome. Nonetheless, how MMR loss contributes to tumorigenesis is not completely understood. In addition to preventing the accumulation of mutations, MMR also directs cellular responses, such as cell cycle checkpoint or apoptosis activation, to different forms of DNA damage. Understanding this MMR-dependent DNA damage response may provide insight into the full tumor suppressing capabilities of the MMR pathway. Here, we delve into the proposed mechanisms for the MMR-dependent response to DNA damaging agents. We discuss how these pre-clinical findings extend to the clinical treatment of cancers, emphasizing MMR status as a crucial variable in selection of chemotherapeutic regimens. Also, we discuss how loss of the MMR-dependent damage response could promote tumorigenesis via the establishment of a survival advantage to endogenous levels of stress in MMR-deficient cells.


Survival of cells and DNA of Aeromonas salmonicida released into aquatic microcosms.
The survival of the bacterial fish pathogen Aeromonas salmonicida, and persistence of its DNA, were monitored in aquatic microcosms using selective culture and most probable number PCR. Bacterial cells and naked DNA were released into natural non-sterile microcosms consisting of lake sediment overlayered with lake water. Two different types of surface sediment were used. One was sandy in character, taken from the shoreline whilst the other was a littoral loamy surface mud. Inoculated cells and naked DNA became undetectable from water overlayers within 4 weeks of release. Colony counts of Aer. salmonicida declined below detectable limits after 4 weeks in loamy sediment or 7 weeks in sandy sediment; however, naked DNA and DNA from released cells remained detectable for more than 13 weeks.


Magnetic resonance imaging in psychiatry.
Magnetic resonance imaging (MRI) is a relatively new radiological technique that may be useful in the study of psychiatric illness. MRI gives detailed structural information about the brain and also allows quantification of functional change. Current areas of study relevant to psychiatry include: schizophrenia, dementia, epilepsy and, to a lesser extent, alcohol and affective disorders. The authors review the basic principles of MRI, discuss the recent application to psychiatry, indicate its potential advantages and comment on the current limitations of this imaging modality.


Understanding the magnetic anisotropy for linear sandwich [Er(COT)]+-based compounds: a theoretical investigation.
A series of linear sandwich single-ion magnets containing [Er(COT)]+ fragment were selected to probe the magneto-structural correlations using ab initio methods. For prolate shaped ErIII ion, an equatorially coordinating geometry is preferable to achieve high axial anisotropy. Our calculations confirm that the increasing transversal crystal field (CF) induced by equatorial ligands truly enhances the energy barrier. However, if we continue to strengthen the transversal CF in the equatorial plane, the energy barrier inversely decreases. Our further results show that a medium ligand ring of benzene is preferable for prolate shaped ErIII ion, which can induce the modest energy splitting and the small temperature-assisted quantum tunneling of magnetization. Although the obtained energy barrier of 343.1 cm-1 for our created model [(C6H6)Er(COT)]+ is the largest, it is also much smaller than the DyIII-based compounds.


Two new polyacetylene glycosides from the roots of Codonopsis tangshen Oliv.
Two new polyacetylene glycosides, tangshenyne A (1) and tangshenyne B (2), along with six known polyacetylenes were isolated from an 85% MeOH extract of the roots of Codonopsis tangshen Oliv. The chemical structures of the new compounds were determined on the basis of extensive spectroscopic analyses, including UV, IR, 1D and 2D NMR ((1)H-(1)H COSY, HSQC and HMBC) and HR-ESI-MS.


Evidence for common expression mechanisms underlying heterosynaptic and associative long-term depression in the dentate gyrus.
1. The extent to which heterosynaptic and prime-associative stimulation protocols generate different forms of long-term depression (LTD) was assessed in the lateral perforant path synapses terminating on dentate gyrus granule cells in pentobarbital-anesthetized rats. 2. Heterosynaptic LTD was induced in the lateral path by repeated tetanization of the medial path. Prime-associative LTD of the lateral path was induced by alternating high-frequency conditioning trains to the medial path and single shocks to the lateral path at 100-ms intervals, all occurring 10 min after priming stimulation of the lateral path (5 Hz, 80 pulses). 3. Induction of LTD by one administration of the prime-associative protocol was normally greater in magnitude than the LTD induced by the heterosynaptic protocol. Saturation of LTD by repeated delivery of the prime-associative protocol completely occluded the subsequent induction of LTD by the heterosynaptic protocol. Saturation of LTD by repeated delivery of the heterosynaptic protocol produced an 80% occlusion of the LTD generated by the prime-associative protocol. 4. These data support the hypothesis that activity-dependent (associative) and activity-independent (heterosynaptic) LTD involve overlapping expression mechanisms, despite having demonstrably different induction mechanisms.


Attachment affects social information processing: Specific electrophysiological effects of maternal stimuli.
Attachment is critical to each individual. It affects the cognitive-affective processing of social information. The present study examines how attachment affects the processing of social information, specifically maternal information. We assessed the behavioral and electrophysiological responses to maternal information (compared to non-specific others) in a Go/No-go Association Task (GNAT) with 22 participants. The results illustrated that attachment affected maternal information processing during three sequential stages of information processing. First, attachment affected visual perception, reflected by enhanced P100 and N170 elicited by maternal information as compared to others information. Second, compared to others, mother obtained more attentional resources, reflected by faster behavioral response to maternal information and larger P200 and P300. Finally, mother was evaluated positively, reflected by shorter P300 latency in a mother + good condition as compared to a mother + bad condition. These findings indicated that the processing of attachment-relevant information is neurologically differentiated from other types of social information from an early stage of perceptual processing to late high-level processing.


Requirement of carotene isomerization for the assembly of photosystem II in Synechocystis sp. PCC 6803.
Carotene isomerase mutant (crtH mutant) cells of Synechocystis sp. PCC 6803 can accumulate beta-carotene under light conditions. However, the mutant cells grown under a light-activated heterotrophic growth condition contained detectable levels of neither beta-carotene nor D1 protein of the photosystem (PS) II reaction center, and no oxygen-evolving activity of PSII was detected. beta-Carotene and D1 protein appeared and a high level of PSII activity was detected after the cells were transferred to a continuous light condition. The PSI activities of thylakoid membranes from mutant cells were almost the same as those of thylakoid membranes from wild-type cells, both before and after transfer to the continuous light condition. These results suggest that beta-carotene is required for the assembly of PSII but not for that of PSI.


First Latin American and Caribbean interlaboratory comparison exercise for SSDLs on reference irradiation capabilities in personal dose equivalent.
A comparison exercise of Latin American and Caribbean Secondary Standards Dosimetry Laboratories (SSDLs) was jointly organized by the International Atomic Energy Agency (IAEA) and the Ionizing Radiation Metrology Laboratory at the Federal University of Pernambuco (LMRI-DEN/UFPE). This exercise was organized during an IAEA regional meeting on the review and update of calibration capabilities in Latin America, held in Recife, during the period from 23 to 27 April 2018 under the technical cooperation project ME-RLA 9085-170572. Fifteen participating SSDLs were required to irradiate optically stimulated personal dosimeters in terms of the personal dose equivalent Hp(10) in137Cs radiation quality. In addition, the IAEA Dosimetry Laboratory in Seibersdorf, Austria, and the National Physical Laboratory in Teddington, Middlesex, UK participated in this exercise as reference institutes. Each participant received 10 dosimeters that were hand-carried directly to the SSDL. Two nominal dose values of 2 mSv and 4 mSv were selected for this exercise. The participants irradiated the dosimeters using the setup and the procedures which are normally used in their standard laboratory for Hp(10) dosimeter irradiations. The dosimeters were evaluated as they were received by the coordinating laboratory, using a single BeOSL Reader. The results show that, except for one laboratory, the differences between the dosimeter reading and the assigned values were within 10%; this is consistent with the expanded uncertainty. The results indicate that most of the participant laboratories have a good capability to irradiate personal dosimeters in the quantity Hp(10).


