Methods for assessing pre-induction cervical ripening.
Induction of labour is the artificial initiation of labour in a pregnant woman after the age of fetal viability but without any objective evidence of active phase labour and with intact fetal membranes. The need for induction of labour may arise due to a problem in the mother, her fetus or both, and the procedure may be carried out at or before term. Obstetricians have long known that for this to be successful, it is important that the uterine cervix (the neck of the womb) has favourable characteristics in terms of readiness to go into the labour state. To compare Bishop score with any other method for assessing pre-induction cervical ripening in women admitted for induction of labour. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 March 2015) and reference lists of retrieved studies to identify randomised controlled trials (RCTs). All RCTs comparing Bishop score with any other methods of pre-induction cervical assessment in women admitted for induction of labour. Cluster-RCTs were eligible for inclusion but none were identified. Quasi-RCTs and studies using a cross-over design were not eligible for inclusion. Studies published in abstract form were eligible for inclusion if they provided sufficient information.Comparisons could include the following.1. Bishop score versus transvaginal ultrasound (TVUS).2. Bishop score versus Insulin-like growth factor binding protein-1 (IGFBP-1).3. Bishop score versus vaginal fetal fibronectin (fFN).However, we only identified data for a comparison of Bishop score versus TVUS. Two review authors independently assessed the trials for inclusion, extracted the data and assessed trial quality. Data were checked for accuracy. We included two trials that recruited a total of 234 women. The overall risk of bias was low for the two studies. Both studies compared Bishop score withTVUS.The two included studies did not show any clear difference between the Bishop score and TVUS groups for the following main outcomes: vaginal birth (RR 1.07, 95% CI 0.92 to 1.25, moderate quality evidence), caesarean delivery (RR 0.81, 95% CI 0.49 to 1.34, moderate quality evidence), neonatal admission into neonatal intensive care unit (RR 1.67, 95% CI 0.41 to 6.71, moderate quality evidence). Both studies only provided median data in relation to induction-delivery interval and reported no clear difference between the Bishop and TVUS groups. Perinatal mortality was not reported in the included studies.For the review's secondary outcomes, the need for misoprostol for cervical ripening was more frequent in the TVUS group compared to the Bishop score group (RR 0.52, 95% CI 0.41 to 0.66, two studies, 234 women, moderate quality evidence). In contrast, there were no clear differences between the Bishop scope and TVUS groups in terms of meconium staining of the amniotic fluid, fetal heart rate abnormality in labour, and Apgar score less than seven. Only one trial reported median data on the induction-delivery interval and induction to active phase interval, the trialist reported no difference between the Bishop group and the TVUS group for this outcome. Neither of the included studies reported on uterine rupture. Moderate quality evidence from two small RCTs involving 234 women that compared two different methods for assessing pre-induction cervical ripening (Bishop score and TVUS) did not demonstrate superiority of one method over the other in terms of the main outcomes assessed in this review. We did not identify any data relating to perinatal mortality. Whilst use of TVUS was associated with an increased need for misoprostol for cervical ripening, both methods could be complementary.The choice of a particular method of assessing pre-induction cervical ripening may differ depending on the environment and need where one is practicing since some methods (i.e. TVUS) may not be readily available and affordable in resource-poor settings where the sequelae of labour and its management is prevalent.The evidence in this review is based on two studies that enrolled a small number of women and there is insufficient evidence to support the use of TVUS over the standard digital vaginal assessment in pre-induction cervical ripening. Further adequately powered RCTs involving TVUS and the Bishop score and including other methods of pre-induction cervical ripening assessment are warranted. Such studies need to address uterine rupture, perinatal mortality, optimal cut-off value of the cervical length and Bishop score to classify women as having favourable or unfavourable cervices and cost should be included as an outcome.


Ovulation suppression for endometriosis.
Although the etiology of endometriosis is unknown, several theories exist, the most popular of which is retrograde menstruation. As endometriosis can only be diagnosed by laparoscopy, neither the incidence (annual occurrence) nor the prevalence (proportion of the population affected) of endometriosis is known. The association between endometriosis and infertility isn't clear in Stage I (minimal) and Stage II (mild) endometriosis. Endometriosis appears to be an estrogen dependent condition. At the time of menopause, most endometriosis becomes quiescent. This hormonal dependency prompted researchers to seek agents which would suppress ovarian activity. To determine effectiveness of a) ovulation suppression with danazol, medroxy progesterone acetate, gestrinone, combined oral contraceptive pills and GnRH analogues versus placebo or no treatment and b) any of the above agents versus danazol, for the treatment of endometriosis explained infertility in terms of clinical pregnancy rate. The Cochrane Subfertility Review Group specialised register of controlled trials was searched. Four RCTs with five treatment arms compared an ovulation suppression agent with placebo or no treatment. Eight trials were identified comparing a suppressive agent with danazol. A diverse search strategy was employed, including hand-search of 43 core journals from 1966 to the present, bibliographies of relevant trials, MEDLINE database, abstracts from North American and European meetings and contact with authors of relevant papers. Relevant data were extracted independently by two reviewers using the standardised data extraction sheet. Validity was assessed in terms of method of randomisation, completeness of follow-up, presence or absence of crossover and co-intervention. 2x2 tables were generated for all relevant outcomes. Odds ratios were generated using the Peto modified Mantel-Haenszel technique. Statistical heterogeneity was assessed using x2. The common odds ratio for pregnancy following ovulation suppression versus placebo or no treatment was 0.83 (95% CI 0.5-1.39). These data were statistically homogeneous although clinical heterogeneity was present. Their consistency in showing no treatment benefit suggests that this group of interventions is ineffective. Common odds ratio for pregnancy following all agents versus danazol was 1.20 (95% CI 0. 85-1.68). Again these data were homogeneous and suggest no significant treatment benefit in terms of pregnancy rate. Given the significant period of amenorrhea associated with ovulation suppression, the lack of treatment benefit demonstrated and the adverse effects commonly associated with these treatments, ovulation suppression cannot be recommended as a standard therapy for endometriosis-associated infertility.


Invited commentary: multilevel analysis of individual heterogeneity-a fundamental critique of the current probabilistic risk factor epidemiology.
In this issue of the Journal, Dundas et al. (Am J Epidemiol. 2014;180(2):197-207) apply a hitherto infrequent multilevel analytical approach: multiple membership multiple classification (MMMC) models. Specifically, by adopting a life-course approach, they use a multilevel regression with individuals cross-classified in different contexts (i.e., families, early schools, and neighborhoods) to investigate self-reported health and mental health in adulthood. They provide observational evidence suggesting the relevance of the early family environment for launching public health interventions in childhood in order to improve health in adulthood. In their analyses, the authors distinguish between specific contextual measures (i.e., the association between particular contextual characteristics and individual health) and general contextual measures (i.e., the share of the total interindividual heterogeneity in health that appears at each level). By doing so, they implicitly question the traditional probabilistic risk factor epidemiology including classical "neighborhood effects" studies. In fact, those studies use simple hierarchical structures and disregard the analysis of general contextual measures. The innovative MMMC approach properly responds to the call for a multilevel eco-epidemiology against a widespread probabilistic risk factors epidemiology. The risk factors epidemiology is not only reduced to individual-level analyses, but it also embraces many current "multilevel analyses" that are exclusively focused on analyzing contextual risk factors.


Spontaneous and directed application of verbal learning strategies in bipolar disorder and obsessive-compulsive disorder.
Individuals with bipolar disorder exhibit neuropsychological impairments when they are euthymic (neither depressed nor manic). One of the most consistently reported cognitive problems in euthymic individuals with bipolar disorder is impairment in verbal episodic memory. Recent findings suggest that episodic memory difficulties in these individuals are attributable to difficulties using organizational strategies during encoding. The purpose of the present study was (i) to investigate whether difficulties using organizational strategies in bipolar disorder are due to a failure in spontaneously initiating verbal organization strategies or are due to difficulties implementing such strategies, and (ii) to compare the characteristics of verbal organizational impairment in bipolar disorder with those observed in individuals with obsessive-compulsive disorder (OCD). Study participants were 20 individuals with bipolar I disorder (BP-I), 20 individuals with OCD, and 20 healthy control participants matched for age, gender, and education. Participants completed a verbal encoding paradigm that involved spontaneous and directed use of verbal organization strategies during encoding of word lists. Compared with control subjects, both BP-I and OCD participants showed impaired verbal organization in the spontaneous encoding condition. In the directed encoding condition, OCD patients organized the word lists as well as control participants whereas BP-I participants exhibited lower verbal organization than both control and OCD participants. OCD and BP-I participants' free recall performance did not differ from that of control participants in the spontaneous encoding condition. In the directed encoding condition, BP-I participants recalled fewer words than OCD or control participants. Episodic memory difficulties in OCD are associated with difficulties spontaneously initiating verbal organization strategies during encoding whereas the ability to implement verbal organization when instructed to do so is preserved. BP-I participants, on the other hand, exhibit difficulties in both spontaneously initiating verbal organization strategies and in the ability to implement such strategies when instructed to do so.


Purification and characterization of endo-beta-N-acetylglucosaminidase of Aspergillus oryzae.
An endo-beta-N-acetylglucosaminidase which hydrolyzes the N,N'-diacetylchitobiosyl linkage in asparagine-linked oligosaccharides was purified from the enzyme product of Aspergillus oryzae. Its substrate specificity was similar to that of endo-beta-N-acetylglucosaminidase H from Streptomyces griseus with respect to the relative activities toward the glycopeptides obtained from ovalbumin and bovine IgG. The present endoglycosidase exhibited a broad optimum pH range and was relatively stable. Metal ions, chelating agents and D-mannose did not have a significant effect on the enzyme activity.


