A reverse transcriptase PCR technique for the detection and viability assessment of Kluyveromyces marxianus in yoghurt.
A fast and sensitive reverse transcriptase PCR (RT-PCR) method was developed for the detection of viable Kluyveromyces marxianus in yoghurt. Yeast-specific primers were used with the RT-PCR to evaluate the suitability of 18S rRNA as a target for the detection of viable yeasts in pure culture and yoghurt. The RT-PCR assay was able to detect down to 10(2) CFU ml(-1) in yoghurt samples contaminated with viable yeast cells. Application of the RT-PCR method to commercial yoghurt samples demonstrated the utility of this technique for detection of low concentrations of viable yeast cells in naturally contaminated dairy products. The 18S rRNA molecule is an appropriate target for cell viability assessment because of its limited persistence after cell death and the resultant high level of sensitivity of the assay.


Laparoscopic colectomy.
Recent interest in laparoscopic surgery has led to an increasing number of procedures being performed by minimally invasive techniques. Initial experience with laparoscopic cholecystectomy and advances in instrument design and surgical technique have enabled more sophisticated procedures such as laparoscopic colectomy to be performed.


Cryptococcal arthritis and cellulitis.
A middle-aged man with diabetes mellitus and cardiomyopathy developed both cryptococcal arthritis and cellulitis. Unusual aspects included the benign nature of the joint effusion and lack of contiguous osteomyelitis.


Recent Advances on Spinel Zinc Manganate Cathode Materials for Zinc-Ion Batteries.
Zinc metal is abundant in nature, non-toxic, harmless, and cheap. Zinc-ion batteries (ZIBs) have also emerged as the times require, which has attracted scholars' research interest. In the zinc-ion batteries, the cathode material is indispensable. Manganese oxides are widely used in electrode materials because of their various valence states (+2, +3, +4, +7). ZnMn2 O4 (ZMO) is a mixed metal oxide with a spinel structure similar to LiMn2 O4 . Due to the synergistic effect of Zn and Mn, it has the advantages of high theoretical capacity. In recent years, researchers have gradually applied ZnMn2 O4 to zinc ion batteries. In order to obtain high-energy-density zinc ion batteries, it is also very important to match electrolytes with a wide operating voltage window and develop a highly reversible anode. In the first instance, we investigate the research progress of spinel ZnMn2 O4 as a reliable candidate material for zinc ion batteries. Later on, we review the optimization and modification measures of anode and electrolyte to improve the electrochemical properties of spinel ZnMn2 O4 . On this basis, we propose the reasonable research direction and development prospects for this material. It is hoped that there will be a help to researchers in this field.


[Does the use of a polyurethane patch in the CVC dressing further reduce the risk of infection compared with sterile gauze dressing?].
Half of the patients hospitalized in intensive care units have a central venous catheter (CVC) inserted. Management of CVC is not simple and the wrong medication on the insertion site may cause many complications including sepsis. Among the various modes of dressing are transparent polyurethane patches and sterile gauze, and both have both advantages and drawbacks. The aim of this literature review is to compare these two methods in terms of effectiveness in reducing infections. Seven bio-medical databases of the primary and secondary literature were consulted. We considered all articles published in the last five years, in Italian or English, and research that studies purely human subjects. Moreover, the work was limited to all RCT, all systematic reviews and guidelines published on the databases consulted. Only five studies tackled the research question. The results show that CVC-related infections are a frequent problem in intensive care units. This research found two systematic reviews and two randomized controlled trials. None of the studies show any evidence of the type of dressing applied to the CVC. In conclusion, despite consulting several databases, we found no evidence recommending the type of medication to apply.


p160 Myb-binding protein interacts with Prep1 and inhibits its transcriptional activity.
Prep1 is known to interact in vivo with Pbx1 to regulate development and organogenesis. We have identified a novel Prep1-interacting protein, p160 c-Myb binding protein (p160). p160 and Pbx1 compete for Prep1 in vitro, and p160 inhibits Prep1-dependent HoxB2 expression in retinoic acid-treated NT2-D1 cells. The N-terminal physiologically truncated form of p160, p67, binds the sequence 63LFPLL67 in the HR1 domain of Prep1. Mutation of both L63 and L66 impairs the binding of Prep1 to both p160/p67 and Pbx1. The sequences required to bind Prep1 are mainly located in residues 51 to 151. Immunofluorescence colocalization and coimmunoprecipitation of endogenous p160 and Prep1 are induced by ActD, which translocates p160 from the nucleolus to the nucleoplasm. These data therefore show that p160 is a novel regulator of Prep1-Pbx1 transcriptional activity.