Characterization of seventy polymethoxylated flavonoids (PMFs) in the leaves of Murraya paniculata by on-line high-performance liquid chromatography coupled to photodiode array detection and electrospray tandem mass spectrometry.
A sensitive HPLC-DAD-ESI-MS/MS method was established to screen and identify the polymethoxylated flavonoids (PMFs) in the leaves of Murraya paniculata (L.) Jack. 16 PMF standards were first to be analyzed in positive mode by the CID-MS/MS. For polymethoxylated flavones, the fragments of [M+H-n×15](+) produced by loss of one or more methyl radicals from the protonated molecule, as well as [M+H-16](+), [M+H-28](+), [M+H-29](+), [M+H-31](+), [M+H-33](+), [M+H-43](+), [M+H-44](+), [M+H-46](+) and [M+H-61](+) fragment ions were detected, which could be taken as their diagnostic characters. For polymethoxylated flavanones and chalcones, their [M+H](+) ions usually underwent RDA cleavage fragmentation of the C-ring prior to the similar loss of diagnostic fragment ions as polymethoxylated flavones, which could be adopted as a shortcut to distinguish them from ordinary flavones rapidly. For the PMF glycosides, the neutral loss of the similar fragments with polymethoxylated flavones from their [aglycone+H](+) could be adopted as a simple method to screen them out from complex mixture. Based on these characterizations of PMFs and the results of EIC-MS/MS experiment, 70 PMFs including 45 flavones, 17 flavanones or chalcones and 8 PMFs glycosides were screened out from the complex extract of the leaves of M. paniculata. Among them, 16 compounds were unambiguously identified by comparison with reference substances. The results indicated that the developed analysis method could be employed as a rapid, effective technique for structural characterization of PMFs.


Surgical site infection in clean and clean-contaminated cases.
The rate of surgical site infections and the frequency of various pathogens causing surgical site infection with their antibiotic resistance pattern in general surgery units were studied. In the period from May 2001 to July 2002, 190 patients admitted for surgery (clean and clean-contaminated elective cases) were assessed preoperatively, intraoperatively and postoperatively. Normal microbial flora was studied within 24 to 48 hours of admission and patients were followed up to 30 days postoperatively. Infected wounds were studied bacteriologically and clinically. The overall infection rate was 8.95%. Surgical site infection rate was 3.03% in clean surgeries and 22.41% in clean-contaminated surgeries. Significant increase was seen in surgical site infection rate with an increase in preoperative stay. The increase in duration of surgery was associated with a significant rise in the rate of surgical site infection. Surgical site infection rate was much higher (22.41%) in cases where a drain was used than in non-drained wounds (3.03%). The most common isolate was Staphylococcus aureus followed by Pseudomonas aeruginosa.


Predictors of residential treatment retention among individuals with co-occurring substance abuse and mental health disorders.
A significant number of individuals with co-occurring substance abuse and mental health disorders do not engage, stay, and/or complete residential treatment. The purpose of this study is to identify factors during the initial phase of treatment which predict retention in private residential treatment for individuals with co-occurring substance use and mental health disorders. The participants were 1,317 individuals with co-occurring substance abuse and mental health disorders receiving treatment at three residential treatment centers located in Memphis, TN, Malibu, CA, and Palm Springs, CA. Bivariate analysis and logistic regression were utilized to identify factors that predict treatment retention at 30 days. The findings indicate a variety of factors including age, gender, types of drug, Addiction Severity Index Medical and Psychiatric scores, and readiness to change. These identified factors could be incorporated into pretreatment assessments, so that programs can initiate preventive measures to decrease attrition and improve treatment outcomes.


Opposing effects of pro- and anti-inflammatory cytokine gene polymorphisms on the risk for breast cancer in western Indian women: a pilot study.
In an earlier study, the genotypes associated with higher level of transforming growth factor-β1 (TGF-β1) were found to reduce the risk for breast cancer in western Indian women. This observation implied that gene polymorphisms affecting the levels of pro- and anti-inflammatory cytokines may influence the risk for breast cancer in this population. Hence, we performed genotyping for three more functional single-nucleotide polymorphisms (SNPs) responsible for variations in the levels of cytokines associated with inflammation. To that effect, polymorphisms in genes coding for IL-4 (IL-4 C-590T; rs2243250), IFN-γ (IFN-G A + 874T; rs2430561) and MCP-1 (MCP-1 A-2578G; rs1024611) were examined in premenopausal, healthy women (N = 239) and patients with breast cancer (N = 182) from western India. In carriers of the IL-4*590T allele, a reduced risk for the disease (dominant model; OR = 0.61, 95% CI 0.37-0.98) was seen similar to that seen in TGF-B1*10C carriers. An opposite trend was observed with respect to the alleles associated with higher expression of MCP-1 or IFN-γ. In individuals positive for three or more alleles associated with higher levels of either pro- or anti-inflammatory cytokines, an additive effect on the modulation of risk for the disease was evident (for TGF-B1 & IL-4, OR = 0.33, 95% CI 0.12-0.87; for IFN-G & MCP-1, OR = 2.29, 95% CI 0.95-5.51). In the context of contrasting observations in other populations, these results indicate a significant contribution of anti-inflammatory genotypes in the modulation of risk for breast cancer in western Indian women.


Drug monitoring of PEG-asparaginase treatment in childhood acute lymphoblastic leukemia and non-Hodgkin's lymphoma.
This is an updated review of the pharmacokinetic profile of PEG-asparaginase (PEG-ASNase) in childhood acute lymphoblastic leukemia (ALL) or non-Hodgkin's lymphoma (NHL). In a total of 271 children undergoing ALL/NHL or relapsed ALL treatment according to the Berlin-Frankfurt-Münster (BFM) protocols, drug monitoring of ASNase serum activity was performed after PEG-ASNase infusions. From December 1996 to July 2000, 1667 samples after 362 intravenous administrations of either 500, 750, 1000 or 2500 IU/m2 PEG-ASNase were analyzed. Three weeks after infusion when relating the ASNase activity to the four-dose levels significant differences were not observed. Large interpatient variability was seen at each dose level resulting in a relevant number of patients not achieving adequate treatment intensity. Neither the extent of ASNase pre-treatment nor a prior event of a hypersensitivity reaction against unmodified ASNase had any impact on PEG-ASNase pharmacokinetics. It is concluded that escalation of the dose of PEG-ASNase did not result in a significant prolongation of time with activity values considered therapeutic. Depending on the desired endpoint, a second administration of PEG-ASNase seems to be more favorable than increasing the dose. For a safer recommendation, further investigations assessing the pharmacodynamic profile are required. Drug monitoring is advisable for early detection of patients with rapid elimination in order to ensure maximum treatment intensity.


Rapamycin resistance in ataxia-telangiectasia.
The gene mutated in the human genetic disorder ataxia-telangiectasia (A-T) has been described recently (Savitsky et al., 1995a) and the complete coding sequence of this gene, ATM, has been reported (Savitsky et al., 1995b). The derived amino acid sequence demonstrates significant homologies to several proteins containing a phosphatidylinositol 3-kinase (PI3-kinase) domain, including the yeast TOR proteins and the human protein FRAP. Since the TOR and FRAP proteins are targets for the immunosuppressive drug rapamycin, we have investigated the effects of this compound on A-T cells. We report here that 3 A-T cell lines are more resistant than control cells to rapamycin's growth inhibiting effects but were more sensitive to the PI3-kinase inhibitor wortmannin. As expected rapamycin (1 nM) inhibited the rate of exit of control cells from G1 phase but failed to perturb the progression of A-T cells. This difference in cell cycle progress after rapamycin treatment is reflected in ribosomal S6 protein kinase (p70S6k) by both a downward mobility shift on SDS-PAGE and inhibition of activity. Furthermore, the G1 phase cyclin-dependent kinase, cyclin E-cdk2, was rapidly inhibited in control cells post-treatment, whereas in A-T cells it took considerably longer to observe inhibition. There was no evidence that a GST-FKBP12 fusion protein specifically precipitated the ATM protein in the presence of rapamycin in either cell type. These results demonstrate that the ATM protein is not a direct target for rapamycin but its functional loss renders cells more resistant to this compound.


[Association of the renin-angiotensin system gene polymorphism with nephropathy in type II diabetes].
Diabetic nephropathy is the most frequent cause of end-stage renal failure. One of the crucial factors in a development of renal and cardiovascular complications of diabetes is genetic predisposition. The genes of the renin-angiotensin system are important group of candidate genes involved in pathogenesis of chronic renal diseases. The purpose of our study was the evaluation of a possible role of genetic polymorphisms of some of the RAS system genes in the nephropathy in type 2 diabetes. The study was performed in 117 patients with diabetic nephropathy, compared with 200 healthy subjects as a control group. The following polymorphisms: insertion/deletion (I/D) of the angiotensin-converting enzyme gene (ACE), M235T of the angiotensinogen gene (AGT) and A1166C of the angiotensin II type 1 receptor gene (AT1R) were evaluated by polymerase chain reaction (PCR). No statistically significant differences between groups were found in the allele frequency and genotype distribution for ACE and AGT polymorphisms. The results for the AT1R gene polymorphism revealed significant differences in allele and genotype frequencies. The homozygous CC genotype was more frequent in patients with diabetic nephropathy than in control group. Both genotypes with the C allele (AC + CC) were found in 56% of patients compared to 38% in control group. These results suggest increased susceptibility to diabetic nephropathy in individuals carrying the CC genotype. Therefore, the A1166C polymorphism of the AT1R gene could be a potential genetic marker for increased susceptibility to renal complications in type 2 diabetes.


