Fear relevance and diminution of unconditioned skin conductance responses.
According to Donegan and Wagner's priming model [1987], a signalled UCS will elicit a smaller UCR than an unsignalled UCS. Assuming that fear-relevant CSs are good predictors of aversive UCSs, while fear-irrelevant CSs are relatively bad predictors of aversive UCSs, the present study examined the effect of fear relevance on electrodermal UCR diminution during the acquisition phase of a single cue conditioning procedure. Four groups were studied, each of which consisted of 12 subjects. Group 1 had a fear-relevant CS (a slide of an angry face) paired with a UCS (7 mA shock), whereas group 2 had a fear-irrelevant CS (a slide of a happy face) paired with a UCS. Groups 3 and 4 had unpaired presentations of the CS and UCS and served as control groups for 1 and 2. There were 4 habituation, 8 acquisition, 4 recovery (UCS-only), and 6 extinction (CS-only) trials. While overall UCR levels were lower in the paired than in the unpaired control groups, it was also found that the size of UCR decrement and subsequent recovery was greater in the angry face CS-paired group than in the happy face CS-paired group. This finding is in line with the predictions that flow from the Donegan and Wagner model.


Work Disability Trajectories Among Individuals with a Sick-Leave Spell Due to Depressive Episode ≥ 21 Days: A Prospective Cohort Study with 13-Month Follow Up.
Background Despite the increasing pattern of sick leave associated with depression in western countries, little is known about future work disability patterns among such sickness absentees. Aim To identify work disability (sick leave and disability pension) trajectories after the 21st day of a sick-leave spell due to depressive episode, and to investigate sociodemographic and morbidity characteristics of individuals in different trajectory groups. Methods This is a prospective cohort study using Swedish nationwide register data. We studied future work disability days (mean net days of sick leave and disability pension per month) among all individuals with a new sick-leave spell due to depressive episode (ICD-10 F32) ≥ 21 days during the first 6 months of 2010 (n = 10,327). Using group-based trajectory modeling, we identified work disability trajectories for the following 13 months. BIC value, group sizes, and average group probability were used to determine number of trajectories. Sociodemographic and morbidity characteristics were compared by χ2 tests. Results We identified six trajectories of work disability: "decrease to 0 after 4 months" (43% of the cohort); "decrease to 0 after 9 months" (22%); "constant high" (11%); "decrease, then high increase" (9%); "slow decrease" (9%); and "decrease, then low increase" (6%). Those in the groups "constant high" and "decrease then high increase" were older and had the highest proportion with sick leave the year before. Conclusion A majority of the cohort (65%) had no work disability by the end of follow up. Sociodemographic and morbidity characteristics differed between trajectory groups among people on sick leave due to a depressive episode.


The effect of combined immunosuppression with systemic low-dose cyclosporin and topical fluocinolone acetonide on the survival of rat hind-limb allografts.
Sixty rat hind-limb allotransplantations across strong histocompatibility barriers were performed. Group I (isograft controls), (Lewis-Brown-Norway [LBN] to LBN) limb transplantations were performed; Group II (rejection controls), LBN limbs transplanted to Lewis rat LEW recipients with no immunosuppressive treatment; Group III (steroid group), fluocinolone acetonide (50 micrograms/ml) was applied topically; Group IV (cyclosporine group), 4 mg/kg of cyclosporine was administered subcutaneously daily; Group V (combination group), combined systemic cyclosporine with topical fluocinolone acetonide was administered daily. Group II: Limb rejection was present on the fourth day. Group III: Limb survival was extended for 3 weeks with no signs of skin rejection in 75% of animals. Group IV: Rejection was complete at 3 weeks. Group V: Limbs survived to 6 weeks. Topical steroid prevented skin rejection and delayed rejection of other components of the composite allograft. Combined treatment of topical steroid and low cyclosporine doses significantly extended survival rate of limb allografts.


HPLC-MS-based untargeted metabolomic analysis of differential plasma metabolites and their associated metabolic pathways in reproductively anosmic black porgy, Acanthopagrus schlegelii.
Olfaction, a universal form of chemical communication, is a powerful channel for animals to obtain social and environmental cues. The mechanisms by which fish olfaction affects reproduction, breeding and disease control are not yet clear. To evaluate metabolites profiles, plasma from anosmic and control black porgy during reproduction was analyzed by non-targeted metabolomics using ultra high-performance liquid chromatography-mass spectrometry and multivariate statistical analysis techniques, including principal component analysis and orthogonal partial least squares discriminant analysis. The metabolite profiles of anosmia and control groups were found to be significantly separated. Ten different differential metabolites, mainly including amino acids, such as isoleucine and methionine, and lipids, such as phosphatidylserine, were screened based on the combined analysis of variable importance in the projection and p values. In addition, six key differential metabolic pathways were analyzed using the Kyoto Encyclopedia of Genes and Genomes and enriched for four metabolic pathways including the citrate acid (TCA) cycle, tyrosine metabolism, arginine and proline metabolism, and arginine synthesis. The TCA cycle enhances fertility through the reduction of pyruvate kinase, and intermediate derivatives (acetyl CoA, malonyl CoA) act as signaling factors that regulate immune cell function. The tyrosine cycle can indirectly participate and promote reproduction in black porgy through melanin-concentrating hormone. Arginine and proline metabolism can promote reproduction by promoting growth hormone and enhance immunity in anosmic black porgy by stimulating T lymphocytes. Our metabolomic study revealed that anosmia in black porgy played an active role in immunity and reproduction and provided theoretical support for breeding and disease control.


Frail2Fit study protocol: a feasibility and acceptability study of a virtual multimodal intervention delivered by volunteers to improve functional outcomes in older adults with frailty after discharge from hospital.
Physical activity (PA) and replete nutritional status are key to maintaining independence and improving frailty status among frail older adults. In response to the COVID-19 pandemic, healthcare has increasingly turned to virtual modes of delivery and there is interest in the use of trained volunteers to deliver PA and nutrition interventions. We aim to evaluate the feasibility and acceptability of training hospital volunteers to deliver an online intervention, comprising exercise, behaviour change and nutrition support, to older people with frailty after discharge from hospital. We will use a quasi-experimental mixed methods approach. Hospital volunteers (n=6) will be trained to deliver an online, 3-month, multimodal intervention to frail (Clinical Frailty Scale ≥5) adults ≥65 years (n=30) after discharge from hospital. Feasibility will be assessed by determining the number of volunteers recruited, trained and retained at the end of the study; the proportion of intervention sessions delivered; participant recruitment, retention and adherence to the intervention. To determine the acceptability of the intervention, interviews will be conducted among a purposive sample of older adults, and volunteers. Secondary outcomes will include physical function, appetite, well-being, quality of life, anxiety and depression, self-efficacy for managing chronic disease and PA. Outcomes will be measured at baseline, 3 months and 6 months. Descriptive statistics will be used to describe feasibility and adherence to the intervention. Secondary outcomes at baseline will be compared at 3 and 6 months. Interviews will be transcribed verbatim and analysed using thematic analysis. Health Research Authority ethical approval was obtained on 30 May 2022 (reference: 22/WA/0155). Results will be disseminated through peer-reviewed journal articles, volunteer organisations, National Health Service communication systems and social media platforms. A toolkit will be developed to facilitate roll out of volunteer training. NCT05384730.


Synthesis, Spectroscopic, X-ray Diffraction and DFT Studies of Novel Benzimidazole Fused-1,4-Oxazepines.
A series of benzimidazole-tethered oxazepine heterocyclic hybrids has been synthesized in good to excellent yields from an N-alkylated benzimidazole 2-carboxaldehyde, which in turn was accomplished from o-phenylenediamine in three good yielding steps. The calculated molecular structure of compounds 2-methyl-4-(2-((phenylimino)methyl)-1H-benzo-[d]imidazol-1-yl)-butan-2-ol 9 and 10 3,3-dimethyl-N-phenyl-1,2,3,5-tetrahydrobenzo-[4,5]imidazo[2,1-c][1,4]oxazepin-5-amine using the B3LYP/6-31 G(d, p) method were found to agree well with their X-ray structures. The charge distributions at the different atomic sites were computed using the natural bond orbital (NBO) method. The regions of electrophilic and nucleophilic reactivity were shown using a molecular electrostatic potential (MEP) map. In addition, the frontier molecular orbitals of these compounds were discussed at the same level of theory. Nonlinear optical (NLO) properties have also been investigated by computational hyperpolarizability studies, and it was found that Compound 9 is the best candidate for NLO applications.


Total-scattering pair-distribution function of organic material from powder electron diffraction data.
This paper shows that pair-distribution function (PDF) analyses can be carried out on organic and organometallic compounds from powder electron diffraction data. Different experimental setups are demonstrated, including selected area electron diffraction and nanodiffraction in transmission electron microscopy or nanodiffraction in scanning transmission electron microscopy modes. The methods were demonstrated on organometallic complexes (chlorinated and unchlorinated copper phthalocyanine) and on purely organic compounds (quinacridone). The PDF curves from powder electron diffraction data, called ePDF, are in good agreement with PDF curves determined from X-ray powder data demonstrating that the problems of obtaining kinematical scattering data and avoiding beam damage of the sample are possible to resolve.


[Efficiency of structural antigipoxants in perioperative period of patients with lower limbs fractures].
The aim of the study was to study the effectiveness of pathogenetic correction of the metabolism with the inclusion of reamberin (1.5% sodium meglumine succinate solution) in patients with lesions of large segments of the lower limbs. In connection with the task, the efficiency pathogenetic correction of metabolism in 211 patients with diaphyseal hip and shin bones fractures had been analyzed. Patients were divided into the main and control groups. In the main group (86 patients), intravenous infusions of reamberin were administered intravenously at a rate of 1 ml/min at a rate of 10 ml/kg of body weight 1 time per day, a course of 10 days. Patients in the comparison group (125 patients) received an infusion therapy with isotonic solution. The parameters of functional activity and peripheral blood dates had been analyzed. The analysis showed that the use of antihypoxants in the perioperative period provides an earlier recovery of the physical component of quality of life in patients with lesions of large segments of the lower limbs that have undergone stably - functional osteosynthesis according to the principles of Damage control.


