Mutations in the RNA binding domain of stem-loop binding protein define separable requirements for RNA binding and for histone pre-mRNA processing.
Expression of replication-dependent histone genes at the posttranscriptional level is controlled by stem-loop binding protein (SLBP). One function of SLBP is to bind the stem-loop structure in the 3' untranslated region of histone pre-mRNAs and facilitate 3' end processing. Interaction of SLBP with the stem-loop is mediated by the centrally located RNA binding domain (RBD). Here we identify several highly conserved amino acids in the RBD mutation of which results in complete or substantial loss of SLBP binding activity. We also identify residues in the RBD which do not contribute to binding to the stem-loop RNA but instead are required for efficient recruitment of U7 snRNP to histone pre-mRNA. Recruitment of the U7 snRNP to the pre-mRNA also depends on the 20-amino-acid region located immediately downstream of the RBD. A critical region of the RBD contains the sequence YDRY. The tyrosines are required for RNA binding, and the DR dipeptide is essential for processing but not for RNA binding. It is likely that the RBD of SLBP interacts directly with both the stem-loop RNA and other processing factor(s), most likely the U7 snRNP, to facilitate histone pre-mRNA processing.


Extracellular matrix proteoglycans control the fate of bone marrow stromal cells.
Extracellular matrix glycoproteins and proteoglycans bind a variety of growth factors and cytokines thereby regulating matrix assembly as well as bone formation. However, little is known about the mechanisms by which extracellular matrix molecules modulate osteogenic stem cells and bone formation. Using mice deficient in two members of the small leucine-rich proteoglycans, biglycan and decorin, we uncovered a role for these two extracellular matrix proteoglycans in modulating bone formation from bone marrow stromal cells. Our studies showed that the absence of the critical transforming growth factor-beta (TGF-beta)-binding proteoglycans, biglycan and decorin, prevents TGF-beta from proper sequestration within the extracellular matrix. The excess TGF-beta directly binds to its receptors on bone marrow stromal cells and overactivates its signaling transduction pathway. Overall, the predominant effect of the increased TGF-beta signaling in bgn/dcn-deficient bone marrow stromal cells is a "switch in fate" from growth to apoptosis, leading to decreased numbers of osteoprogenitor cells and subsequently reduced bone formation. Thus, biglycan and decorin appear to be essential for maintaining an appropriate number of mature osteoblasts by modulating the proliferation and survival of bone marrow stromal cells. These findings underscore the importance of the micro-environment in controlling the fate of adult stem cells and reveal a novel cellular and molecular basis for the physiological and pathological control of bone mass.


Management of home blood pressure by amlodipine combined with angiotensin II receptor blocker in type 2 diabetes.
Angiotensin II receptor blocker (ARB) as a first-line drug for hypertension in diabetes often fails to control blood pressure adequately. The objective of the study was to evaluate the effect of amlodipine combined therapy on home blood pressure (HBP) useful for management of hypertension. A total of 263 type 2 diabetes with hypertension refractory to standard dose of ARB were randomized to increased ARB regimen (n=132) or amlodipine combination regimen (n=131). The primary endpoint was change in morning HBP at 1 year. The combination regimen significantly lowered morning HBP than the increased ARB regimen (158.2/82.5 mmHg in the combination regimen, 157.3/84.4 mmHg in the increased ARB regimen, at baseline; 142.7/76.3 vs. 155.0/83.1 mmHg, respectively, P<0.001 for both, at 8 weeks; 139.6/74.6 vs. 149.1/78.1 mmHg, respectively, P<0.001 for systolic and P=0.010 for diastolic, at 1 year). The combination regimen showed significantly higher rates of achieving target morning HBP at 8 weeks (11.3% vs. 2.7%, P=0.015). In the combination regimen, estimated glomerular filtration rate declined slower, and carotid intima-media thickness decreased in contrast to the increased ARB regimen. In type 2 diabetes patients with hypertension refractory to standard dose of ARB, the amlodipine combination regimen provides superior antihypertensive effect on HBP to the increased ARB regimen, and beneficial effects on reducing risks of cardiovascular events.


Activity of everolimus (RAD001) in relapsed and/or refractory multiple myeloma: a phase I study.
The mammalian target of rapamycin plays an important role in multiple myeloma. The allosteric mammalian target of rapamycin inhibitor everolimus has long been approved for immunosuppression and has shown activity in certain cancers. This investigator-initiated phase I trial explored the use of everolimus in relapsed and/or refractory multiple myeloma patients who had received two or more lines of prior treatment. Following a dose-escalation design, it called for a fixed dose of oral everolimus. Blood drug levels were monitored and the biological activity of everolimus was evaluated in bone marrow. Seventeen patients were enrolled (age range, 52 to 76 years). All had been previously treated with stem cell transplantation and proteasome inhibitors and almost all with immunomodulatory drugs. No dose-limiting toxicity was observed and the intended final daily dose of 10 mg was reached. Only one severe adverse event was assessed as possibly related to the study drug, namely atypical pneumonia. Remarkably few infections were observed. Although the trial was mainly designed to evaluate feasibility, anti-myeloma activity, defined as clinical benefit, was documented in ten of 15 evaluable patients at every dose level including eight patients with stable disease, one patient with minor remission and one with partial remission. However, the median time to progression was 90 days (range, 13 to 278 days). The biomarker study documented on-target activity of everolimus in malignant plasma cells as well as the microenvironment. The observed responses are promising and allow further studies to be considered, including those testing combination strategies addressing escape pathways. This trial is registered with EudraCT number 2006-002675-41.


Focused ion beam milling of microchannels in lithium niobate.
We present experimental and simulation results for focused ion beam (FIB) milling of microchannels in lithium niobate in this paper. We investigate two different cuts of lithium niobate, Y- and Z-cuts, and observe that the experimental material removal rate in the FIB for both Y-cut and Z-cut samples was 0.3 μm(3)/nC, roughly two times greater than the material removal rate previously reported in the literature but in good agreement with the value we obtain from stopping and range of ions in matter (SRIM) simulations. Further, we investigate the FIB milling rate and resultant cross-sectional profile of microchannels at various ion beam currents and find that the milling rate decreases as a function of ion dose and correspondingly, the cross-sectional profiles change from rectangular to V-shaped. This indicates that material redeposition plays an important role at high ion dose or equivalently, high aspect ratio. We find that the experimental material removal rate decreases as a function of aspect ratio of the milled structures, in good agreement with our simulation results at low aspect ratio and in good agreement with the material removal rates previously reported in the literature at high aspect ratios. Our results show that it is indeed easier than previously assumed to fabricate nanochannels with low aspect ratio directly on lithium niobate using the FIB milling technique.


The magic of words reconsidered: Investigating the automaticity of reading color-neutral words in the Stroop task.
In 2 variants of the color-word Stroop task, we compared 5 types of color-neutral distractors-real words (e.g., HAT), pseudowords (e.g., HIX), consonant strings (e.g., HDK), symbol strings (e.g., #$%), and a row of Xs (e.g., XXX)-as well as incongruent color words (e.g., GREEN displayed in red). When participants named the color, relative to a row of Xs, words and pseudowords interfered equally and more than the consonant strings, which in turn interfered more than the symbols. In contrast, when participants identified the color by manual key-press responses, all 5 types of neutral strings produced equal color response latencies. In both tasks, the incongruent color words produced robust interference relative to the color-neutral words. Reaction time (RT) distribution analyses showed that all interference effects (relative to the row of Xs) increased across the quantiles. We interpret these results in terms of an evidence accumulation process in which the interfering distractor reduces the effective rate of evidence accumulation for the color target. We take the results to argue that the task of reading, even when triggered unintentionally, is not an invariant process driven solely by the stimulus properties, and is instead guided by the task goal. (PsycINFO Database Record


Nitrogenase from nifV mutants of Klebsiella pneumoniae contains an altered form of the iron-molybdenum cofactor.
When the iron-molybdenum cofactor (FeMoco) was extracted from the MoFe protein of nitrogenase from a nifV mutant of Klebsiella pneumoniae and combined with the FeMoco-deficient MoFe protein from a nifB mutant, the resultant MoFe protein exhibited the NifV phenotype, i.e. in combination with wild-type Fe protein it exhibited poor N2-fixation activity and its H2-evolution activity was inhibited by CO. These data provide strong evidence that FeMoco contains the active site of nitrogenase. The metal contents and e.p.r. properties of FeMoco from wild-type and nifV mutants of K. pneumoniae are very similar.


Vitamin D, parathyroid hormone, and sudden cardiac death: results from the Cardiovascular Health Study.
Recent studies have demonstrated greater risks of cardiovascular events and mortality among persons who have lower 25-hydroxyvitamin D (25-OHD) and higher parathyroid hormone (PTH) levels. We sought to evaluate the association between markers of mineral metabolism and sudden cardiac death (SCD) among the 2312 participants from the Cardiovascular Health Study who were free of clinical cardiovascular disease at baseline. We estimated associations of baseline 25-OHD and PTH concentrations individually and in combination with SCD using Cox proportional hazards models after adjustment for demographics, cardiovascular risk factors, and kidney function. During a median follow-up of 14 years, there were 73 adjudicated SCD events. The annual incidence of SCD was greater among subjects who had lower 25-OHD concentrations, 2 events per 1000 for 25-OHD ≥20 ng/mL and 4 events per 1000 for 25-OHD <20 ng/mL. Similarly, SCD incidence was greater among subjects who had higher PTH concentrations, 2 events per 1000 for PTH <65 pg/mL and 4 events per 1000 for PTH ≥65 pg/mL. Multivariate adjustment attenuated associations of 25-OHD and PTH with SCD. Finally, 267 participants (11.7% of the cohort) had high PTH and low 25-OHD concentrations. This combination was associated with a >2-fold risk of SCD after adjustment (hazard ratio: 2.19 [95% CI: 1.17-4.10]; P=0.017) compared with participants with normal levels of PTH and 25-OHD. The combination of lower 25-OHD and higher PTH concentrations appears to be associated independently with SCD risk among older adults without cardiovascular disease.


[Clinical and morphologic correlations in bronchoalveolar cancer].
Bronchioloalveolar carcinoma is a variety of lung adenocarcinoma featuring peculiar morphological pattern, period of latency, long symptom-free course, no association with smoking, younger age of victims and prevalent frequency in women. While there are no reliable diagnostic criteria, radical surgery has good prognosis (3-year overall or relapse-free survival is 88.9 and 66.7%, respectively). Prognostically significant are such morphological subtypes as mucigenous and non-mucigenous carcinoma. The study included patients with stage I and II carcinoma. Regional dissemination incidence was significantly lower than in other varieties of lung adenocarcinoma.