Activation of distinct cAMP-dependent and cGMP-dependent pathways by nitric oxide in cardiac myocytes.
Nitric oxide (NO) donors were recently shown to produce biphasic contractile effects in cardiac tissue, with augmentation at low NO levels and depression at high NO levels. We examined the subcellular mechanisms involved in the opposing effects of NO on cardiac contraction and investigated whether NO modulates contraction exclusively via guanylyl cyclase (GC) activation or whether some contribution occurs via cGMP/PKG-independent mechanisms, in indo 1-loaded adult cardiac myocytes. Whereas a high concentration of the NO donor S-nitroso-N-acetylpenicillamine (SNAP, 100 micromol/L) significantly attenuated contraction amplitude by 24.4+/-4.5% (without changing the Ca2+ transient or total cAMP), a low concentration of SNAP (1 micromol/L) significantly increased contraction amplitude (38+/-10%), Ca2+ transient (26+/-10%), and cAMP levels (from 6.2 to 8.5 pmol/mg of protein). The negative contractile response of 100 micromol/L SNAP was completely abolished in the presence of the specific blocker of PKG KT 5823 (1 micromol/L); the positive contractile response of 1 micromol/L SNAP persisted, despite the presence of the selective inhibitor of GC 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 10 micromol/L) alone, but was completely abolished in the presence of ODQ plus the specific inhibitory cAMP analog Rp-8-CPT-cAMPS (100 micromol/L), as well as by the NO scavenger oxyhemoglobin. Parallel experiments in cell suspensions showed significant increases in adenylyl cyclase (AC) activity at low concentrations (0.1 to 1 micromol/L) of SNAP (AC, 18% to 20% above basal activity). We conclude that NO can regulate both AC and GC in cardiac myocytes. High levels of NO induce large increases in cGMP and a negative inotropic effect mediated by a PKG-dependent reduction in myofilament responsiveness to Ca2+. Low levels of NO increase cAMP, at least in part, by a novel cGMP-independent activation of AC and induce a positive contractile response.


Cloning and expression of a novel Mu class murine glutathione transferase isoenzyme.
The present study describes the cDNA cloning, expression and characterization of a novel Mu class murine glutathione transferase (GST) isoenzyme. Screening of a cDNA library from the small intestine of a female A/J mouse using consensus probes derived from Mu class murine GST genes (mGSTM1-mGSTM5) resulted in the isolation of a full-length cDNA clone of a previously unknown Mu class GST gene (designated as mGSTM7). The choice of tissue was based on our previous identification in female A/J mouse small intestine of a potentially novel Mu class GST isoenzyme. The deduced amino acid sequence of mGSTM7, which comprises of 218 amino acid residues, exhibited about 67-78% identity with other Mu class murine GSTs. Recombinant mGSTM7-7 cross-reacted with anti-(GST Mu) antibodies, but not with anti-(GST Alpha) or anti-(GST Pi) antibodies. The pI and the reverse-phase-HPLC elution profile of recombinant mGSTM7-7 were different from those of other Mu class murine GSTs. The substrate specificity of mGSTM7-7 was also different compared with other Mu class murine GSTs. Interestingly, mGSTM7 had a higher identity with the human Mu class isoenzyme hGSTM4 (87% identity and 94% similarity in the amino acid sequence) than with any of the known mouse Mu class GSTs. Specific activities of recombinant mGSTM7-7 and human GSTM4-4 were comparable towards several substrates. For example, similar to hGSTM4-4, recombinant mGSTM7-7 was poorly active in catalysing the GSH conjugation of 1-chloro-2,4-dinitrobenzene and ethacrynic acid, and lacked activity towards 1,2-dichloro-4-nitrobenzene and 1,2-epoxy-3-(p-nitrophenoxy)propane. These results suggested that hGSTM4-4 might be the human counterpart of mouse GSTM7-7. Reverse transcription-PCR analysis using mGSTM7-specific primers revealed that mGSTM7 is widely expressed in tissues of female A/J mice, including liver, forestomach, lung, kidney, colon and spleen.


Influence of the mycotoxins alpha- and beta-zearalenol (ZOL) on regulators of cap-dependent translation control in pig endometrial cells.
The molecular mechanisms that control the mycotoxin-mediated effects in porcine endometrial cells are far from being completely understood. Recent results show that they could inhibit cell proliferation. Therefore, the present study investigated the effects of the mycotoxins alpha-zearalenol (alpha-ZOL) and beta-zearalenol (beta-ZOL) on a cellular level. Mainly, the abundance and phosphorylation state (activity) of the cell cycle-dependent kinases MAPK and Akt (PKB) and their potential targets eIF4E (eukaryotic initiation factor 4E) and 4E-BP1 (4E binding protein, eIF4E repressor protein) were investigated. The results show that alpha-ZOL has apparently only a slight influence on the phosphorylation state of MAP kinases, Akt and on eIF4E and 4E-BP1. In contrast, their phosphorylation was strongly reduced in beta-ZOL-treated cells in a concentration-dependent manner. Therefore, our results indicate that beta-ZOL potentially not only influences transcription but also effects gene expression on translational level. The effect of alpha- and beta-ZOL on endometrial cell proliferation and their toxicology are discussed.


Effect of dietary antioxidant and increasing corn oil inclusion on milk fat yield and fatty acid composition in dairy cattle.
The objective of this study was to examine the effect of a dietary synthetic antioxidant on feed intake, yields of milk and milk components and milk fatty acids (FA), in combination with increasing concentrations of dietary corn oil to provide increasing rumen unsaturated fatty acid load (RUFAL) challenges. Twenty-six Holstein cows (177 ± 57 d in milk; mean ± standard deviation) were assigned to treatment in a randomized complete block design. Treatments were a control diet (CON; n=13 cows) or the same diet supplemented with a synthetic antioxidant (AOX; 6.1g/d; dry blend of ethoxyquin and propyl gallate, Novus International Inc., St. Charles, MO; n=13 cows). In period 1 (21 d), no supplemental corn oil was fed; in periods 2, 3, and 4 (14 d each), corn oil was supplemented at 0.7, 1.4, and 2.8% of the diet [dry matter (DM) basis] to incrementally increase RUFAL. For all variables measured, no significant interactions were detected between treatment and period, indicating no differences between the CON and AOX treatments at all levels of oil inclusion. Intake of DM was lower for AOX compared with CON but AOX had no effect on milk yield or milk fat concentration and yield. Milk protein yield and feed efficiency (energy-corrected milk/DM intake) tended to be greater for AOX compared with CON. Increasing dietary corn oil concentration (RUFAL) decreased DM intake, milk yield, milk fat concentration and yield, and feed efficiency. The AOX treatment increased the concentration and yield of 16-carbon milk FA, with no effect on de novo (<16 carbon) or preformed (>16 carbon) milk FA. Milk FA concentration of trans-10 C18:1, trans-10,cis-12 C18:2, and trans-9,cis-11 C18:2 were unaffected by AOX but increased with increasing RUFAL. In conclusion, supplementation with AOX did not overcome the dietary-induced milk fat depression caused by increased RUFAL.


A feminist critique on the use of the Internet in nursing research.
With the increasing use of the Internet, the importance of incorporating this new technology in nursing research increases. Yet nursing has been slow in adopting this new technology as a research method, and the use of the Internet in nursing research rarely has been discussed and critiqued. In this article, use of the Internet in nursing research is analyzed and critiqued from a feminist perspective. The analysis indicates that use of the Internet in research frequently brings about selection biases because of a limited pool of potential participants, it usually does not provide contextual data on research encounters, it might not uncover women's subjective experiences under marginalized situations, and it tends to raise power issues related to the relationships between researchers and participants. Despite the limitations, use of the Internet in research provides better communication channels for research participants, more flexibility in time and place of data collection, and less expense for data collection. Based on the critique, feminist challenges for future use of the Internet in nursing research are proposed.