Color-tunable fluorescent organogels: columnar self-assembly of pyrene-containing oligo(glutamic acid)s.
New fluorescent gelators containing pyrene moieties and dendritic oligopeptides have been developed. These molecules self-assemble into 1D helical columnar structures that lead to the formation of 3D fibrous random networks. The resulting gel materials show monomer emission of pyrenes because the hydrogen-bonded array of the oligopeptide moieties greatly suppresses the formation of pyrene excimers. In contrast, in the sol states green excimer emission of the pyrenes is observed because of the dissociation of intermolecular hydrogen bonds. This is the first example of the reverse-mode color switching of fluorescence for supramolecular pyrene assemblies.


Study of the thermal diffusion behavior of alkane/benzene mixtures by thermal diffusion forced rayleigh scattering experiments and lattice model calculations.
In this work the thermal diffusion behavior of binary mixtures of linear alkanes (heptane, nonane, undecane, tridecane, pentadecane, heptadecane) in benzene has been investigated by thermal diffusion forced Rayleigh scattering (TDFRS) for a range of concentrations and temperatures. The Soret coefficient ST of the alkane was found to be negative for these n-alkane/benzene mixtures indicating that the alkanes are enriched in the warmer regions of the liquid mixtures. For the compositions investigated in this work, the magnitude of the Soret coefficient decreases with increasing chain length and increasing alkane content of the mixtures. The temperature dependence of the Soret coefficient depends on mixture composition and alkane chain length; the slope of ST versus temperature changes from positive to negative with increasing chain length at intermediate compositions. To study the influence of molecular architecture on the Soret effect, mixtures of branched alkanes (2-methylhexane, 3-methylhexane, 2,3-dimethylpentane, 2,4-dimethylpentane, 2,2,3-trimethylbutane, and 2,2,4-trimethylpentane) in benzene were also investigated. Our results for the Soret coefficients show that the tendency for the alkanes to move to the warmer regions of the fluid decreases with increasing degree of branching. The branching effect is so strong that for 2,2,4-trimethylpentane/benzene mixtures the Soret coefficient changes sign at high alkane content and that equimolar 2,2,3-trimethylbutane/benzene mixtures have positive Soret coefficients in the investigated temperature range. In order to investigate the effect of molecular interactions on thermal diffusion, we adapted a recently developed two-chamber lattice model to n-alkane/benzene mixtures. The model includes the effects of chain-length, compressibility, and orientation dependence of benzene-benzene interactions and yields good qualitative predictions for the Soret effect in n-alkane/benzene mixtures. For the branched isomers, we find some correlations between the moments of inertia of the molecules and the Soret coefficients. PACS numbers: 66.10.Cb, 61.25.Hq.


Harnessing chondroitin sulphate in composite scaffolds to direct progenitor and stem cell function for tissue repair.
The development of bioscaffolds that incorporate chondroitin sulphate (CS) and their applications with progenitor and stem cells in cartilage, bone, cornea, skin, and neural repair are reviewed. CS is a heterogeneous structure due to the organisation of multiple CS disaccharide sulphation motifs, giving rise to a vast range of CS chain structures, and hence the wide range of biological activity. The incorporation of this biological molecule represents a significant advance in bioscaffold design and performance in tissue repair strategies. The intrinsic stem-cell directive properties of CS are covered in the context of tissue development, and the differing CS disaccharide motifs, referred to as the 'glyco-code'. These structural motifs contribute to stem cell proliferation and differentiation in the scaffold environment and improve outcomes in terms of tissue repair or regeneration worthy of future research.


Providing Evidence for Dogma: Risk of Epistaxis After COVID-19 Nasal-Screening Swab.
There is anecdotal evidence SARS-CoV-2 (COVID) RT-PCR screening nasal swabs confer an elevated epistaxis risk. We aimed to assess the association between epistaxis and exposure to a COVID nasal swab. A matched pairs design was used. The study was performed in a single, integrated health care system. All patients who received a single COVID nasal swab at our institution between April 2020 and March 2021 were included. McNemar's test was used to compare rates of epistaxis between the 7 days following the index COVID swab (hazard period), and the 7 days preceding the index COVID swab (control period). Conditional logistic regression was used to evaluate sociodemographic and clinical risk factors for epistaxis. A total of 827,987 participants were included, with 1047 epistaxis encounters. The prevalence of epistaxis during the hazard and control periods were 0.08% and 0.04%, respectively. Swab exposure was associated with 1.92-fold odds of epistaxis during the hazard period (95% confidence interval [1.73, 2.12]). Older age, Asian/Pacific Islander (PI) (compared to white), male sex, hypertension, prior facial trauma, and warfarin or direct-acting oral anticoagulant use were also associated with significantly increased odds of epistaxis (p ≦ 0.01). COVID nasal swabs are associated with increased odds of epistaxis. Physicians should counsel patients, particularly those at the highest risk, including a history of prior facial trauma, anticoagulants/antiplatelets, or hypertension.