Diabetes self management: are Cuban Americans receiving quality health care?
We investigated the relationship among factors predicting inadequate glucose control among 182 Cuban-American adults (Females = 110, Males = 72) with type 2 diabetes mellitus (CAA). Cross-sectional study of CAA from a randomized mailing list in two counties of South Florida. Fasted blood parameters and anthropometric measures were collected during the study. BMI was calculated (kg/m2). Characteristics and diabetes care of CAA were self-reported Participants were screened by trained interviewers for heritage and diabetes status (inclusion criteria: self-reported having type 2 diabetes; age > or = 35 years, male and female; not pregnant or lactating; no thyroid disorders; no major psychiatric disorders). Participants signed informed consent form. Statistical analyses used SPSS and included descriptive statistic, multiple logistic and ordinal logistic regression models, where all CI 95%. Eighty-eight percent of CAA had BMI of > or = 25 kg/m2. Only 54% reported having a diet prescribed/told to schedule meals. We found CAA told to schedule meals were 3.62 more likely to plan meals (1.81, 7.26), p < 0.001) and given a prescribed diet, controlling for age, corresponded with following a meal plan OR 4.43 (2.52, 7.79, p < 0.001). The overall relationship for HbA1c < 8.5 to following a meal plan was OR 9.34 (2.84, 30.7. p < 0.001). The advantage of having a medical professional prescribe a diet seems to be an important environmental support factor in this sample's diabetes care, since obesity rates are well above the national average. Nearly half CAA are not given dietary guidance, yet our results indicate CAA may improve glycemic control by receiving dietary instructions.


Lack of susceptibility of baboons to infection with hepatitis B virus.
Historically, hepatitis B virus (HBV) has been considered species specific and unable to infect baboons. Based on this premise, two patients with HBV endstage liver disease underwent baboon liver xenotransplantation. To study whether baboons are susceptible to HBV infection, four baboons (two receiving immunosuppressive therapy) were inoculated with HBV. Animals were followed for 6 months: clinical examinations and biochemical studies were normal, hepatitis B surface antigen and hepatitis B core antigen staining of biopsies was negative, and HBV serology remained negative. HBV polymerase chain reaction was transiently positive in one animal, which most likely reflects the initial inoculation. This pilot study corroborates historical evidence and beliefs that baboons are resistant to HBV.


Functional Plasmon-Activated Water Increases Akkermansia muciniphila Abundance in Gut Microbiota to Ameliorate Inflammatory Bowel Disease.
Inflammatory bowel disease (IBD) is associated with dysbiosis and intestinal barrier dysfunction, as indicated by epithelial hyperpermeability and high levels of mucosal-associated bacteria. Changes in gut microbiota may be correlated with IBD pathogenesis. Additionally, microbe-based treatments could mitigate clinical IBD symptoms. Plasmon-activated water (PAW) is known to have an anti-inflammatory potential. In this work, we studied the association between the anti-inflammatory ability of PAW and intestinal microbes, thereby improving IBD treatment. We examined the PAW-induced changes in the colonic immune activity and microbiota of mice by immunohistochemistry and next generation sequencing, determined whether drinking PAW can mitigate IBD induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS) and dysbiosis through mice animal models. The effects of specific probiotic species on mice with TNBS-induced IBD were also investigated. Experimental results indicated that PAW could change the local inflammation in the intestinal microenvironment. Moreover, the abundance of Akkermansia spp. was degraded in the TNBS-treated mice but elevated in the PAW-drinking mice. Daily rectal injection of Akkermansia muciniphila, a potential probiotic species in Akkermansia spp., also improved the health of the mice. Correspondingly, both PAW consumption and increasing the intestinal abundance of Akkermansia muciniphila can mitigate IBD in mice. These findings indicate that increasing the abundance of Akkermansia muciniphila in the gut through PAW consumption or other methods may mitigate IBD in mice with clinically significant IBD.


Vaccination of pregnant women in the Valencian Community during the 2014-15 influenza season: a multicentre study.
To study influenza vaccination uptake in pregnant women from three Health Departments in the Valencian Community (Spain) during the 2014-15 flu season, to identify degree of knowledge, sources of information and attitudes toward immunization against influenza. Multicentre cross-sectional descriptive study during the 2014-15 vaccination campaign. Vaccine coverage was determined using the Nominal Vaccination Registry (NVR). Subsequently, a telephone survey was carried out on a sample of vaccinated and unvaccinated postpartum women. The NVR had information on 934 (59.5%) out of 1,569 postpartum women; distribution per Health Departments was: 420 (44.9%), 161 (17.2%) and 353 (37.8%) in La Ribera, Torrevieja and Elx-Crevillent respectively. Vaccine uptake was 27.9% (n = 261). According to the "Country of Origin" variable, 77.5% (n = 724) of women were Spanish, with a vaccination rate of 26.7% (n = 193), compared to 22.5% (n = 210) who were non-Spanish, with a rate of 32.4% (n = 68). The main source of information was midwives for 83.7% (n = 159) of vaccinated pregnant women and for 44.6% (n = 127) of non-vaccinated women. The main reasons for vaccine refusal were lack of awareness (29.5%, n = 84) and not considering it necessary (25.6%, n = 73). Despite their high willingness to be vaccinated after receiving information about the flu vaccine, the vaccination coverage in pregnant women studied is still low and can be improved. Health professionals need new information strategies to extend vaccine uptake to a larger number of pregnant women in Spain. Midwife advice plays an essential role in transmitting information on influenza vaccination in pregnant women and has a significant impact on uptake.


Activation of aniline by extracts from plants and induction of chromosomal damages in Chinese hamster ovary cells.
Activation of aniline by plant extracts was studied by a chromosomal damage induction assay in Chinese hamster ovary (CHO) cells in vitro. Extracts from roots of Vicia faba activated aniline and the activation caused increases in chromosomal aberrations (CAs) and endoreduplicated cells (ERCs), but did not cause sister-chromatid exchanges (SCEs). Extracts from Pisum sativum and Lactuca sativa, however, did not activate aniline. All C-hydroxylated metabolites of aniline, o-aminophenol, m-aminophenol and p-aminophenol, induced not only CAs but also SCEs in CHO cells. These results show that the pathway for aniline activation by Vicia extracts is by means other than the C-hydroxylation.


Eicosanoids in inflammation: biosynthesis, pharmacology, and therapeutic frontiers.
In mammalian cells, eicosanoid biosynthesis is usually initiated by the activation of phospholipase A2 and the release of arachidonic acid (AA) from membrane phospholipids. The AA is subsequently transformed by cyclooxygenase (COX) and lipoxygenase (LO) pathways to prostaglandins, thromboxane and leukotrienes collectively termed eicosanoids. Eicosanoid production is considerably increased during inflammation. Both COX and LO pathways are of particular clinical relevance. The COX pathway is the major target for non-steroidal anti-inflammatory drugs (NSAIDs), the most popular medications used to treat pain, fever and inflammation. Although their anti-inflammatory effects are well known, their long-term use is associated with gastrointestinal (GI) complications such as ulceration. In 1991, it was discovered that COX exists in two distinct isozymes, COX-1 and COX-2, of which COX-2 is primarily expressed at sites of inflammation and produces pro-inflammatory eicosanoids. For this reason, COX-2 selective inhibitors (COXIBs) have been developed recently as anti-inflammatory agents to minimize the risk of GI toxicity. Recently, some COX-2 selective inhibitors have shown adverse cardiovascular side effects, resulting in the withdrawal of rofecoxib and valdecoxib from the market. Selective inhibition of COX-2 without reducing COX-1-mediated thromboxane production could alter the balance between prostacyclin and thromboxane and promote a prothrombotic state, thereby explaining the observed COX-2 cardiovascular risk. In this review, we describe mechanisms for the production of pro-inflammatory eicosanoid mediators contributing to inflammation and summarize promising options for the prevention of inflammatory mediator formation and the therapeutic inhibition of pain and inflammation.


In Search of Trustworthy and Transparent Intelligent Systems With Human-Like Cognitive and Reasoning Capabilities.
At present we are witnessing a tremendous interest in Artificial Intelligence (AI), particularly in Deep Learning (DL)/Deep Neural Networks (DNNs). One of the reasons appears to be the unmatched performance achieved by such systems. This has resulted in an enormous hope on such techniques and often these are viewed as all-cure solutions. But most of these systems cannot explain why a particular decision is made (black box) and sometimes miserably fail in cases where other systems would not. Consequently, in critical applications such as healthcare and defense practitioners do not like to trust such systems. Although an AI system is often designed taking inspiration from the brain, there is not much attempt to exploit cues from the brain in true sense. In our opinion, to realize intelligent systems with human like reasoning ability, we need to exploit knowledge from the brain science. Here we discuss a few findings in brain science that may help designing intelligent systems. We explain the relevance of transparency, explainability, learning from a few examples, and the trustworthiness of an AI system. We also discuss a few ways that may help to achieve these attributes in a learning system.


A Dual Anion Chemistry-Based Superionic Glass Enabling Long-Cycling All-Solid-State Sodium-Ion Batteries.
Glassy Na-ion solid-state electrolytes (GNSSEs) are an important group of amorphous SSEs. However, the insufficient ionic conductivity of state-of-the-art GNSSEs at room temperature lessens their promise in the development of all-solid-state Na-ion batteries (ASSNIBs) with high energy density and improved safety. Here we report the discovery of a new sodium superionic glass, 0.5Na2 O2 -TaCl5 (NTOC), based on dual-anion sublattice of oxychlorides. The unique local structures with abundant bridging and non-bridging oxygen atoms contributes to a highly disordered Na-ion distribution as well as low Na+ migration barrier within NTOC, enabling an ultrahigh ionic conductivity of 4.62 mS cm-1 at 25 °C (more than 20 times higher than those of previously reported GNSSEs). Moreover, the excellent formability of glassy NTOC electrolyte and its high electrochemical oxidative stability ensure a favourable electrolyte-electrode interface, contributing to superior cycling stability of ASSNIBs for over 500 cycles at room temperature. The discovery of glassy NTOC electrolyte would reignite research enthusiasm in superionic glassy SSEs based on multi-anion chemistry.