Genetically engineered plants and foods: a scientist's analysis of the issues (part II).
Genetic engineering provides a means to introduce genes into plants via mechanisms that are different in some respects from classical breeding. A number of commercialized, genetically engineered (GE) varieties, most notably canola, cotton, maize and soybean, were created using this technology, and at present the traits introduced are herbicide and/or pest tolerance. In 2007 these GE crops were planted in developed and developing countries on more than 280 million acres (113 million hectares) worldwide, representing nearly 10% of rainfed cropland. Although the United States leads the world in acres planted with GE crops, the majority of this planting is on large acreage farms. In developing countries, adopters are mostly small and resource-poor farmers. For farmers and many consumers worldwide, planting and eating GE crops and products made from them are acceptable and even welcomed; for others GE crops raise food and environmental safety questions, as well as economic and social issues. In Part I of this review, some general and food issues related to GE crops and foods were discussed. In Part II, issues related to certain environmental and socioeconomic aspects of GE crops and foods are addressed, with responses linked to the scientific literature.


Absence of interaction between ofloxacin and phenprocoumon.
The effect of ofloxacin on steady-state phenprocoumon pharmacodynamics was investigated in 7 healthy male volunteers taking daily sub-therapeutic doses of phenprocoumon. Ofloxacin 200 mg once daily for 7 days did not alter the anti-coagulant response (Quick values) to phenprocoumon after a stabilization phase of 2 weeks. Mean Quick values during the steady-state phase before and during ofloxacin administration were 54% and 52%, respectively. In vitro studies with concentrations of 0 to 100 mg ofloxacin/1 added to plasma also failed to show any interaction. The results indicate, therefore, that ofloxacin does not interfere with vitamin K-dependent coagulation cascade, as seen after other antibiotics.


Sexually Dimorphic Properties in Meiotic Chromosome.
Meiosis is a crucial process for germ cell development. It consists of 1 round of DNA replication followed by 2 rounds of chromosome segregation, producing haploid gametes from diploid cells. During meiotic prophase, chromosomes are organized into axis-loop structures, which underlie meiosis-specific events such as meiotic recombination and homolog synapsis. Meiosis-specific cohesin plays a pivotal role in establishing higher-order chromosome architecture and regulating chromosome dynamics. Notably, sexually dimorphic properties of chromosome architecture are prominent during meiotic prophase, despite the same axial proteins being conserved between male and female. The difference in chromosome structure between the sexes gives sexual differences in the regulation of meiotic recombination and crossover distribution. This review mainly focuses on the sexual differences of meiosis from the viewpoint of chromosome structure in mammals, elucidating the differences in meiotic recombination and homolog synapsis between the sexes.


Sonochemical reaction of fullerene[C60] with several 2'-azidoethyl per-O-acetyl glycosides.
Cycloadditive reaction of fullerene[C60] with various 2'-azidoethyl per-O-acetyl glycopyranoside of D-mannose, D-galactose, D-glucose, D-xylose and D-maltose, respectively gave the glycosyl fullerene[C60] derivatives 2a-2e such as alpha-D-mannosyl fullerene[C60] under ultrasonication. Based on analyses using 1H- and 13C-NMR, UV-vis, FT-IR, and FAB-MS spectroscopies of the glycosyl fullerene[C60] derivatives, the products were composed of a mixture of [5,6]- and [6,6]-junction isomers which were predominantly the closed [5,6]-junction isomer.


An evaluation of the physical activity and health status of British Columbian Aboriginal populations.
Aboriginal people have experienced elevated rates of obesity, diabetes, cardiovascular disease, and other chronic conditions that are disproportionate to the general Canadian population. We sampled British Columbian Aboriginal populations to determine the current health status of this population. A total of 882 Aboriginal adults ≥16 years of age from 25 locations around the province were sampled from 2007-2011. Health measurements evaluated included body mass index, waist circumference, physical activity, smoking behaviours, and resting blood pressure as well as histories of diabetes, cardiovascular disease, and hypertension. Nonfasting measures of blood sugar, total cholesterol, and high-density lipoprotein cholesterol were also recorded. We used logistical regression to quantify variations in diabetes and cardiovascular disease risk factors with age, gender, geographic location, on- and off-reserve and urban-rural areas of residence, smoking, and physical activity behaviour. The prevalence of diabetes, hypertension, and high total cholesterol were found to be greater among males, while females experienced greater rates of abdominal obesity and physical inactivity. Rates of chronic conditions were similar across on- and off-reserve, urban-rural areas, and geographic region residences, though rural, on-reserve, and northern residents experienced greater risk of poor health status. Larger proportions of on-reserve, rural, and interior individuals were found to be more physically inactive. Aboriginal populations still experience substantially poorer health status in comparison with the general population. Initiatives to improve the health of this population are urgently needed addressing all sectors of the Aboriginal population, all geographic regions, and all areas of residence, with special emphasis on rural, on-reserve, and northern populations.


Doxorubicin induces drug efflux pumps in Candida albicans.
Candida albicans is one of the most important opportunistic fungal pathogens. It can cause serious fungal diseases in immunocompromised patients, including those with cancer. Treatment failures due to the emergence of drug-resistant C. albicans strains have become a serious clinical problem. Resistance incidents were often mediated by fungal efflux pumps which are closely related to the human ABC transporter P-glycoprotein (P-gp). P-gp is often overexpressed in cancer cells and confers resistance to many cytotoxic drugs. We examined whether cytotoxic drugs commonly used for cancer treatment (doxorubicin and cyclophosphamide) could alter the expression of genes responsible for the development of fluconazole resistance in Candida cells in the way they can influence homologous genes in cancer cell lines. ABC transporters (CDR1 and CDR2) and other resistance genes (MDR1 and ERG11) were tested by real-time PCR for their expression in C. albicans cells at the mRNA level after induction by antineoplastic drugs. The results were confirmed by a lacZ gene reporter system and verified at the protein level using GFP and immunoblotting. We showed that doxorubicin is a potent inducer of CDR1/CDR2 expression in C. albicans at both the mRNA and protein level and thus causes an increase in fluconazole MIC values. However, cyclophosphamide, which is not a substrate of human P-gp, did not induce ABC transporter expression in C. albicans. Neither doxorubicin nor cyclophosphamide could influence the expression of the other resistance genes (MDR1 and ERG11). The induction of CDR1/CDR2 by doxorubicin in C. albicans and the resulting alteration of antifungal susceptibility might be of clinical relevance for the antifungal treatment of Candida infections occurring after anticancer chemotherapy with doxorubicin.


Total quality management: doing things right.
Total quality management transforms quality assurance performance controls into a dynamic system for continuously improving healthcare services to internal and external "customers" in terms of outcomes. Success depends upon gaining and maintaining commitment of physicians, top management and key staff members through a working environment which values and rewards improvement efforts.


Definitions, models, and methods in research on sociocultural factors in American Indian alcohol use.
This paper presents a critical discussion of the definitions, conceptual models, and methodological issues that researchers should consider in studies of sociocultural influences on drinking practices and problems. In particular, these concerns are related to studies of American Indian and Alaskan Native people. In an effort to avoid overgeneralized explanatory statements, it is recommended that efforts be made to study more specific aspects of such loosely defined terms as culture, alcoholism, and "Indianness." Research in this area might usefully be guided by parsimonious conceptual models developed and investigated in the dominant culture; however the extent to which relationships observed within one group generalized to another group remains an empirical question. While there may be a common set of operationalizing variables and collecting valid data cannot be assumed to have equal applicability with different subgroups. By remaining sensitive to the methodological implications of sociocultural differences, investigators can more accurately clarify the processes by which complex biological, psychological, and sociocultural factors influence alcohol use and misuse in any individual or group.


[Prevalence of hazardous and harmful consumption of alcohol in the insured population of the Mexican Social Security Institute].
To estimate the prevalence of hazardous and harmful alcohol consumption among the insured population of Instituto Mexicano del Seguro Social (Mexican Social Security Institute, IMSS). A cross-sectional survey was conducted in 45,117 insured subjects from Mexico's 36 political districts; study subjects were interviewed using a structured and self-applied questionnaire on alcohol consumption, using the ten-item screening instrument AUDIT (Alcohol Use Disorder Identification Test). The first three questions refer to the amount and frequency of drinking, the following three question to alcohol dependence, and the last four to alcohol-related problems. Each item has three to five options and each is scored progressively from zero to four. The prevalence of alcohol consumption was estimated with 95% confidence intervals. The prevalence of problem drinkers (hazardous and harmful) was 12.8% (IC 95% 12.5-13.2); it was higher in men (22.2%; IC 95% 21.7-22.8) than in women (3.4%; IC 95% 3.1-3.6). An age effect was observed in men, while in women alcohol consumption was more homogeneous. In both genders consumption was higher in productive-age groups. The prevalence of hazardous and harmful alcohol consumption is high in the insured population of the IMSS in Mexico. There is a need to implement health policies and health programs to diminish this serious health problem. The English version of this paper is available at: http://www.insp.mx/salud/index.html.