Perspective on calf and mammary gland development through changes in the bovine milk proteome over a complete lactation.
Milk contains all the nutrients for the growth and development of the neonate. However, milk composition is not constant during lactation. To study the changes of the milk proteome over lactation, filter-aided sample preparation combined with dimethyl labeling followed by liquid chromatography tandem mass spectrometry was used to identify and quantify milk proteins from 4 cows. A total of 229 proteins were identified, of which 219 were quantified. An 80% overlap was found in identified and quantified proteins between the 4 individual cows during lactation. Over lactation, the number of quantified proteins changed slightly (less than 10%), whereas the concentration of proteins changed considerably. Transport proteins involved in lipid synthesis (fatty acid-binding protein, perilipin-2, butyrophilin) increased, whereas proteins related to cholesterol transport (apolipoprotein E) decreased. The changes of lipid synthesis proteins are in accordance with the increased milk fat yield over lactation, indicating the increase of de novo mammary fatty acid synthesis as lactation advances. The high abundance of immune-related proteins in early lactation indicates the important role of these proteins for immune system development of calves. The increase in immune-related proteins (immunoglobulins, osteopontin, lactoferrin) and the decrease of proteins related to milk component synthesis (α-lactalbumin, β-lactoglobulin, fatty acid-binding protein, perilipin-2, butyrophilin) in late lactation can be associated with the protection of the mammary gland. In conclusion, the changes of proteins with different biological functions reflect not only the changing needs of calves but also the development and protection of the mammary gland over lactation.


Phytochemical complementarities among endophyte-infected tall fescue, reed canarygrass, birdsfoot trefoil and alfalfa affect cattle foraging.
We determined whether plant diversity and sequence of plant ingestion affected foraging when cattle chose from plants that varied in concentrations of alkaloids, tannins and saponins. We hypothesized cattle that ate high-alkaloid grasses (endophyte-infected tall fescue (TF) or reed canarygrass (RCG)) would prefer forages high in tannins (birdsfoot trefoil, BFT+) or saponins (alfalfa, ALF+), because tannins and saponins can bind to alkaloids, presumably reducing their absorption. We further hypothesized that forages with tannins or saponins consumed before, rather than after, foraging on high-alkaloid grasses would promote greater use of those grasses presumably by binding to alkaloids, thereby reducing their absorption. In Phase 1, cattle (n = 32) grazed on either high (+) or low (-) alkaloid grass (TF or RCG) pastures for 30 min each morning at 0600 h and were then offered a choice of BFT+, BFT-, ALF+ and ALF- for 60 min each day for 12 days. In Phase 2, cattle (n = 32) were first offered a choice of BFT+ or ALF+ for 30 min at 0600 h and then placed on grass (TF+ or -, or RCG+ or -) pastures for 60 min for 12 days. In both phases, we had four spatial replications of four treatments with 2 per calves assigned to each of the 16 replications per treatment combinations. Scan samples of individuals at 2-min intervals were used to determine incidence of foraging on each plant species (%). Cattle grazed more on RCG than on TF in Phases 1 (62% v. 27%; P = 0.0015) and 2 (71% v. 32%; P = 0.0005). In Phase 1, cattle that first foraged on RCG+ or TF- subsequently preferred ALF over BFT, whereas cattle offered RCG- or TF+ foraged on ALF and BFT equally. Foraging by cattle on RCG was cyclic during Phase 1, whereas cattle foraging on TF markedly decreased incidence of use of TF from 41% to only 16% by the end of the 12-day trial (P = 0.0029). Contrary to the cyclic (RCG) or steadily declining (TF) use of grasses in Phase 1, cattle steadily and dramatically increased foraging on both RCG and TF throughout Phase 2, when they first grazed BFT+ or ALF+ followed by high-alkaloid grasses (P = 0.0159). Our findings suggest that in plant species the sequence of ingestion influenced foraging behavior of cattle and that secondary compounds influenced those responses.


Simultaneous determination of bacterial viability and identity in biofilms using ethidium monoazide and fluorescent in situ hybridization.
A protocol for simultaneously interrogating bacterial viability and identity using in situ, culture-independent methods is described. Viability is assayed using ethidium monoazide (EMA) staining of cells with compromised membranes, and identity is determined using fluorescent in situ hybridization (FISH). Experiments with planktonic cultures were used to demonstrate the compatibility of EMA staining and FISH after covalently bonding EMA to nucleic acids by photoreaction. Applications to biofilm samples showed that diffusion limitations in the biofilm matrix were not problematic and that effective discrimination of viable target cells within a mixed microbial community was possible.


Automated in-season rice crop mapping using Sentinel time-series data and Google Earth Engine: A case study in climate-risk prone Bangladesh.
High-resolution mapping of rice fields is crucial for understanding and managing rice cultivation in countries like Bangladesh, particularly in the face of climate change. Rice is a vital crop, cultivated in small scale farms that contributes significantly to the economy and food security in Bangladesh. Accurate mapping can facilitate improved rice production, the development of sustainable agricultural management policies, and formulation of strategies for adapting to climatic risks. To address the need for timely and accurate rice mapping, we developed a framework specifically designed for the diverse environmental conditions in Bangladesh. We utilized Sentinel-1 and Sentinel-2 time-series data to identify transplantation and peak seasons and employed the multi-Otsu automatic thresholding approach to map rice during the peak season (April-May). We also compared the performance of a random forest (RF) classifier with the multi-Otsu approach using two different data combinations: D1, which utilizes data from the transplantation and peak seasons (D1 RF) and D2, which utilizes data from the transplantation to the harvest seasons (D2 RF). Our results demonstrated that the multi-Otsu approach achieved an overall classification accuracy (OCA) ranging from 61.18% to 94.43% across all crop zones. The D2 RF showed the highest mean OCA (92.15%) among the fourteen crop zones, followed by D1 RF (89.47%) and multi-Otsu (85.27%). Although the multi-Otsu approach had relatively lower OCA, it proved effective in accurately mapping rice areas prior to harvest, eliminating the need for training samples that can be challenging to obtain during the growing season. In-season rice area maps generated through this framework are crucial for timely decision-making regarding adaptive management in response to climatic stresses and forecasting area-wide productivity. The scalability of our framework across space and time makes it particularly suitable for addressing field data scarcity challenges in countries like Bangladesh and offers the potential for future operationalization.


Telomere measurement by quantitative PCR.
It has long been presumed impossible to measure telomeres in vertebrate DNA by PCR amplification with oligonucleotide primers designed to hybridize to the TTAGGG and CCCTAA repeats, because only primer dimer-derived products are expected. Here we present a primer pair that eliminates this problem, allowing simple and rapid measurement of telomeres in a closed tube, fluorescence-based assay. This assay will facilitate investigations of the biology of telomeres and the roles they play in the molecular pathophysiology of diseases and aging.


Functional analysis of the Drosophila twist promoter reveals a dorsal-binding ventral activator region.
twist is one of the earliest expressed zygotically active genes required for dorsal-ventral pattern formation in the Drosophila embryo. Genetic studies suggest that this gene is activated in the ventral part of the blastoderm by maternally expressed dorsal gene product. Using P-element-mediated germ-line transformation, we have mapped a small (260 bp) dorsal-dependent ventral activator region (VAR) in the 5'-flanking region of the twist promoter that can direct the early ventral expression of a heterologous promoter. The VAR contains binding sites for a number of proteins present in extracts of Drosophila embryos. One of these sites bears homology to known binding sites for the dorsal transcription factor and is specifically bound by bacterially expressed dorsal protein. Furthermore, a 37-bp deletion that removes the dorsal-binding sequences abolishes the ventral-specific activity of the twist promoter constructs. Our data also show that additional sequences within the VAR are required to render the dorsal-binding sites functional. Finally, reverse genetic and biochemical data suggest that the transcription factor, encoded by the zeste gene may help control the overall level, if not the pattern, of twist expression.


[Formation of ion channels in the Escherichia coli cytoplasmic membrane after exposure to bacteriophages T4 and lambda].
The effects of phage T4 and lambda on the ion permeability of the E. coli cytoplasmic membrane were studied. It was shown that the phage-induced depolarization of the membrane is coupled with a simultaneous increase in a transmembrane pH gradient. Hence, the total value of the proton-motive force remains unchanged at moderate multiplicity of infection. The rise in the pH gradient occurs due to an increase in the activity of the redox H+-pump of the E. coli membrane. Analysis of the temperature dependence showed that the stimulating effect of the phage is observed at 6-8 degrees C. Apart from the phages, gramicidin is also capable of stimulating the H+-pump under these conditions, while the stimulating effect of valinomycin is diminished. These data suggest that the ion-permeable channels are formed in the membrane during the interaction of E. coli cells with the phages. The experimental results demonstrate that the channels are permeable to ions of monovalent metals. The phage can also increase the permeability of cell membranes to protons; however, the permeability to monovalent ions is higher when these ions are in excess.


TMT-Based Multiplexed Quantitation of N-Glycopeptides Reveals Glycoproteome Remodeling Induced by Oncogenic Mutations.
Glycoproteomics, or the simultaneous characterization of glycans and their attached peptides, is increasingly being employed to generate catalogs of glycopeptides on a large scale. Nevertheless, quantitative glycoproteomics remains challenging even though isobaric tagging reagents such as tandem mass tags (TMT) are routinely used for quantitative proteomics. Here, we present a workflow that combines the enrichment or fractionation of TMT-labeled glycopeptides with size-exclusion chromatography (SEC) for an in-depth and quantitative analysis of the glycoproteome. We applied this workflow to study the cellular glycoproteome of an isogenic mammary epithelial cell system that recapitulated oncogenic mutations in the PIK3CA gene, which codes for the phosphatidylinositol-3-kinase catalytic subunit. As compared to the parental cells, cells with mutations in exon 9 (E545K) or exon 20 (H1047R) of the PIK3CA gene exhibited site-specific glycosylation alterations in 464 of the 1999 glycopeptides quantified. Our strategy led to the discovery of site-specific glycosylation changes in PIK3CA mutant cells in several important receptors, including cell adhesion proteins such as integrin β-6 and CD166. This study demonstrates that the SEC-based enrichment of glycopeptides is a simple and robust method with minimal sample processing that can easily be coupled with TMT-labeling for the global quantitation of glycopeptides.


Successful implementation of immediate postpartum intrauterine contraception services in Edinburgh and framework for wider dissemination.
Provision of immediate postpartum intrauterine device (PPIUD) insertion within maternity settings can overcome many of the barriers faced by women in accessing this method after childbirth. Uptake of PPIUD can help reduce the risk of a subsequent unintended pregnancy and improve spacing between births. PPIUD insertion is not yet routinely available in the UK and evidence to support the practical implementation of the service in this setting is lacking. Shared learning and experience of providers may assist in the wider availability of PPIUD. A routine PPIUD service has been successfully established within a public maternity setting in Edinburgh (UK) and this article utilizes an implementation framework to discuss the approach.