NSC126188 induces apoptosis of prostate cancer PC-3 cells through inhibition of Akt membrane translocation, FoxO3a activation, and RhoB transcription.
We previously reported that NSC126188 caused apoptosis of cancer cells by inducing expression of RhoB. We here present that NSC126188 induces apoptosis of prostate cancer PC-3 cells by inhibiting Akt/FoxO3 signaling, which mediates RhoB upregulation. The apoptosis and Akt dephosphorylation caused by NSC126188 was not substantially relieved by overexpressing wild-type Akt but was relieved by overexpressing constitutively active Akt (CA-Akt) or myristoylated Akt (myr-Akt). Furthermore, overexpression of CA-Akt or myr-Akt downregulated RhoB expression, indicating that RhoB expression is regulated by Akt signaling. Interestingly, membrane translocation of GFP-Akt by insulin exposure was abolished in the cells pretreated with NSC126188 suggesting that NSC126188 directly interfered with translocation of Akt to the plasma membrane. In addition, NSC126188 activated FoxO3a by dephosphorylating S253 via Akt inhibition. Activated FoxO3a translocated to the nucleus and increased transcription of RhoB and other target genes. PC-3 cells transiently overexpressing FoxO3a exhibited increased RhoB expression and apoptosis in response to NSC126188. Conversely, FoxO3a knockdown reduced NSC126188-induced RhoB expression and cell death. These results suggest that RhoB may be a target gene of FoxO3a and is regulated by Akt signaling. Taken together, NSC126188 induces apoptosis of PC-3 cells by interfering with membrane recruitment of Akt, resulting in Akt dephosphorylation and FoxO3a activation, which leads to transcription of RhoB.


Paraplegic and quadriplegic patients undergoing emergency abdominal surgery: sicker presentations, worse outcomes.
Patients with paraplegia or quadriplegia presenting with abdominal surgical emergencies pose major clinical challenges. Difficulties in prompt diagnosis and treatment may influence patient outcomes. This is an American College of Surgeons National Surgical Quality Improvement Program study of patients undergoing an emergent abdominal operation. Patients were stratified into paraplegic (PARA), quadriplegic (QUAD), and control (CONT). PARA and QUAD groups were matched with controls by 1:2 ratio. Regression models were used to analyze the effect of paraplegia and quadriplegia on outcome. A total of 76,766 patients underwent emergent abdominal operations: 274 PARA, 132 QUAD, and 76,356 CONT patients. Lower gastrointestinal operations were the most common procedures in PARA and QUAD groups; appendectomy was the most common in the CONT group. After cohort matching, patients with cord paralysis were significantly more likely to present with severe sepsis, have "infected" wounds at operation, and have increased rates of postoperative sepsis and need for reoperation. Patients with paraplegia or quadriplegia with acute abdominal surgical emergencies are more likely to present late and have a significantly higher incidence of postoperative septic complications and longer hospital stay. Early surgical consultation and aggressive evaluation and postoperative management are warranted in these populations. Epidemiologic study, level III; therapeutic study, level IV.


Effects of oxyanions, natural organic matter, and bacterial cell numbers on the bioreduction of lepidocrocite (gamma-FeOOH) and the formation of secondary mineralization products.
Microbial reduction of Fe(III) oxides results in the production of Fe(II) and may lead to the subsequent formation of Fe(II)-bearing secondary mineralization products including magnetite, siderite, vivianite, chukanovite (ferrous hydroxy carbonate (FHC)), and green rust; however, the factors controlling the formation of specific Fe(II) phases are often not well-defined. This study examined effects of (i) a range of inorganic oxyanions (arsenate, borate, molybdate, phosphate, silicate, and tungstate), (ii) natural organic matter (citrate, oxalate, microbial extracellular polymeric substances [EPS], and humic substances), and (iii) the type and number of dissimilatory iron-reducing bacteria on the bioreduction of lepidocrocite and formation of Fe(II)-bearing secondary mineralization products. The bioreduction kinetics clustered into two distinct Fe(II) production profiles. "Fast" Fe(II) production kinetics [19-24 mM Fe(II) d(-1)] were accompanied by formation of magnetite and FHC in the unamended control and in systems amended with borate, oxalate, gellan EPS, or Pony Lake fulvic acid or having "low" cell numbers. Systems amended with arsenate, citrate, molybdate, phosphate, silicate, tungstate, EPS from Shewanella putrefaciens CN32, or humic substances derived from terrestrial plant material or with "high" cell numbers exhibited comparatively slow Fe(II) production kinetics [1.8-4.0 mM Fe(II) d(-1)] and the formation of green rust. The results are consistent with a conceptual model whereby competitive sorption of more strongly bound anions blocks access of bacterial cells and reduced electron-shuttling compounds to sites on the iron oxide surface, thereby limiting the rate of bioreduction.


c-Abl-Mediated Tyrosine Phosphorylation of PARP1 Is Crucial for Expression of Proinflammatory Genes.
Poly(ADP-ribosyl)ation is a rapid and transient posttranslational protein modification mostly catalyzed by poly(ADP-ribose) polymerase-1 (PARP1). Fundamental roles of activated PARP1 in DNA damage repair and cellular response pathways are well established; however, the precise mechanisms by which PARP1 is activated independent of DNA damage, and thereby playing a role in expression of inflammatory genes, remain poorly understood. In this study, we show that, in response to LPS or TNF-α exposure, the nonreceptor tyrosine kinase c-Abl undergoes nuclear translocation and interacts with and phosphorylates PARP1 at the conserved Y829 site. Tyrosine-phosphorylated PARP1 is required for protein poly(ADP-ribosyl)ation of RelA/p65 and NF-κB-dependent expression of proinflammatory genes in murine RAW 264.7 macrophages, human monocytic THP1 cells, or mouse lungs. Furthermore, LPS-induced airway lung inflammation was reduced by inhibition of c-Abl activity. The present study elucidated a novel signaling pathway to activate PARP1 and regulate gene expression, suggesting that blocking the interaction of c-Abl with PARP1 or pharmaceutical inhibition of c-Abl may improve the outcomes of PARP1 activation-mediated inflammatory diseases.


The "moral career" of perinatally HIV-infected children: revisiting Goffman's concept.
HIV-infected children usually live in vulnerable situations, experiencing discrimination and stigma commonly felt by other people living with HIV/AIDS. The present study aims to analyse primary socialisation of HIV-infected children and adolescents recruited from a public health service in Rio de Janeiro (Brazil) as a social process that shapes a new generation of stigmatised and vulnerable persons. Research was informed by an interactionist perspective, focusing on key aspects of HIV-infected children and adolescents life histories under the conceptual frame of Erving Goffman's theories regarding "moral careers". Goffman defines the making of a moral career as the process through which a person learns that she/he possesses a particular attribute, which may lead her/him to be discredited by members of the surrounding society. We have identified aspects of life histories of HIV-vertically infected children and adolescents for each aspect of "moral career" as described by Goffman, relating them to as family structure, the experience of living HIV within the family, and the position and family role of a given subject. The patterns of "moral career" proposed by Goffman in 1963 were useful in identifying components of HIV-related stigma among children and adolescents. These include gender and social disadvantages, difficulty in coping with a child with a potentially severe disease, orphanhood, abandonment, adoption and disclosure of one's HIV serostatus. Primary socialisation of HIV-infected children and adolescents is a key piece of the complex HIV/AIDS-labelling process that could be targeted by interventions aiming to decrease stigma and marginalisation. Health care workers and stakeholders should be committed to ensuring education and guaranteeing the legal rights of this specific population, including the continuous provision of quality health care, full access to school and support to full disclosure of HIV diagnosis.


Physical measures of physical functioning as prognostic factors to predict outcomes in low back pain: Protocol for a systematic review.
Low back pain (LBP) is a highly prevalent condition that substantially impairs individuals' physical functioning. This highlights the need for effective management strategies to improve patient outcomes. It is, therefore, crucial to have knowledge of physical functioning prognostic factors that can predict outcomes to facilitate the development of targeted treatment plans aiming to achieve better patient outcomes. There is no synthesis of evidence for physical functioning measures as prognostic factors in the LBP population. The objective of this systematic review is to synthesize evidence for physical measures of physical functioning as prognostic factors to predict outcomes in LBP. The protocol is registered in the International Prospective Register of Systematic Reviews and reported in line with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P). Prospective longitudinal observational studies investigating potential physical prognostic factors in LBP and/or low back-related leg pain population will be included, with no restriction on outcome. Searches will be performed in MEDLINE, EMBASE, Scopus, CINAHL databases, grey literature search using Open Grey System and ProQuest Dissertations and Theses, hand-searching journals, and reference lists of included studies. Two independent reviewers will evaluate the eligibility of studies, extract data, assess risk of bias and quality of evidence. Risk of bias will be assessed using the Quality in Prognostic Studies (QUIPS) tool. Adequacy of clinical, methodological, and statistical homogeneity among included studies will decide quantitative (meta-analysis) or qualitative analysis (narrative synthesis) focused on prognostic factors and strength of association with outcomes. Quality of cumulative evidence will be evaluated using a modified Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Information about prognostic factors can be used to predict outcomes in LBP. Accurate outcome prediction is essential for identifying high-risk patients that allows targeted allocation of healthcare resources, ultimately reducing the healthcare burden. PROSPERO, CRD42023406796.


Scaling the Andean Shilajit: A Novel Neuroprotective Agent for Alzheimer's Disease.
Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder without a cure, despite the enormous number of investigations and therapeutic approaches. AD is a consequence of microglial responses to "damage signals", such as aggregated tau oligomers, which trigger a neuro-inflammatory reaction, promoting the misfolding of cytoskeleton structure. Since AD is the most prevalent cause of dementia in the elderly (>60 years old), new treatments are essential to improve the well-being of affected subjects. The pharmaceutical industry has not developed new drugs with efficacy for controlling AD. In this context, major attention has been given to nutraceuticals and novel bioactive compounds, such as molecules from the Andean Shilajit (AnSh), obtained from the Andes of Chile. Primary cultures of rat hippocampal neurons and mouse neuroblastoma cells were evaluated to examine the functional and neuroprotective role of different AnSh fractions. Our findings show that AnSh fractions increase the number and length of neuronal processes at a differential dose. All fractions were viable in neurons. The AnSh fractions inhibit tau self-aggregation after 10 days of treatment. Finally, we identified two candidate molecules in M3 fractions assayed by UPLC/MS. Our research points to a novel AnSh-derived fraction that is helpful in AD. Intensive work toward elucidation of the molecular mechanisms is being carried out. AnSh is an alternative for AD treatment or as a coadjuvant for an effective treatment.