Let-7b Regulates Myoblast Proliferation by Inhibiting IGF2BP3 Expression in Dwarf and Normal Chicken.
The sex-linked dwarf chicken is caused by the mutation of growth hormone receptor (GHR) gene and characterized by shorter shanks, lower body weight, smaller muscle fiber diameter and fewer muscle fiber number. However, the precise regulatory pathways that lead to the inhibition of skeletal muscle growth in dwarf chickens still remain unclear. Here we found a let-7b mediated pathway might play important role in the regulation of dwarf chicken skeletal muscle growth. Let-7b has higher expression in the skeletal muscle of dwarf chicken than in normal chicken, and the expression of insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3), which is a translational activator of IGF2, showed opposite expression trend to let-7b. In vitro cellular assays validated that let-7b directly inhibits IGF2BP3 expression through binding to its 3'UTR region, and the protein level but not mRNA level of IGF2 would be reduced in let-7b overexpressed chicken myoblast. Let-7b can inhibit cell proliferation and induce cell cycle arrest in chicken myoblast through let-7b-IGF2BP3-IGF2 signaling pathway. Additionally, let-7b can also regulate skeletal muscle growth through let-7b-GHR-GHR downstream genes pathway, but this pathway is non-existent in dwarf chicken because of the deletion mutation of GHR 3'UTR. Notably, as the loss binding site of GHR for let-7b, let-7b has enhanced its binding and inhibition on IGF2BP3 in dwarf myoblast, suggesting that the miRNA can balance its inhibiting effect through dynamic regulate its binding to target genes. Collectively, these results not only indicate that let-7b can inhibit skeletal muscle growth through let-7b-IGF2BP3-IGF2 signaling pathway, but also show that let-7b regulates myoblast proliferation by inhibiting IGF2BP3 expression in dwarf and normal chickens.


Perfusion computed tomographic measurements of cerebral blood flow variables in live Holstein calves.
OBJECTIVE To measure cerebral blood flow (CBF) and cerebral blood volume (CBV) by means of perfusion CT in clinically normal Holstein calves. ANIMALS 9 Holstein calves. PROCEDURES Each of the 9 calves (mean age, 20.2 days) was anesthetized and received an injection of iodinated contrast medium into the right jugular vein at a rate of 4.0 mL/s. Dynamic CT scanning of the head at a level that included the mandibular condyle was initiated at the time of the contrast medium injection and continued for 100 seconds. A deconvolution method was used as an analytic algorithm. RESULTS Among the 9 calves, the mean ± SD CBF in the cerebral cortex, white matter, and thalamus was 44.3 ± 10.3 mL/100 g/min, 36.1 ± 7.5 mL/100 g/min, and 40.3 ± 7.5 mL/100 g/min, respectively. The CBF in white matter was significantly lower than that in the cerebral cortex or thalamus. The mean CBV in the cerebral cortex, white matter, and thalamus was 6.8 ± 1.0 mL/100 g, 5.2 ± 1.0 mL/100 g, and 5.7 ± 0.7 mL/100 g, respectively. The CBV in the cerebral cortex was significantly higher than that in the white matter or thalamus. CONCLUSIONS AND CLINICAL RELEVANCE Measurement of CBF and CBV in clinically normal calves by means of perfusion CT was feasible. The data obtained may be useful as baseline values for use in future research or for comparison with findings from calves with CNS diseases. Investigations to determine the lower limit of blood flow at which brain function can still be restored are warranted.


Cellular 5-hydroxylmethylcytosine content determines tumorigenic potential and prognosis of pancreatic ductal adenocarcinoma.
We stratified pancreatic ductal adenocarcinoma (PDAC) based on the tumorigenic properties of cancer cells, and aimed to identify clinically useful immunohistochemical (IHC) markers with mechanistic insights. The tumorigenic properties of PDACs were determined using patient-derived xenograft in NOD/SCID/IL2Rγnull mice. The success of tumor engraftment was significantly correlated to poor survival, and its predictive values were superior to clinicopathological parameters. To search IHC-based biomarkers as surrogate for high tumorigenicity with prognostic values, 11 candidates of potentially clinical useful prognostic markers were selected. Among them, 5hmC content of the cancer cells was validated. Elevated 5hmC content positively correlated with in vivo tumorigenicity and poor prognosis in both primary and validation cohorts. Enrichment of cancer-associated 5hmC in CDX2 and FOXA1 lineage-specific transcriptional factor genes further pointed out the potential role of 5hmC in modulating cellular differentiation to enhance tumor malignancy during PDAC progression. Tumor-associated 5hmC content defined a subpopulation of PDAC with high lineage plasticity and tumorigenic potential, and was a prognostic IHC marker that provided a clinical basis for future management of PDAC.