Mechanisms and Active Compounds Polysaccharides and Bibenzyls of Medicinal Dendrobiums for Diabetes Management.
Medicinal dendrobiums are used popularly in traditional Chinese medicine for the treatment of diabetes, while their active compounds and mechanism remain unclear. This review aimed to evaluate the mechanism and active compounds of medicinal dendrobiums in diabetes management through a systematic approach. A systematic approach was conducted to search for the mechanism and active phytochemicals in Dendrobium responsible for anti-diabetic actions using databases PubMed, Embase, and SciFinder. Current literature indicates polysaccharides, bibenzyls, phenanthrene, and alkaloids are commonly isolated in Dendrobium genusin which polysaccharides and bibenzyls are most aboundant. Many animal studies have shown that polysaccharides from the species of Dendrobium provide with antidiabetic effects by lowering glucose level and reversing chronic inflammation of T2DM taken orally at 200 mg/kg. Dendrobium polysaccharides protect pancreatic β-cell dysfunction and insulin resistance in liver. Dendrobium polysaccharides up-regulate the abundance of short-chain fatty acid to stimulate GLP-1 secretion through gut microbiota. Bibenzyls also have great potency to inhibit the progression of the chronic inflammation in cellular studies. Polysaccharides and bibenzyls are the major active compounds in medicinal dendrobiums for diabetic management through the mechanisms of lowering glucose level and reversing chronic inflammation of T2DM by modulating pancreatic β-cell dysfunction and insulin resistance in liver as a result from gut microbita regulation.


CPCCOEt, a noncompetitive metabotropic glutamate receptor 1 antagonist, inhibits receptor signaling without affecting glutamate binding.
Metabotropic glutamate receptors (mGluRs) are a family of G protein-coupled receptors characterized by a large, extracellular N-terminal domain comprising the glutamate-binding site. In the current study, we examined the pharmacological profile and site of action of the non-amino-acid antagonist 7-hydroxyiminocyclopropan[b]chromen-1a-carboxylic acid ethyl ester (CPCCOEt). CPCCOEt selectively inhibited glutamate-induced increases in intracellular calcium at human mGluR1b (hmGluR1b) with an apparent IC50 of 6.5 microM while having no agonist or antagonist activity at hmGluR2, -4a, -5a, -7b, and -8a up to 100 microM. Schild analysis indicated that CPCCOEt acts in a noncompetitive manner by decreasing the efficacy of glutamate-stimulated phosphoinositide hydrolysis without affecting the EC50 value or Hill coefficient of glutamate. Similarly, CPCCOEt did not displace [3H]glutamate binding to membranes prepared from mGluR1a-expressing cells. To elucidate the site of action, we systematically exchanged segments and single amino acids between hmGluR1b and the related subtype, hmGluR5a. Substitution of Thr815 and Ala818, located at the extracellular surface of transmembrane segment VII, with the homologous amino acids of hmGluR5a eliminated CPCCOEt inhibition of hmGluR1b. In contrast, introduction of Thr815 and Ala818 at the homologous positions of hmGluR5a conferred complete inhibition by CPCCOEt (IC50 = 6.6 microM), i.e., a gain of function. These data suggest that CPCCOEt represents a novel class of G protein-coupled receptor antagonists inhibiting receptor signaling without affecting ligand binding. We propose that the interaction of CPCCOEt with Thr815 and Ala818 of mGluR1 disrupts receptor activation by inhibiting an intramolecular interaction between the agonist-bound extracellular domain and the transmembrane domain.


Stressors and Protective Factors among Veterinary Students in New Zealand.
A study was undertaken to investigate the stressors faced by veterinary students and the protective factors against those stressors. The study was conducted as a workshop during which students collaborated with their peers through an iterative process to identify personal and external factors that contributed to or protected against stress as a veterinary student, and then to suggest strategies that would protect their mental health and well-being. Workload and assessment were the most commonly reported stressors. Students reported a variety of effective coping strategies and avoidance behaviors, although most of the suggested solutions revolved around organizational change within the university. Students also recognized that their own perspectives, traits, and behavior could enhance their student experience or increase their perceived levels of stress. While it is important that educators monitor student feedback about the program and make changes when required, students must recognize that stress is an expected component of life and develop effective coping strategies. They should develop a balanced view of the positive and negative aspects of the student experience and, ultimately, of working as a veterinary professional.


Bone healing in critical-size defects treated with platelet-rich plasma activated by two different methods. A histologic and histometric study in rat calvaria.
The purpose of this study was to analyze histologically the influence of platelet-rich plasma (PRP) coagulated with two different activators on bone healing in surgically created critical-size defects (CSD) in rat calvaria. Forty-eight rats were divided into three groups: C, PRP-C and PRP-T. An 8 mm diameter CSD was created in the calvarium of each animal. In group C, the defect was filled by a blood clot only. In groups PRP-C and PRP-T, the defect was filled with PRP activated with either calcium chloride or thromboplastin solution, respectively. Each group was divided into two subgroups (n = 8 per subgroup) and killed at either 4 or 12 weeks postoperatively. Histologic and histometric analyses were performed. The amount of new bone formed was calculated as a percentage of the total area of the original defect. Percentage data were transformed into arccosine for statistical analysis (analysis of variance, Tukey's post hoc test, p < 0.05). No defect completely regenerated with bone. Group PRP-C had a statistically greater amount of bone formation than groups C and PRP-T at both time points of analysis. No statistically significant differences were observed between groups C and PRP-T. It can be concluded that the type of activator used to initiate PRP clot formation influences its biological effect on bone healing in CSD in rat calvaria.


Claudin-3 and claudin-19 partially restore native phenotype to ARPE-19 cells via effects on tight junctions and gene expression.
Mutations of claudin-19 cause severe ocular deficits that are not easily reconciled with its role in regulating the outer blood retinal barrier. ARPE-19 is a widely used culture model of the retinal pigment epithelium (RPE). ARPE-19 is unique among epithelial cell lines, because it expresses all tight junction proteins except claudin family members. ARPE-19 also loses aspects of the RPE phenotype with cell passage. This study asks whether exogenous expression of the main RPE claudins, claudin-3 and claudin-19, would restore RPE phenotype, and whether these claudins have distinct roles in RPE. An Ussing chamber was used to measure the transepithelial electrical resistance and transepithelial electrical potential. These measurements were used to estimate the permeability co-efficients of ions. The transepithelial diffusion of polyethylene glycols were used to examine the leak pathway of tight junctions. Wound-healing, quantitative RT-PCR and immunoblotting examined diverse aspects of the RPE phenotype. Over-expression of either claudin decreased the permeability of small ions and polyethylene glycol. Both claudins were slightly cation-specific, but claudin-3 was less permeable to large solutes. Claudin expression widely affected gene expression to partially restore RPE phenotype. Claudins redistributed filamentous actin from stress fibers to circumferential bands associated with tight junctions, and made wound-healing more epithelial-like. Both claudins increased the expression of genes related to RPE core functions and increased steady-state levels of phosphorylated-AKT. In conclusion, claudin-3 and claudin-19 formed general permeability barriers and affected cell morphology, proliferation, migration, AKT signaling, and gene expression. When claudins are exogenously expressed, ARPE-19 more closely model native RPE.


Gene expression profile in mouse bacterial chronic rhinosinusitis.
Persistent infection in the paranasal sinuses impairs sinus drainage and leads to bacterial chronic rhinosinusitis. Greater knowledge of the key molecules in the pathology will help to clarify the pathogenesis. Study of the gene expression profile and analysis of the associated pathway is important to identify key molecules. This study investigates the expression of different genes and analyzes the key pathway in the pathological process of bacterial chronic rhinosinusitis. Bacterial chronic rhinosinusitis was induced in mice using a Merocel nasal pack inoculated with Staphylococcus aureus. Three months of mucosa samples were collected for histological and ELISA analysis, and gene expression was tested using DNA microarray. Differentially expressed genes were selected and verified for pathway analysis. The nasal mucosa of mice with chronic rhinosinusitis showed epithelial damage and lamina propria edema in extra cellular matrix with obvious mucosal inflammation. A total of 6,018 genes in bacterial chronic rhinosinusitis group were differentially expressed compared with the control. Among them, plasma, coagulation factors, urokinase plasminogen activator and urokinase receptor plasminogen activator expression were increased. Following gene ontology analysis and reverse transcription-quantitative polymerase chain reaction, coagulation cascades associated cytokines were found to be upregulated in bacterial chronic rhinosinusitis. The present results suggest that, bacterial chronic rhinosinusitis showed severe mucosal inflammation and genes differential expression in the pathogenesis. In this process, the coagulation cascades pathways were upregulated.