GW0742 reduces mast cells degranulation and attenuates neurological impairments via PPARβ/δ/CD300a/SHP1 pathway after GMH in neonatal rats.
Activation of mast cells plays an important role in brain inflammation. CD300a, an inhibitory receptor located on mast cell surfaces, has been reported to reduce the production of pro-inflammatory cytokines and exert protective effects in inflammation-related diseases. Peroxisome proliferator-activated receptor β/δ (PPARβ/δ), a ligand-activated nuclear receptor, activation upregulates the transcription of CD300a. In this study, we aim to investigate the role of PPARβ/δ in the attenuation of germinal matrix hemorrhage (GMH)-induced mast cell activation via CD300a/SHP1 pathway. GMH model was induced by intraparenchymal injection of bacterial collagenase into the right hemispheric ganglionic eminence in P7 Sprague Dawley rats. GW0742, a PPARβ/δ agonist, was administered intranasally at 1 h post-ictus. CD300a small interfering RNA (siRNA) and PPARβ/δ siRNA were injected intracerebroventricularly 5 days and 2 days before GMH induction. Behavioral tests, Western blot, immunofluorescence, Toluidine Blue staining, and Nissl staining were applied to assess post-GMH evaluation. Results demonstrated that endogenous protein levels of PPARβ/δ and CD300a were decreased, whereas chymase, tryptase, IL-17A and transforming growth factor β1 (TGF-β1) were elevated after GMH. GMH induced significant short- and long-term neurobehavioral deficits in rat pups. GW0742 decreased mast cell degranulation, improved neurological outcomes, and attenuated ventriculomegaly after GMH. Additionally, GW0742 increased expression of PPARβ/δ, CD300a and phosphorylation of SHP1, decreased phosphorylation of Syk, chymase, tryptase, IL-17A and TGF-β1 levels. PPARβ/δ siRNA and CD300a siRNA abolished the beneficial effects of GW0742. GW0742 inhibited mast cell-induced inflammation and improved neurobehavior after GMH, which is mediated by PPARβ/δ/CD300a/SHP1 pathway. GW0742 may serve as a potential treatment to reduce brain injury for GMH patients.


Pressure relief and load redistribution by custom-made insoles in diabetic patients with neuropathy and foot deformity.
To study the effects of custom-made insoles on plantar pressures and load redistribution in neuropathic diabetic patients with foot deformity. Cross-sectional. Although custom-made insoles are commonly prescribed to diabetic patients, little quantitative data on their mechanical action exists. Regional in-shoe peak pressures and force-time integrals were measured during walking in the feet of 20 neuropathic diabetic subjects with foot deformity who wore flat or custom-made insoles. Twenty-one feet with elevated risk for ulceration at the first metatarsal head were analysed. Load redistribution resulting from custom-made insoles was assessed using a new load-transfer algorithm. Custom-made insoles significantly reduced peak pressures and force-time integrals in the heel and first metatarsal head regions; pressures and integrals were significantly increased in the medial midfoot region compared with flat insoles. Custom-made insoles successfully reduced pressures in and integrals at the first metatarsal head in 7/21 feet, were moderately successful in another seven, but failed in the remaining seven. Load transfer was greatest from the lateral heel to the medial midfoot regions. Custom-made insoles were more effective than flat insoles in off-loading the first metatarsal head region, but with considerable variability between individuals. Most off-loading occurred in the heel (not a region typically at risk). The load transfer algorithm effectively analyses custom-made-insole action. Because similar insole modifications apparently exert different effects in different patients, a comprehensive evaluation of custom designs using in-shoe pressure measurement should ideally be conducted before dispensing insoles to diabetic patients with neuropathy and foot deformity.


Growth-mediated plant movements: hidden in plain sight.
While fast plant movements are spectacular but rare, almost all plants exhibit relatively slow, growth-mediated tropic movements that are key to their survival in the natural world. In this brief review, we discuss recent insights into the molecular mechanisms underlying phototropism, gravitropism, hydrotropism, and autostraightening. Careful molecular genetic and physiological studies have helped confirm the importance of lateral auxin gradients in gravitropic and phototropic responses. However, auxin signaling does not explain all tropisms: recent work has shown that abscisic acid signaling mediates root hydrotropism and has implicated mechanosensing in autostraightening, the organ straightening process recently modeled as a proprioceptive response. The interactions between distinct tropic signaling pathways and other internal and external sensory processes are also now being untangled.


CD4+Foxp3+ regulatory T cell expansion induced by antigen-driven interaction with intestinal epithelial cells independent of local dendritic cells.
Regulatory T cells (T(regs)) have potential anti-inflammatory effects and are likely to be important in the pathogenesis of chronic inflammatory bowel disease (IBD). However, the induction and expansion of T(regs) at sites of mucosal inflammation are not yet fully understood and may involve antigen presentation by local dendritic cells (DCs) and/or intestinal epithelial cells (IECs). To determine the unique ways in which the gut induces or expands T(regs), a transgenic mouse model that is based on the specific expression of a model autoantigen (influenza haemagglutinin (HA)) in the intestinal epithelium (VILLIN-HA) was used. Gut-associated DCs and IECs isolated from these mice were phenotypically and functionally characterised for the potential to interact with HA-specific T(regs) in vitro and in vivo. Intestinal self-antigen expression leads to peripheral expansion of antigen-specific CD4(+)Foxp3(+) T(regs). Although gut-associated DCs can induce antigen-specific CD4(+)Foxp3(+) T cell proliferation, in vivo depletion of DCs did not preclude proliferation of these cells. Interestingly, antigen presentation by primary IECs is sufficient to expand antigen-specific CD4(+)Foxp3(+) T(regs) efficiently. This is dependent on major histocompatibility complex class II, but, in contrast to DCs, is unlikely to require transforming growth factor beta and retinoic acid. This study provides experimental evidence for a new concept in mucosal immunity: in contrast to current thinking, expansion of T(regs) can be achieved independently of local DCs through antigen-specific IEC-T cell interactions.


Effects of somatostatin/octreotide treatment in neonates with congenital chylothorax.
The influence of somatostatin/octreotide treatment on outcomes of neonates with congenital chylothorax remains controversial. We retrospectively reviewed our experience with somatostatin/octreotide therapy in neonates with this very rare disease.Fourteen neonates with congenital chylothorax who were treated with somatostatin (3.5-7 μg/kg/h, before 2016) or octreotide (1-6 μg/kg/h, after January 2016), along with traditional management between 2013 and 2016, were retrospectively reviewed in this observational study. Their daily volumes of pleural drainage and parameters of respiratory support were recorded, and the potential side effects of somatostatin/octreotide were screened.Four patients (28.6%) had a unilateral presentation of pleural effusion, whereas 10 patients (71.4%) had a bilateral presentation. Twelve patients (85.7%) survived until discharge without later recurrence or death, whereas 2 patients (14.3%) died within the first 3 days after birth. Somatostatin/octreotide treatment was maintained for a median period of 6 days (range 1-16 days). The chest tube was removed after a median duration of 14 days (range 2-51 days), and no patient needed pleurodesis or thoracic duct ligation surgery. The average daily drain output within 3 days post-treatment (median 62 mL, range 10-651 mL) was significantly lower than that before treatment (median 133 mL, range 70-620 mL) (P = .002). The need for ventilation support was reduced in most patients (85.7%) after the initiation of somatostatin/octreotide therapy. No serious side effects were identified.Somatostatin/octreotide treatment reduced pleural drainage and respiratory support without significant side effects. Further randomized controlled studies with more patients are necessary to ascertain the benefits of somatostatin/octreotide in neonates with congenital chylothorax.


The avian acanthocephalan Plagiorhynchus cylindraceus (Palaeacanthocephala) parasitizing the European hedgehog (Erinaceus europaeus) in Europe and New Zealand.
The palaeacanthocephalan Plagiorhynchus cylindraceus is a common intestinal parasite of passerine birds, which can also occur parenterally or in the intestinal tract of mammals, often as an invading species in many countries worldwide. In this survey, introduced hedgehogs (Erinaceus europaeus, n = 183) killed in New Zealand during a biocontrol campaign and conspecifics (n = 174) that had died in hedgehog rehabilitation centers in Germany and Britain were examined for this parasite. In New Zealand, P. cylindraceus is recorded for the first time here, in the vicinity of Auckland. In Europe, prevalences ranged from 4.2% up to 47.6%, while in New Zealand, only 1.6% (Auckland 7.9%). Most of the worms occurred inside the peritoneal cavity where they had partly degenerated. Since hedgehogs are seldom preyed upon in continental Europe but often become traffic victims, we hypothesize that the worms inside them, whether extra- or intraperitoneally, contribute to the abundance and persistence of the parasite by being ingested by scavenging birds. Accordingly, we consider P. cylindraceus as a "modern parasite" taking advantage of two aspects of global change: anthropogenic promoted transmission (road kills) and the transcontinental spread of infected intermediate and/or final hosts caused by humans.


Distribution and possible interactions of actin-associated proteins and cell adhesion molecules of nerve growth cones.
Actin filaments and their interactions with cell surface molecules have key roles in tissue cell behaviour. Axonal pathfinding during embryogenesis, an especially complex cell behaviour, is based on the migration of nerve growth cones. We have used fluorescence immunocytochemistry to examine the distribution in growth cones, their filopodia and lamellipodia of several actin-associated proteins and nerve cell adhesion molecules. The leading margins of chick dorsal root ganglion nerve growth cones and their protrusions stain strongly for f-actin, filamin, alpha-actinin, myosin, tropomyosin, talin and vinculin. MAP2 is absent from DRG growth cones, and staining for spectrin fodrin extends into growth cones, but not along filopodia. Thus, organization of the leading margins of growth cones may strongly resemble the leading lamella of migrating fibroblasts. The adhesion-mediating molecules integrin, L1, N-CAM and A-CAM are all found on DRG neurites and growth cones. However, filopodia stain relatively more strongly for integrin and L1 than for A-CAM or N-CAM. In fact, the 180 X 10(3) Mr form of N-CAM may be absent from most of the length of filopodia. DRG neurones cultured in cytochalasin B display differences in immunofluorescence staining which further emphasize that these adhesion molecules interact differentially with the actin filament system of migrating growth cones. Several models for neuronal morphogenesis emphasize the importance of regulation of the expression of adhesion molecules. Our results support hypotheses that cellular distribution and transmembrane interactions are key elements in the functions of these adhesion molecules during axonal pathfinding.