Generation of patterned neuronal networks on cell-repellant poly(oligo(ethylene glycol) methacrylate) films.
The utilization of non-biofouling poly(oligo(ethylene glycol) methacrylate) (pOEGMA) films as a background material for the generation of neuronal patterns is reported here. Our previously reported method, which was surface-initiated, atom transfer radical polymerization of OEGMA, and subsequent activation of terminal hydroxyl groups of pOEGMA with disuccinimidyl carbonate, was employed for the generation of activated pOEGMA films on glass. Poly-L-lysine was then microcontact-printed onto the activated polymer films, followed by backfilling with poly(ethylene glycol) moieties. E18 hippocampal neurons were cultured on the chemically patterned substrate, and the resulting neuronal networks were analyzed by phase-contrast microscopy and whole-cell patch clamp method. The results indicated that the pOEGMA films played an important role in the generation of good-quality neuronal patterns for up to two weeks without any negative effects to neurons.


Molecular Epidemiology and Risk Factors of Carbapenemase-Producing Enterobacteriaceae Isolates in Portuguese Hospitals: Results From European Survey on Carbapenemase-Producing Enterobacteriaceae (EuSCAPE).
In Portugal, the epidemiological stage for the spread of carbapenemase-producing Enterobacteriaceae (CPE) increased from sporadic isolates or single hospital clones (2010-2013), to hospital outbreaks, later. Here we report data from a 6-month study performed under the European Survey on Carbapenemase-Producing Enterobacteriaceae (EuSCAPE). During the study period, 67 isolates (61 Klebsiella pneumoniae and 6 Escherichia coli) non-susceptible to carbapenems were identified in participant hospital laboratories. We detected 37 bla KPC-type (including one new variant: bla KPC-21), 1 bla GES-5, and 1 bla GES-6 plus bla KPC-3, alone or in combination with other bla genes. Bioinformatics analysis of the KPC-21-producing E. coli identified the new variant bla KPC-21 in a 12,748 bp length plasmid. The bla KPC-21 gene was harbored on a non-Tn4401 element, presenting upstream a partial ISKpn6 (ΔISKpn6/ΔtraN) with the related left IR (IRL) and downstream a truncated Tn3 transposon. PFGE and MLST analysis showed an important diversity, as isolates belonged to distinct PFGE and STs profiles. In this study, we highlighted the presence of the high-risk clone E. coli sequence-type (ST) 131 clade C/H30. This worldwide disseminated E. coli lineage was already detected in Portugal among other antibiotic resistance reservoirs. This study highlights the intra- and inter-hospital spread and possible intercontinental circulation of CPE isolates.


Adverse events in 50 cats with allergic dermatitis receiving ciclosporin.
Ciclosporin is an immunosuppressive drug that has been used to treat allergies and other immune-mediated diseases in cats, dogs and humans. Information about the adverse effects of ciclosporin in cats has been limited to smaller studies and case reports. Adverse effects in dogs are mainly gastrointestinal in nature, but humans can also experience hypertension and altered renal function. The aim of this retrospective case series study was to document the occurrence and clinical appearance of adverse events in cats receiving ciclosporin to treat allergic skin disease. The medical records of 50 cats with allergic dermatitis treated with oral ciclosporin (1.9-7.3 mg/kg/day) were reviewed. Adverse events occurred in 66% (33 cats). Adverse events likely to be associated with ciclosporin included the following: vomiting or diarrhoea within 1-8 weeks of receiving ciclosporin (24%), weight loss (16%), anorexia and subsequent hepatic lipidosis (2%) and gingival hyperplasia (2%). Other adverse events less likely to be associated with ciclosporin therapy included the following: weight gain (14%), dental tartar and gingivitis (10%), otitis (4%), chronic diarrhoea (4%), inflammatory bowel disease with indolent gastrointestinal lymphoma (2%), urinary tract infection (2%), cataract (2%), elevated liver enzymes (2%), hyperthyroidism and renal failure (2%) and transient inappropriate urination (2%). Some cats experienced multiple adverse events. Case-control studies are needed to prove cause and effect of ciclosporin with regard to these adverse events.


Multigenerational family structure in Japanese society: impacts on stress and health behaviors among women and men.
Rapid population aging in Japan has led to rising demands for informal care giving. Traditionally, care giving for aging parents has fallen disproportionately on the shoulders of women living in multigenerational households. However, rising labor force participation by Japanese women, declining marriage and fertility rates, and women's changing expectations have combined to produce unprecedented strains on traditional multigenerational households where care giving to elders traditionally takes place. In this paper, we explored gender-specific relationships between family structure, stress and worries, and health behaviors, using linked data from two national surveys conducted in Japan: the 1995 Comprehensive Survey of the Living Conditions of People on Health and Welfare, and the 1995 National Nutrition Survey. We found that women in multigenerational households reported more care-giving worries, and also less future health and financial worries. Living with parents was associated with protective health behaviors (less smoking, less heavy drinking), but also more sedentary behavior among women, while men in "sandwich" families (i.e., living with both parents and children) reported heavier smoking. The association of family structure and health behavior was not mediated by worries. Living alone was associated with worse health for women. These findings suggest gender-specific patterns of worries and health behaviors that reflect both the health-protecting and health-damaging effects of living in multigenerational households.


Young coconut juice can accelerate the healing process of cutaneous wounds.
Estrogen has been reported to accelerate cutaneous wound healing. This research studies the effect of young coconut juice (YCJ), presumably containing estrogen-like substances, on cutaneous wound healing in ovairectomized rats. Four groups of female rats (6 in each group) were included in this study. These included sham-operated, ovariectomized (ovx), ovx receiving estradiol benzoate (EB) injections intraperitoneally, and ovx receiving YCJ orally. Two equidistant 1-cm full-thickness skin incisional wounds were made two weeks after ovariectomy. The rats were sacrificed at the end of the third and the fourth week of the study, and their serum estradiol (E2) level was measured by chemiluminescent immunoassay. The skin was excised and examined in histological sections stained with H&E, and immunostained using anti-estrogen receptor (ER-α an ER-β) antibodies. Wound healing was accelerated in ovx rats receiving YCJ, as compared to controls. This was associated with significantly higher density of immunostaining for ER-α an ER-β in keratinocytes, fibroblasts, white blood cells, fat cells, sebaceous gland, skeletal muscles, and hair shafts and follicles. This was also associated with thicker epidermis and dermis, but with thinner hypodermis. In addition, the number and size of immunoreactive hair follicles for both ER-α and ER-β were the highest in the ovx+YCJ group, as compared to the ovx+EB group. This study demonstrates that YCJ has estrogen-like characteristics, which in turn seem to have beneficial effects on cutaneous wound healing.


Bipolar disorder affects behavior and social skills on the Internet.
Bipolar disorder (BD) is a significant cause of functional, cognitive, and social impairment. However, classic studies of functioning and social skills have not investigated how BD may impact behavior on the Internet. Given that the digital age has been changing the way people communicate, this study aims to investigate the pattern of Internet use in patients with BD. This cross-sectional study assessed 30 patients with BD I or II and 30 matched controls. Patients were not in an acute mood episode, according to DSM-IV. A standard protocol examined sociodemographic variables and social behavior on the Internet, assessed by Facebook number of friends (FBN) and lifetime estimated number of offline contacts (social network number, SNN). SNN (p<0.001) and FBN (p = 0.036) of patients with BD were significantly lower than those of controls. Also, variables related with Internet use were significantly lower in patients, e.g., close contacts on Facebook (p = 0.021), Internet experience (p = 0.020), and knowledge of terms associated with social networking sites (p = 0.042). Also, patients showed lower rates of the expected pattern of Internet use (based on their age generation), including a poorer knowledge of SNS (p = 0.018) and a lower frequency of Internet use (p = 0.010). This study suggests that patients with BD show smaller social networks both in real-world settings and on the Internet. Also, patients tend to use the Internet and social networking sites less frequently and show a poorer knowledge of Internet and social media than healthy controls, below the expected for their generation. These significant differences between patients and controls suggest that the effects of BD on social relationships and functioning extend to electronic media.


Rho-GTPase effector ROCK phosphorylates cofilin in actin-meditated cytokinesis during mouse oocyte meiosis.
During oocyte meiosis, a spindle forms in the central cytoplasm and migrates to the cortex. Subsequently, the oocyte extrudes a small body and forms a highly polarized egg; this process is regulated primarily by actin. ROCK is a Rho-GTPase effector that is involved in various cellular functions, such as stress fiber formation, cell migration, tumor cell invasion, and cell motility. In this study, we investigated possible roles for ROCK in mouse oocyte meiosis. ROCK was localized around spindles after germinal vesicle breakdown and was colocalized with cytoplasmic actin and mitochondria. Disrupting ROCK activity by RNAi or an inhibitor resulted in cell cycle progression and polar body extrusion failure. Time-lapse microscopy showed that this may have been due to spindle migration and cytokinesis defects, as chromosomes segregated but failed to extrude a polar body and then realigned. Actin expression at oocyte membranes and in cytoplasm was significantly decreased after these treatments. Actin caps were also disrupted, which was confirmed by a failure to form cortical granule-free domains. The mitochondrial distribution was also disrupted, which indicated that mitochondria were involved in the ROCK-mediated actin assembly. In addition, the phosphorylation levels of Cofilin, a downstream molecule of ROCK, decreased after disrupting ROCK activity. Thus, our results indicated that a ROCK-Cofilin-actin pathway regulated meiotic spindle migration and cytokinesis during mouse oocyte maturation.


Accuracy of self-reported educational attainment among diverse patient populations: a preliminary investigation.
Despite speculation concerning the accuracy of self-reported information, particularly from certain patient populations, many neuropsychologists continue to estimate premorbid intellectual functioning on the basis of self-reported educational attainment. This study examined 116 individuals with diverse diagnoses [i.e., alcoholism, posttraumatic stress disorder (PTSD), schizophrenia or schizoaffective, and dementia] to determine the accuracy of their self-reported high school educational attainment. Results suggest that at least half of all participants were inaccurate as defined by discrepancies between actual and estimated GPA greater than.5 on a traditional 4-point grading scale. Most patients were inaccurate in the direction of overestimating their educational attainment. Patients diagnosed with alcoholism and PTSD were significantly less accurate in recalling their educational history when compared to a group of normal-control subjects. Several subjects, whose records could not be verified, were found to have not attended high school as they had claimed. These results underscore the potential inaccuracy that exists when estimating premorbid intelligence using self-reported information.