Relations between multi-informant assessments of ADHD symptoms, DAT1, and DRD4.
Researchers conducting candidate gene studies of attention-deficit/hyperactivity disorder (ADHD) typically obtain symptom ratings from multiple informants (i.e., mothers, fathers, and teachers) and use a psychologist's best estimate or a simple algorithm, such as taking the highest symptom ratings across informants, to construct diagnostic phenotypes for estimating association. Nonetheless, these methods have never been empirically validated in the context of a molecular genetic study. In the current study, the authors systematically evaluated several methods of operationalizing phenotypes and the resulting evidence for association between ADHD and the candidate genes: dopamine transporter gene (DAT1) and dopamine D4 receptor gene (DRD4). Use of symptom scores as continuous scales in regression analysis suggested that the combination of mother and teacher ratings yielded the strongest evidence for association between hyperactive-impulsive ADHD symptoms and DAT1 and between inattentive ADHD symptoms and DRD4. Teacher ratings alone were sufficient for evaluating the association between inattentive symptoms and DAT1. Further, this regression-based method consistently yielded stronger evidence for association among ADHD symptoms, DAT1, and DRD4 than did three simple algorithms (i.e., the and, or, and averaging rules). The implications of these results for future molecular genetic studies of ADHD are discussed.


Long-distance activation of the Myc protooncogene by provirus insertion in Mlvi-1 or Mlvi-4 in rat T-cell lymphomas.
T-cell lymphomas induced by Moloney murine leukemia virus frequently have proviruses integrated at the Mlvi-4 and Mlvi-1 loci, which map approximately 30 and 270 kilobases 3' of the promoter region of the Myc protooncogene, respectively. Provirus insertion in these loci is responsible for the activation of adjacent genes. To determine whether Myc expression was also affected by these provirus insertions, we constructed T-cell hybrids between two rat thymic lymphomas containing a provirus in Mlvi-4 or Mlvi-1 and the murine T-cell lymphoma line BW5147. These hybrids segregated the provirus-containing rearranged alleles from the normal nonrearranged alleles of Mlvi-4 and Mlvi-1, and they carried an intact copy of rat Myc. Using an S1 nuclease protection assay, we observed that the expression of the rat Myc cosegregated with the rearranged Mlvi-4 or Mlvi-1 locus. However, provirus insertion in these loci had no effect on promoter utilization or on the expression of the murine Myc locus. We conclude that provirus insertion exerts a long-range cis effect on the expression of Myc. Therefore, provirus integration in a single locus may affect the expression of multiple genes, some of which may be located a long distance from the site of integration.


Poverty and childhood malnutrition: Evidence-based on a nationally representative survey of Bangladesh.
Malnutrition contributes to children's morbidity and mortality, and the situation undermines the economic growth and development of Bangladesh. Malnutrition is associated with lower levels of education that decrease economic productivity and leads to poverty. The global burden of malnutrition continues to be unacceptably high amid social and economic growth, including in Bangladesh. Therefore, identifying the factors associated with childhood malnutrition and poverty is necessary to stop the vicious cycle of malnutrition leaded poverty. The study utilized the 2017-18 Bangladesh Demographic and Health Survey (BDHS), accumulating 7,738 mother-child pairs. Associations between potential risk factors and nutritional status were determined using chi-square tests, and multivariate logistic regression models were utilized on significant risk factors to measure their odds ratio (OR) with their 95% confidence intervals (CI). The prevalence of moderate and severe wasting was 7.0% and 1.8%, respectively, whereas the prevalence of moderate and severe stunting was 19.2% and 8.0%, while 16.4% and 3.6% of children were moderately and severely underweight. Children from the poorest and poor households were suffering from at least one form of malnutrition. Adjusted ORs were estimated by controlling socio-economic and demographic risk factors, such as poor maternal body mass index, parents' lower education level, use of unhygienic toilet, child age in months, and recent experience of diarrhea and fever. The pattern was almost similar for each malnutrition status (i.e., stunting, underweight, and wasting) in the poorest and poor households. Bangladesh achieved the Millennium Development Goals, focusing primarily on health-related indicators and working to achieve the Sustainable Development Goals. Even considering this success, the prevalence of malnutrition and poverty in same household remains relatively high compared to other developing countries. Therefore, the study recommends the implementation of nationwide systematic measures to prevent poverty and malnutrition.


Bacteria reactive to plaque-toxin-neutralizing monoclonal antibodies are related to the severity of gingivitis at the sampled site.
Certain monoclonal antibodies (Mabs) neutralize the inhibition of HL60 cell growth by bacterial plaque extracts. The aim of this study was to enumerate and identify the bacteria reactive to these Mabs at sites where periodontal disease was measured by gingival index, pocket depth and attachment loss. The bacterial colonies were grown on blood agar and the colonies counted directly and after immunoblotting. Sites that bled on probing (n = 15) had a mean of 3.35% Mab-positive colonies (SEM = 0.52%) and sites that did not bleed (n = 9) had a mean of 1.61% (SEM = 0.41%). The percentage of Mab-positive colonies also correlated with gingival index but not with the total number of colonies sampled, attachment loss or pocket depth. Antigen was expressed by 4 genera: strains of Streptococcus sanguis and/or Eikenella corrodens (8 sites), Staphylococcus epidermidis (4 sites) and Corynebacterium minutissimus (1 site). The results suggest that the antigens detected on these bacteria by the Mabs may be processed to form toxins and maintain gingivitis by irritating the surrounding cells.


Cloning of flanking sequence in transgenic plants by restriction site-anchored single-primer polymerase chain reaction.
Determining the insertion position of an exogenous gene in the target plant genome is one of the main issues in the transgenic plant field. This study introduced a simple, rapid, and accurate method to clone the flanking sequences of the transgenic bar gene as the anchoring gene in the transgenic maize genome using single-primer polymerase chain reaction (PCR). This method was based on the distribution of restriction sites in the maize genome and adopted the single-primer PCR method. Cloning the flanking sequences with the restriction site-anchored single-primer PCR simplified the experimental procedures by about 70% and reduced the experimental time by more than 80%. In conclusion, the restriction site-anchored single-primer PCR was a simple, rapid method to obtain the unknown flanking sequences in the transgenic plants.


Biotinylation of an enkephalin-containing heptapeptide via various spacer arms. Synthesis, comparative binding studies toward avidin, and application as substrates in enzymatic reactions.
The preparation of an enkephalin-containing heptapeptide of the sequence Tyr-Gly-Gly-Phe-Leu-Arg-Arg-OH with a biotinyl moiety linked to the carboxy terminus is described. A series of biotinylated derivatives, each containing a different linker (LC) moiety between the biotin function and the carboxyterminal Arg residue, were synthesized by solution-phase chemistry following the coupling of the side chain protected peptide with previously prepared appropriate biotinylamine derivative. Both linear and flexible spacer arms of variable chain lengths [LC = (CH2)x, x = 2, 4, or 6] as well as semirigid cyclohexyl spacers (racemic 1,2-cyclohexane, cis or trans) were incorporated. The relative binding aptitudes of these molecules toward the glycoprotein, avidin, either in immobilized form or in solution were compared using both 125I-labeled and unlabeled peptide derivatives and were found to be in the following order, trans > or = 6C > 4C > 2C > cis. The potential application of these materials as substrates for enzymatic analysis is illustrated for one of the derivatives, namely the LC-2C analogue.


ALDH2 restores exhaustive exercise-induced mitochondrial dysfunction in skeletal muscle.
Mitochondrial aldehyde dehydrogenase 2 (ALDH2) is highly expressed in heart and skeletal muscles, and is the major enzyme that metabolizes acetaldehyde and toxic aldehydes. The cardioprotective effects of ALDH2 during cardiac ischemia/reperfusion injury have been recognized. However, less is known about the function of ALDH2 in skeletal muscle. This study was designed to evaluate the effect of ALDH2 on exhaustive exercise-induced skeletal muscle injury. We created transgenic mice expressing ALDH2 in skeletal muscles. Male wild-type C57/BL6 (WT) and ALDH2 transgenic mice (ALDH2-Tg), 8-weeks old, were challenged with exhaustive exercise for 1 week to induce skeletal muscle injury. Animals were sacrificed 24 h post-exercise and muscle tissue was excised. ALDH2-Tg mice displayed significantly increased treadmill exercise capacity compared to WT mice. Exhaustive exercise caused an increase in mRNA levels of the muscle atrophy markers, Atrogin-1 and MuRF1, and reduced mitochondrial biogenesis and fusion in WT skeletal muscles; these effects were attenuated in ALDH2-Tg mice. Exhaustive exercise also enhanced mitochondrial autophagy pathway activity, including increased conversion of LC3-I to LC3-II and greater expression of Beclin1 and Bnip3; the effects of which were mitigated by ALDH2 overexpression. In addition, ALDH2-Tg reversed the increase of an oxidative stress biomarker (4-hydroxynonenal) and decreased levels of mitochondrial antioxidant proteins, including manganese superoxide dismutase and NAD(P)H:quinone oxidoreductase 1, in skeletal muscle induced by exhaustive exercise. ALDH2 may reverse skeletal muscle mitochondrial dysfunction due to exhaustive exercise by regulating mitochondria dynamic remodeling and enhancing the quality of mitochondria.


Methylation and expression of mismatch repair gene human mutS homolog 2 in myelodysplastic syndromes.
As a highly heterogeneous disease, the pathogenesis of myelodysplastic syndrome (MDS) has not been well defined. In the present study, human mutS homolog 2 (hMSH2) promoter methylation was detected with methylation-specific polymerase chain reaction (PCR). The function of hMSH2 was analyzed by microsatellite instability (MSI) detection of BAT-26, and hMSH2 expression was evaluated using reverse transcription-quantitative PCR in 60 patients with MDS. The results revealed methylation of the hMSH2 promoter in 18 patients with MDS who have an overall prevalence of 30% (95% confidence interval, 18.4-41.6%). Among the patients with hMSH2 methylation, 2 patients exhibited MSI. It was demonstrated that hMSH2 promoter methylation was increased in MDS with an increase in Revised International Prognostic Scoring System (IPSS-R) risk, and patients with higher hMSH2 promoter methylation had shorter overall survival by Kaplan-Meier analysis (P=0.011). In addition, it was also observed that decreased hMSH2 mRNA expression was associated with high IPSS-R risk group (high/very high vs. intermediate, P=0.003), and hMSH2 mRNA expression in CD34 positive bone marrow cells was lower compared with that in CD34 negative cells of patients with MDS (P=0.029). Methylation of hMSH2 may be valuable for prognostic evaluation and progression prediction of MDS. Furthermore, hMSH2 may serve a key function in the pathogenesis and prognosis of MDS.