Bifocal compression-distraction in the acute treatment of grade III open tibia fractures with bone and soft-tissue loss: a report of 24 cases.
To evaluate the results of bifocal compression-distraction method for the acute treatment of open tibia fractures with bone and soft-tissue loss. Patients were selected for bifocal compression-distraction (shortening and lengthening) who had open tibia fractures with bone and soft-tissue loss and a Mangled Extremity Severe Score of 6 and below indicating good leg viability. Bifocal compression-distraction osteogenesis using the Ilizarov type circular external fixator was applied to 24 patients with 14 grade IIIA and 10 grade IIIB open tibia fractures with bone and soft-tissue loss. Mean age of the patients was 30.6 years (range 18-53). The mean bone defect was 5 cm (range 3-8.5). The mean soft tissue defect was 2.5 x 3.5 (1 x 2-10 x 5) cm. Acute shortening at the fracture site was done for patients with bone defects up to 3 cm to achieve apposition of bone ends. Gradual shortening at a rate of 2 mm/d was done for patients who had bone defects more than 3 cm. Leg length discrepancy was overcome by lengthening at the same time through a corticotomy at a proximal or distal level depending on fracture localization, until there was equalization of leg lengths. Mean follow-up period was 30 months (range 18-60). Mean bone healing time was 7.5 months (range 4-11). The mean time in external fixation was 7.1 months (range 3-10), and the average external fixator index was 1.4 months/cm. Results were evaluated using the Paley bone and functional assessment scores. The bone assessment results were excellent in 21 and good in 3 patients. Functional assessment scores were excellent in 19, good in 4, and fair in 1 patient. Pin site infections were present in 10.7% of the pin sites. There were 52 complications in 24 patients, for a complication rate per patient of 2.08. Of the complications, 48.1% were problems (minor complications), 38.5% obstacles (major complications requiring a surgical solution), and 13.4% sequelae (true complications). Minor complications included soft tissue inflammation and infection, translation/angulation, and delayed maturation during distraction and transient knee contracture and loss of motion. All grade 1 and 2 soft tissue inflammations and infections healed with nonoperative therapy. Major complications included pin tract infection and reinfection, equinus deformity, frame failure, and premature consolidation, all of which required additional surgery to correct the problem. Sequelae included leg length discrepancy, loss of knee/ankle range of motion, knee flexion contracture, malalignment, and chronic osteomyelitis. Bifocal compression-distraction osteogenesis is a safe, reliable, and largely successful method for the acute treatment of open tibia fractures with bone and soft-tissue loss. Further nonoperative or operative treatment can correct most complications.


Experiences with a three-current ionization chamber as primary detector standard for absolute calibration in space.
With ISS-SOLAR-SolACES, a new approach in terms of calibrating solar spectral irradiance (SSI) data was validated during the mission period from 2008 to 2017: an ionization chamber (IC) as primary detector standard, operated in space, allowed daily calibration measurements. Though primary photo-ionization efficiencies and higher-order ionization effects from photoelectrons are constant with time, filter transmissions and signal contributions from solar x-rays are to be determined for the SSI data evaluation, requiring a deeper investigation. The experiences made with ionization chambers in the laboratory and aboard the ISS-SOLAR-SolACES mission are presented. They include the determination of higher-order ionization effects, the measured transmission of the filters with time, and the treatment of the solar soft x-ray background. Recommended combinations of IC filling gases and filter materials as well as laboratory and in-space measurements will provide correction procedures for different levels of solar activity to achieve further improvement of SSI data accuracy in the spectral range from 1 nm to 133 nm. Results and Perspectives. The usage of the IC technology aims for establishing absolute SolACES-type calibration equipment in space, providing reference SSI data sets in solar and solar-terrestrial science, as well as in related applications such as global navigation satellite system signal evaluation.


The role of genetic information in personalized medicine.
Personalized medicine is the latest promise of a gene-centered biomedicine to provide treatments custom-tailored to the specific needs of patients. Although surrounded by much hype, personalized medicine at present lacks the empirical and theoretical foundations necessary to render it a realistic long-term perspective. In particular, the role of genetic data and the relationship between causal understanding, prediction, prevention, and treatment of a disease need clarifying. This article critically examines the concept of information in genetics and its relation to modern-day genetic determinism, using pharmacogenetics, personalized medicine's core discipline, as a test case. The article concludes that: (1) genetic knowledge does not constitute a privileged basis for personalized medicine because there is an a priori complete causal parity of genetic and nongenetic resources of development; and (2) prediction, prevention, and treatment all depend on a causal-mechanistic understanding that will follow only from integrating data across the whole gamut of developmental factors-genetic and non-genetic. In a future successful personalized medicine, genes will have no special status, either as determinants of phenotype, markers of disease or as targets of treatment.


Chronic pain after femoral hernia repair: a cross-sectional study.
To explore the prevalence of and to identify possible risk factors for chronic pain after surgery for femoral hernia. Chronic pain has become a very important outcome in quality assessment of inguinal hernia surgery. There are no studies on the risk for chronic pain after femoral hernia surgery. The Inguinal Pain Questionnaire was sent to 1967 patients who had had a repair for primary unilateral femoral hernia between January 1, 1997 and December 31, 2006. A follow-up period of at least 18 months was chosen. Answers from 1461 patients were matched with data recorded in the Swedish Hernia Register and analyzed. Some degree of pain during the previous week was reported by 24.2% (354) of patients. Pain interfered with daily activities in 5.5% (81) of patients. Emergency surgery (OR = 0.54; 95% CI = 0.40-0.74) and longer time since surgery (OR = 0.93; 95% CI = 0.89-0.98 for each year added) were associated with lower risk for chronic postoperative pain, whereas a high level of preoperative pain was associated with a higher risk for chronic pain (OR = 1.17; 95% CI = 1.10-1.25). Surgical technique was not found to influence the risk for chronic pain in multivariate logistic regression analysis. Chronic postoperative pain is as important a complication after femoral hernia surgery as it is after inguinal hernia surgery. In contrast to inguinal hernia surgery, no risk factor related to surgical technique was found. Further investigations into the role of preoperative pain are necessary.


Reduced ITPase activity and favorable IL28B genetic variant protect against ribavirin-induced anemia in interferon-free regimens.
Genetic variants of inosine triphosphatase (ITPA) that confer reduced ITPase activity are associated with protection against ribavirin(RBV)-induced hemolytic anemia in peginterferon(IFN)/RBV-based treatment of hepatitis C virus (HCV). Patients with reduced ITPase activity showed improved treatment efficacy when treated with IFN/RBV. In addition, a genetic polymorphism near the IL28B gene is associated with an improved response to IFN/RBV treatment. RBV has been an important component of IFN-containing regimens, and is currently recommended in combination with several IFN-free regimens for treatment of harder to cure HCV infections. To evaluate whether genetic variations that reduce ITPase activity impact RBV-induced anemia in IFN-free/RBV regimens. In this study, genetic analyses were conducted in the PEARL-IV trial to investigate the effect of activity-reducing ITPA variants as well as IL28B polymorphism on anemia, platelet (PLT) counts, and virologic response in HCV genotype1a-infected patients treated with the direct-acting antiviral (DAA) regimen of ombitasvir/paritaprevir/ritonavir and dasabuvir±RBV. Reduction in ITPase activity and homozygosity for the IL28Brs12979860 CC genotype protected against RBV-induced anemia. In patients receiving RBV, reduced ITPase activity was associated with reduced plasma RBV concentration and higher PLT counts. ITPase activity had no impact on response to DAA treatment, viral kinetics, or baseline IP-10 levels. Our study demonstrates that genetics of ITPA and IL28B may help identify patients protected from RBV-induced anemia when treated with IFN-free regimens. Our work demonstrates for the first time that IL28B genetics may also have an impact on RBV-induced anemia. This may be of particular significance in patients with difficult-to-cure HCV infections, such as patients with decompensated cirrhosis where RBV-containing regimens likely will continue to be recommended.


The effect of Astragaloside IV on ethanol-induced gastric mucosal injury in rats: Involvement of inflammation.
The present study aimed to investigate the potential protective effects of Astragaloside IV (AS-IV) against ethanol-induced gastric mucosal injury in rats. The animals were divided into 7 groups and pretreated with vehicle, various doses of AS-IV (1,2 and 4mg/kg, i.p.) or omeprazole (40mg/kg), 75min later, the gastric mucosal injury was induced by oral administration of ethanol. One hour after ethanol ingestion, the rats were euthanized and gastric tissues were collected to biochemical analyze. Myeloperoxidase (MPO), tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), interleukin 10 (IL-10), nuclear factor kappa B (NF-κB) p65 protein, TNF receptor-associated factor 2 (TRAF2) and nuclear NF-κB (nNF-κB) proteins were estimated by enzyme-linked immunosorbent assay or western blot analysis. The gastric mucosal lesions were assessed by macroscopic and histopathological examinations. The results showed pretreatment with AS-IV attenuated the severity of ethanol gastric mucosal damage as evidenced by lowering of injury scores, histopathologic aberrations and leukocyte invasion. These actions were analogous to the reference omeprazole. AS-IV suppressed gastric inflammation by curbing of MPO, TNF-α levels along with NF-κB p65 and TRAF2 expression. It also augmented the anti-inflammatory IL-10 levels. Meanwhile, AS-IV could inhibit NF-κB transcription by inhibiting the expression of NF-κB p65 and increasing the expression of nNF-κB. It seems that AS-IV as an anti-inflammatory agent may have a protective effect against ethanol-induced mucosal injury by inhibition of neutrophil infiltration and reducing the expression of NF-κB p65, TRAF2 and inflammatory cytokines via regulating TNF-α/NF-κB signal pathway in gastric tissue.


A cost-effectiveness analysis of the number of samples to collect and test from a sexual assault.
Although the backlog of untested sexual assault kits in the United States is starting to be addressed, many municipalities are opting for selective testing of samples within a kit, where only the most probative samples are tested. We use data from the San Francisco Police Department Criminalistics Laboratory, which tests all samples but also collects information on the samples flagged by sexual assault forensic examiners as most probative, to build a standard machine learning model that predicts (based on covariates gleaned from sexual assault kit questionnaires) which samples are most probative. This model is embedded within an optimization framework that selects which samples to test from each kit to maximize the Combined DNA Index System (CODIS) yield (i.e., the number of kits that generate at least one DNA profile for the criminal DNA database) subject to a budget constraint. Our analysis predicts that, relative to a policy that tests only the samples deemed probative by the sexual assault forensic examiners, the proposed policy increases the CODIS yield by 45.4% without increasing the cost. Full testing of all samples has a slightly lower cost-effectiveness than the selective policy based on forensic examiners, but more than doubles the yield. In over half of the sexual assaults, a sample was not collected during the forensic medical exam from the body location deemed most probative by the machine learning model. Our results suggest that electronic forensic records coupled with machine learning and optimization models could enhance the effectiveness of criminal investigations of sexual assaults.