Grieving characteristics after spontaneous abortion: a management approach.
Twenty-two women who experienced a spontaneous abortion were treated during a 15-month period. All patients were seen for counseling sessions immediately after the spontaneous abortion. The initial counseling was followed by patient contacts and by a second counseling session four to six weeks later. All 22 women demonstrated intense emotional reactions to their pregnancy loss, characterized by the seven stages of grief. Guilt was the state that appeared to be the most difficult for the women and their spouses to resolve without help. Counseling sessions are considered an essential part of the total obstetric care for patients who experience a pregnancy loss.


Accumulation of caspase-3 messenger ribonucleic acid and induction of caspase activity in the ovine corpus luteum following prostaglandin F2alpha treatment in vivo.
Caspase-3, a vertebrate homologue of the protein encoded by the Caenorhabditis elegans cell death gene, ced-3, induces apoptosis when overexpressed in eukaryotic cells. Since apoptosis occurs during corpus luteum (CL) regression in many species, including the ewe, these studies were conducted to 1) isolate a cDNA encoding ovine caspase-3, 2) measure steady state amounts of caspase-3 mRNA in the CL during luteolysis induced by prostaglandin F2alpha (PGF2alpha) and during the time of maternal recognition of pregnancy, and 3) measure changes in caspase activity during PGF2alpha-initiated luteal regression. Oligonucleotide primers corresponding to a human caspase-3 cDNA sequence were combined with total RNA from ovine CL in a reverse transcription-polymerase chain reaction-based procedure to amplify a 640-base pair partial cDNA with a nucleotide sequence 86% and 81% identical to the human and rat caspase-3 cDNAs, respectively. CL were collected from ewes at 0, 12, or 24 h after treatment with PGF2alpha on Day 10 of the estrous cycle and from nonpregnant and pregnant ewes on Day 12 or Day 14 of the cycle. Northern blot analysis of total cellular RNA from ovine CL and a radiolabeled ovine caspase-3 cRNA probe indicated the presence of a single mRNA transcript of approximately 2.5 kilobases. Levels of caspase-3 mRNA were approximately 3-fold higher (p < 0.05) in CL at 12 h and 24 h after PGF2alpha in comparison to those levels measured in matched CL from untreated ewes. There were no differences (p > 0.05) in amounts of caspase-3 mRNA in CL on Day 12 or Day 14 of the estrous cycle compared to Day 12 or Day 14 of pregnancy, respectively. Caspase activity in CL (measured by the ability of CL lysates to cleave an artificial caspase substrate) was also significantly (p < 0.05) increased in CL collected after treatment with PGF2alpha compared to CL collected from nontreated ewes. We conclude that physiological cell death during PGF2alpha-induced luteal regression in the ewe is mediated, at least in part, via increased expression and activity of the caspase family of pro-apoptotic proteases.


Role of apoptosis and mitosis during human eye development.
The spatial and temporal distribution as well as ultrastructural and biochemical characteristics of apoptotic and mitotic cells during human eye development were investigated in 14 human conceptuses of 4-9 postovulatory weeks, using electron and light microscopy. In the 5th developmental week, apoptotic and mitotic cells were found in the neuroepithelium of the optic cup and stalk, being the most numerous at the borderline between the two layers of the optic cup, and at the place of transition of the optic cup into stalk. They were also found at the region of detachment of the lens pit from the surface ectoderm. In the later developmental stages (the 6th-the 9th week), apoptotic and mitotic cells were observed in the neural retina and the anterior lens epithelium. Throughout all stages examined, mitotic cells were found exclusively adjacent to the lumen either of the intraretinal space or the optic stalk ventricle, or were restricted to the superficial epithelial layer of the lens primordium. Unlike mitotic cells, apoptotic cells occurred throughout the whole width both of the neuroepithelium and the surface epithelium. Ultrastructurally, apoptotic cells were characterised by round- or crescent-shaped condensations of chromatin near the nuclear membrane, while in the more advanced stages of apoptosis by apoptotic bodies. The distribution of caspase-3-positive cells coincided with the location of apoptotic cells described by morphological techniques indicating that the caspase-3-dependent apoptotic pathway operates during the all stages of human eye development. The location of cells positive for anti-apoptotic bcl-2 protein was in accordance with the regions of eye with high mitotic activity, confirming the role of bcl-2 in protecting cells from apoptosis. In the earliest stage of eye development, apoptosis and mitosis might be associated with the sculpturing of the walls of optic cup and stalk, while high mitotic activity along the intraretinal space and optic stalk ventricle indicates its role in the gradual luminal closure. These processes also participate in the detachment of the lens pit epithelium from the surface ectoderm as well as in further closure of the lens vesicle. Later on, both processes seem to be involved in the neural retina differentiation, lens morphogenesis and secondary lens fibre differentiation.