Molecular Subtypes of Oral Squamous Cell Carcinoma Based on Immunosuppression Genes Using a Deep Learning Approach.
Background: The mechanisms through which immunosuppressed patients bear increased risk and worse survival in oral squamous cell carcinoma (OSCC) are unclear. Here, we used deep learning to investigate the genetic mechanisms underlying immunosuppression in the survival of OSCC patients, especially from the aspect of various survival-related subtypes. Materials and methods: OSCC samples data were obtained from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), and OSCC-related genetic datasets with survival data in the National Center for Biotechnology Information (NCBI). Immunosuppression genes (ISGs) were obtained from the HisgAtlas and DisGeNET databases. Survival analyses were performed to identify the ISGs with significant prognostic values in OSCC. A deep learning (DL)-based model was established for robustly differentiating the survival subpopulations of OSCC samples. In order to understand the characteristics of the different survival-risk subtypes of OSCC samples, differential expression analysis and functional enrichment analysis were performed. Results: A total of 317 OSCC samples were divided into one inferring cohort (TCGA) and four confirmation cohorts (ICGC set, GSE41613, GSE42743, and GSE75538). Eleven ISGs (i.e., BGLAP, CALCA, CTLA4, CXCL8, FGFR3, HPRT1, IL22, ORMDL3, TLR3, SPHK1, and INHBB) showed prognostic value in OSCC. The DL-based model provided two optimal subgroups of TCGA-OSCC samples with significant differences (p = 4.91E-22) and good model fitness [concordance index (C-index) = 0.77]. The DL model was validated by using four external confirmation cohorts: ICGC cohort (n = 40, C-index = 0.39), GSE41613 dataset (n = 97, C-index = 0.86), GSE42743 dataset (n = 71, C-index = 0.87), and GSE75538 dataset (n = 14, C-index = 0.48). Importantly, subtype Sub1 demonstrated a lower probability of survival and thus a more aggressive nature compared with subtype Sub2. ISGs in subtype Sub1 were enriched in the tumor-infiltrating immune cells-related pathways and cancer progression-related pathways, while those in subtype Sub2 were enriched in the metabolism-related pathways. Conclusion: The two survival subtypes of OSCC identified by deep learning can benefit clinical practitioners to divide immunocompromised patients with oral cancer into two subpopulations and give them target drugs and thus might be helpful for improving the survival of these patients and providing novel therapeutic strategies in the precision medicine area.


[Effect of Zaditen in patients with atopic bronchial asthma at Sandanski health resort].
Zaditen effect was studied in 20 patients with atopic bronchial asthma, aged from 16 to 48 (average age 34.2 years) with a duration of the disease from 1 to 18 years. The study was conducted in the Sandanski resort zone, characterized by exceptionally favourable bioclimatic constants for climate-treatment of patients with respiratory diseases. All patients, in an open experiment, received 1 mg Zaditen two times daily. The results obtained were with a positive effect in 90 per cent. Very good effect from the treatment was established in 80 per cent of the patients. The functional, biochemical, enzymatic and immunologic indices were favourably affected. Zaditen treatment, under the conditions of Sandanski resort, proved to be highly effective.


Predictors of resourcefulness in school-aged children.
Children need to develop appropriate cognitive-behavioral repertoires to maintain mental health and prevent depression. Resourcefulness is learned throughout life in the context of one's environment. However, environmental or situational factors and individual factors in children's development of resourcefulness have not been studied. This study examined the effects of the situational factors of family context (one or two parents, and number of siblings) and maternal characteristics (employment, learned resourcefulness, and adaptive functioning), and individual (child) factors (gender, academic performance, and automatic thoughts) on learned resourcefulness in school-aged children. A convenience sample of 122 fifth and sixth graders was recruited from four public schools. The child's automatic thoughts and maternal resourcefulness were predictors of child's resourcefulness. Further research is needed to examine additional factors that may promote resourcefulness in school-aged children, so that appropriate nursing strategies can be implemented.


Auxin-cytokinin and auxin-gibberellin interactions during morphogenesis of the compound leaves of pea (Pisum sativum).
A number of mutations that alter the form of the compound leaf in pea (Pisum sativum) has proven useful in elucidating the role that auxin might play in pea leaf development. The goals of this study were to determine if auxin application can rescue any of the pea leaf mutants and if gibberellic acid (GA) plays a role in leaf morphogenesis in pea. A tissue culture system was used to determine the effects of various auxins, GA or a GA biosynethesis inhibitor (paclobutrazol) on leaf development. The GA mutant, nana1 (na1) was analyzed. The uni-tac mutant was rescued by auxin and GA and rescue involved both a conversion of the terminal leaflet into a tendril and an addition of a pair of lateral tendrils. This rescue required the presence of cytokinin. The auxins tested varied in their effectiveness, although methyl-IAA worked best. The terminal tendrils of wildtype plantlets grown on paclobutrazol were converted into leaflets, stubs or were aborted. The number of lateral pinna pairs produced was reduced and leaf initiation was impaired. These abnormalities resembled those caused by auxin transport inhibitors and phenocopy the uni mutants. The na1 mutant shared some morphological features with the uni mutants; including, flowering late and producing leaves with fewer lateral pinna pairs. These results show that both auxin and GA play similar and significant roles in pea leaf development. Pea leaf morphogenesis might involve auxin regulation of GA biosynthesis and GA regulation of Uni expression.


Surgery in late melanoma adrenal metastasis.
Metastatic melanoma to adrenal gland are very infrequent, being generally associated with additional evidence of systemic disease and, consequently, with short-term survival. However, the prognosis and the therapeutic management vary depending on some important oncological features. Long-term survival rates have been described after complete resection of metastatic disease. Here, we report the case of a woman aged 41 years diagnosed with a cutaneous melanoma on the right side of her paravertebral region, level III of Clark, in 2002, who underwent surgical excision of the tumour with negative margins and a negative sentinel node. She posteriorly developed pulmonary metastasis in 2006 and 2009, both resected with curative intention and in 2013, she was diagnosed with an adrenal metastasis. Therefore, she was submitted to an uneventful right laparoscopic adrenalectomy. The pathology report described metastasis of a cutaneous melanoma, negative for BRAF mutation. The patient is actually disease-free after 30 months of follow-up.


Polyclonal B-cell stimulative and immunosuppressive activities at different developmental stages of Trypanosoma gambiense.
Bloodstream trypomastigote and cultured procyclic (insect midgut) forms of a monomophic strain of Trypanosoma gambiense were tested for their abilities to induce polyclonal B-cell activation (PBA) and immunosuppression (IS) in mice. Injection of a cell homogenate of bloodstream trypomastigotes induced both PBA and IS, while neither PBA nor IS was observed in mice injected with a cell homogenate of cultured procyclics. The results indicate that the substance(s) inducing PBA or IS is related to the developmental stage of the parasites.


HIF-1alpha: a valid therapeutic target for tumor therapy.
Hypoxia plays a major role in the induction of angiogenesis during tumor development. One mechanism by which tumor cells respond to a reduced oxygen level is via the activation of hypoxia-inducible factor-1 (HIF-1). HIF-1 is an oxygen-dependent transcriptional activator that plays crucial roles in the angiogenesis of tumors and mammalian development. HIF-1 consists of a constitutively expressed HIF-1beta subunit and the highly regulated HIF-1alpha subunits. The stability and activity of HIF-1alpha are regulated by various post-translational modifications, hydroxylation, acetylation, phosphorylation and sumoyaltion. Therefore, HIF-1alpha interacts with several protein factors including PHD, pVHL, ARD-1, SUMO and p300/CBP. Under normoxia, the HIF-1alpha subunit is rapidly degraded via the von Hippel-Lindau tumor suppressor gene product (pVHL)-mediated ubiquitin/proteasome pathway. The association of pVHL and HIF-1alpha under normoxic conditions is triggered by the hydroxylation of prolines and the acetylation of lysine within a polypeptide segment known as the oxygen-dependent degradation (ODD) domain. On the contrary, under the hypoxia condition, the HIF-1alpha subunit becomes stable and interacts with coactivators such as p300/CBP to modulate its transcriptional activity. Under hypoxic conditions, HIF-1 eventually acts as a master regulator of numerous hypoxia-inducible genes. The target genes of HIF-1 are especially related to angiogenesis, cell proliferation and survival, and to glucose and iron metabolism. Moreover, it was reported that the activation of HIF-1alpha is closely associated with a variety of tumors and oncogenic pathways. Hence, the blocking of HIF-1alpha itself or the blocking of HIF-1alpha interacting proteins inhibits tumor growth. Based on these findings, HIF-1 can be a prime target for anticancer therapies. Therefore, this review summarizes the molecular mechanism of HIF-1alpha stability, the biological functions of HIF-1 and its potential applications for cancer therapies.


Ovarian Hyperstimulation Caused by Gonadotroph Pituitary Adenoma--Review.
Ovarian hyperstimulation syndrome (OHSS) occurs mostly as an iatrogenic complication of assisted reproductive technology. Gonadotroph pituitary adenomas are rarely associated with OHSS. To the authors' knowledge, to date only 30 cases of spontaneous ovarian stimulation associated with gonadotroph adenomas have been reported in women and only 2 in children. The most common symptoms in such cases included menstrual disturbances, abdominal or pelvic pain, abdominal distension and increased girth. Galactorrhea, nausea and vomiting were also reported. Neurological symptoms occurred when the size of the pituitary tumor reached at least 20 mm. Transvaginal ultrasound examination usually demonstrated enlarged multicystic ovaries. MRIs of the pituitary revealed macroadenomas up to 61 mm in maximum diameter. The hormonal profiles of the reported cases showed normal or elevated FSH levels, suppressed LH levels, elevated estradiol levels and supranormal concentrations of prolactin. Transsphenoidal surgery is the therapy of choice, however other treatment modalities can be utilized in selected cases.