[« More time for patients » : a reorganization of medical wards at the University Hospitals of Geneva].
The University Hospitals of Geneva initiated their latest strategic plan by consulting widely with employees and patients. Nine main avenues were defined as priority projects for the institution. The project « More time for patients » aims at simplifying clinical and administrative processes using tools from Lean management and Design Thinking. Its objectives are to redefine the organization of the healthcare-related tasks in order to optimize the time spent with patients and relatives, increase patients' involvement and shared decision making, and improve both the communication with patients, as well as the interdisciplinary collaboration, with patients always at the heart of care.


Enumeration of Porphyromonas gingivalis, Prevotella intermedia and Actinobacillus actinomycetemcomitans in subgingival plaque samples by a quantitative-competitive PCR method.
Porphyromonas gingivalis, Prevotella intermedia and Actinobacillus actinomycetemcomitans are believed to play an important role in adult periodontitis, but the significance of their relative numbers and progress of the disease is still unclear. Traditional quantitative methods are generally time-consuming and inaccurate. The aim of this study was to develop a sensitive, quantitative PCR technique that would be useful for enumerating P. gingivalis, Pr. intermedia and A. actinomycetemcomitans in subgingival plaque samples from subjects with adult periodontitis. Primers to the following genes were employed: the fimbrial gene (fimA) of P. gingivalis, the 16S rRNA gene of Pr. intermedia and the leukotoxin-A (lktA) gene of A. actinomycetemcomitans. Competitive templates were constructed either by sequence deletion between primer binding sites or by annealing of the primer binding sites to an appropriate DNA core so as to yield products of a different size from that obtained with the target template. Coamplification of target and competitive templates yielded products of expected size and non-specific recognition by the primers was not found. The sensitivity of the designed primers was 100 cells of P. gingivalis, 100 cells of Pr. intermedia and 10 cells of A. actinomycetemcomitans. The three species were found in subgingival plaque samples collected from both healthy and diseased sites by the quantitative-competitive (QC)-PCR method and the technique was more sensitive than cultural methods. For determining the proportions of each of the three periodontopathogens, the total number of bacteria in the samples was enumerated by quantitative-PCR with 16S rRNA universal primers (27f and 342r). The findings indicate that QC-PCR is a useful method for enumerating bacteria in clinical oral specimens and the technique could play a role in the investigation of disease progression.


Successful Integration of Hepatitis C Virus Point-of-Care Tests into the Denver Metro Health Clinic.
Background. The Centers for Disease Control and Prevention (CDC) recommends testing and linkage to care for persons most likely infected with hepatitis C virus (HCV), including persons with human immunodeficiency virus. We explored facilitators and barriers to integrating HCV point-of-care (POC) testing into standard operations at an urban STD clinic. Methods. The OraQuick HCV rapid antibody test was integrated at the Denver Metro Health Clinic (DMHC). All clients with at least one risk factor were offered the POC test. Research staff conducted interviews with clients (three HCV positive and nine HCV negative). Focus groups were conducted with triage staff, providers, and linkage-to-care counselors. Results. Clients were pleased with the ease of use and rapid return of results from the HCV POC test. Integrating the test into this setting required more time but was not overly burdensome. While counseling messages were clear to staff, clients retained little knowledge of hepatitis C infection or factors related to risk. Barriers to integrating the HCV POC test into clinic operations were loss to follow-up and access to care. Conclusion. DMHC successfully integrated HCV POC testing and piloted a HCV linkage-to-care program. Providing testing opportunities at STD clinics could increase identification of persons with HCV infection.


A nonsense mutation in the tyrosinase gene causes albinism in water buffalo.
Oculocutaneous albinism (OCA) is an autosomal recessive hereditary pigmentation disorder affecting humans and several other animal species. Oculocutaneous albinism was studied in a herd of Murrah buffalo to determine the clinical presentation and genetic basis of albinism in this species. Clinical examinations and pedigree analysis were performed in an affected herd, and wild-type and OCA tyrosinase mRNA sequences were obtained. The main clinical findings were photophobia and a lack of pigmentation of the hair, skin, horns, hooves, mucosa, and iris. The results of segregation analysis suggest that this disease is acquired through recessive inheritance. In the OCA buffalo, a single-base substitution was detected at nucleotide 1,431 (G to A), which leads to the conversion of tryptophan into a stop codon at residue 477. This premature stop codon produces an inactive protein, which is responsible for the OCA buffalo phenotype. These findings will be useful for future studies of albinism in buffalo and as a possible model to study diseases caused by a premature stop codon.


Efficacy of ivermectin on the infectivity of Leishmania major promastigotes.
Ivermectin is widely used as an antiparasitic drug for livestock and recently used for some human parasites. The effect of ivermectin on the infectivity of Leishmania major promastigotes was studied in Syrian golden hamsters. The results showed that hamsters infected with promastigotes treated for one day with 100 micrograms/ml ivermectin in culture medium did not develop skin lesion at the site of infection. However, amastigotes were demonstrated in Giemsa stained splenic smears. On the other hand, promastigotes treated for two days with 90 micrograms/ml ivermectin did not acquired the infection. i.e. the promastigotes died or lost their infectivity.


Gene content evolution in Discobid mitochondria deduced from the phylogenetic position and complete mitochondrial genome of Tsukubamonas globosa.
The unicellular eukaryotic assemblage Discoba (Excavata) comprises four lineages: the Heterolobosea, Euglenozoa, Jakobida, and Tsukubamonadida. Discoba has been considered as a key assemblage for understanding the early evolution of mitochondrial (mt) genomes, as jakobids retain the most gene-rich (i.e., primitive) genomes compared with any other eukaryotes determined to date. However, to date, mt genome sequences have been completed for only a few groups within Discoba, including jakobids, two closely related heteroloboseans, and kinetoplastid euglenozoans. The Tsukubamonadida is the least studied lineage, as the order was only recently established with the description of a sole representative species, Tsukubamonas globosa. The evolutionary relationship between T. globosa and other discobids has yet to be resolved, and no mt genome data are available for this particular organism. Here, we use a "phylogenomic" approach to resolve the relationship between T. globosa, heteroloboseans, euglenozoans, and jakobids. In addition, we have characterized the mt genome of T. globosa (48,463 bp in length), which encodes 52 putative protein-coding and 29 RNA genes. By mapping the gene repertoires of discobid mt genomes onto the well-resolved Discoba tree, we model gene loss events during the evolution of discobid mt genomes.


Multiphoton excitation ionization of N(2) following collisional energy transfer with H(2)O: a potential measure of molecular mixing.
A multiphoton ionization excitation of N(2) following collisional energy exchange with optically excited H(2) O was demonstrated, and its potential for measuring H(2) O-N(2) mixing at the molecular level was evaluated. In this process, N(2) is sensitized by a collisional energy exchange with H(2)O molecules excited by a tunable KrF laser. The sensitized N(2) molecules are further excited and ionized by two additional photons of the same laser pulse. Independent images of sensitized N2(+) emission at 391.4 nm and by OH at 308 nm formed by the dissociation of excited H(2)O were obtained along a laser beam traversing slow dry-air and N(2) jets entering room air. Although effects of O(2) and N(2) collisional quenching were noted, such images can potentially be used to measure H(2)O-N(2) molecular mixing and the concentration of H(2)O independently. The detection of H(2)O nucleation by this technique suggests that imaging of H(2)O droplet evaporation or visualizing and monitoring H(2)O condensation may also be possible.


Prolonged perturbation of the oscillations of hepatoma Fao cell proliferation by a single small dose of methotrexate.
The proliferation rate of various cell types in vitro, including hepatoma Fao cells, displays aperiodic oscillations. The frequency of these oscillations is about one every 3-5 weeks, and there are variations in cell functions and polarity. Topological analysis has showed that these oscillations in growth rate are determined, and presumably chaotic. One characteristic of complex chaotic systems is that their dynamics can be persistently modified by a small external perturbation. We show that treatment with a single small dose of the anticancer drug methotrexate causes long-term stable alteration of the oscillatory dynamics of Fao cell proliferation. The oscillations of growth rate are shifted, and their mean level decreased according to a fractal pattern.


Human rights and access to healthcare services for indigenous peoples in Africa.
In September 2015, the United Nations adopted the sustainable development goals (SDGs) to address among others poverty and inequality within and among countries of the world. In particular, the SDGs aim at ameliorating the position of disadvantaged and vulnerable groups in societies. One of the over-arching goals of the SDGs is to ensure that no one is left behind in the realisation of their access to health care. African governments are obligated under international and regional human rights law to ensure access to healthcare services for everyone, including indigenous populations, on a non-discriminatory basis. This requires the governments to adopt appropriate measures that will remove barriers to healthcare services for disadvantaged and marginalised groups such as indigenous peoples.


[Role of ontogenetically different thymocytes in subpopulations of T-cells in releasing a humoral lymphocytic factor].
The activated mouse T-cells release in the culture medium a factor suppressing the ability of stem hemopoietic cells to form hemopoietic colonies in the spleens of lethally irradiated recipients. The factor of stem cell inhibition (FISC) obtained from the mouse thymocytes on the 1st, 7th and 10th day of postnatal life does not differ, by its inhibiting activity, from that obtained from the adult thymocytes, whereas the embryonic thymocytes under similar experimental conditions released FISC with a low inhibiting activity. A study of some physical-chemical and biological properties of FISC has shown that the latter is actively synthesized both by cortical and medullary thymocytes, has no (linear) specificity and resembles, by its characteristics, lymphokins of a wide effect, such as MIF and LT, rather than short-distant mediators, such as suppressor and helper factors.


Lithium carbonate in the treatment of tardive dyskinesia.
Six patients with tardive dyskinesia were treated with lithium carbonate in an open clinical trial. Evaluations using a new tardive dyskinesia rating scale showed statistically significant improvement in dyskinetic movements while the patients received lithium. This improvement was consistently observed in all patients but was relatively small when compared to the amount of pathology present.