The effects of minute direct electrical currents on cultured chick embryo trigeminal ganglia.
The effects of low levels of electric current were determined on organ cultures of 6- to 19-day-old chick embryo trigeminal ganglia. Current levels ranged from 0.00115 to 11.5 nA/mm2; the time of electrical treatment varied from 2 h to 96 h. Low levels of electricity were found to have at least three major effects on this system of mixed cellular types: (1) Outgrowth of nerve fibers from the explant was enriched. This resulted in a greater number of fibers which were longer and more highly branched than those in control cultures. (2) Survival of neurons within the original explanted ganglion was enchanced by treatment with electricity. The presence of healthy neurons was found in 93.1% of the treated cultures and in 53.5% of untreated cultures. (3) Neurons, fibers and non-neural cells were stimulated to grow in the direction of the cathode. The rate of cathodal migration was calculated to be 0.1 mm/h (2.4 mm/day) in an explant from 12-day-old embryo. No differences were observed between surviving treated and control cultures in histochemical tests for acetycholinesterase. A similarity between the action of low levels of electrical current and nerve growth factor (NGF) is suggested.


Protein kinase c-beta-like immunoreactivity in the developing and adult rat adrenal gland.
Protein kinase c-beta-like immunoreactivity was studied in the adrenal gland of adult rats and at different pre- and postnatal stages of development (E17-P21) with an antibody specific to both the beta 1 and beta 2 subtypes of the kinase. In the adult rat adrenal gland, the immunoreactivity was seen in numerous nerve fibres in the adrenal medulla both in bundles and individually forming occasionally dense networks around chromaffin cell groups. Several protein kinase c-beta-immunoreactive fibres were also observed transversing the adrenal cortex towards the medulla. No remaining immunoreactive fibres two weeks after transection of the splanchnic nerve could be seen; nor was any immunoreactivity observed in the chromaffin cells of the adrenal medulla or in the cortical cells, but some faintly immunoreactive ganglion cells were detected in the adrenal medulla. The amount and distribution of protein kinase c-beta-like immunoreactivity in the fetal and developing adrenals was very similar to that seen in the adrenal glands of adult rats. On the basis of its localization, the beta-subtype of protein kinase c does not appear to be directly involved in the release of catecholamines from the adrenal medulla, but it might have a role in the regulation of neurotransmitter release from preganglionic cholinergic neurons.


Defining the biology of intrahepatic cholangiocarcinoma: molecular pathways and early detection of precursor lesions.
Intrahepatic cholangiocarcinoma (ICC) is a rare malignant tumor of the biliary tract with growing incidence and dismal prognosis. It is responsible for 10-20% of primary liver cancer worldwide, but early diagnosis is still a challenge and few treatment options are available. Aim of this review is to summarize the current knowledge about biological features and arising molecular patterns of this disease. The identification of emerging biomarkers and early detection of precursor lesions shall play a key role in the perspective of future tailored targeted therapies.


Nutrition at school: preparing for the future. The Thirteenth Annual Nutrition Symposium.
Two of the best ways to improve the quality of childhood nutrition are (a) more collaboration at the national, State, and local levels and (b) adoption of innovative and multimedia learning methods, according to the leaders of nutrition education. These themes were discussed at the 13th Annual Nutrition Symposium, which was held March 9, 1994, in Washington, DC. In recognition of National Nutrition Month, a collaborative effort of the Public Health Service's Office of Disease Prevention and Health Promotion and the Centers for Disease Control and Prevention, the meeting was attended by more than 300 public and private sector nutrition educators and public health professionals. Their assignment was to analyze school-based nutrition education programs and the research being conducted on nutrition. Keynote speaker Surgeon General M. Joycelyn Elders, MD, issued the challenge for all Federal and State agencies to work with schools and nutrition education professionals to overcome limited resources and children's current eating habits to improve the nutritional status of children. Responding to that challenge, speakers from the Department of Health and Human Services, the agency sponsoring the meeting, the Department of Agriculture, the Department of Education, as well as from the Congress, business, and public schools addressed several initiatives.