Susceptibility of women athletes to injury. Myths vs reality.
To separate fact from fiction regarding the susceptibility of women athletes to injury, three surveys were conducted. The initial data were collected from the athletic departments of collegiate institutions, and the final material was assembled from certified athletic trainers at these institutions, plus an extensive computer search of applicable publications. The collected statistical data were tabulated, and a written commentary was evaluated by the authors. It was established that injuries sustained by female athletes, aside from those related to different biological structures, were essentially no different than those of men, nor are well-trained women athletes more prone to injury. Ankle and knee injuries are most frequent, and women sustain many contusions, sprains, and shin splints. It is anticipated that the overall number of injuries will decrease as better coaches and trainers become available to women athletes.


The effectiveness of a lipid peroxide in oxidizing protein and non-protein thiols.
1. Thiol oxidation by a lipid peroxide or hydrogen peroxide was as efficient in denatured non-haem proteins as in small thiols. Both peroxides were relatively ineffective in oxidizing haemoprotein thiols, especially at low pH. Increased amounts of haematin decreased greatly the efficiency of GSH oxidation by peroxides especially at low pH. 2. Other than the haematin ring, the thiol group was found to be probably the group in proteins most sensitive to modification by peroxides. 3. At low concentrations, the fatty acid moiety of a lipid peroxide appeared to impede thiol oxidation in proteins, probably by hydrophobic bonding to the protein, rather than to stimulate thiol oxidation by denaturing the protein and thereby increasing the exposure and reactivity of the thiol group. 4. The relative rates of thiol oxidation by peroxides in the different thiols were: haemoprotein thiols>small thiols>other protein thiols. In all cases, thiol oxidation was much more rapid by the lipid peroxide than by hydrogen peroxide.


Using health production functions to evaluate treatment effectiveness: an application to a community mental health service.
The randomized controlled trial (RCT) is the recommended means of evaluating health care effectiveness and cost-effectiveness. Whilst representing a 'gold-standard' in health services research, RCT evidence on the clinical and economic desirability of services and treatments is often absent. Where RCT evidence is lacking, or where it is infeasible to implement randomized controlled comparisons, longitudinal observational and naturalistic data sources when analysed appropriately can yield useful insights regarding the clinical effectiveness and economic efficiency of treatments. In this paper we demonstrate the utility of applying panel estimation methods to data from an Italian psychiatric case register as a means of modelling the mental health outcomes of patients referred to a community-based mental health service. Emphasis is placed on quantifying the clinical effectiveness of consultations with different mental health professionals (including in-patient days) and whether service outcomes are affected by psychiatric diagnosis. The impact of service consultations and their interaction with different types of psychiatric diagnosis on a measure of patient mental health are found to be statistically significant, although the size of these effects are not substantial from a clinical perspective.


Evaluation and management of pathological nipple discharges without using intraductal imaging methods.
The most common cause of pathological nipple discharge (PND) is single papilloma, which is a benign intraductal lesion (BIL). However, underlying malign (MIL) or high-risk intraductal lesions (HIL) should be considered during examination. To reveal the value of conventional imaging methods (CIM), discharge characteristics, and cytology in lack of intraductal imaging methods to detect intraductal lesions (IL) and MIL that cause PND. We compared the pathological findings with the characteristics of discharge, CIM, and cytology findings of the patients who admitted to our clinic with nipple discharge and underwent duct excision (n = 111). IL were detected in 69 (62.2%) patients as BIL (n = 31), HIL (n = 23), and MIL (n = 15). Most of the IL was observed with bloody, serosanguineous, and serous discharges (83.3%, 76.2%, and 69.2%, respectively). The sensitivities of ultrasonography, MRI, and cytology in detecting IL were found to be 50.7%, 42.6%, and 74.1%, while their specificities were found to be 73.8%, 88.2%, and 48.6%, respectively. None of the CIM was sufficient to detect MIL in 5 (33.3%) patients. The appearance of red blood cells detailed in cytology was significantly related to IL (p < 0.01), whereas the presence of inflammatory cells was related to ductal ectasia and periductal mastitis (p < 0.001). Although patients' physical examinations, CIM, and cytology findings were normal, duct excision procedures should be applied to exclude MIL or HIL, which can be a cause of discharge in case of suspicious color. The details in cytology reports have a role in increasing the value of cytology.


Developing human factors/ergonomics as a design discipline.
This paper deals with internal challenges that the human factors/ergonomics (HFE) research faces when wishing to strengthen its contribution to development of work systems. Three established characteristics of high-quality HFE, i.e., HFE takes a systems approach, HFE is design-driven, and HFE focuses on two closely related outcomes, performance and well-being, are taken as a starting point of a methodological discussion, in which conceptual innovations, e.g. adopting the technology-in-use perspective, are proposed to support development of HFE towards the high-quality aims. The feasibility of the proposed conceptual choices is demonstrated by introducing a naturalistic HFE analysis approach including four HFE functions. The gained experience of the use of this approach in a number of complex work domains allows the conclusion that becoming design-driven appears as that most difficult quality target for HFE to reach. Creating an own design discipline identity in a multi-voiced collaboration is the key internal challenge for human factors/ergonomics.


Isolation of a sixth dynein subunit adenosine triphosphatase of Chlamydomonas axonemes.
This study of the axoneme led to the identification of a previously unknown adenosine triphosphatase (ATPase), which is likely a major component of inner dynein arms. The ATPase was isolated from a soluble fraction of axonemes obtained from pf 28, a Chlamydomonas mutant lacking the outer dynein arms. The activity hydrolyzed up to 2.3 mumol of ATP.min-1.mg-1 of protein (at pH 7.2, in the presence of both Ca++ and Mg++), had a sedimentation coefficient of 11S in sucrose gradient, and cosedimented with four polypeptides of apparent molecular weight 325,000, 315,000 140,000, and 42,000. Several arguments indicate that the new ATPase is a component of the inner dynein arms. Three or four polypeptides cosedimenting with the activity belong to a group of axonemal components that are deficient in the axonemes of pf 23 and pf 30, two mutants that display different levels of inner dynein arm deficiency. The 42,000 component is axonemal actin, a subunit of two other inner dynein ATPases. The two polypeptides of molecular weight greater than 300,000 have electrophoretic mobility similar to that of high molecular weight components of outer and inner dynein arms. In spite of some similarities each ATPase isolated from inner or outer arms is composed of a different set of polypeptides. Different ATPases may be required for the modulation of localized sliding of adjacent outer double microtubules in the axoneme.


Activins and follistatins: Emerging roles in liver physiology and cancer.
Activins are secreted proteins belonging to the TGF-β family of signaling molecules. Activin signals are crucial for differentiation and regulation of cell proliferation and apoptosis in multiple tissues. Signal transduction by activins relies mainly on the Smad pathway, although the importance of crosstalk with additional pathways is increasingly being recognized. Activin signals are kept in balance by antagonists at multiple levels of the signaling cascade. Among these, follistatin and FLRG, two members of the emerging family of follistatin-like proteins, can bind secreted activins with high affinity, thereby blocking their access to cell surface-anchored activin receptors. In the liver, activin A is a major negative regulator of hepatocyte proliferation and can induce apoptosis. The functions of other activins expressed by hepatocytes have yet to be more clearly defined. Deregulated expression of activins and follistatin has been implicated in hepatic diseases including inflammation, fibrosis, liver failure and primary cancer. In particular, increased follistatin levels have been found in the circulation and in the tumor tissue of patients suffering from hepatocellular carcinoma as well as in animal models of liver cancer. It has been argued that up-regulation of follistatin protects neoplastic hepatocytes from activin-mediated growth inhibition and apoptosis. The use of follistatin as biomarker for liver tumor development is impeded, however, due to the presence of elevated follistatin levels already during preceding stages of liver disease. The current article summarizes our evolving understanding of the multi-faceted activities of activins and follistatins in liver physiology and cancer.


Central alpha 2-adrenergic stimulation increases neurointermediate lobe immunoreactive beta-endorphin in spontaneously hypertensive rats.
A possible influence of the central alpha 2-adrenergic system on beta-endorphin was examined in rat anterior pituitary, neurointermediate lobe, and plasma. The concentration of beta-endorphin in anterior pituitary, neurointermediate lobe, and plasma was determined by radioimmunoassay 15 minutes after subcutaneous injection of clonidine in 14-week-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Clonidine reduced the concentration of the plasma beta-endorphinlike immunoreactivity in SHR and to a lesser extent in WKY. No significant changes in the concentration of beta-endorphinlike immunoreactivity were observed in anterior pituitary. Clonidine increased the concentration of neurointermediate lobe beta-endorphinlike immunoreactivity in SHR in a dose-related manner but did not affect the concentration in WKY. Administration of yohimbine (1 mg/kg) completely blocked the clonidine-induced increase of neurointermediate lobe beta-endorphinlike immunoreactivity in SHR, while prazosin (1 mg/kg) had no effect. These data suggest that the central alpha 2-adrenergic activation increases the neurointermediate lobe concentration of beta-endorphinlike immunoreactivity in SHR by suppressing beta-endorphin release from the neurointermediate lobe into the circulation.