Pheromones and other semiochemicals of the acari.
In contrast to the exceptional diversity of semiochemical-regulated behavior in the insects, chemical communication in the Acari is restricted to a few limited roles. These include clustering, mate-finding processes, host- and food-finding processes, and dispersal. No evidence of pheromones regulating oviposition, necrophoric behavior, recognition of hive mates, or many other processes found in numerous insect groups has been reported in the Acari. Perhaps the most noteworthy feature of acarine pheromones or allomones is the use of the same or similar molecules by many species. Metastriate ixodids use volatile phenols to regulate courtship behavior and, in at least one species, feeding site selection and attachment as well. Argasid ticks use a water- or saline-soluble assembly pheromone, which appears to represent a single type of compound, if not the identical compound in all cases. Acarid mites use terpenoids as alarm pheromones and allomones, while certain phytoseiid and tetranychnid mites use terpene alcohols as arrestant sex pheromones. Another notable feature of acarine pheromones is the use of multicomponent signals to regulate different events in the behavioral process. Thus, two separate sex pheromones are necessary to successfully complete courtship in certain Dermacentor ticks, while three pheromones appear necessary to complete feeding-site selection, attachment, and clasping in certain Amblyomma species. In other cases, a combination of chemical and physiological signals is used to regulate courtship. Although the same or similar compounds may be used for chemical communication, no universal model describes the behavior of all species in an acarine family or order. Species-specific differences in perception of pheromone concentration, molecular composition, aphrodisiacs, and other selective signals facilitate species isolation, even though the initial steps in the behavior are similar in all species. This combination of unity and diversity allows economy in the biosynthesis of semiochemicals without compromising species integrity. In the brief period following the pioneering discoveries of pheromones in ticks (8) and mites (16, 17), evidence of a variety of acarine semiochemicals has been obtained, several pheromones and allomones have been identified, a sex pheromone gland has been described, and considerable effort has been directed to understanding the regulation of pheromone activity. Nevertheless, our knowledge of communication in this large and exceptionally diverse group is meager.(ABSTRACT TRUNCATED AT 400 WORDS)


Adjusting the number needed to treat: incorporating adjustments for the utility and timing of benefits and harms.
The number needed to treat is a unique and cognitively useful summary measurement for the description of medical treatments. However, the original concept lacks the means to account for multiple benefits and harms or differences in the utilities or timings of patient outcomes. The authors describe an "adjusted" number needed to treat that allows for the inclusion of multiple harms and benefits, and also adjustments for the utilities and timings of these outcomes. The expanded version offers a richer description of medical outcomes, and may be utilized as an adjunct to traditional risk-benefit, cost-effectiveness, and decision-analytic techniques.


The Laccase Gene Family Mediate Multi-Perspective Trade-Offs during Tea Plant (Camellia sinensis) Development and Defense Processes.
Laccase (LAC) plays important roles in different plant development and defense processes. In this study, we identified laccase genes (CsLACs) in Camellia sinensis cv 'Longjing43' cultivars, which were classified into six subclades. The expression patterns of CsLACs displayed significant spatiotemporal variations across different tissues and developmental stages. Most members in subclades II, IV and subclade I exhibited contrasting expression patterns during leaf development, consistent with a trade-off model for preferential expression in the early and late developmental stages. The extensive transcriptional changes of CsLACs under different phytohormone and herbivore treatment were observed and compared, with the expression of most genes in subclades I, II and III being downregulated but genes in subclades IV, V and VI being upregulated, suggesting a growth and defense trade-off model between these subclades. Taken together, our research reveal that CsLACs mediate multi-perspective trade-offs during tea plant development and defense processes and are involved in herbivore resistance in tea plants. More in-depth research of CsLACs upstream regulation and downstream targets mediating herbivore defense should be conducted in the future.


Autophagosome formation and molecular mechanism of autophagy.
Autophagy (macroautophagy), or the degradation of large numbers of cytoplasmic components, is induced by extracellular and intracellular signals, including oxidative stress, ceramide, and endoplasmic reticulum stress. This dynamic process involves membrane formation and fusion, including autophagosome formation, autophagosome-lysosome fusion, and the degradation of intra-autophagosomal contents by lysosomal hydrolases. Autophagy is associated with tumorigenesis, neurodegenerative diseases, cardiomyopathy, Crohn's disease, fatty liver, type II diabetes, defense against intracellular pathogens, antigen presentation, and longevity. Among the proteins and multimolecular complexes that contribute to autophagosome formation are the PI(3)-binding proteins, the PI3-phosphatases, the Rab proteins, the Atg1/ULK1 protein-kinase complex, the Atg9•Atg2-Atg18 complex, the Vps34-Atg6/beclin1 class III PI3-kinase complex, and the Atg12 and Atg8/LC3 conjugation systems. Two ubiquitin-like modifications, the Atg12 and LC3 conjugations, are essential for membrane elongation and autophagosome formation. Recent findings have revealed that processes of selective autophagy, including pexophagy, mitophagy, ERphagy (reticulophagy), and the p62-dependent degradation of ubiquitin-positive aggregates, are physiologically important in various disease states, whereas "classical" autophagy is considered nonselective degradation. Processes of selective autophagy require specific Atg proteins in addition to the "core" Atg complexes. Finally, methods to monitor autophagic activity in mammalian cells are described.


Fault Detection and Diagnosis of Railway Point Machines by Sound Analysis.
Railway point devices act as actuators that provide different routes to trains by driving switchblades from the current position to the opposite one. Point failure can significantly affect railway operations, with potentially disastrous consequences. Therefore, early detection of anomalies is critical for monitoring and managing the condition of rail infrastructure. We present a data mining solution that utilizes audio data to efficiently detect and diagnose faults in railway condition monitoring systems. The system enables extracting mel-frequency cepstrum coefficients (MFCCs) from audio data with reduced feature dimensions using attribute subset selection, and employs support vector machines (SVMs) for early detection and classification of anomalies. Experimental results show that the system enables cost-effective detection and diagnosis of faults using a cheap microphone, with accuracy exceeding 94.1% whether used alone or in combination with other known methods.


Mechanisms in organ allograft rejection. An experimental and clinical study.
Experimental and clinical aspects of organ allograft rejection were studied. The grafts of ten patients subjected to transplantectomy due to irreversible rejection or viral infection were investigated with immunohistochemistry. T lymphocytes were abundant in the cellular infiltrates of the rejected grafts and cells with 'helper/inducer' phenotype were more numerous than cells with 'suppressor/cytotoxic' phenotype. The expression of HLA-DR antigens was found to differ from that of HLA-DQ antigens in healthy human kidneys as well as in infected or rejected kidney grafts. HLA-DR but not -DQ antigens were thus detected in proximal tubular cells and increased during rejection or infection. Serum levels of interferon were found to be related to the occurrence of clinical signs of rejection or viral infection in renal transplant patients. Class II MHC antigen expression and cellular infiltrates were immunohistochemically characterized in untreated rejecting rat kidney grafts and were compared to the reactions of syngeneic renal grafts in the same model. The infiltrates of the syngeneic grafts were smaller and occurred later than those of the allografts and were dominated by cells with the 'helper/inducer' T cell phenotype. The number of class II antigen expressing renal tubules was markedly increased in allogeneic grafts and, to a lesser extent, also in syngeneic grafts. The effects of different monoclonal T cell antibodies were investigated in a rat heart allograft model. A 'pan' T cell antibody and a 'suppressor/cytotoxic' T cell antibody significantly prolonged graft survival and caused expression of class II antigen as well as of T cell 'suppressor/cytotoxic' antigen on graft parenchymal cells. Permanent survival of heart grafts could be achieved after induction with antithymocyte globulin. Grafts functioning for more than eight months were found to have myocardial fibrosis, intimal thickening and fibrosis of vessels, mild lymphocyte infiltration and increased class II antigen expression. The changes observed were similar to those seen in chronic rejection.