International variation in vitamin prescription and association with mortality in the Dialysis Outcomes and Practice Patterns Study (DOPPS).
The prevalence of water-soluble vitamin use among hemodialysis (HD) patients and whether mortality and hospitalization are associated with water-soluble vitamin use by HD patients have not previously been reported. The present study investigates patterns of water-soluble vitamin use among HD patients in the Dialysis Outcomes and Practice Patterns Study (DOPPS) I and evaluates outcomes associated with vitamin use. The study sample came from the DOPPS I, a prospective observational study of adult HD patients (N = 16,345) randomly selected from 308 representative dialysis facilities in France, Germany, Italy, Japan, Spain, the United Kingdom, and the United States. Time-dependent Cox regression models were used to assess relative risk (RR) for mortality and hospitalization for patients administered water-soluble vitamins versus those not administered water-soluble vitamins. There was large variation by region in the percentage of patients administered water-soluble vitamins: Europe ranged from a low of 3.7% in the United Kingdom to a high of 37.9% in Spain; 5.6% in Japan; and 71.9% in the United States. Patient use of water-soluble vitamins was associated with a substantially and significantly lower risk for mortality (RR, 0.84; P = 0.001). Lower RR for facility-level mortality also was associated with greater water-soluble vitamin use (RR, 0.98; P = 0.05 per 10% more patients administered water-soluble vitamins at the facility). Although only a randomized trial could prove that water-soluble vitamins improve outcomes, use of water-soluble vitamins is a minimal-risk practice pattern associated with improved outcomes in this prospective observational study.


Persistent ectopic pregnancy--a case report.
The following case report describes a case of persistent ectopic pregnancy following laparoscopic segmental salpingectomy. The patient had an unusual presentation of acute abdomen and focal haemorrhage from omental implantation of the trophoblastic tissue.


Neural correlates of tactile hardness intensity perception during active grasping.
While tactile sensation plays an essential role in interactions with the surroundings, relatively little is known about the neural processes involved in the perception of tactile information. In particular, it remains unclear how different intensities of tactile hardness are represented in the human brain during object manipulation. This study aims to investigate neural responses to various levels of tactile hardness using functional magnetic resonance imaging while people grasp objects to perceive hardness intensity. We used four items with different hardness levels but otherwise identical in shape and texture. A total of Twenty-five healthy volunteers participated in this study. Before scanning, participants performed a behavioral task in which they received a pair of stimuli and they were to report the perceived difference of hardness between them. During scanning, without any visual information, they were randomly given one of the four objects and asked to grasp it. We found significant blood oxygen-level-dependent (BOLD) responses in the posterior insula in the right hemisphere (rpIns) and the right posterior lobe of the cerebellum (rpCerebellum), which parametrically tracked hardness intensity. These responses were supported by BOLD signal changes in the rpCerebellum and rpIns correlating with tactile hardness intensity. Multidimensional scaling analysis showed similar representations of hardness intensity among physical, perceptual, and neural information. Our findings demonstrate the engagement of the rpCerebellum and rpIns in perceiving tactile hardness intensity during active object manipulation.


Lysosomal dysfunction-induced autophagic stress in diabetic kidney disease.
The catabolic process that delivers cytoplasmic constituents to the lysosome for degradation, known as autophagy, is thought to act as a cytoprotective mechanism in response to stress or as a pathogenic process contributing towards cell death. Animal and human studies have shown that autophagy is substantially dysregulated in renal cells in diabetes, suggesting that activating autophagy could be a therapeutic intervention. However, under prolonged hyperglycaemia with impaired lysosome function, increased autophagy induction that exceeds the degradative capacity in cells could contribute toward autophagic stress or even the stagnation of autophagy, leading to renal cytotoxicity. Since lysosomal function is likely key to linking the dual cytoprotective and cytotoxic actions of autophagy, it is important to develop novel pharmacological agents that improve lysosomal function and restore autophagic flux. In this review, we first provide an overview of the autophagic-lysosomal pathway, particularly focusing on stages of lysosomal degradation during autophagy. Then, we discuss the role of adaptive autophagy and autophagic stress based on lysosomal function. More importantly, we focus on the role of autophagic stress induced by lysosomal dysfunction according to the pathogenic factors (including high glucose, advanced glycation end products (AGEs), urinary protein, excessive reactive oxygen species (ROS) and lipid overload) in diabetic kidney disease (DKD), respectively. Finally, therapeutic possibilities aimed at lysosomal restoration in DKD are introduced.