Recent Advances in Kaempferia Phytochemistry and Biological Activity: A Comprehensive Review.
Plants belonging to the genus Kaempferia (family: Zingiberaceae) are distributed in Asia, especially in the southeast region, and Thailand. They have been widely used in traditional medicines to cure metabolic disorders, inflammation, urinary tract infections, fevers, coughs, hypertension, erectile dysfunction, abdominal and gastrointestinal ailments, asthma, wounds, rheumatism, epilepsy, and skin diseases. Herein, we reported a comprehensive review, including the traditional applications, biological and pharmacological advances, and phytochemical constituents of Kaempheria species from 1972 up to early 2019. All the information and reported studies concerning Kaempheria plants were summarized from library and digital databases (e.g., Google Scholar, Sci-finder, PubMed, Springer, Elsevier, MDPI, Web of Science, etc.). The correlation between the Kaempheria species was evaluated via principal component analysis (PCA) and agglomerative hierarchical clustering (AHC), based on the main chemical classes of compounds. Approximately 141 chemical constituents have been isolated and reported from Kaempferia species, such as isopimarane, abietane, labdane and clerodane diterpenoids, flavonoids, phenolic acids, phenyl-heptanoids, curcuminoids, tetrahydropyrano-phenolic, and steroids. A probable biosynthesis pathway for the isopimaradiene skeleton is illustrated. In addition, 15 main documented components of volatile oils of Kaempheria were summarized. Biological activities including anticancer, anti-inflammatory, antimicrobial, anticholinesterase, antioxidant, anti-obesity-induced dermatopathy, wound healing, neuroprotective, anti-allergenic, and anti-nociceptive were demonstrated. Up to date, significant advances in phytochemical and pharmacological studies of different Kaempheria species have been witnessed. So, the traditional uses of these plants have been clarified via modern in vitro and in vivo biological studies. In addition, these traditional uses and reported biological results could be correlated via the chemical characterization of these plants. All these data will support the biologists in the elucidation of the biological mechanisms of these plants.


Estrogen-related receptor alpha in human breast carcinoma as a potent prognostic factor.
Estrogen-related receptor alpha (ERRalpha) was identified as a gene related to estrogen receptor alpha (ERalpha) and belongs to a class of nuclear orphan receptors. ERRalpha binds to estrogen responsive element(s) (ERE) and is considered to be involved in modulation of estrogenic actions. However, biological significance of ERRalpha remains largely unknown. Therefore, we examined the expression of ERRalpha in human breast carcinoma tissues using immunohistochemistry (n = 102) and real-time reverse transcription-PCR (n = 30). ERRalpha immunoreactivity was detected in the nuclei of carcinoma cells in 55% of breast cancers examined, and relative immunoreactivity of ERRalpha was significantly (P = 0.0041) associated with the mRNA level. Significant associations were detected between ERalpha and ERE-containing estrogen-responsive genes, such as pS2 (P < 0.0001) and EBAG9/RCAS1 (P = 0.0214), in breast carcinoma tissues. However, no significant association was detected between ERalpha and pS2 (P = 0.1415) in the ERRalpha-positive cases (n = 56) or between ERalpha and EBAG9/RCAS1 (P = 0.8271) in the ERRalpha-negative group (n = 46). ERRalpha immunoreactivity was significantly associated with an increased risk of recurrence and adverse clinical outcome by both uni- (P = 0.0097 and P = 0.0053, respectively) and multi- (P = 0.0215 and P = 0.0118, respectively) variate analyses. A similar tendency was also detected in the group of breast cancer patients who received tamoxifen therapy after surgery. Results from our study suggest that ERRalpha possibly modulates the expression of ERE-containing estrogen-responsive genes, and ERRalpha immunoreactivity is a potent prognostic factor in human breast carcinoma.


Proximal migration of a 3 French pancreatic stent in a patient with pancreas divisum: suggested technique for successful retrieval.
Pancreatic stents may be placed during therapeutic ERCP for a variety of indications. One such indication is to prophylax against the development of pancreatitis following sphincterotomy of the minor papilla in patients with recurrent acute pancreatitis and pancreas divisum. Increasingly, endoscopists that perform pancreatic ERCP are placing small caliber (3 Fr), unflanged, single pigtail stents into the long axis of the pancreatic duct with the expectation that these stents will only stay in place for a few days and the majority will pass spontaneously on their own without the need for follow-up endoscopic retrieval. As such, these stents are generally regarded as safer and associated with a lower rare of complication than larger (5 and 7 Fr), double flanged pancreatic stents. We present the case of a 3 Fr stent that migrated proximally into the dorsal duct in a patient with recurrent pancreatitis and pancreas divisum. Due to the small size of the patient's dorsal duct, it was difficult to pass appliances alongside the stent to facilitate retrieval and a variety of appliances were used before success was achieved. The medical literature contains series of proximally migrated larger caliber flanged, pancreatic stents but proximal migration of small caliber, unflanged, pigtail stents has not yet been reported. As the use of these small stents increases, we feel that it is important to highlight the potential for this complication and discuss how we successfully treated our patient.


The Experience of Living to an Extreme Age: A Meta-Ethnography.
Advances in health care mean that we can now treat diseases that once cut lives short. However, the increase in life expectancy has not been matched by improvements in quality of life. The World Health Organization warns us that all countries should prepare to meet the challenges of an aging population and this is integral to the United Nations 2030 Agenda for Sustainable Development. This may require a shift in attitude toward aging. We aimed to use meta-ethnography to explore the experience of adults living beyond the age of 80. Our conceptual model illuminates the phenomenon of connection in older age and reflects on the paradox of time: ephemeral, yet interminable. Our findings encourage us to reflect on the influence of enlightenment philosophies that underpin the desire for autonomy at all costs. Our study challenges the stereotypes of old age and has the potential to influence people's perspectives toward aging.


Efficacy and toxicity of MDR versus HDR brachytherapy for primary vaginal cancer.
The retrospective analysis includes a group of 50 patients with primary, invasive vaginal cancer treated with brachytherapy in the period of 1982-1993. Over 80% cases were squamous cell carcinoma. There were 14 patients in stage I according to FIGO classification and 20%, 36%, and 16% of patients in stage II, III and IV, respectively. Twenty one patients (42%) received MDR brachytherapy using Cs137 source, the remaining 29 (58%) were treated with HDR using Co60 or Ir192 sources. Among 50 patients 31 (62%) received also external beam irradiation. An overall 5-year actuarial disease-free survival was 40%, and it was 78.6% (11/14), 40% (4/10), 27.8% (5/18), 0% (0/8) for stage I, II, III and IV, respectively. For MDR or HDR5-year disease-free survival was 38% and 41%, respectively. No influence of dose rate on survival has been found (p=0.7). Local failure occurred in 20 patients (40%). Recurrences appeared in 10 patients (20%). Late complications rate was 0% and 17% for MDR and HDR, respectively. Effectiveness of brachytherapy MDR and HDR was similar, whereas serious late complications developed more often after HDR brachytherapy.


A novel TRPC6 mutation that causes childhood FSGS.
TRPC6, encoding a member of the transient receptor potential (TRP) superfamily of ion channels, is a calcium-permeable cation channel, which mediates capacitive calcium entry into the cell. Until today, seven different mutations in TRPC6 have been identified as a cause of autosomal-dominant focal segmental glomerulosclerosis (FSGS) in adults. Here we report a novel TRPC6 mutation that leads to early onset FSGS. We identified one family in whom disease segregated with a novel TRPC6 mutation (M132T), that also affected pediatric individuals as early as nine years of age. Twenty-one pedigrees compatible with an autosomal-dominant mode of inheritance and biopsy-proven FSGS were selected from a worldwide cohort of 550 families with steroid resistant nephrotic syndrome (SRNS). Whole cell current recordings of the mutant TRPC6 channel, compared to the wild-type channel, showed a 3 to 5-fold increase in the average out- and inward TRPC6 current amplitude. The mean inward calcium current of M132T was 10-fold larger than that of wild-type TRPC6. Interestingly, M132T mutants also lacked time-dependent inactivation. Generation of a novel double mutant M132T/N143S did not further augment TRPC6 channel activity. In summary, our data shows that TRPC6 mediated FSGS can also be found in children. The large increase in channel currents and impaired channel inactivation caused by the M132T mutant leads to an aggressive phenotype that underlines the importance of calcium dose channeled through TRPC6.


Fragment reattachment after complicated crown-root fractures of anterior teeth: A systematic review.
Fragment reattachment is a procedure that can immediately restore form and function in crown-root fracture cases and is considered a minimally invasive and cost-effective treatment option. The aim of this systematic review was to analyze the methods used and the outcome of fragment reattachment for complicated crown-root fractures of anterior teeth. Five electronic databases (PubMed, Web of Science, Embase, Scopus, and Google Scholar) were searched for English language articles regarding fragment reattachment after complicated crown-root fractures of anterior teeth. Twelve case reports and two case series were selected for this review after applying the inclusion and exclusion criteria. In eleven articles, the fracture line was exposed prior to reattachment. Root canal treatment was performed in all cases except one, where conservative pulp treatment was done prior to reattachment. A post was used as part of the restoration in 85% of the cases. Additional fragment preparation was done in 42% of the cases in the form of beveling and groove formation. Adhesive strategies used to reattach the coronal fragments were total-etch, self-etch, or self-cure adhesive. Intermediate materials used for reattachment were resin cement, glass-ionomer cement, composite and self-adhesive cement. Treatment outcomes were favorable in all the included articles and the follow-up period ranged from three months to seven years. Fragment reattachment after complicated crown-root fractures of anterior teeth can be considered as a viable treatment option if the clinical conditions are favorable.


Can routine automated urinalysis reduce culture requests?
There are a substantial number of unnecessary urine culture requests. We aimed to investigate whether urine dipstick and microscopy results could accurately rule out urinary tract infection (UTI) without urine culture. The study included a total of 32,998 patients (11,928 men and 21,070 women, mean age: 39 ± 32 years) with a preliminary diagnosis of UTI and both urinalysis and urinary culture were requested. All urine cultures were retrospectively reviewed; association of culture positivity with a positive urinalysis result for leukocyte esterase (LE) and nitrite in chemical analysis and pyuria (WBC) and bacteriuria in microscopy was determined. Diagnostic performance of urinalysis parameters for detection of UTI was evaluated. In total, 758 (2.3%) patients were positive by urine culture. Out of these culture positive samples, ratios of positive dipstick results for LE and nitrite were 71.0% (n=538) and 17.7% (n=134), respectively. The positive microscopy results for WBC and bacteria were 68.2% (n=517) and 78.8% (n=597), respectively. Negative predictive values for LE, nitrite, bacteriuria and WBC were very close to 100%. Most of the samples have no or insignificant bacterial growth. Urine dipstick and microscopy can accurately rule out UTI. Automated urinalysis is a practicable and faster screening test which may prevent unnecessary culture requests for majority of patients.