Anti-apoptotic effect of banhasasim-tang on chronic acid reflux esophagitis.
To evaluate the anti-apoptotic effect of banhasasim-tang (BHSST) on chronic acid reflux esophagitis (CARE) using a rat model. A surgically-induced CARE model was established in Sprague-Dawley rats. The modeled rats were divided into a treatment group or untreated group, and given BHSST (1 g/kg body weight per day) or water, respectively, for 15 consecutive days (n = 7 each group). Changes in expression of proteins related to nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and apoptosis were assessed by western blotting. Changes in esophageal pathology were analyzed by gross and histological examinations. The CARE exposure modeled rats showed increased levels of the NADPH oxidase subunit, NOX4 and p47phox in the esophagus. The BHSST treatment completely resolved these CARE-related increases. The CARE rats also showed markers of cytokine stress, including elevated levels of TNF-α and reactive oxygen species as well as of the consequent increase in JNK activation, and subsequent decrease in pro-survival gene expression, such as of Bcl-2. BHSST treatment resolved the CARE-related changes. BHSST also exerted an anti-apoptotic effect, as evidenced by altered expression of the apoptosis-related genes for bax, cytochrome c, and caspase 3. Finally, the BHSST treatment markedly ameliorated the CARE-related esophageal mucosal ulcerations. In the rat model of CARE, BHSST can suppress development of esophageal mucosal ulceration via regulation of reactive oxygen species-dependent apoptosis.


Clinical features to predict hypoxia and/or hypercapnia in acute asthma attacks.
Arterial blood gas data were correlated with clinical variables including patients' perception of dyspnea and spirometry in 79 episodes of acute asthma attacks. Among several variables that showed univariate significance with severity, only subjective degree of dyspnea rated on a modified Borg scale (MBS) remained predictive to discriminate the presence or absence of hypoxia/hypercapnia in multivariate analyses. MBS alone could predict the arterial blood gas status with accuracy of approximately 75%. Therefore, patients' sensation of dyspnea seemed to be an important factor in the evaluation of acute asthma in an emergency room.


Direct evidence for the interaction of the nucleotide affinity analog 5'-p-fluorosulfonylbenzoyl adenosine with a platelet ADP receptor.
Previous reports have indicated that the nucleotide affinity analog 5'-p-fluorosulfonylbenzoyl adenosine (FSBA) at concentrations between 40 and 100 mumol/L and at times greater than 20 minutes covalently modifies a single protein component on the external platelet membrane surface and that adenosine diphosphate (ADP) protects against this reaction. That this protein is an ADP receptor linked to platelet activation is shown by FSBA inhibition of ADP-mediated platelet shape change, aggregation, and fibrinogen receptor exposure. In this report, further evidence for the interaction of FSBA with the ADP receptor on platelets is provided by the observation that FSBA at high concentrations (100 to 500 mumol/L) behaves as a weak agonist to produce platelet shape change within one minute as detected by spectroscopic assay and scanning electron microscopy with concomitant phosphorylation of the light chain of platelet myosin. The specificity of FSBA as an agonist is demonstrated by inhibition of FSBA-induced shape change by ATP and the covalent incorporation of SBA as well as the failure of 5'-fluorosulfonylbenozoyl guanosine (FSBG) to cause shape change. In contrast, incubation of platelets with low concentrations of [3H]-FSBA (40 mol/L) is not associated with stimulation of platelet shape change or myosin light chain phosphorylation.


Imagery for Self-Healing and Integrative Nursing Practice.
Imagery has been used as a healing practice since ancient times. Its reemergence in modern medicine began in the second half of the 20th century, when research suggested that imagery could help reduce patients' pain and anxiety and improve their quality of life and outlook on their illness. While current evidence is insufficient to support claims that imagery affects disease progression, research suggests that this method of inducing relaxation encourages patients' healing process and gives them a greater sense of autonomy in relation to disease and its management. Because imagery is noninvasive, the risks associated with its use are minimal and it is now widely used in integrative nursing. The author discusses imagery's uses and benefits, as well as the potential pitfalls in its use, and describes an imagery technique she has found effective in practice, providing a sample script and explaining how the technique might be used to help patients in various settings.


How to (and how not to) manage the patient with a lump in the neck.
In the management of a patient with an isolated lump in the neck, knowing what actions should not be taken is as crucial as knowing what should be done. A careful history and physical examination as well as guidelines such as the low prevalence of malignant lesions in children but the high prevalence in adults can aid the primary physician in reaching an accurate diagnosis. An extensive radiographic work-up, and possible peroral panendoscopy, may be required when malignancy is suspected but undiagnosed in adults. Biopsy of the mass itself should only be done as a last resort.


The AE gene family of Cl/HCO3- exchangers.
Tubular acid-base transport regulates systemic acid-base balance. Transepithelial acid-base transport across nephron segments requires the coordinated control of intracellular pH and cellular volume by transporters of protons and bicarbonate. Bicarbonate transporter polypeptides are encoded by at least two gene families, SLC4 and SLC26. The SLC4 gene family includes at least three Na()+)-independent chloride-bicarbonate exchanger genes and multiple Na(+)-bicarbonate cotransporter and Na(+)-dependent anion exchanger genes. The most extensively studied among them are the Na(+)-independent anion exchangers, AE1, AE2, and AE3, all of which are expressed in kidney. The AE1 gene encodes eAE1 (band 3), the major intrinsic protein of the erythrocyte, as well as kAE1, the basolateral Cl/HCO3 exchanger of the acid-secreting Type A intercalated cell. Mutations in AE1 are responsible for some forms of heritable distal renal tubular acidosis. The widely expressed AE2 anion exchanger participates in recovery from alkaline load and in regulatory cell volume increase following shrinkage. AE2 can also be regulated by ammonium ion. These properties are not shared by the closely related AE1 anion exchanger. Less is known about AE3 in kidney. Structure-function studies of recombinant proteins involving chimeras, deletions, and point mutations have delineated regions of AE2 which are important in exhibition of the regulatory properties absent from AE1. These include regions of the transmembrane domain and the N-terminal cytoplasmic domain. Noncontiguous regions in the middle of the N-terminal cytoplasmic domain are of particular importance for acute regulation by several types of stimulus.


Ligand-mediated Targeted Drug Delivery Approaches against Hepatocellular Carcinoma.
One of the most important health problems in the world today is cancer. The World Health Organization (WHO) reported that it results in 8.9 million deaths annually. Malignant tumours and unregulated cell proliferation are features of malignant neoplasms, which can also invade nearby body regions. Hepatocellular carcinoma is the third most prevalent cause of cancer-related death worldwide and the fifth most common kind of cancer, according to a recent analysis. Patients with liver disease as well as chronic hepatitis B and C are more likely to develop hepatocellular carcinoma (HCC). Physical barriers, including RES absorption, opsonization, and first-pass drug metabolism, make drug therapy more challenging. Conventional cancer therapy procedures have a low response rate or may continue to be unsuccessful due to multi-drug resistance (MDR), high clearance rates, and other side effects because of suboptimal drug distribution and insufficient drug concentration reaching cancer cells. Innovative target drug molecules that are tailored to the injured liver cells must be developed in order to improve medication administration and drug targeting. The use of targeting ligands that have been joined to drug molecules or nanocarriers forms the basis of innovative targeting techniques. After being conjugated with the treatment method, ligands for targeting hepatocellular carcinoma cells included asialoglycoprotein, galactoside, lactobionic acid, mannose-6-phosphate, PDGF, antibodies, and aptamers.


Are psychological features useful in classifying patients with somatic symptoms?
To evaluate psychological characteristics that could be used for the classification of somatic syndromes requesting medical care. Positive psychological classification criteria are needed to justify the classification of somatic syndromes as Diagnostic and Statistical Manual of Mental Disorders- or International Classification of Diseases-10 section F/mental disorders diagnosis. From a population-based sample of 2510 people, subsamples reporting high scores for somatic symptoms (SOM+; n = 154) versus average scores for somatic symptoms (SOM-; n = 167) were defined. Telephone interviews (e.g., structured interviews for diagnoses, healthcare use, symptom history, possible psychological characteristics), self-rating scales (e.g., Pain Disability Index, depression scale Patient Health Questionnaire-9), and general practitioners reports were collected for these subsamples. In addition to somatic symptoms, we used healthcare use and disability as major external validation criteria. There was strong evidence for ten of the 28 binary coded psychological variables to identify those people with somatic symptoms who needed medical help and/or were seriously disabled. These variables included "avoidance of physical activities," "bias for somatic illness attributions," "self-concept of being physically weak," and "desperation because of somatic symptoms." The relevance of these psychological characteristics was partially further confirmed by stepwise regression analyses, which showed incremental validity compared with variables like somatic symptoms and depression. This study identified several psychological characteristics of people with somatic complaints who need medical care. These features can be assessed, using binary variables that are more feasible for classification processes. These psychological criteria should be included in classification rules for people with somatic syndromes (e.g., somatoform disorders).


Loss of cholinergic muscarinic receptors in the frontal cortex of alcohol abusers.
Alcohol abuse causes impairment of cognitive function ranging from mild forms to end-stage dementia. Alcohol-related dementia accounts for nearly 20% of all admissions to state mental hospitals and may result from head trauma, thiamine deficiency, Alzheimer's, and other brain diseases that can be diagnosed conclusively only at autopsy. However, we postulate that after all these conditions have been excluded, an "alcohol encephalopathy" remains. This is characterized by impaired synaptic function, which underlies the continuum of impaired intellectual function. We found in 79 histologically normal brains of a nondemented general hospital population a 40% decrease in the density of cholinergic muscarinic receptors in the frontal cortex of alcoholics when compared with matched controls of the same age. Only alcohol abuse and not aging, postmortem changes, medications, clinical (including liver) diseases, or differences in causes of death could account for this loss.


An Ultrasensitive Plasmonic Nanosensor for Aldehydes.
Glucose is the most common but important aldehyde, and it is necessary to create biosensors with high sensitivity and anti-interference to detect it. Under the existence of silver ions and aldehyde compounds, single gold nanoparticles and freshly formed silver atoms could respectively act as core and shell, which finally form a core-shell structure. By observing the reaction between glucose and Tollens' reagent, metallic silver was found to be reduced on the surface of gold nanoparticles and formed Au@Ag nanoparticles that lead to a direct wavelength shift. Based on this principle and combined with in situ plasmon resonance scattering spectra, a plasmonic nanosensor was successfully applied in identifying aldehyde compounds with excellent sensitivity and specificity. This ultrasensitive sensor was successfully further utilized to detect blood glucose in mice serum samples, exhibiting good anti-interference ability and great promise for future clinical application.