Quantifying Neonicotinoid Insecticide Residues Escaping during Maize Planting with Vacuum Planters.
Neonicotinoid residues escaping in vacuum-planter exhaust during maize planting were measured in 25 fields in southwestern Ontario in 2013-2014 using filter bags to collect planter exhaust dust and horizontal and vertical sticky traps to collect planter operation-generated dust. Atrazine residues were used to differentiate between neonicotinoid residues originating from seed or from disturbed soil. Recovery rates of seed-applied neonicotinoids in exhaust were 0.014 and 0.365% in 2013 and 2014, respectively, calculated on the basis of neonicotinoid concentrations in preplant soil and seed application rates. Neonicotinoid exhaust emission rates were 0.0036 and 0.1104 g/ha for 2013 and 2014, respectively, with 99.9472 and 99.7820% originating from treated seed in 2013 and 2014, respectively, calculated on the basis of the atrazine marker. Rates of recovery of seed-applied neonicotinoid residues by exhaust filter bags were 0.015 and 0.437% for 2013 and 2014, respectively. Neonicotinoid residues captured on horizontal and vertical traps were 1.10 ng/cm2 (0.1104 g/ha) and 1.45 ng/cm2 (0.0029 g/ha), respectively, with 92.31 and 93.03% originating from treated seed, respectively, representing 0.3896% of the original active ingredient applied to the seed planted. Exposure to pollinators can be best reduced by strategies to keep active ingredient on the seed, below the soil surface, and in the field where applied.


Comparative Evaluation of Shear Bond Strength of Luting Cements to Different Core Buildup Materials in Lactic Acid Buffer Solution.
The core buildup material is used to restore badly broken down tooth to provide better retention for fixed restorations. The shear bond strength of a luting agent to core buildup is one of the crucial factors in the success of the cast restoration. The aim of this invitro study was to evaluate and compare the shear bond strength of luting cements with different core buildup materials in lactic acid buffer solution. Two luting cements {Traditional Glass Ionomer luting cement (GIC) and Resin Modified Glass Ionomer luting cement (RMGIC)} and five core buildup materials {Silver Amalgam, Glass ionomer (GI), Glass Ionomer Silver Reinforced (GI Silver reinforced), Composite Resin and Resin Modified Glass Ionomer(RMGIC)} were selected for this study. Total 100 specimens were prepared with 20 specimens for each core buildup material using a stainless steel split metal die. Out of these 20 specimens, 10 specimens were bonded with each luting cement. All the bonded specimens were stored at 37(0)c in a 0.01M lactic acid buffer solution at a pH of 4 for 7days. Shear bond strength was determined using a Universal Testing Machine at a cross head speed of 0.5mm/min. The peak load at fracture was recorded and shear bond strength was calculated. The data was statistically analysed using Two-way ANOVA followed by HOLM-SIDAK method for pair wise comparison at significance level of p<0.05. Two-Way ANOVA showed significant differences in bond strength of the luting cements (p<0.05) and core materials (p<0.05) and the interactions (p<0.05). Pairwise comparison of luting cements by HOLM-SIDAK test, showed that the RMGIC luting cement had higher shear bond strength values than Traditional GIC luting cement for all the core buildup materials. RMGIC core material showed higher bond strength values followed by Composite resin, GI silver reinforced, GI and silver amalgam core materials for both the luting agents. Shear bond strength of RMGIC luting cement was significantly higher than traditional GIC luting cement for all core buildup materials except, for silver amalgam core buildup material. RMGIC core material showed highest shear bond strength values followed by Composite resin, GI Silver Reinforced, GI and Silver Amalgam core materials irrespective of luting cements.


Specific antigenic relationships between the RNA-dependent DNA polymerases of avian reticuloendotheliosis viruses and mammalian type C retroviruses.
Immunoglobulin G directed against the DNA polymerase of Rauscher murine leukemia virus (R-MuLV) could bind to 125I-labeled DNA polymerase of spleen necrosis virus (SNV), a member of the reticuloendotheliosis virus (REV) species. Competition radioimmunoassays showed the specificity of this cross-reaction. The antigenic determinants common to SNV and R-MuLV DNA polymerases were shared completely by the DNA polymerases of Gross MuLV, Moloney MuLV, RD 114 virus, REV-T, and duck infectious anemia virus. Baboon endogenous virus and chicken syncytial virus competed partially for antibodies directed against the common antigenic determinants of SNV and R-MuLV DNA polymerases. DNA polymerases of avian leukosis viruses, pheasant viruses, and mammalian type B and D retroviruses and particles with RNA-dependent DNA polymerase activity from the allantoic fluid of normal chicken eggs and from the medium of a goose cell culture did not compete for the antibodies directed against the common antigenic determinants of SNV and R-MuLV DNA polymerases. We also present data about a factor in normal mammalian immunoglobulin G that specifically inhibits the DNA polymerases of REV and mammalian type C retrovirus DNA polymerases.