Erythema nodosum induced by kerion celsi of the scalp in a woman.
A 35-year-old woman, with a 3-week history of an enlarging erythematous, scaly plaque of the scalp vertex associated with the onset of some painful, subcutaneous nodules on her pretibial regions. Trichophyton mentagrophytes was isolated from the scalp lesion and the histological examination of one of the nodular lesions of the legs showed a septal panniculitis. The diagnosis of erythema nodosum (EN) induced by kerion celsi was made and the patient started therapy with oral terbinafine 250 mg per day for 4 weeks associated with naproxene per os 1 g per day for 2 weeks. Erythema nodosum is considered a reaction pattern to a wide variety of microbial and non-microbial stimuli: dermatophytic infections are rarely associated with EN.


Myocardial blood flow distribution during ischemia-induced coronary vasodilation in the unanesthetized dog.
This study was designed to determine whether coronary vasodilation distal to a flow-limiting coronary artery stenosis could result in redistribution of myocardial blood flow to produce subendocardial underperfusion. Studies were performed in 10 awake dogs chronically prepared with electromagnetic flow-meters and hydraulic occluders on the left circumflex coronary artery. Regional myocardial blood flow was measured using radionuclide-labeled microspheres, 7-10 mum in diameter, injected into the left atrium. A 5(-s) coronary artery occlusion was followed by reactive hyperemia with excess inflow of arterial blood effecting 375+/-20% repayment of the blood flow debt incurred during occlusion. When, after a 5(-s) occlusion, the occluder was only partially released to hold arterial inflow to the preocclusion level for 20 s before complete release, the delayed reactive hyperemia was augmented (mean blood flow repayment = 610+/-45%, P < 0.01). This augmentation of the reactive hyperemia suggested that ischemia was continuing during the interval of coronary vasodilation when coronary inflow was at the preocclusion level. Measurements of regional myocardial blood flow demonstrated that endocardial flow slightly exceeded epicardial flow during control conditions. When arterial inflow was limited to the preocclusion rate during vasodilation after a 5(-s) total coronary artery occlusion, however, flow to the subepicardial myocardium was increased at the expense of underperfusion of the subendocardial myocardium. Thus, in the presence of a flow-limiting proximal coronary artery stenosis, ischemia-induced coronary vasodilation resulted in redistribution of myocardial blood flow with production of subendocardial ischemia in the presence of a net volume of arterial inflow which, if properly distributed, would have been adequate to prevent myocardial ischemia.


Phosphodiester modifications in mRNA poly(A) tail prevent deadenylation without compromising protein expression.
Chemical modifications enable preparation of mRNAs with augmented stability and translational activity. In this study, we explored how chemical modifications of 5',3'-phosphodiester bonds in the mRNA body and poly(A) tail influence the biological properties of eukaryotic mRNA. To obtain modified and unmodified in vitro transcribed mRNAs, we used ATP and ATP analogs modified at the α-phosphate (containing either O-to-S or O-to-BH3 substitutions) and three different RNA polymerases-SP6, T7, and poly(A) polymerase. To verify the efficiency of incorporation of ATP analogs in the presence of ATP, we developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for quantitative assessment of modification frequency based on exhaustive degradation of the transcripts to 5'-mononucleotides. The method also estimated the average poly(A) tail lengths, thereby providing a versatile tool for establishing a structure-biological property relationship for mRNA. We found that mRNAs containing phosphorothioate groups within the poly(A) tail were substantially less susceptible to degradation by 3'-deadenylase than unmodified mRNA and were efficiently expressed in cultured cells, which makes them useful research tools and potential candidates for future development of mRNA-based therapeutics.


The Sun: Our own backyard plasma laboratory.
The Sun's atmosphere increases in temperature from 6000 degrees at the surface to over a million degrees at heights of a few thousand kilometers. This surprising temperature increase is still an active area of scientific study, but is generally thought to be driven by the dynamics of the Sun's magnetic field. The combination of a 2-to-3 order of magnitude temperature range and a low plasma density makes the solar atmosphere perhaps the best natural laboratory for the study of ionized atoms. Atomic transitions at ultraviolet (UV) and X-ray wavelength regions generally show no optical depth effects, and the lines are not subject to the interstellar absorption that affects astronomical sources. Here I highlight the importance of atomic data to modeling UV and X-ray solar spectra, with a particular focus on the CHIANTI atomic database. Atomic data needs and problems are discussed and future solar mission concepts presented.


Acetyl analogs of combretastatin A-4: synthesis and biological studies.
The combretastatins have received significant attention because of their simple chemical structures, excellent antitumor efficacy and novel antivascular mechanisms of action. Herein, we report the synthesis of 20 novel acetyl analogs of CA-4 (1), synthesized from 3,4,5-trimethoxyphenylacetone that comprises the A ring of CA-4 with different aromatic aldehydes as the B ring. Molecular modeling studies indicate that these new compounds possess a 'twisted' conformation similar to CA-4. The new analogs effectively inhibit the growth of human and murine cancer cells. The most potent compounds 6k, 6s and 6t, have IC(50) values in the sub-μM range. Analog 6t has an IC(50) of 182 nM in MDA-MB-435 cells and has advantages over earlier analogs due to its enhanced water solubility (456 μM). This compound initiates microtubule depolymerization with an EC(50) value of 1.8 μM in A-10 cells. In a murine L1210 syngeneic tumor model 6t had antitumor activity and no apparent toxicity.


Retroperitoneal Nephrometry Scoring System (RETRO) for Minimal-Invasive Partial Nephrectomy.
To propose a standardized scoring system of renal tumors suitable for partial nephrectomy based on mini-invasiveness and retroperitoneal approach. One-hundred and five patients in retroperitoneal group were prospectively enrolled from January 2017 to December 2018. Perioperative characteristics of all patients were collected: age, gender, BMI, preoperative blood test and imaging results, operation time (the time period starts from the skin incision to the final skin closure), estimated blood lost, clamping time, complications within 30 days, American Society of Anesthesiologists (ASA) score, pathology. An algorithm was extracted, and it was used to predict the risk of complications. Symptoms, ASA score and RETRO score were significantly correlated to postoperative complications, excluding tumor size, ischemia time and operation time. Adjusted RETRO points were an independent factor to predict complication rate (p = 0.006). Limitation was that it did not analyze the relationship between the RETRO score and the long-term outcomes. The RETRO score simplifies the risk evaluation of partial nephrectomy for patients with renal tumor, especially benefits those surgeries performed under robot-assisted laparoscope via retroperitoneal approach. The new RETRO score system that we developed is a selection criterion to perform surgery via different approaches, and an accurate system to evaluate the complexity during partial nephrectomy.


[Projections of the neurons of the medial terminal nucleus of the accessory optic tract to the caudate nucleus of the cat detected by the combined methods of retrograde axonal transport and experimental degeneration].
Projections of neurons of the medial terminal nucleus of the accessory optic tract receiving direct retinal inputs to the head and body of caudate nucleus are shown in cat by the retrograde axonal transport of horseradish peroxidase and experimental degeneration. These projections are mainly ipsilateral and uniformly distributed in the above mentioned parts of the nucleus. The neurons of the medial terminal nucleus establishing synaptic connections with caudate neurons have different shapes and sizes (from 20 X 10 microns to 37.5 X 18 microns) and are located both in the ventral and dorsal parts of the nucleus. Conclusions are made about functional significance of these projections in the regulation of the muscular tension.


Changes in Sensorimotor Cortical Activation in Children Using Prostheses and Prosthetic Simulators.
This study aimed to examine the neural responses of children using prostheses and prosthetic simulators to better elucidate the emulation abilities of the simulators. We utilized functional near-infrared spectroscopy (fNIRS) to evaluate the neural response in five children with a congenital upper limb reduction (ULR) using a body-powered prosthesis to complete a 60 s gross motor dexterity task. The ULR group was matched with five typically developing children (TD) using their non-preferred hand and a prosthetic simulator on the same hand. The ULR group had lower activation within the primary motor cortex (M1) and supplementary motor area (SMA) compared to the TD group, but nonsignificant differences in the primary somatosensory area (S1). Compared to using their non-preferred hand, the TD group exhibited significantly higher action in S1 when using the simulator, but nonsignificant differences in M1 and SMA. The non-significant differences in S1 activation between groups and the increased activation evoked by the simulator's use may suggest rapid changes in feedback prioritization during tool use. We suggest that prosthetic simulators may elicit increased reliance on proprioceptive and tactile feedback during motor tasks. This knowledge may help to develop future prosthesis rehabilitative training or the improvement of tool-based skills.


Vulnerability to food insecurity in urban slums: experiences from Nairobi, Kenya.
Food and nutrition security is critical for economic development due to the role of nutrition in healthy growth and human capital development. Slum residents, already grossly affected by chronic poverty, are highly vulnerable to different forms of shocks, including those arising from political instability. This study describes the food security situation among slum residents in Nairobi, with specific focus on vulnerability associated with the 2007/2008 postelection crisis in Kenya. The study from which the data is drawn was nested within the Nairobi Urban Health and Demographic Surveillance System (NUHDSS), which follows about 70,000 individuals from close to 30,000 households in two slums in Nairobi, Kenya. The study triangulates data from qualitative and quantitative sources. It uses qualitative data from 10 focus group discussions with community members and 12 key-informant interviews with community opinion leaders conducted in November 2010, and quantitative data involving about 3,000 households randomly sampled from the NUHDSS database in three rounds of data collection between March 2011 and January 2012. Food security was defined using the Household Food Insecurity Access Scale (HFIAS) criteria. The study found high prevalence of food insecurity; 85% of the households were food insecure, with 50% being severely food insecure. Factors associated with food security include level of income, source of livelihood, household size, dependence ratio; illness, perceived insecurity and slum of residence. The qualitative narratives highlighted household vulnerability to food insecurity as commonplace but critical during times of crisis. Respondents indicated that residents in the slums generally eat for bare survival, with little concern for quality. The narratives described heightened vulnerability during the 2007/2008 postelection violence in Kenya in the perception of slum residents. Prices of staple foods like maize flour doubled and simultaneously household purchasing power was eroded due to worsened unemployment situation. The use of negative coping strategies to address food insecurity such as reducing the number of meals, reducing food variety and quality, scavenging, and eating street foods was prevalent. In conclusion, this study describes the deeply intertwined nature of chronic poverty and acute crisis, and the subsequent high levels of food insecurity in urban slum settings. Households are extremely vulnerable to food insecurity; the situation worsening during periods of crisis in the perception of slum residents, engendering frequent use of negative coping strategies. Effective response to addressing vulnerability to household food insecurity among the urban poor should focus on both the underlying vulnerabilities of households due to chronic poverty and added impacts of acute crises.