Recurrent ventricular tachycardia in hypothyroidism--report of a case and review of the literature.
A 47-year-old woman suffered from recurrent attacks of ventricular tachycardia. Her electrocardiogram showed low voltage, right bundle branch block and prolonged QT interval. Hormonal studies disclosed primary hypothyroidism. The arrhythmia responded to treatment with procainamide and did not recur following thyroid replacement therapy. The QT interval returned to normal. Five similar cases reported in the literature are reviewed, emphasizing the importance of QT prolongation, in the context of hypothyroidism, as a risk factor for the occurrence of ventricular tachycardia.


[The skin in the elderly].
Skin changes in advanced age consist mainly of an atrophy of the epidermis and of the appendices as well as of degeneration within the corium which cause asteatosis, purpura, de and hyperpigmentation and elastosis. The regulation of the body-temperature is altered. The influence of light leads up to actinic keratoses and to skin cancer. Diseases of the sebaceous glands and seborrheic dermatoses are rarely seen in the aged. Tumors of the skin occur in about 4% of persons in their forties but in 20% at 70 years of age. Systemic treatment has to take into consideration an increased inclination to complications and frequently also a reduced effect due to decreased blood circulation in the skin. Ointment bases consisting of oil/water emulgations with addition of fat or water are usually well tolerated. The use of soap and detergents should be restricted. The application of ointments containing UV filter substances is recommended at sun exposure.


Risk of arterial thromboembolic events with sunitinib and sorafenib: a systematic review and meta-analysis of clinical trials.
Sunitinib and sorafenib are oral vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) used in a vast range of cancers. Arterial thromboembolic events (ATE) have been described with these agents, although the overall risk remains unclear. We did a systematic review and meta-analysis to determine the incidence and the relative risk (RR) associated with the use of sunitinib and sorafenib. PubMed databases were searched for articles published from January 1966 to July 2009, and abstracts presented at the American Society of Clinical Oncology (ASCO) and the European Society of Medical Oncology (ESMO) meetings held between 2004 and 2009 were searched for relevant clinical trials. Eligible studies included phase II and III trials and expanded access programs. Statistical analyses were conducted to calculate the summary incidence, RRs, and 95% CIs, using random-effects or fixed-effects models based on the heterogeneity of included studies. A total of 10,255 patients were selected for this meta-analysis. The incidence for ATE was 1.4% (95% CI, 1.2% to 1.6%). The RR of ATEs associated with sorafenib and sunitinib was 3.03 (95% CI, 1.25 to 7.37; P = .015) compared with control patients. The analysis was also stratified for the underlying malignancy (renal cell cancer v non-renal cell cancer) and TKI (sunitinib v sorafenib), but no significant differences in incidence or RR were observed. Treatment with VEGFR TKIs sunitinib and sorafenib is associated with a significant increase in the risk of ATEs.


Development of a TB vaccine trial site in Africa and lessons from the Ebola experience.
Tuberculosis is the deadliest infection of our time. In contrast, about 11,000 people died of Ebola between 2014 and 2016. Despite this manifest difference in mortality, there is now a vaccine licensed in the United States and by the European Medicines Agency, with up to 100% efficacy against Ebola. The developments that led to the trialing of the Ebola vaccine were historic and unprecedented. The single licensed TB vaccine (BCG) has limited efficacy. There is a dire need for a more efficacious TB vaccine. To deploy such vaccines, trials are needed in sites that combine high disease incidence and research infrastructure. We describe our twelve-year experience building a TB vaccine trial site in contrast to the process in the recent Ebola outbreak. There are additional differences. Relative to the Ebola pipeline, TB vaccines have fewer trials and a paucity of government and industry led trials. While pathogens have varying levels of difficulty in the development of new vaccine candidates, there yet appears to be greater interest in funding and coordinating Ebola interventions. TB is a global threat that requires similar concerted effort for elimination.


Evaluation of group B Streptococci colonization rate in pregnant women and their newborn.
Group B Streptococcus (GBS) is one of the most important bacteria in the majority of maternal and neonatal infections, such as chorioamnionitis, endometritis, bacteremia, sepsis and meningitis. During pregnancy, GBS screening is one of the recommended strategies that are recommended by center of disease control (CDC). This study was aimed to determine the rectovaginal colonization prevalence among pregnant women, and also the rate of transmission to their offspring. Between June 2008 and April 2009, two hundred pregnant women admitted in department of Obstetrics and Gynecology (Ghaem Hospital, Mashhad, Iran) were enrolled in present study. Samples from maternal rectum and vagina as well as neonate ear and umbilical cord were taken for culture. The colonization rate for GBS in pregnant women and their neonates was around 6% and 5% respectively. All the carrier mothers were cases with premature rupture of membranes (at least 18 hours before delivery). In terms of colonization, there was a significant correlation between mothers and newborns, and more than 80% of neonates from GBS carrier mothers were colonized by GBS.


Assessment of the risk of dermal exposure to pesticides during treatment with a back-pack sprayer in the presence and absence of vegetation.
Assessing the dermal exposure of applicators to pesticides is still an important issue, and the measurement methods used remain open to improvement. This is particularly true when it comes to characterising the exposure of applicators using back-pack sprayers. The scenarios used for the different mathematical models continue to be riddled with approximations and uncertainties. With a view to improving these scenarios, test were performed in an open environment to measure the levels of dermal exposure on various parts of an operator's body during treatment with this type of equipment. The main parameters studied are the presence of vegetation and the height of the crop. The method uses a tracer (fluorescein salt) and collectors placed all over the body in order to determine which parts are subject to most contamination during spraying. The quantitative determinations of the tracer show that exposure, in the presence of vegetation, reaches levels of 0.02%, 0.006% and 0.04% of the total quantity applied in treatment, at heights of 0.5, 1 and 2 m respectively. In the absence of vegetation, it stands at 0.21%, 0.61% and 0.62% of the total quantity applied at heights of 0.5, 1 and 2 m. In each of these situations, the lower limbs of the body (shins and thighs) collected large proportions of fluorescein. The contamination of the upper parts of the body increases in proportion to the height of treatment. These results show that the presence of vegetation and the spraying height are important parameters to be considered and to be integrated into the models, to validly assess the exposure of operators using a backpack sprayer.


Tensorial elastic properties and stability of interface states associated with Σ5(210) grain boundaries in Ni3(Al,Si).
Grain boundaries (GBs) represent one of the most important types of defects in solids and their instability leads to catastrophic failures in materials. Grain boundaries are challenging for theoretical studies because of their distorted atomic structure. Fortunately, quantum-mechanical methods can reliably compute their properties. We calculate and analyze (tensorial) anisotropic elastic properties of periodic approximants of interface states associated with GBs in one of the most important intermetallic compounds for industrial applications, Ni3Al, appearing in Ni-based superalloys. Focusing on the Σ5(210) GBs as a case study, we assess the mechanical stability of the corresponding interface states by checking rigorous elasticity-based Born stability criteria. The critical elastic constant is found three-/five-fold softer contributing thus to the reduction of the mechanical stability of Ni3Al polycrystals (experiments show their GB-related failure). The tensorial elasto-chemical complexity of interface states associated with the studied GBs exemplifies itself in high sensitivity of elastic constants to the GB composition. As another example we study the impact caused by Si atoms segregating into the atomic layers close to the GB and substituting Al atoms. If wisely exploited, our study paves the way towards solute-controlled design of GB-related interface states with controlled stability and/or tensorial properties.


[Clinical usefulness of three-dimensional brain imaging with N-isopropyl-p-[123I]iodoamphetamine (IMP)].
Three-dimensional reconstruction from N-isopropyl-p-[123I]iodoamphetamine (IMP) tomography has been applied clinically to the detection of perfusion defects in 22 cases (15 cerebrovascular diseases and 7 normal controls confirmed by CT and MRI), with data being analyzed in terms of receiver operating characteristic curves (ROC). The results showed that three-dimensional (3-D) image could make better diagnostic capability especially in inexperienced examiner and that it was useful decreasing of difference of diagnostic capability. 3-D image could be taken within 1 minute and 15 seconds. We concluded that the three-dimensional brain imaging with IMP using this system was clinically useful because examiner could easily diagnose perfusion defects.


[Recent palmar dislocations of the proximal interphalangeal joint].
Recent anterior dislocations of the proximal interphalangeal (PIP) joint are uncommon injuries. Chronic and irreducible dislocations have been most often reported. This study aims to precise the anatomic and radiologic aspects of these lesions about three cases, and to compare these cases and their treatment with thirteen cases published in the literature between 1966 and 1994. Three patients presented an anterior dislocation of the PIP joint after direct or twisting traumatism. One had an avulsion of the central slip of the extensor tendon and remained unstable after closed reduction needing pin fixation. Two had a longitudinal tear between central and lateral bands of the tendon with an entrapment of the condyle of the proximal phalanx, and the dislocations were irreducible. After open reduction, the joint was stable. The first case showed a limited flexion after three months. In the two other cases without rupture, full range of motion was recovered after two months. These cases have been compared with thirteen cases of recent papers from nine authors. Two types of anterior dislocations of the PIP joint may be described. TYPE I: Without rupture of the central slip fo the extensor tendon. One distal condyle of the proximal phalanx is entrapped between the central slip and a lateral band of the extensor tendon, that are separated by a longitudinal partial tear. The deformity is made by flexion, axial rotation and lateral displacement of the middle phalanx. Open reduction is required and may carry out good functional result. With rupture of the central slip of the extensor tendon. These very unstable lesions need a fixation after closed or open procedure. The treatment is often lately carried out, and the results not so good as in type I. Two different types of PIP joint anterior dislocations are described. Earlier diagnosis and surgical treatment can allow early rehabilitation and better final functional results.


Epidemiology of intensive care unit (ICU)-acquired infections in a 14-month prospective cohort study in a single mixed Scandinavian university hospital ICU.
Our aim was to evaluate the epidemiology of intensive care unit (ICU)-acquired infections in a prospective cohort study. Patients with longer than a 48-h stay in an adult mixed medical-surgical ICU in a tertiary level teaching hospital were included. The incidence (per cent) and incidence density (per 1000 patient days) of ICU-acquired infections and the device-associated infection rates per 1000 device days were analysed prospectively in a 14-month study. Eighty (23.9%) of 335 patients, whose ICU stay was longer than 48 h, acquired a total of 107 infections (1.3 per patient) during their ICU stay, with an infection rate of 48 per 1000 patient days. The most common infections were ventilator-associated pneumonia (VAP) [33.8% (18.8 per 1000 respiratory days)], other lower respiratory tract infections (LRTIs) (20%) and sinusitis (13.8%). The rate of central catheter-related (CRI) or primary bloodstream infections was 6.3% (2.2 per 1000 central venous catheter days), and the rate of urinary tract infections was 1.3% (0.5 per 1000 urinary catheter days). The first ICU infection was observed in 58.8% (47/80) of cases within 6 days after admission. The median time from admission to the diagnosis of an ICU-acquired infection was 4 days (25th-75th percentiles, 4.0-6.0) for VAP, 6.0 days (4.5-7.0) for LRTIs and 9.5 days (6.5-13.0) for CRIs. The rates of urinary tract infections and bloodstream infections were lower than reported previously, differentiating our results from the classic pattern of ICU-acquired infections, with the exception of the predominance of VAP.