Suppression of proline-directed protein kinase F(A) expression inhibits the growth of human chronic myeloid leukaemia cells.
Initial studies revealed that proline-directed protein kinase F(A) (PDPK F(A)) was overexpressed in various cancerous tissues relative to normal controls. However, the functional role of overexpressed PDPK F(A) in cancer remains to be established. In this report, we explore the potential role of PDPK F(A) in leukaemia cell growth by investigating the effects of partial inhibition of this kinase on the malignant phenotype of human chronic myeloid leukaemia cells (K562). Cloning of PDPK F(A) cDNA and its recombinant antisense expression vector and PDPK F(A)-specific antibody were successfully developed. Two stable antisense clones of K562 cells were subcloned which expressed 70% and 45% of PDPK F(A) respectively, compared with control-transfected clone in both immunoprecipitate activity assay and immunoblot analysis. In sharp contrast, these two antisense clones expressed no significant suppression of any other related PDPK family members, indicating the specificity of these two antisense clones. Moreover, these antisense clones proportionally and potentially exhibited cell growth retardation, poor clonogenic growth in soft agar and loss of serum independence. The results demonstrate that specific antisense suppression of PDPK F(A) is sufficient to interfere with the growth of K562 cells, indicating that PDPK F(A) is essential for human chronic myeloid leukaemia cell growth.


Intravitreal bevacizumab for a subfoveal myopic choroidal neovascularization in the first trimester of pregnancy.
To report the clinical course of a highly myopic woman treated by a single intravitreal injection of bevacizumab during the first trimester of pregnancy. Observational case report. A 35-year-old woman affected by pathologic myopia complained of blurred vision in her left eye in the fourth week of pregnancy. A subfoveal myopic choroidal neovascularization (CNV) was diagnosed on the basis of slit-lamp fundus biomicroscopy and fluorescein angiography. After discussing the treatment-related risks, she was administered an intravitreal injection of bevacizumab in her seventh gestational week. During pregnancy, fetal ultrasound and ophthalmic examination were performed monthly. After delivery, the mother and infant were followed quarterly for 12 months. The patient had an uneventful prenatal course and delivered a healthy full-term infant. Significant visual improvement with no documented adverse events related to treatment was obtained. In our experience, a single intravitreal bevacizumab injection administered during the first trimester of pregnancy did not provoke any complications, and was effective in myopic CNV treatment. Further studies are warranted to provide more detailed information about this treatment and the related risks in pregnant women.


Charge density waves and Fermi surface reconstruction in the clean overdoped cuprate superconductor Tl2Ba2CuO6+δ.
Hall effect and quantum oscillation measurements on high temperature cuprate superconductors show that underdoped compositions have small Fermi surface pockets whereas when heavily overdoped, a single much larger pocket is found. The origin of this change in electronic structure has been unclear, but may be related to the high temperature superconductivity. Here we show that the clean overdoped single-layer cuprate Tl2Ba2CuO6+δ (Tl2201) displays CDW order with a remarkably long correlation length ξ ≈ 200 Å which disappears above a hole doping of pCDW ≈ 0.265. We show that the evolution of the electronic properties of Tl2201 as the doping is lowered may be explained by a Fermi surface reconstruction which accompanies the emergence of the CDW below pCDW. Our results demonstrate importance of CDW correlations in understanding the electronic properties of overdoped cuprates.


A submillimetric 3-DOF force sensing instrument with integrated fiber Bragg grating for retinal microsurgery.
Vitreoretinal surgery requires very fine motor control to perform precise manipulation of the delicate tissue in the interior of the eye. Besides physiological hand tremor, fatigue, poor kinesthetic feedback, and patient movement, the absence of force sensing is one of the main technical challenges. Previous two degrees of freedom (DOF) force sensing instruments have demonstrated robust force measuring performance. The main design challenge is to incorporate high sensitivity axial force sensing. This paper reports the development of a submillimetric 3-DOF force sensing pick instrument based on fiber Bragg grating (FBG) sensors. The configuration of the four FBG sensors is arranged to maximize the decoupling between axial and transverse force sensing. A superelastic nitinol flexure is designed to achieve high axial force sensitivity. An automated calibration system was developed for repeatability testing, calibration, and validation. Experimental results demonstrate a FBG sensor repeatability of 1.3 pm. The linear model for calculating the transverse forces provides an accurate global estimate. While the linear model for axial force is only locally accurate within a conical region with a 30° vertex angle, a second-order polynomial model can provide a useful global estimate for axial force. Combining the linear model for transverse forces and nonlinear model for axial force, the 3-DOF force sensing instrument can provide sub-millinewton resolution for axial force and a quarter millinewton for transverse forces. Validation with random samples show the force sensor can provide consistent and accurate measurement of 3-D forces.


Chromatographic characterization of substance P endopeptidase in the rat brain reveals affected enzyme activity following heat stress.
This paper describes a study of substance P endopeptidase (SPE)-like activity in various regions of the brain from male rats subjected to heat stress (HS). The enzyme activity was found to be affected in several brain areas including cerebellum, cerebral cortex, hippocampus, hypothalamus[sol ]thalamus and the spinal cord following HS. Significant increases in SPE activity were observed in, for example, hippocampus and the spinal cord. SPE-containing extracts from hippocampus were pooled and subsequently purified by size exclusion chromatography (using a Superdex 75 HR column) and by anion-exchange chromatography (using Resource Q column). The gel permeation chromatography separated the SPE-like activity into two fractions, one of which was suggested to be identical to neutral endopeptidase owing to its molecular size and inhibitory profile. The other active enzyme fraction behaved in conformity with SPE, previously identified in human cerebrospinal fluid. The activity of the purified fraction of these two enzymes was found to be increased (27%) in HS-treated animals.


Does alcohol affect memory for emotional and non-emotional experiences in different ways?
Alcohol has been shown to have both impairing and facilitating effects on memory, depending on the sequencing of learning and ingestion of the drug. Its effects on memory for emotional material, however, have not been shown reliably. The current experiment sought to investigate the effects of alcohol on later recall of emotional and neutral events experienced before and after alcohol drinking. Using an incidental-learning paradigm, alcohol (0.65 g/kg) or placebo was administered in a double-blind randomized design to 34 participants, between two learning phases in which they viewed and rated positive, negative and neutral images. The drug's effects on memory were assessed in a surprise test of free recall. In addition, impact of alcohol on ratings of mood states, and of valence and arousal that the pictures evoked, was examined. Alcohol facilitated memory for material seen before, and impaired memory for material seen after, its administration. Furthermore, under alcohol, emotional images in the first set were more recalled over neutral than in the second set, indicating a higher retrograde facilitation for emotional than for neutral material. Alcohol improved positive mood states but had no effect on negative mood states. Evaluation of pictures with regard to valence showed an increase of the ratings for the positive and neutral images after alcohol and a decrease after placebo. No drug effects were found for arousal ratings. Whether a picture was likely to be remembered or not (tested only for set 2) was dependent on the intensity of the arousal but not of the valence that the picture evoked in the participants. Pictures that were rated high in arousal were also remembered better, and this effect was irrespective of alcohol or placebo ingestion. These data have shown that alcohol elicits retrograde facilitation and anterograde impairment for emotional materials. Furthermore, these data demonstrate that alcohol selectively facilitates memories for emotional events experienced before administration, and suggest a possible explanation for the reinforcing effects of drinking.


Peripheral blast counts at diagnosis of late isolated bone marrow relapse of childhood acute lymphoblastic leukemia predict response to salvage chemotherapy and outcome. Berlin-Frankfurt-Münster Relapse Study Group.
In newly diagnosed childhood acute lymphoblastic leukemia (ALL), a high tumor burden indicates a poor prognosis, while no such link has been established yet after relapse. The impact of the absolute peripheral blast count (PBC) at the time of relapse on the response to salvage chemotherapy after a late isolated bone marrow (BM) relapse is the subject of this prospective analysis. Since 1983, 260 children with a first isolated BM relapse of ALL that occurred 6 months or later after elective cessation of front-line therapy were enrolled onto four consecutive multicenter trials of the Berlin-Frankfurt-Münster (BFM) Relapse Study Group. All patients received intensive multiagent induction and consolidation chemotherapy for 6 months, followed by maintenance therapy with methotrexate (MTX) and thioguanine for 2 years. Treatment of subclinical meningeal leukemia consisted of high-dose intravenous MTX and intrathecally administered cytostatic drugs, which was augmented by cranial irradiation since 1988. At the time relapse was diagnosed, PBC varied considerably among patients (median, 1,060/microL; range, 0 to 106,800/microL). Achievement of a second complete remission (CR) was not significantly different in children without detectable circulating blasts at relapse (37 of 38) and those with moderate (1 to 9,999/microL) PBC (165 of 171). In contrast, only 42 of 51 children with high PBC (> or = 10,000/microL) achieved a second CR (P = .0015). At a median follow-up time of 40 months, the 10-year event-free survival (EFS) probability was significantly (P = .0001) higher in children without circulating blasts (.64) than in children with moderate PBC (.32) or high PBC (.10). There was a preponderance of boys in the group without detectable circulating blasts, while the three PBC-defined groups did not differ with respect to frontline treatment, age at initial diagnosis, age at relapse, time off therapy, or salvage treatment protocol. On sequential univariate and multivariate analysis, only duration of first remission > or = 48 months was an additional independent indicator of adverse prognosis, while preventive cranial irradiation improved outcome independently of PBC. The absence of blasts on peripheral-blood smears at the time of a first late isolated BM relapse of childhood ALL is associated with a favorable response and prognosis in chemotherapy-treated children, who should be regarded as ineligible for bone marrow transplantation (BMT) unless a second round of chemotherapy has failed to produce a response.