Training and competition workloads and fatigue responses of elite junior cricket players.
This study investigated key fatigue and workload variables of cricket fast bowlers and nonfast bowlers during a 7-wk physical-preparation period and 10-d intensified competition period. Twenty-six elite junior cricketers (mean ± SD age 17.7 ± 1.1 y) were classified as fast bowlers (n = 9) or nonfast bowlers (n = 17). Individual workloads were measured via global positioning system technology, and neuromuscular function (countermovement jump [relative power and flight time]), endocrine (salivary testosterone and cortisol concentrations), and perceptual well-being (soreness, mood, stress, sleep quality, and fatigue) markers were recorded. Fast bowlers performed greater competition total distance (median [interquartile range] 7049 [3962] m vs 5062 [3694] m), including greater distances at low and high speeds, and more accelerations (40 [32] vs 19 [21]) and had a higher player load (912 [481] arbitrary units vs 697 [424] arbitrary units) than nonfast bowlers. Cortisol concentrations were higher in the physical-preparation (mean ± 90% confidence intervals, % likelihood; d = -0.88 ± 0.39, 100%) and competition phases (d = -0.39 ± 0.30, 85%), and testosterone concentrations, lower (d = 0.56 ± 0.29, 98%), in the competition phase in fast bowlers. Perceptual well-being was poorer in nonfast bowlers during competition only (d = 0.36 ± 0.22, 88%). Differences in neuromuscular function between groups were unclear during physical preparation and competition. These findings demonstrate differences in the physical demands of cricket fast bowlers and nonfast bowlers and suggest that these external workloads differentially affect the neuromuscular, endocrine, and perceptual fatigue responses of these players.


[Placental permeability to thyroxine].
This is an experimental work. Investigations were carried out on albino rats on the 18th day of pregnancy. A study was made of I-131-labelled thyroxin penetration from the maternal organism into the fetus and vice versa. Radiological and radiochromatographic analysis of the blood samples of both the mother and the fetuses at various time intervals after the administration of radioactive thyroxin showed that the isotope in the form of thyroxin failed to penetrate from the mother to the fetus and vice versa. A conclusion was drawn that during prenatal development the function of the fetal thyroid gland was automatic.


Resilience Building Practices for Women Physicians.
Women now make up more than half of the physician workforce, but they are disproportionately plagued by burnout. Medicine is a fast-paced stressful field, the practice of which is associated with significant chronic stress due to systems issues, crowding, electronic medical records, and patient case mix. Hospitals and health care systems are responsible for mitigating system-based burnout-prone conditions, but often their best efforts fail. Physicians, particularly women, must confront their stressors and the daily burden of significant system strain when this occurs. Those who routinely exceed their cumulative stress threshold may experience burnout, career dissatisfaction, and second victim syndrome and, ultimately, may prematurely leave medicine. These conditions affect women in medicine more often than men and may also produce a higher incidence of health issues, including depression, substance use disorder, and suicide. The individual self-care required to maintain health and raise stress thresholds is not widely ingrained in provider practice patterns or behavior. However, the successful long-term practice of high-stress occupations, such as medicine, requires that physicians, especially women physicians, attend to their wellness. In this article, we address one aspect of health, resilience, and review six practices that can create additional stores of personal resilience when proactively integrated into a daily routine.


Optimal prescription method for cancer chemotherapy.
A reexamination of the guidelines for prescriptions for cancer chemotherapy suggests that the use of body surface area (BSA) offers a simplification that may be open to some question. The same drug dose per BSA will give approximately the same toxicity in different age groups and species. This simplification appears to be fortuitous, however, as BSA does not correlate with the dose-limiting target cells, i.e., the hemopoietic stem cell. In patients with an unmodified hemopoietic system, body weight correlates significantly with hemopoietic stem cell concentration. It can be shown that changing the prescription unit from BSA to kilogram (kg) could lead to safer doses in children and neonates. In general, because of low therapeutic index, the expression of cancer chemotherapy drugs per dose-limiting normal tissue target cells could lead to safer and more effective cancer chemotherapy. New assays for prospective in vitro enumeration of dose-limiting target cells need to be developed. The indiscriminate use of BSA as a drug dose unit is discouraged.


Curcumin inhibits telomerase activity through human telomerase reverse transcritpase in MCF-7 breast cancer cell line.
The inhibitory effect of curcumin, the yellow-colored pigment from turmeric, on telomerase activity was analyzed in human mammary epithelial (MCF-10A) and breast cancer (MCF-7) cells. Telomerase activity in MCF-7 cells is 6.9-fold higher than that of human mammary epithelial cells. In MCF-7 cells, telomerase activity decreased with increasing concentrations of curcumin, inhibiting about 93.4% activity at 100 microM concentration. The inhibition of telomerase activity in MCF-7 cells may be due to down-regulation of hTERT expression. Increasing concentrations of curcumin caused a steady decrease in the level of hTERT mRNA in MCF-7 cells whereas the level of hTER and c-myc mRNAs remained the same. Our results suggest that curcumin inhibits telomerase activity by down-regulating hTERT expression in breast cancer cells and this down-regulation is not through the c-myc pathway.


The association between maternal interaction and infant cortisol stress reactivity among preterm and full term infants at 4 months adjusted age.
The purpose of this study was to assess the association between maternal interactive behavior and infant cortisol stress reactivity in response to the Still Face paradigm (SF) in a cohort of four-month old infants (adjusted age) born preterm (<32 weeks gestation, N = 22) compared with infants born full term (>37 weeks gestation, N = 28). Infant cortisol reactivity was calculated as area under the curve (AUC) from baseline to the third cortisol sample (30 min post-SF) using the trapezoidal rule, while the percent of time mothers spent using a contingent interaction style was measured (0-100%) during episodes 1 (Play; baseline), 3 (Reunion#1), and 5 (Reunion#2) while mother-infant dyads participated in the SF paradigm. We hypothesized that because infants born preterm are at increased risk for dysregulation, they would show, compared to full-term infants, a blunted stress response, involving under-responsiveness. We found blunted cortisol stress reactivity among the preterm infants. We also found that mothers of preterm infants demonstrated less contingent maternal interaction during Renion#1 of the SF; and that contingent maternal interaction at Reunion#2 of the SF was protective against cortisol stress reactivity in response to the SF. However, we did not find that the influence of maternal interaction on cortisol reactivity was moderated by gestational age group (full term vs preterm): the association between contingent maternal interaction and stress reactivity was similar for both gestational groups across episodes. In order to improve self-regulation and longer term social and cognitive developmental outcomes in medically at-risk infants, future research is warranted to determine how these findings relate to infants' stress reactions in naturalistic settings, and the directionality and temporal relationship between cortisol stress responses and maternal interactive behavior.


Prevention of surface-to-human transmission of rotaviruses by treatment with disinfectant spray.
A model was developed to examine the effects of disinfectants on the transmission of infectious rotavirus from a dried surface to humans. The initial experiments were designed to find a method of preserving rotavirus infectivity during drying. Culture-adapted human rotavirus (CJN strain) was dried at room temperature in different organic suspensions, including fecal matter, several laboratory media, and nonfat dry milk (NDM). Recoveries of infectious virus were then compared. Fecal matter provided little protection in this study relative to distilled water, but the other suspensions were quite protective, especially NDM, which consistently allowed recoveries of greater than 50%. When 10(3) focus-forming units of unpassaged CJN virus were dried in NDM and administered to subjects who licked the dried material, 100% (8 of 8) became infected. The effect of Lysol brand disinfectant spray (LDS) was next examined. Although NDM provided some protection against inactivation by LDS, spraying under conditions recommended by the manufacturer consistently caused the CJN virus titer to decrease greater than 5 log10. Consumption of CJN virus (10(3) focus-forming units) sprayed with LDS caused no infection in 14 subjects, whereas 13 of 14 subjects who consumed the unsprayed virus became infected (P less than 0.00001). The methods developed in this study could be used to test the effects of other disinfectants on the spread of infectious rotavirus from inanimate surfaces to humans.


Nucleosome positioning changes during human embryonic stem cell differentiation.
Nucleosomes are the basic unit of chromatin. Nucleosome positioning (NP) plays a key role in transcriptional regulation and other biological processes. To better understand NP we used MNase-seq to investigate changes that occur as human embryonic stem cells (hESCs) transition to nascent mesoderm and then to smooth muscle cells (SMCs). Compared to differentiated cell derivatives, nucleosome occupancy at promoters and other notable genic sites, such as exon/intron junctions and adjacent regions, in hESCs shows a stronger correlation with transcript abundance and is less influenced by sequence content. Upon hESC differentiation, genes being silenced, but not genes being activated, display a substantial change in nucleosome occupancy at their promoters. Genome-wide, we detected a shift of NP to regions of higher G+C content as hESCs differentiate to SMCs. Notably, genomic regions with higher nucleosome occupancy harbor twice as many G↔C changes but fewer than half A↔T changes, compared to regions with lower nucleosome occupancy. Finally, our analysis indicates that the hESC genome is not rearranged and has a sequence mutation rate resembling normal human genomes. Our study reveals another unique feature of hESC chromatin, and sheds light on the relationship between nucleosome occupancy and sequence G+C content.


Developing medical ethics in China's reform era.
The paper gives an analytical synopsis of the problem of developing medical ethics in the early half of the 1990s in China, as perceived by Chinese scholars and medical professionals interested in medical ethics. The views captured and analyzed here were expressed in one of the two major journals on medical ethics in China: Chinese Medical Ethics. The economic reform unleashed profound changes in Chinese society, including in the medical field, creating irregularities and improprieties in the profession. Furthermore, the market reform also created new values that were in tension with existing values. In this transitional period, Chinese medical ethicists saw the need to rebuild medical morality for the new era. Using the code of conduct promulgated by the Chinese Ministry of Health in 1989 as a basis, assessment and education aspects of the institutionalization of medical ethics are discussed. In addition to institutional problems of institutionalising ethics, there are philosophical and methodological issues that are not easy to solve. After all, to institutionalize medical ethics is no easy task for a country as old and as big as China. Chinese medical ethicists seem ready to confront these difficulties in their effort to develop medical ethics in Reform China.