Re-entry device use in the endovascular treatment of aorto-iliac occlusive disease.
The treatment of peripheral arterial occlusive disease with endovascular therapy is rapidly becoming the standard of care. Akin to the movement towards percutaneous coronary interventions that occurred with gusto throughout the 1980s and 1990 s, treatment for the peripheral vasculature has undergone its own paradigm shift. Such that many feel that a first-line catheter-based approach is justified for the majority of patients in 2012. Extensive occlusive disease of the aorto-iliac segment is an area where open surgery has historically been preferred over endovascular therapy. This is partly because the open surgical standard of aorto-bi-femoral bypass has durability unrivalled by other forms of peripheral revascularisation surgery. Furthermore, some have avoided endovascular interventions in this region because of fears of perforation, bleeding and limited technical success in an area where the blood vessels carry a heavy burden of disease and a large thrombotic load. Throughout surgical history we have seen advances in technology emerge to provide a medium through which the proceduralist may extend their indications for treatment. A number of re-entry devices which provide a reliable method of wire passage beyond chronic occlusions of the aorta and iliac arteries have emerged and for the first time are safely facilitating high technical success rates in the treatment of aorto-iliac occlusive disease (AIOD). What follows is a summary of both open and endovascular treatment options for AIOD. Moreover, this review will provide an evidence based description of the emerging litany of devices which aid in wire passage through this most challenging of vascular territories.


Further studies on the inhibition of pepsin by bile salts.
A higher incidence of peptic ulceration has been reported in patients recovering from operations that divert bile from the duodenum. Previous studies have shown that hydroxylated bile salts inhibit the proteolytic activity of pepsin, an integral agent in the production of peptic ulcer. In this study, the pepsin inhibitory activity of 16 bile salts (6 unconjugated, 5 glycoconjugated, and 5 tauroconjugated bile salts), including bile salts with no hydroxyl groups, was tested in vitro. All bile salts inhibited pepsin proteolytic activity and the degree of pepsin inhibition increased in proportion to their concentrations. The range of maximal inhibition was 90-73% for unconjugated bile salts; 74-35% for glycoconjugated bile salts; and 71-46% for tauroconjugated bile salts. These findings support the need for clinical studies to evaluate administration of bile acids to bile-diverted patients.


Correlation between Depression with Serum Levels of Vitamin D, Calcium and Magnesium in Women of Reproductive Age.
Introduction: Micronutrient deficiency is one of the common problems in women of reproductive age. This study was conducted with the aim of determining the correlation between the depression with serum levels of vitamin D, calcium and magnesium in women of reproductive age. Methods: This study was a cross-sectional study .In this study 100 women 15-44 years old with inclusion criteria of the study were called through an invitation in Urmia Motahari hospital in Iran. Demographic and obstetric information as well as the short form Beck Depression Inventory were completed, and then ten ml of venus blood was obtained from the subjects after about 12 hours of fasting. The data were analyzed, by SPSS software. Results: The mean of the depression score was 5.24, and the mean (SD) of the serum levels of vitamin D, calcium, and magnesium were 15.53 (13.41) (ng/ml), 9.14 (0.24) (mg/dL), and 2.07 (0.13) (mg/dl), respectively. Women's depression scores showed a significant inverse correlation with the serum level of vitamin D (r= -0.21, P= 0.03). Conclusion: It is recommended that interventional programs should be carried out for women of reproductive age to improve their vitamin D status.


Specialization for resistance in wild host-pathogen interaction networks.
Properties encompassed by host-pathogen interaction networks have potential to give valuable insight into the evolution of specialization and coevolutionary dynamics in host-pathogen interactions. However, network approaches have been rarely utilized in previous studies of host and pathogen phenotypic variation. Here we applied quantitative analyses to eight networks derived from spatially and temporally segregated host (Linum marginale) and pathogen (Melampsora lini) populations. First, we found that resistance strategies are highly variable within and among networks, corresponding to a spectrum of specialist and generalist resistance types being maintained within all networks. At the individual level, specialization was strongly linked to partial resistance, such that partial resistance was effective against a greater number of pathogens compared to full resistance. Second, we found that all networks were significantly nested. There was little support for the hypothesis that temporal evolutionary dynamics may lead to the development of nestedness in host-pathogen infection networks. Rather, the common patterns observed in terms of nestedness suggests a universal driver (or multiple drivers) that may be independent of spatial and temporal structure. Third, we found that resistance networks were significantly modular in two spatial networks, clearly reflecting spatial and ecological structure within one of the networks. We conclude that (1) overall patterns of specialization in the networks we studied mirror evolutionary trade-offs with the strength of resistance; (2) that specific network architecture can emerge under different evolutionary scenarios; and (3) network approaches offer great utility as a tool for probing the evolutionary and ecological genetics of host-pathogen interactions.


Bi-paternal litter in finn raccoon (Nyctereutes procyonoides Gray 1834) detected by polymorphic DNA markers.
The present paper demonstrates novel results confirming the phenomenon of multipaternity in Finn raccoons. The purpose of the study was to affirm the occurrence of bi-paternal litters in Finn raccoons using polymorphic microsatellite markers. The study was carried out on 37 Finn raccoon females, males that mated with them and the resulting offspring (176 individuals). The offspring came from females mating with two or three different males during one estrus. Parentage testing of 15 microsatellites was used inthe present study. Based on genetic analysis including the control of the origin of the Finn raccoons, it was observed that in the case of double-mating with two different males, as well as triple-mating with three different males, there were 47.06% and 54.55%, respectively, of maternal half-sibs, i.e., animals born in one litter but with different fathers. Paternity was wrongly ascribed in 18.2% of the offspring in the examined Finn raccoon population. The conducted research indicates a necessity to check the origin of young animals selected for breeding stock in Finn raccoon breeding farms.


A systematic review of the prevalence and impact of urinary incontinence in cystic fibrosis.
This systematic review synthesizes published articles investigating the prevalence, severity and impact of urinary incontinence (UI), a condition associated with cystic fibrosis (CF). References were identified through searching Medline, Embase and PubMed using the medical subject headings 'cystic fibrosis' AND 'urinary incontinence'. Articles were included if UI prevalence was investigated as an outcome. Twelve studies met selection criteria. The prevalence of UI ranged from 5% to 76%. Age and gender contributed to this variability. When assessed, UI commonly limited airway clearance, exercise and/or spirometry, and had a variable impact on patients' lives. Worry and embarrassment were features for many; others were less affected. In CF, UI is common and can interfere with respiratory care and social well-being. The prevalence, characteristics and impact are poorly understood, which is made worse by inconsistent definitions across studies. Future research is needed to improve approaches to prevention, identification, management and education.


Clinical and obstetrical management of pregnant women with autoimmune hepatitis complicated by moderate or severe thrombocytopenia.
To describe the management of prenatal care and delivery in patients bearing autoimmune hepatitis associated with moderate or severe thrombocytopenia. This study was performed in a tertiary level university hospital. Thirteen pregnancies in ten patients diagnosed with autoimmune hepatitis, complicated by thrombocytopenia, were retrospectively analyzed. The inclusion criteria were as follows: clinical diagnosis of autoimmune hepatitis, moderate or severe thrombocytopenia (platelet count < 100 x 103/mm3), gestational age at birth over 22 weeks, and patient followed-up by a specialized team at the institution. The variables studied were: maternal age, parity, treatment regimen, platelet count, examinations for investigation of hepatic function, type of delivery, weight at birth, and gestational age at the time of delivery. The average maternal age was 24.5 years (SD = 5.3) and six (50%) occurred in nulliparous women. During pregnancy, monotherapy with prednisone was adopted in 11 cases (92%). According to the autoantibody profiles, seven pregnancies (58%) had the autoimmune hepatitis type I diagnosis, two pregnancies had type II (17%), and three pregnancies (25%) had cryptogenic chronic hepatitis (undetectable titers of autoantibodies). Portal hypertension was featured in 11 pregnancies (92%). The average gestational age at delivery was 36.9 weeks (SD = 1.5 weeks), with an average weight at birth of 2,446 g (SD = 655 g). Eight infants (67%) were small for gestational age. At the time of delivery, severe thrombocytopenia was featured in four cases (33%) and cesarean surgery was performed in seven cases (58%). Complications at delivery occurred in three cases (25%), one patient presented uterine atony, and two patients presented perineal bruising. There was no perinatal or maternal death. The complications of thrombocytopenic patients with autoimmune hepatitis are elevated; nevertheless, with appropriate attention and care, they can be resolved. The association between two severe pathologies appears to increase the risk of prematurity and fetal growth restriction, demanding specialized prenatal care, as well as surveillance of newborn well-being.


Effect of pindolol and propranolol on plasma renin and aldosterone in patients with renal allograft.
To investigate the effect of propranolol and pindolol on renin and aldosterone secretion, blood samples of 12 nephrectomized kidney transplant recipients were taken after 1 hour in supine position and 30 and 60 minutes after posture change. This procedure was repeated after 4 days under pindolol (3 X 5 mg/day) or propranolol (4 X 40 mg/day). Both pindolol and propranolol suppressed the significant orthostatic rise of plasma renin activity (PRA) seen without medication. Pindolol increased basal PRA markedly, whereas basal PRA under propranolol was the same as without betablockers. Plasma aldosterone (PA) showed significant orthostatic rise under all conditions and thus did not parallel PRA under betablockers. Suppression of PRA response to posture change by betablockers indicates that circulating catecholamines may be involved in orthostatic PRA regulation. The intrinsic sympathetic activity of pindolol results in an increase of basal PRA. In nephrectomized renal transplant recipients, postural PA changes do not seem to be triggered by PRA.