[Continuous oral hydration or with fractionated doses in acute diarrhea-induced dehydration in children].
To evaluate the safety and effectiveness of two oral rehydration techniques. A randomized clinical trial was conducted at the oral rehydration unit of Hospital Infantil de Mexico "Federico Gomez", between September 1998 and June 1999. Forty patients five-year old and younger children, dehydrated due to acute diarrhea, were given oral rehydration solution (ORS) ad libitum (AL group); another forty patients received ORS in fractionated doses (FD group). Clinical characteristics were similar in both groups. Results are presented as means, standard deviations and medians, according the distribution of simple and relative frequencies. The mean stool output in the AL group was 11.0 +/- 7.5 g/kg/h; as compared to 7.1 +/- 7.4 in the FD group (p = 0.03). ORS intake, rehydration time, and mean diuresis values were similar in both groups (p > 0.05). Six patients in the AL group and five in the FD group had high stool output (> 10 g/kg/h), that improved after administration of rice starch solution. One patient in the AL group and two in the FD group had persistent vomiting that improved with gastroclisis. No patient required intravenous rehydration. These results suggest that ORS administration ad libitum under supervision, is a technique as safe and effective as the fractionated doses technique, for the treatment of dehydrated children due to acute diarrhea.


Relational diagnosis: an idea whose time has come?
Many marital and family therapists in the U.S., as well as the major organizations to which they belong, recognize that the DSMs and ICDs have become the accepted manuals for classification of individual mental and emotional dysfunctions. Because we/they have come to believe that many disorders emanate from interpersonal problems rather than from individual intrapsychic distress, a strong movement has mushroomed to develop a diagnostic system that describes relational disorders and to press for the inclusion of these in future versions of DSM and ICD. This commentary chronicles the evolution and accomplishments to date of those involved in this effort.


Malnutrition risk in hospitalized children: use of 3 screening tools in a large European population.
Several malnutrition screening tools have been advocated for use in pediatric inpatients. We evaluated how 3 popular pediatric nutrition screening tools [i.e., the Pediatric Yorkhill Malnutrition Score (PYMS), the Screening Tool for the Assessment of Malnutrition in Pediatrics (STAMP), and the Screening Tool for Risk of Impaired Nutritional Status and Growth (STRONGKIDS)] compared with and were related to anthropometric measures, body composition, and clinical variables in patients who were admitted to tertiary hospitals across Europe. The 3 screening tools were applied in 2567 inpatients at 14 hospitals across 12 European countries. The classification of patients into different nutritional risk groups was compared between tools and related to anthropometric measures and clinical variables [e.g., length of hospital stay (LOS) and infection rates]. A similar rate of completion of the screening tools for each tool was achieved (PYMS: 86%; STAMP: 84%; and STRONGKIDS: 81%). Risk classification differed markedly by tool, with an overall agreement of 41% between tools. Children categorized as high risk (PYMS: 25%; STAMP: 23%; and STRONGKIDS: 10%) had a longer LOS than that of children at low risk (1.4, 1.4, and 1.8 d longer, respectively; P < 0.001). In high-risk patients identified with the PYMS, 22% of them had low (<-2) body mass index (BMI) SD-scores (SDSs), and 8% of them had low height-for-age SDSs. For the STAMP, the percentages were 19% and 14%, respectively, and for the STRONGKIDS, the percentages were 23% and 19%, respectively. The identification and classification of malnutrition risk varied across the pediatric tools used. A considerable portion of children with subnormal anthropometric measures were not identified with all of the tools. The data obtained do not allow recommending the use of any of these screening tools for clinical practice. This study was registered at clinicaltrials.gov as NCT01132742.


Computational analysis of genome-wide DNA methylation during the differentiation of human embryonic stem cells along the endodermal lineage.
The generation of genome-wide data derived from methylated DNA immunoprecipitation followed by sequencing (MeDIP-seq) has become a major tool for epigenetic studies in health and disease. The computational analysis of such data, however, still falls short on accuracy, sensitivity, and speed. We propose a time-efficient statistical method that is able to cope with the inherent complexity of MeDIP-seq data with similar performance compared with existing methods. In order to demonstrate the computational approach, we have analyzed alterations in DNA methylation during the differentiation of human embryonic stem cells (hESCs) to definitive endoderm. We show improved correlation of normalized MeDIP-seq data in comparison to available whole-genome bisulfite sequencing data, and investigated the effect of differential methylation on gene expression. Furthermore, we analyzed the interplay between DNA methylation, histone modifications, and transcription factor binding and show that in contrast to de novo methylation, demethylation is mainly associated with regions of low CpG densities.


Positive Effects of an Online Workplace Exercise Intervention during the COVID-19 Pandemic on Quality of Life Perception in Computer Workers: A Quasi-Experimental Study Design.
Computer workers' sedentary work, together with less active lifestyles, aggravated by the COVID-19 pandemic, represents a high risk for many chronic diseases, leading to a decrease in health-related quality of life (QoL). Workplace exercises consist of a set of physical exercises, implemented during work breaks, that have multiple benefits for workers' health. To assess the impact of online workplace exercises on computer workers' perception of quality of life. Quasi-experimental study with two groups: a control group (n = 26) and an intervention group (n = 13). The inclusion criteria were that participants must be aged between 18 and 65 years old and the exclusion criteria included diagnosis of non-work-related medical conditions. The interventions consisted of workplace exercises, which were applied for 17 consecutive weeks, each session lasting 15 min, three times a week. The exercise programme, performed online and guided by a physiotherapist, consisted of mobility exercises, flexibility and strength exercises, with the help of a TheraBand® for elastic resistance. The control group were not subjected to any intervention. A socio-demographic questionnaire and the Health Survey Questionnaire (SF-36v2) were used in two assessment stages (M0-baseline and M1-final of intervention). A mixed ANOVA with interaction time*group was used to evaluate the effect of the exercise programme. A good perception of the QoL was obtained in both stages. The exercise programme had a positive effect in the domains of Pain (ptime*group = 0.012, η2p = 0.158), Physical Function (ptime*group = 0.078, η2p = 0.082), Physical Performance (ptime*group = 0.052, η2p = 0.098), and Emotional Performance (ptime*group = 0.128, η2p = 0.061). After 17 weeks of workplace exercises, it became clear that the intervention group positively increased their QoL perception, with this improvement being significant in the Pain domain, which resulted in an improvement in their health condition. Therefore, further studies are needed to determine the optimal exercise for CWs, with detailed exercise types, different intensities and focused on various health conditions.


Contrast Sensitivity after Pars Plana Vitrectomy: Comparison between Macula-On and Macula-Off Rhegmatogenous Retinal Detachment.
To evaluate the contrast sensitivity (CS) of eyes successfully repaired by vitrectomy for rhegmatogenous retinal detachment (RRD) with or without preoperative macular involvement. In this retrospective, consecutive, interventional case series, 109 eyes received primary vitrectomy for RRD, of which 36 with at least 12 months of follow-up and a best-corrected visual acuity (BCVA) ≥1 at 12 months postoperatively were investigated. The main outcome measurements were BCVA and CS at 12 months postoperatively. Patients with macula-on RRD preoperatively were included in the macula-on group, and patients with macula-off RRD preoperatively were included in the macula-off group. The between-group difference in CS under evening vision conditions was measured with a Takagi glare tester CGT-2000 at 6 visual angles and 13 contrast levels with and without glare. CS was significantly lower in the macula-off group for targets with visual angles of 1.6, 1.0, and 0.64° with glare (p < 0.05) and for the target with a visual angle of 0.64° without glare (p < 0.05). CS in the higher spatial frequency range (especially with glare) is reduced in macula-off RRD patients with good postoperative BCVA compared to macula-on RRD patients with good postoperative BCVA.


Metformin and energy metabolism in breast cancer: from insulin physiology to tumour-initiating stem cells.
A whole new area of investigation has emerged recently with regards to the anti-diabetic drug metformin and breast cancer. Metformin's anti-breast cancer actions, observed in population studies, in rodents and in cultured tumour cells, are especially encouraging because they attack not only the most common bulk of the tumour cells but also the more rare tumour-initiating stem cells. Here, we illustrate the multifaceted and redundant mechanisms through which metformin-reprogrammed energy metabolism at both the organismal and cellular levels constitutes a novel and valuable strategy to prevent and treat breast cancer disease.