Why is there no impact of the host species on the cold tolerance of a generalist parasitoid?
For generalist parasitoids such as those belonging to the Genus Aphidius, the choice of host species can have profound implications for the emerging parasitoid. Host species is known to affect a variety of life history traits. However, the impact of the host on thermal tolerance has never been studied. Physiological thermal tolerance, enabling survival at unfavourable temperatures, is not a fixed trait and may be influenced by a number of external factors including characteristics of the stress, of the individual exposed to the stress, and of the biological and physical environment. As such, the choice of host species is likely to also have implications for the thermal tolerance of the emerging parasitoid. The current study aimed to investigate the effect of cereal aphid host species (Sitobion avenae, Rhopalosiphum padi and Metopolophium dirhodum) on adult thermal tolerance, in addition to sex and size, of the aphid parasitoids Aphidius avenae, Aphidius matricariae and Aphidius rhopalosiphi. Results revealed no effect of host species on the cold tolerance of the emerging parasitoid, as determined by CTmin and Chill Coma, for all parasitoid species. Host species significantly affected the size of the emerging parasitoid for A. rhopalosiphi only, with individuals emerging from R. padi being significantly larger than those emerging from S. avenae, although this did not correspond to a difference in thermal tolerance. Furthermore, a significant difference in the size of male and female parasitoids was observed for A. avenae and A. matricariae, although, once again this did not correspond to a difference in cold tolerance. It is suggested that potential behavioural thermoregulation via host manipulation may act to influence the thermal environment experienced by the wasp and thus wasp thermal tolerance and, in doing so, may negate physiological thermal tolerance or any impact of the aphid host.


Is web interviewing a good alternative to telephone interviewing? Findings from the International Tobacco Control (ITC) Netherlands survey.
Web interviewing is becoming increasingly popular worldwide, because it has several advantages over telephone interviewing such as lower costs and shorter fieldwork periods. However, there are also concerns about data quality of web surveys. The aim of this study was to compare the International Tobacco Control (ITC) Netherlands web and telephone samples on demographic and smoking related variables to assess differences in data quality. Wave 1 of the ITC Netherlands Survey was completed by 1,668 web respondents and 404 telephone respondents of 18 years and older. The two surveys were conducted in parallel among adults who reported smoking at least monthly and had smoked at least 100 cigarettes over their lifetime. Both the web and telephone survey had a cooperation rate of 78%. Web respondents with a fixed line telephone were significantly more often married, had a lower educational level, and were older than web respondents without a fixed line telephone. Telephone respondents with internet access were significantly more often married, had a higher educational level, and were younger than telephone respondents without internet. Web respondents were significantly less often married and lower educated than the Dutch population of smokers. Telephone respondents were significantly less often married and higher educated than the Dutch population of smokers. Web respondents used the "don't know" options more often than telephone respondents. Telephone respondents were somewhat more negative about smoking, had less intention to quit smoking, and had more self efficacy for quitting. The known association between educational level and self efficacy was present only in the web survey. Differences between the web and telephone sample were present, but the differences were small and not consistently favourable for either web or telephone interviewing. Our study findings suggested sometimes a better data quality in the web than in the telephone survey. Therefore, web interviewing can be a good alternative to telephone interviewing.


Characterization of 6q deletions in mature B cell lymphomas and childhood acute lymphoblastic leukemia.
The study was undertaken with the aim to outline deletion patterns involving the long arm of chromosome 6, a common abnormality in lymphoproliferative disorders. Using a chromosome 6 specific tile path array, 60 samples from in total 49 cases with mantle cell lymphoma (MCL), de novo diffuse large B-cell lymphoma (DLBCL), transformed DLBCL as well as preceding follicular lymphoma (FL), and childhood acute lymphoblastic leukemia (ALL), were characterized. Twenty-six of the studied cases, representing all diagnoses, showed a 6q deletion among which 85% involved a 3 Mb region in 6q21. The minimal deleted interval in 6q21 encompasses the FOXO3A, PRDM1 and HACE1 candidate genes. The PRDM1 gene was found homozygously deleted in a case of DLBCL. Moreover, in two DLBCL cases, an overlapping homozygous deletion was identified in 6q23.3 - 24.1, encompassing the TNFAIP3 gene among others. Taken together, we refined the deletion pattern within the long arm of chromosome 6 in four different types of hematological malignances, suggesting the location of tumor suppressor genes involved in the tumor progression.


[31P-NMR study of P-compounds metabolism in the liver of mice under stress].
A method for quantitative calculation of 31P-NMR spectra of tissues is proposed. Change dynamics of concentrations of phosphor-containing metabolites in the mouse liver under starvation, physical load (swimming) and glucose load (intraperitoneally) was investigated. It has been shown that using starvation as a method for object standardization 12-24 hours starvation is the optimal one.


Improving the quality of health care: what's taking so long?
Nearly fourteen years ago the Institute of Medicine's report, To Err Is Human: Building a Safer Health System, triggered a national movement to improve patient safety. Despite the substantial and concentrated efforts that followed, quality and safety problems in health care continue to routinely result in harm to patients. Desired progress will not be achieved unless substantial changes are made to the way in which quality improvement is conducted. Alongside important efforts to eliminate preventable complications of care, there must also be an effort to seriously address the widespread overuse of health services. That overuse, which places patients at risk of harm and wastes resources at the same time, has been almost entirely left out of recent quality improvement endeavors. Newer and much more effective strategies and tools are needed to address the complex quality challenges confronting health care. Tools such as Lean, Six Sigma, and change management are proving highly effective in tackling problems as difficult as hand-off communication failures and patient falls. Finally, the organizational culture of most American hospitals and other health care organizations must change. To create a culture of safety, leaders must eliminate intimidating behaviors that suppress the reporting of errors and unsafe conditions. Leaders must also hold everyone accountable for adherence to safe practices.


Pleiotropic effect of vitamin D in cystic fibrosis.
Cystic fibrosis - CF - is the most common recessively autosomally and inherited disorder in the Caucasian population. It is incurable, multi-systemic disease with progressive course. CF is caused by CFTR gene mutation, the product of which is Cystic Fibrosis Transmembrane Conductance Regulator (CFTR). CF patients are exposed to fat-soluble vitamins deficiency, including vitamin D. It is due to the fat malabsorption (caused by exacerbation exocrine pancreatic insufficiency), decreased sun exposure (caused by receiving antibiotics photophobia), reduction of adipose tissue and insufficient supply with food. The discovery of vitamin D receptor (VDR) presence outside the skeletal system allowed to conclude, that vitamin D is responsible not only for mineral economy, but also for immunological processes, respiratory status, intestial microflora and cystic fibrosis - related diabetes (CFRD) course. Based on literature data, it is suggested that vitamin D plays an important role in the prevention of diseases coexisting with CF. The right dosage of vitamin D allows to maintain a better lung function and prevent chronic pulmonary infections. It has also been shown that normal levels of vitamin D may be important in increasing the chances of successful lung transplant surgery. Taking the wide spectrum of vitamin D effect into account, it is recommended to maintain serum concentrations above the minimum in patients with CF. In summary, maintaining the proper vitamin D levels in patients with CF is important because of its pleiotropic effect. It can be achieved through regular monitoring of vitamin D levels and individual supplementary dose for each patients.


Forecasting future recruitment success for Atlantic cod in the warming and acidifying Barents Sea.
Productivity of marine fish stocks is known to be affected by environmental and ecological drivers, and global climate change is anticipated to alter recruitment success of many stocks. While the direct effects of environmental drivers on fish early life stage survival can be quantified experimentally, indirect effects in marine ecosystems and the role of adaptation are still highly uncertain. We developed an integrative model for the effects of ocean warming and acidification on the early life stages of Atlantic cod in the Barents Sea, termed SCREI (Simulator of Cod Recruitment under Environmental Influences). Experimental results on temperature and CO2 effects on egg fertilization, egg and larval survival and development times are incorporated. Calibration using empirical time series of egg production, temperature, food and predator abundance reproduces age-0 recruitment over three decades. We project trajectories of recruitment success under different scenarios and quantify confidence limits based on variation in experiments. A publicly accessible web version of the SCREI model can be run under www.oceanchange.uni-bremen.de/;SCREI. Severe reductions in average age-0 recruitment success of Barents Sea cod are projected under uncompensated warming and acidification toward the middle to end of this century. Although high population stochasticity was found, considerable rates of evolutionary adaptation to acidification and shifts in organismal thermal windows would be needed to buffer impacts on recruitment. While increases in food availability may mitigate short-term impacts, an increase in egg production achieved by stock management could provide more long-term safety for cod recruitment success. The SCREI model provides a novel integration of multiple driver effects in different life stages and enables an estimation of uncertainty associated with interindividual and ecological variation. The model thus helps to advance toward an improved empirical foundation for quantifying climate change impacts on marine fish recruitment, relevant for ecosystem-based assessments of marine systems under climate change.


Homocysteine: a biomarker in neurodegenerative diseases.
Diseases of the central nervous system are found in patients with severe hyperhomocysteinemia (HHcy). Epidemiological studies show a positive, dose-dependent relationship between mild-to-moderate increases in plasma total homocysteine concentrations (Hcy) and the risk of neurodegenerative diseases, such as Alzheimer's disease, vascular dementia, cognitive impairment or stroke. HHcy is a surrogate marker for B vitamin deficiency (folate, B12, B6) and a neurotoxic agent. The concept of improving the patient's clinical outcome by lowering of Hcy with B vitamins seems to be attractive. Recent B vitamin supplementation trials demonstrated a slowing of brain atrophy and improvement in some domains of cognitive function. Meta-analysis of secondary prevention trials showed that B vitamins supplementation caused a decrease in plasma Hcy and a trend for lowering the risk of stroke. HHcy is common in elderly people. Therefore, it seems prudent to identify B vitamin deficient subjects and to ensure sufficient vitamin intake. Therefore, recent evidence supports the role of Hcy as a potential biomarker in age-related neurodegenerative diseases.