Randomized phase II trial of Onartuzumab in combination with erlotinib in patients with advanced non-small-cell lung cancer.
Increased hepatocyte growth factor/MET signaling is associated with poor prognosis and acquired resistance to epidermal growth factor receptor (EGFR) -targeted drugs in patients with non-small-cell lung cancer (NSCLC). We investigated whether dual inhibition of MET/EGFR results in clinical benefit in patients with NSCLC. Patients with recurrent NSCLC were randomly assigned at a ratio of one to one to receive onartuzumab plus erlotinib or placebo plus erlotinib; crossover was allowed at progression. Tumor tissue was required to assess MET status by immunohistochemistry (IHC). Coprimary end points were progression-free survival (PFS) in the intent-to-treat (ITT) and MET-positive (MET IHC diagnostic positive) populations; additional end points included overall survival (OS), objective response rate, and safety. There was no improvement in PFS or OS in the ITT population (n = 137; PFS hazard ratio [HR], 1.09; P = .69; OS HR, 0.80; P = .34). MET-positive patients (n = 66) treated with erlotinib plus onartuzumab showed improvement in both PFS (HR, .53; P = .04) and OS (HR, .37; P = .002). Conversely, clinical outcomes were worse in MET-negative patients treated with onartuzumab plus erlotinib (n = 62; PFS HR, 1.82; P = .05; OS HR, 1.78; P = .16). MET-positive control patients had worse outcomes versus MET-negative control patients (n = 62; PFS HR, 1.71; P = .06; OS HR, 2.61; P = .004). Incidence of peripheral edema was increased in onartuzumab-treated patients. Onartuzumab plus erlotinib was associated with improved PFS and OS in the MET-positive population. These results combined with the worse outcomes observed in MET-negative patients treated with onartuzumab highlight the importance of diagnostic testing in drug development.


Recommendations for developing urban interventions to promote physical activity: interviews with key informants in Europe.
Although there is growing evidence on what interventions can promote physical activity in urban environments, guidance on how to get these interventions implemented is lacking in a European context. To understand the process of developing urban interventions to promote physical activity, we conducted 13 key informant interviews with professionals working in urban development in five European countries, though some worked in more than one country. Participants described their experiences, challenges and recommendations across six European countries. The main challenges faced were political environments, unsupportive contexts, communication issues, working with other sectors, resource limitations and evaluations. We presented recommendations made by participants which can overcome these challenges when developing urban interventions to promote physical activity. Recommendations included obtaining cross-party political support for a project; working with local communities right from the beginning; involving all stakeholders and encouraging their commitment through identification of common goals; asking the market for solutions when faced with resource constraints, and using existing data to facilitate evaluations.


Vitamin D supplementation and calcium absorption during caloric restriction: a randomized double-blind trial.
Weight loss (WL) is associated with a decrease in calcium absorption and may be one mechanism that induces bone loss with weight reduction. Because vitamin D supplementation has been shown to increase true fractional calcium absorption (TFCA), the goal of this study was to examine the effect of vitamin D during WL or weight maintenance (WM). A randomized, placebo-controlled, double-blind 6-wk study was conducted in 82 postmenopausal women [BMI (in kg/m(2); ±SD): 30.2 ± 3.7] with 25-hydroxyvitamin D [25(OH)D] concentrations <70 nmol/L during either WL or WM. All women were given 10 μg vitamin D(3)/d and 1.2 g Ca/d and either weekly vitamin D(3) (375 μg) or a placebo equivalent to 63 μg (2500 IU)/d and 10 μg (400 IU)/d, respectively. We measured TFCA with the use of dual-stable isotopes, 25(OH)D, parathyroid hormone, estradiol, calcitriol, and urinary calcium at baseline and 6 wk in weight loss and vitamin D(3)-supplementation (WL-D; n = 19), weight maintenance and vitamin D(3)-supplementation (WM-D; n = 20), weight loss and placebo (n = 22), and weight maintenance and placebo (n = 21) groups. WL groups lost 3.8 ± 1.1% of weight with no difference between vitamin D(3) supplementation and the placebo. The rise in serum 25(OH)D was greatest in the WL-D group (19.8 ± 14.5 nmol/L) compared with in WM-D (9.1 ± 10.3 nmol/L) and placebo groups (1.5 ± 10.9 nmol/L). TFCA increased with vitamin D(3) supplementation compared with placebo treatment (P < 0.01) and decreased during WL compared with WM. Serum 25(OH)D or 1,25-dihyroxyvitamin D did not correlate with TFCA. These data show that vitamin D supplementation increases TFCA and that WL decreases TFCA and suggest that, when calcium intake is 1.2 g/d, either 10 or 63 μg vitamin D/d is sufficient to maintain the calcium balance. This trial was registered at clinicaltrials.gov as NCT00473031.


Mechanical model testing of rebreathing potential in infant bedding materials.
Rebreathing of expired air may be a lethal hazard for prone sleeping infants. This paper describes a mechanical model to simulate infant breathing, and examines the effects of bedding on exhaled air retention. Under simulated rebreathing conditions, the model allows the monitoring of raised carbon dioxide (CO2) inside an artificial lung-trachea system. Resulting levels of CO2 (although probably exaggerated in the mechanical model compared with an infant, due to the model's fixed breathing rate and volume) suggest that common bedding materials vary widely in inherent rebreathing potential. In face down tests, maximum airway CO2 ranged from less than 5% on sheets and waterproof mattresses to over 25% on sheepskins, bean bag cushions, and some pillows and comforters. Concentrations of CO2 decreased with increasing head angle of the doll, away from the face down position. Recreations of 29 infant death scenes also showed large CO2 increases on some bedding materials, suggesting these infants could have died while rebreathing.


Effects of DNA heterologies on bacteriophage lambda recombination.
Previous studies of bacteriophage lambda recombination have provided indirect evidence that substantial sequence nonhomologies, such as insertions and deletions, may be included in regions of heteroduplex DNA. However, the direct products of heterology-containing heteroduplex DNA--heterozygous progeny phage--have not been observed. We have constructed a series of small insertion and deletion mutations in the cI gene to examine the possibility that small heterologies might be accommodated in heterozygous progeny phage. Genetic crosses were carried out between lambda cI- Oam29 and lambda cI+ Pam80 under replication-restricted conditions. Recombinant O+P+ progeny were selected on mutL hosts and tested for cI heterozygosity. Heterozygous recombinants were readily observed with crosses involving insertions of 4 to 19 base pairs (bp) in the cI gene. Thus, nonhomologies of at least 19 bp can be accommodated in regions of heteroduplex DNA during lambda recombination. In contrast, when a cI insertion or deletion mutation of 26 bp was present, few of the selected recombinants were heterozygous for cI. Results using a substitution mutation, involving a 26-bp deletion with a 22-bp insertion, suggest that the low recovery of cI heterozygotes containing heterologies of 26 bp or more is due to a failure to encapsulate DNA containing heterologies of 26 bp or more into viable phage particles.


Does severity of intellectual disability affect the nutritional status of intellectually disabled children and adolescents?
Background: Balanced and adequate nutrition is important to improve the quality of life of children with intellectual disability but most of these children are negatively affected by nutritional problems. Objective: This study was conducted to determine the nutritional status and effect of the severity of intellectual disability on nutritional status of children and adolescents with intellectual disabilities. Methods: One hundred twenty-two intellectually disabled children aged 4-18 years from five different special education and rehabilitation centers were included in the study. Their socio-demographic characteristics, body weight, height, body mass index (BMI), mid-upper arm circumference (MUAC), and skinfold thickness were examined, and their three-day food consumption record was taken. Results: Anthropometric scores did not differ significantly according to the severity of intellectual disability. According to evaluations made based on the World Health Organization's 2007 percentile curves, 61.4% of the subjects with mild intellectual disability (MID), 57.1% of those with moderate intellectual disability (MOID), and 53.3% of those with severe intellectual disability (SID) were within the normal BMI range for their age. Conclusion: Rates of malnutrition and shortness in children and adolescents with SID were found to be higher than among children with MID and MOID, though the differences were not statistically significant.


Behavioral changes associated with economic development in the South Pacific: health transition in Vanuatu.
Health patterns are changing in developing countries; as diet and activity patterns change with economic development, chronic disease prevalence increases, which is a characteristic of health transition. The islands of Vanuatu (South Pacific) have varying rates of economic development and provide a natural experimental model of health transition. To characterize behavioral changes associated with modernization. We surveyed 425 children and 559 adults on three islands varying in degree of economic development. We assessed diet (24-h dietary recall), physical activity (mode of transport, work activities, and recreation), substance use, and other behavioral patterns. Spending patterns and access to Western foods followed modernization gradients in our sample, whereas occupational patterns and ownership of technological goods were poor markers of modernization. With increasing economic development, participants consumed more animal proteins and simple carbohydrates. Physical activity levels were high; most participants were active in gardening, and sports were popular, especially in urban areas. However, urban participants spent more time in sedentary recreation. Men's use of alcohol and tobacco increased with economic development, but we observed marked differences in substance use patterns between two rural islands-one with and one without tourism. Economic development in Vanuatu is accompanied by nutrition transition and increased sedentary recreation, although physical activity levels remain high. Differences in substance use patterns between rural islands with and without tourism indicate a need for more research in rural areas. These findings might inform research in other communities in the early stages of health transition.


How we can improve patients' comfort after Milligan-Morgan open haemorrhoidectomy.
To demonstrate the value of Diosmin (flavonidic fraction) in the management of post-haemorhoidectomic symptoms. Eighty-six consecutive patients with grades III and IV acute mixed hemorrhoids admitted to the Anorectal Surgical Department of First Affiliated Hospital, Xinjiang Medical University from April 2009 to April 2010, were enrolled in this study. An observer-blinded, randomized trial was conducted to compare post-haemorhoidectomic symptoms with use of Diosmin flavonidic fraction vs placebo. Eighty-six patients were randomly allocated to receive Diosmin flavonidic fraction 500 mg for 1 wk (n = 43) or placebo (n = 43). The Milligan-Morgan open haemorrhoidectomy was performed by a standardized diathermy excision method. Pain, bleeding, heaviness, pruritus, wound edema and mucosal discharge were observed after surgery. The postoperative symptoms and hospitalization time were recorded. The mean age of the Diosmin group and controls was 53.2 and 51.3 years, respectively. In Diosmin group, haemorrhoid piles were of the third degree in 33 patients and the fourth degree in 10; and in the control group, 29 were of the third degree and 14 were of the fourth degree. There was no statistically significance in age, gender distribution, degree and number of excised haemorrhoid piles, and the mean duration of haemorrhoidal disease between the two groups. There was a statistically significant improvement in pain, heaviness, bleeding, pruritus from baseline to the 8th week after operation (P < 0.05). Patients taking Diosmin had a shorter hospitalization stay after surgery (P < 0.05). There was also a significant improvement on the proctoscopic appearance (P < 0.001). However, there was no statistical difference between the two groups in terms of wound mucosal discharge. Two patients experienced minor bleeding at the 8th week in Diosmin group, and underwent surgery. Diosmin is effective in alleviating postoperational symptoms of haemorrhoids. Therefore, it should be considered for the initial treatment after haemorrhoid surgery. However, further prospective randomized trials are needed to confirm the findings of this study.