Fast Determination of Optimal Transmission Rate for Wireless Blockchain Networks: A Graph Convolutional Neural Network Approach.
One of the primary challenges in wireless blockchain networks is to ensure security and high throughput with constrained communication and energy resources. In this paper, with curve fitting on the collected blockchain performance dataset, we explore the impact of the data transmission rate configuration on the wireless blockchain system under different network topologies, and give the blockchain a utility function which balances the throughput, energy efficiency, and stale rate. For efficient blockchain network deployment, we propose a novel Graph Convolutional Neural Network (GCN)-based approach to quickly and accurately determine the optimal data transmission rate. The experimental results demonstrate that the average relative deviation between the blockchain utility obtained by our GCN-based method and the optimal utility is less than 0.21%.


Free-surface instability in electro-osmotic flows of ultrathin liquid films.
The stability of a free surface under electro-osmotic flow in thin liquid films is investigated where the film thickness can be varied over the scale of a thick to thin electrical double layer while considering the relative contribution from the van der Waals forces. The role of interfacial Maxwell stress on thin film stability is highlighted. This configuration gives some interesting insights into the physics of free surface stability at a scale where various competing forces such as the Coulombic force, van der Waals force, and surface tension come into play. The effects of the mentioned forces are incorporated in the Navier-Stokes equations and a linear stability analysis of the resulting governing equations is performed to obtain the Orr-Sommerfeld equations. The characteristic stability curve of the system is obtained through an asymptotic analysis of the Orr-Sommerfeld equations in the long wave limit. In this study, special focus is given to the effect of the interfacial zeta potential on the free surface stability. It is found that when the free surface and the substrate zeta potential have the same polarity the system is unstable. Since the strength of the free surface potential depends upon the nature of the fluid substrate interaction, this study can help in choosing a proper combination of fluid and substrate to design microfluidic and nanofluidic channels with a desired flow rate without triggering the interfacial instability.


RAB23 mutation in a large family from Comoros Islands with Carpenter syndrome.
We report here on a RAB23 mutation (c.86dupA) present in the homozygote state in four relatives of Comorian origin with Carpenter syndrome. All children presented with acrocephaly and polysyndactyly. However, intrafamilial variability was observed with variable severity of craniosynostosis ranging from cloverleaf skull to predominant involvement of the metopic ridge. All children also presented with a combination of brachydactyly with agenesis of the middle phalanges, syndactyly, broad thumbs, and postaxial polydactyly (2/4) in the hands, and preaxial polydactyly (3) and syndactyly (4) in the toes. Mental development was normal in all four children but the eldest one presented with impaired motor development as a result of orthopedic complications. Brain imaging showed hydrocephalus in 2/4 and additional features included genu valgum (2/4), abnormal genitalia (3/4), corneal anomaly (2/4), umbilical hernia (1/4), severe cyphoscoliosis (1), patent ductus arteriosus (1/4), and accessory spleen (1). In contrast to previous reports, growth was below average except for one patient and the eldest one became moderately overweight with time. We conclude from the report of this large unique family with four affected children that Carpenter syndrome is a genetically homogenous but a clinically variable condition.


The Chemotherapeutic Potentials of Compounds Isolated from the Plant, Marine, Fungus, and Microorganism: Their Mechanism of Action and Prospects.
Research on natural products mainly focuses on developing a suitable drug to treat human disease. There has been a sharp increase in the development of drugs from natural products. Most of the drugs that are available are from the terrestrial origin. Marine natural products are less explored. Oceans are considered as a vast ecosystem with a wide variety of living organisms and natural products that are unexplored. Large numbers of antitumor drugs are from natural sources such as plants, marine, and microorganisms. 80% new chemical entities that were launched over the past 60 decades were from a natural source. In this article, the anticancer potential from the natural source such as plants, fungi, microorganisms, marine, and endophytes has been reviewed. Emphasis is given on the compound from the marine, plant, and of bacterial origin. Finally, we consider the future and how we might achieve better sustainability to alleviate human cancer suffering while having fewer side effects, more efficacies, and causing less harm than the present treatments.


Body image construction and mental health levels among college students: a data survey of Chinese university students.
With the rapid changes in body image construction brought about by the upgrading of consumption in China, trend-seeking college students are faced with mental health problems brought about by the pursuit of the "ideal body type," which cannot be ignored. This study aims to explore the relationship between body image construction and mental health among college students. This study utilized data from the Survey on Physical Activity and Mental Health of College Students. A total of 1,192 students were randomly selected as the survey sample, and 1,044 valid samples were obtained. The mean age of the respondents was 19.34 years. First, we categorized body image constructs into three categories based on the differences between subjective and objective body image: high acceptance, low acceptance, and consistency. Second, to ensure analytical rigor and minimize potential confounders, we used a generalized propensity score weighting model. Finally, we used a causal mediation framework to investigate the potential causal mechanisms between the independent variable (perceived body image bias) and the dependent variable (mental health) in order to better understand the "net effect." (1) There is a significant correlation between college students' body image perceptual bias and mental health, i.e., the higher the individual's acceptance of his/her own body image, the higher the level of mental health, and vice versa. (2) Students in humanities and social sciences are more likely to have increased psychological burden due to poor negative body image. (3) In the mediation analysis, although the causal mediating effect of physical exercise was not significant, family and peer support in physical exercise played an important mediating role, especially the influence of peers was more significant. The construction of body image is a double-edged sword that can either promote positive individual development or lead to self-depreciation. Creating a positive climate for physical activity has a positive impact on college students' mental health compared to participation in physical activity behaviors. While improving students' media literacy on college campuses, it is important to enhance adaptive guidance to promote their physical and mental health and personal development.


Acquisition of the feature [+spread glottis] in Icelandic.
The feature [+spread glottis] ([+s.g.]) denotes that a speech sound is produced with a wide glottal aperture with audible voiceless airflow. Icelandic is unusual in the degree to which [+spread glottis] is involved in the phonology: in /h/, pre-aspirated and post-aspirated stops, voiceless fricatives and voiceless sonorants. The ubiquitousness of the feature could potentially affect the rate and process of its acquisition. This paper investigates the development of [+s.g.] in Icelandic, both in general and in a range of contexts, in a cross-sectional study of 433 typically developing Icelandic-speaking children aged two to seven years. As a feature, [+s.g.] is acquired early in Icelandic, although specific sound classes lag behind due to other output constraints. Children reach mastery of [+s.g.] by age three except in word-initial post-aspirated stops and voiceless nasals. Findings are interpreted in light of the literature on the feature and its development.


Probing the Mechanism for Bipolar Resistive Switching in Annealed Graphene Oxide Thin Films.
The bipolar resistive switching (BRS) between a metallic low resistance state (LRS) and an insulating high resistance state (HRS) is demonstrated for annealed graphene oxide (GO) thin film-based device structures with aluminum (Al) as one of the contact electrodes. An optimal switching of ∼104 order is recorded for Al/GO (200 °C)/indium tin oxide (ITO) among the device structures in metal (M2)/GO (T)/metal (M1) configurations (M1 = Al, Au, or ITO and M2 = Au or Al), fabricated using GO (T)/metal (M1), annealed at different temperatures, T = 100, 200, 300, and 400 °C. The initial Ohmic conduction for electronic transport and the presence of metal contents through GO thin films in the X-ray photoelectron spectroscopy support the physical evidence of Al filament formation between the two electrodes as imaged by the high-resolution transmission electron microscopy. The speculated mechanism for BRS in repeated voltage sweep cycles is attributed to the current triggered breaking of metal filaments because of the combined effect of Joule's heating and Peltier heat generation at LRS → HRS transition, and electric field induced migration of metal atoms, leading to the formation of metal filaments through the GO film at the HRS → LRS transition. The higher switching ratio exhibited in the current study could be translated to engineer simple and low-cost resistive memory devices.


Frailty and age-related cataract.
To determine whether there is an association between age-related cataract and frailty that persists after controlling for visual acuity (VA) and comorbid conditions. Cross-sectional. Two thousand three hundred seventy Beaver Dam Eye Study cohort members at 10-year (third) examination with cataract information. Ninety-nine percent of the population was Caucasian. Medical history, blood pressures, height, weight, measures of frailty, and lens photographs were obtained during the study evaluation. Lens photographs were graded according to standardized protocols. Four of frailty (gait time, peak expiratory flow rate, handgrip strength, chair stand) and an index combining all 4 measures. After controlling for age, age squared, comorbidity index, pack-years, sedentary lifestyle, education, and VA, nuclear cataract in women was not associated significantly with any frailty measures; in men, nuclear cataract was associated with slower gait time (P = 0.01) and a poorer frailty index score (P = 0.01) in multivariable analyses. Cortical cataract was associated in women with a lower peak expiratory flow rate (P<0.01) and in men with weaker handgrip strength (P = 0.02) and a poorer frailty index score (P</=0.01) in multivariable analyses. Posterior subcapsular cataract in women was associated significantly with a lower peak expiratory flow rate (P = 0.01). Nuclear and cortical cataract add significant information in explaining frailty index scores in men. Three common types of age-related cataract are associated with some measures of frailty independent of VA and systemic comorbidities. It is possible that age-related cataract may be an indicator of general functional decline in older adults.


Induction of fetal demise in advanced pregnancy terminations: report on a funic potassium chloride protocol.
Advanced pregnancy termination with uterotonic agents with their inherent risk for occurrence of a live birth and surgical evacuation of a fetus perceived to be vigorous can both be sources of emotional anguish for women. They argue for offering women an option for induction of fetal demise prior to uterine evacuation. We report on our experience with 60 pregnancies in which lethal fetal administration of potassium chloride was performed prior to evacuation of the uterus. We describe a double-bolus technique for funic intravascular injection of potassium chloride to arrest the fetal heart. There were no maternal complications and the procedure was successful in 86.7% (n = 52) of the cases; of the remaining 8 cases, 7 had demise induced by direct fetal cardiac injection, and a live birth occurred in 1 case.


[Clinical importance of the paraprotein index in multiple myeloma].
In a group of 54 patients with multiple myeloma, hitherto not treated by chemotherapy, the paraprotein index was assessed. It was revealed that this simple and readily available indicator is related to the degree of anaemia, the serum beta-2-microglobulin value, the degree of bone marrow infiltration by myeloma plasmocytes and the survival period. The authors found no relation to age, albumin, urea, creatinine, serum calcium values and degree of skeletal affection. It was revealed that values of the paraprotein index declined with the advancing disease evaluated according to Durie-Salmon's system. It may be said that the paraprotein index can be considered in patients with multiple myeloma an indicator which contributes to more profound knowledge of individual biological characteristics of the myeloma population and the prognosis of the disease.