Use of inhaled corticosteroids following discharge from an emergency department for an acute exacerbation of asthma.
Most patients who have an asthma exacerbation leading to a visit to an emergency department (ED) will benefit from treatment with inhaled corticosteroids (ICS) at discharge. We investigated whether asthmatic children and adolescents were receiving ICS after discharge from the ED and identified the characteristics of patients and physicians associated with their use. A cohort of 4042 asthmatic patients aged 5-17 years was selected from the administrative database of the Regie de l'assurance maladie du Quebec between 1997 and 1999. The proportion of patients using ICS 1, 3, and 6 months after ED discharge was estimated. Using GEE models the independent contribution of sociodemographic variables, markers of asthma severity, prior use of healthcare services and ICS, and physician characteristics was investigated on the likelihood of using ICS after ED discharge. 68% of children and 51% of adolescents had a valid prescription for ICS in the month following discharge. At 6 months after discharge the corresponding figures were 77% and 60%. The strongest predictors of ICS use were age, with adolescents being less likely to use ICS than children (OR 0.49; 95% CI 0.43 to 0.56), prior use of ICS (OR 2.28; 95% CI 2.00 to 2.61), and filling a prescription for oral corticosteroids in the month following discharge (OR 2.29; 95% CI 2.03 to 2.58). However, patients who had an ED visit or a hospital admission for asthma during the 6 months before discharge were not more likely to use ICS after discharge. A large proportion of patients with clear markers of uncontrolled or severe asthma did not have a valid prescription for an ICS after discharge from the ED.


The burden of nail psoriasis: an introduction.
Nail involvement is an extremely common feature of psoriasis and affects approximately 50% of patients. Despite this, it is an often overlooked feature of the disease, and treatment tends to be focused on clearing the cutaneous component of psoriasis. Clinical manifestations of nail psoriasis are pitting, discolouration, onycholysis and subungual hyperkeratosis as well as nail plate crumbling and splinter haemorrhages. Nail psoriasis is associated with discomfort in many patients and leads to significant functional impairment and psychological stress. The often distressing appearance of affected nails impacts the patient tremendously in both work and social activities. Importantly, 80% of patients with psoriatic arthritis have nail psoriasis. This review discusses the incidence of nail psoriasis and the burden on the patient and illustrates when dermatologists are strategically placed to detect the early signs of more severe disease by promptly diagnosing and managing the nail component of psoriasis.


Stigma experienced by persons under psychiatric care.
Mental health-related stigma causes suffering and interferes with care and social inclusion. This study explored stigma as experienced by mental health service users. Particular attention is given to their use of coping mechanisms. Interviews were held with 167 adults undergoing outpatient psychiatric treatment; two-thirds of them had previously been hospitalized. Examples of frequency of stigma-related situations included the following: Over half of service users expect people to refuse to have a person with a mental disorder as a co-worker or neighbor, or to engage in other types of social contact. A sizeable group acknowledged that they feared or had experienced rejection. A third of respondents reported they feared or had experienced inappropriate treatment by their doctor. Service users utilize several coping mechanisms to deal with stigma, among them: education, withdrawal, secrecy, and positive distinctiveness. Although we studied a convenience sample of service users, our findings provide sufficient basis to suggest different types of intervention, i.e., to address stigma in the course of treatment in the specialist settings, to promote the establishment of mutual support groups, and to raise family physicians' awareness with regard to the stigma that may be present when caring for persons with mental disorders.


The Transcriptome and Flux Profiling of Crabtree-Negative Hydroxy Acid-Producing Strains of Saccharomyces cerevisiae Reveals Changes in the Central Carbon Metabolism.
Saccharomyces cerevisiae (S. cerevisiae) is the yeast cell factory of choice for the production of many biobased chemicals. However, it is a Crabtree-positive yeast and so shuttles a large portion of carbon into ethanol. Ethanol formation can be eliminated by deleting pyruvate decarboxylase (PDC) activity. It is not yet well understood how PDC-negative yeasts are affected when engineered to produce other products than ethanol. In this study, pathways are introduced for the production of three hydroxy acids (lactic, malic, or 3-hydroxypropionic acid [3HP]) into an evolved PDC-negative strain. These strains are characterized via transcriptome and flux profiling to elucidate the effects that the production of these hydroxy acids has on the host strain. Expression of lactic and malic acid biosynthesis pathways improved the maximum specific growth rate (μmax ) of the strain by 64% and 20%, respectively, presumably due to nicotinamide adenine dinucleotide regeneration. All strains show a very high flux ( > 90% of glucose uptake) into the oxidative pentose phosphate pathway under batch fermentation conditions. The study, for the first time, directly compares the flux and transcriptome profiles of several hydroxy acid-producing strains of an evolved PDC-negative S. cerevisiae and suggests directions for future metabolic engineering.


Improved pupil dilation with medication-soaked pledget sponges.
Use of multiple preoperative drops for pupil dilation has been shown to be inexact, to delay surgery, and to cause dissatisfaction among perioperative personnel. This article reports on an evidence-based, quality improvement project to locate and appraise research on improved effectiveness and efficiency of mydriasis (ie, pupillary dilation), and the subsequent implementation of a pledget-sponge procedure for pupil dilation at one ambulatory surgery center. Project leaders used an evidence-based practice model to assess the problem, research options for improvement, define goals, and implement a pilot project to test the new dilation technique. Outcomes from the pilot project showed a reduced number of delays caused by poor pupil dilation and a decrease in procedure turnover time. The project team solicited informal feedback from preoperative nurses, which reflected increased satisfaction in preparing patients for cataract procedures. After facility administrators and surgeons accepted the procedure change, it was adopted for preoperative use for all patients undergoing cataract surgery at the ambulatory surgery center.


Apoptotic cell administration is detrimental in murine renal ischaemia reperfusion injury.
Acute kidney injury induced by renal ischaemia reperfusion injury (IRI) is characterised by renal failure, acute tubular necrosis (ATN), inflammation and microvascular congestion. The administration of apoptotic cells (ACs) has been shown to reduce inflammation in various organs including the liver and kidney. This study explored whether AC administration prior to the induction of renal IRI was protective. Renal IRI was induced in Balb/c mice by clamping the renal blood vessels for either 20, 24 or 25 minutes to induce mild, moderate or severe kidney dysfunction respectively. Renal function and injury was determined 24 hours following IRI by measurement of plasma creatinine and ATN scoring respectively. ACs were generated from Balb/c thymocytes and classified as either predominantly early or late apoptotic by Annexin-V and propidium iodide staining. Early AC administration prior to severe IRI had no influence on plasma creatinine or ATN severity. In contrast, administration of early or late ACs significantly worsened renal function in mice with mild or moderate renal IRI, respectively, compared to PBS treated controls, though ATN scores were comparable. Despite ACs exerting pro-coagulant effects, the worsening of renal function was not secondary to increased microvascular congestion, inferred by fibrin and platelet (CD41) deposition, or inflammation, assessed by neutrophil infiltration. Despite the AC-derived protection demonstrated in other organs, ACs do not protect mice from renal IRI. ACs may in fact further impair renal function depending on injury severity. These data suggest that AC-derived protection is not translationally relevant for patients with acute kidney injury induced by ischaemic injury.


Port exteriorization appendectomy: is it the future?
The time honoured surgical procedure open appendectomy seems to be on the decline, it may be replaced in the modern era by laparoscopic appendectomy ("in appendectomy") performed with three trocars, or by the port exteriorization appendectomy ("out appendectomy") which can be done with two ports or even one. These techniques combine the benefits of decreased tissue trauma and operative time in addition to other advantages of minimal invasion. We conducted this study to know the effectiveness of Port Exteriorization Appendectomy, to analyze its complications and to assess the conversion rate. A one year prospective study consisted of fifty cases; a combination of emergency and elective group. They were operated under general anaesthesia and different variables were documented. Mean operative time, conversion rate, hospital stay, complications and patient satisfaction. There were 27 females with the (F: M) ratio of 1.17:1. The operative time of 23.3 mins, conversion in 4 (8.0%) patients and 2.4 days of hospital stay contributed to 86.0% operative success rate. Surgical site infection was seen in 5 (10.0%) patients and one (2.0%) developed pelvic abscess. On analysis of the satisfaction level, 44(93.6%) were completely satisfied and one (2.1%) patient seemed disappointed with the technique for cosmesis though, 42 (89.3%) remained completely satisfied and 5(10.7%) didn't like their scars. Port exteriorization appendectomy's efficacy can be verified by 86.0% success rate, operative time of 23.3 mins, indoor stay of 2.4 days, and minimal undesirable sequlae. However, more authentic results could be obtained if this technique is compared to open or laparoscopic appendectomy in a well designed randomized controlled clinical trial.