Rotation of the stalk/neck and one head in a new crystal structure of the kinesin motor protein, Ncd.
Molecular motors undergo conformational changes to produce force and move along cytoskeletal filaments. Structural changes have been detected in kinesin motors; however, further changes are expected because previous crystal structures are in the same or closely related conformations. We report here a 2.5 A crystal structure of the minus-end kinesin, Ncd, with the coiled-coil stalk/neck and one head rotated by approximately 75 degrees relative to the other head. The two heads are asymmetrically positioned with respect to the stalk and show asymmetry of nucleotide state: one head is fully occupied, but the other is unstably bound to ADP. Unlike previous structures, our new atomic model can be fit into cryoelectron microscopy density maps of the motor attached to microtubules, where it appears to resemble a one-head-bound motor with the stalk rotated towards the minus end. Interactions between neck and motor core residues, observed in the head that moves with the stalk, are disrupted in the other head, permitting rotation of the stalk/neck. The rotation could represent a force-producing stroke that directs the motor to the minus end.


Detection, Occurrence and Fate of Emerging Contaminants in Agricultural Environments.
A total of 43 papers published in 2014 were reviewed ranging from detailed descriptions of analytical methods, to fate and occurrence studies, to measuring and predicting biological effects for a wide variety of emerging contaminants likely to occur in agricultural environments. New methods and studies on veterinary pharmaceuticals, natural and synthetics steroids, and antibiotic resistance genes in agricultural environments continue to expand our knowledge base on the occurrence and potential impacts of these compounds. This review is divided into the following sections: Introduction, Analytical Methods, Occurrence and Fate, Antibiotic Resistance Genes, and Risk Assessment.


Deep infection in the sinus tarsi after triple arthrodesis in rheumatoid patients: a case report.
Triple arthrodesis can be used to correct hindfoot deformities in rheumatoid patients. Postoperative deep infections after triple arthrodesis are challenging to treat often requiring both operative debridement and antimicrobial therapy. The purpose of the present study was to review the treatment of deep infections in the sinus tarsi region in rheumatoid patients after triple arthrodesis using antimicrobial therapy and Papineau bone grafting or local muscle flap. Seven rheumatoid patients out of 97 who underwent triple arthrodesis between January 1997 and June 2006 had a deep postoperative infection in the sinus tarsi region. These infections were treated with systemic antibiotic therapy combined with open cancellous bone grafting (Papineau technique) in four cases and with a local muscle flap (adductor digiti minimi) in three cases. The median time from diagnosis of the deep infection to complete healing in six patients averaged 22 weeks, while one patient developed sepsis and died one year later. The most common pathogens were staphylococcus epidermis and staphylococcus aureus; a total of 15 pathogens were found. The average number of revision operations before the infection was considered to have resolved completely was seven. The rate of deep infections was 7.2% among rheumatoid patients. Infections are challenging to treat and cause prolonged morbidity. Surgical debridement and systemic antibiotic therapy combined with Papineau grafting or a local muscle flap usually yielded successful results after postoperative deep infection of the sinus tarsi region in rheumatoid patients.


ADH1B and ADH1C genotype, alcohol consumption and biomarkers of liver function: findings from a Mendelian randomization study in 58,313 European origin Danes.
The effect of alcohol consumption on liver function is difficult to determine because of reporting bias and potential residual confounding. Our aim was to determine this effect using genetic variants to proxy for the unbiased effect of alcohol. We used variants in ADH1B and ADH1C genes as instrumental variables (IV) to estimate the causal effect of long-term alcohol consumption on alanine aminotransferase (ALT), γ-glutamyl-transferase (γ-GT), alkaline phosphatase (ALP), bilirubin and prothrombin action. Analyses were undertaken on 58,313 Danes (mean age 56). In both confounder adjusted multivariable and genetic-IV analyses greater alcohol consumption, amongst those who drank any alcohol, was associated with higher ALT [mean difference per doubling of alcohol consumption: 3.4% (95% CI: 3.1, 3.7) from multivariable analyses and 3.7% (-4.5, 11.9) from genetic-IV analyses] and γ-GT [8.2% (7.8, 8.5) and 6.8% (-2.8, 16.5)]. The point estimates from the two methods were very similar and statistically the results from the two methods were consistent with each other for effects with ALT and γ-GT (both pdiff>0.3). Results from the multivariable analyses suggested a weak inverse association of alcohol with ALP [-1.5% (-1 .7, -1.3)], which differed from the strong positive effect found in genetic-IV analyses [11.6% (6.8, 16.4)] (p diff<0.0001). In both multivariable and genetic-IV analyses associations with bilirubin and protrombin action were weak and close to the null. Our results suggest that greater consumption of alcohol is related to poorer liver function as indicated by higher ALT, γ-GT and ALP, but not to clotting or bilirubin.


Developing Defined and Scalable 3D Culture Systems for Culturing Human Pluripotent Stem Cells at High Densities.
Human pluripotent stem cells (hPSCs) - including embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) - are very promising candidates for cell therapies, tissue engineering, high throughput pharmacology screens, and toxicity testing. These applications require large numbers of high quality cells; however, scalable production of human pluripotent stem cells and their derivatives at a high density and under well-defined conditions has been a challenge. We recently reported a simple, efficient, fully defined, scalable, and good manufacturing practice (GMP) compatible 3D culture system based on a thermoreversible hydrogel for hPSC expansion and differentiation. Here, we describe additional design rationale and characterization of this system. For instance, we have determined that culturing hPSCs as a suspension in a liquid medium can exhibit lower volumetric yields due to cell agglomeration and possible shear force-induced cell loss. By contrast, using hydrogels as 3D scaffolds for culturing hPSCs reduces aggregation and may insulate from shear forces. Additionally, hydrogel-based 3D culture systems can support efficient hPSC expansion and differentiation at a high density if compatible with hPSC biology. Finally, there are considerable opportunities for future development to further enhance hydrogel-based 3D culture systems for producing hPSCs and their progeny.


Primary orbital lymphoma.
Primary orbital lymphoma is a rare condition involving primarily the lacrimal glands. We present the second Indian case of right-sided primary orbital lymphoma in an elderly male who presented with the typical features and showed a good response to chemotherapy.


The application of ecological momentary assessment to the study of night eating.
Night eating syndrome (NES) was first described in 1955 by Albert Stunkard and colleagues. NES consists of either overeating at night or waking up during the night and eating. In the current study we used ecological momentary assessment (EMA) to describe 14 self-defined night-eaters. The participants in the current study completed an EMA protocol of approximately two weeks. We found that ratings of hunger appeared to be higher during night awakenings than in the evening. Also, both affect and arousal generally decreased throughout the day and were lowest during awakening episodes. The current study adds interesting data in describing the experience of night-eating behavior with ecological momentary assessments from self-described night-eaters.


Migraine and the extrapyramidal system.
This review explores a large series of observations from clinical and experimental studies on the interactions between migraine and the extrapyramidal system (EPS). A critical appraisal of these data suggests that the EPS is somehow involved in migraine. However, primary involvement of the EPS in the pathophysiology of migraine, as hinted at by the apparent concomitance of migraine, extrapyramidal symptoms and diseases, as well as by the common involvement of neurotransmitters and pathways, cannot as yet be proven. On the other hand, the involvement of EPS in migraine may reflect its more general role in the processing of nociceptive information and/or may be part of the complex behavioural adaptive response that characterizes migraine.


Thermodynamic modelling of synthetic communities predicts minimum free energy requirements for sulfate reduction and methanogenesis.
Microbial communities are complex dynamical systems harbouring many species interacting together to implement higher-level functions. Among these higher-level functions, conversion of organic matter into simpler building blocks by microbial communities underpins biogeochemical cycles and animal and plant nutrition, and is exploited in biotechnology. A prerequisite to predicting the dynamics and stability of community-mediated metabolic conversions is the development and calibration of appropriate mathematical models. Here, we present a generic, extendable thermodynamic model for community dynamics and calibrate a key parameter of this thermodynamic model, the minimum energy requirement associated with growth-supporting metabolic pathways, using experimental population dynamics data from synthetic communities composed of a sulfate reducer and two methanogens. Our findings show that accounting for thermodynamics is necessary in capturing the experimental population dynamics of these synthetic communities that feature relevant species using low energy growth pathways. Furthermore, they provide the first estimates for minimum energy requirements of methanogenesis (in the range of -30 kJ mol-1) and elaborate on previous estimates of lactate fermentation by sulfate reducers (in the range of -30 to -17 kJ mol-1 depending on the culture conditions). The open-source nature of the developed model and demonstration of its use for estimating a key thermodynamic parameter should facilitate further thermodynamic modelling of microbial communities.


Estimating the rate of retinal ganglion cell loss to detect glaucoma progression: An observational cohort study.
This study aimed to evaluate the relationship between glaucoma progression and estimates of the retinal ganglion cells (RGCs) obtained by combining structural and functional measurements in patients with glaucoma.In the present observational cohort study, we examined 116 eyes of 62 glaucoma patients. Using Cirrus optical coherence tomography (OCT), a minimum of 5 serial retinal nerve fiber layer (RNFL) measurements were performed in all eyes. There was a 3-year separation between the first and last measurements. Visual field (VF) testing was performed on the same day as the RNFL imaging using the Swedish Interactive Threshold Algorithm Standard 30-2 program of the Humphrey Field Analyzer. Estimates of the RGC counts were obtained from standard automated perimetry (SAP) and OCT, with a weighted average then used to determine a final estimate of the number of RGCs for each eye. Linear regression was used to calculate the rate of the RGC loss, and trend analysis was used to evaluate both serial RNFL thicknesses and VF progression.Use of the average RNFL thickness parameter of OCT led to detection of progression in 14 of 116 eyes examined, whereas the mean deviation slope detected progression in 31 eyes. When the rates of RGC loss were used, progression was detected in 41 of the 116 eyes, with a mean rate of RGC loss of -28,260 ± 8110 cells/year.Estimation of the rate of RGC loss by combining structural and functional measurements resulted in better detection of glaucoma progression compared to either OCT or SAP.