Affinity purification of influenza virus ribonucleoprotein complexes from the chromatin of infected cells.
Like all negative-strand RNA viruses, the genome of influenza viruses is packaged in the form of viral ribonucleoprotein complexes (vRNP), in which the single-stranded genome is encapsidated by the nucleoprotein (NP), and associated with the trimeric polymerase complex consisting of the PA, PB1, and PB2 subunits. However, in contrast to most RNA viruses, influenza viruses perform viral RNA synthesis in the nuclei of infected cells. Interestingly, viral mRNA synthesis uses cellular pre-mRNAs as primers, and it has been proposed that this process takes place on chromatin. Interactions between the viral polymerase and the host RNA polymerase II, as well as between NP and host nucleosomes have also been characterized. Recently, the generation of recombinant influenza viruses encoding a One-Strep-Tag genetically fused to the C-terminus of the PB2 subunit of the viral polymerase (rWSN-PB2-Strep) has been described. These recombinant viruses allow the purification of PB2-containing complexes, including vRNPs, from infected cells. To obtain purified vRNPs, cell cultures are infected, and vRNPs are affinity purified from lysates derived from these cells. However, the lysis procedures used to date have been based on one-step detergent lysis, which, despite the presence of a general nuclease, often extract chromatin-bound material only inefficiently. Our preliminary work suggested that a large portion of nuclear vRNPs were not extracted during traditional cell lysis, and therefore could not be affinity purified. To increase this extraction efficiency, and to separate chromatin-bound from non-chromatin-bound nuclear vRNPs, we adapted a step-wise subcellular extraction protocol to influenza virus-infected cells. Briefly, this procedure first separates the nuclei from the cell and then extracts soluble nuclear proteins (here termed the "nucleoplasmic" fraction). The remaining insoluble nuclear material is then digested with Benzonase, an unspecific DNA/RNA nuclease, followed by two salt extraction steps: first using 150 mM NaCl (termed "ch150"), then 500 mM NaCl ("ch500") (Fig. 1). These salt extraction steps were chosen based on our observation that 500 mM NaCl was sufficient to solubilize over 85% of nuclear vRNPs yet still allow binding of tagged vRNPs to the affinity matrix. After subcellular fractionation of infected cells, it is possible to affinity purify PB2-tagged vRNPs from each individual fraction and analyze their protein and RNA components using Western Blot and primer extension, respectively. Recently, we utilized this method to discover that vRNP export complexes form during late points after infection on the chromatin fraction extracted with 500 mM NaCl (ch500).


Pulp chamber temperature increase from curing light units: an in vitro study.
The purpose of this study was to compare temperature rises in the pulp chamber induced by halogen, plasma arc, and conventional light-emitting diode (LED) curing units with that induced via a new generation LED-curing unit (VALO) in extra power mode. A Class I cavity was prepared on the occlusal surface of 80 extracted caries- free mandibular third molars, which were filled with a microhybrid composite. A thermocouple wire was inserted into the pulp chamber of each tooth to measure temperature changes. The greatest temperature increases were observed during polymerization of composite resin with a halogen curing unit (3.2 degrees Celsius), followed by plasma arc curing (2.07 degrees Celsius) and VALO curing (1.44 degrees Celsius); the lowest temperature rise was with conventional LED curing (1.01 degrees Celsius). There were no statistically significant differences between conventional LED and VALO curing in extra power mode regarding pulp chamber temperature increases when polymerizing composite resin.


Intracisternal 5,7-dihydroxytryptamine lesions in neonatal and adult rats: comparison of response to 5-hydroxytryptophan.
There have been few previous studies of the functional significance of 5,7-dihydroxytryptamine (5,7-DHT) lesions made in neonatal rats. To study the role of serotonin (5-HT) in recovery of function, rat pups and adult rats were injected intracisternally with 5,7-DHT or saline and challenged acutely with the 5-HT precursor 5-hydroxytryptophan (5-HTP) 4 weeks later as a test of behavioral supersensitivity. Compared to 5,7-DHT lesions in adults, neonatal lesions induced significantly greater 5-HT depletions in brainstem, but 5-HT depletions in other regions were not significantly different in the two groups. Rats with early 5,7-DHT lesions displayed supersensitive behavioral responses to 5-HTP, consisting of all the component myoclonic-serotonergic behaviors seen in rats with 5,7-DHT lesions made as adults. However, there was significantly less 5-HTP-evoked head weaving, truncal myoclonus and shaking behavior in rats treated with 5,7-DHT as neonates. Body weight was reduced both in rats with early and late 5,7-DHT lesions, but reduction persisted in rats with early lesions. These data indicate overall similarity with some differences between neurochemical and behavioral effects of early and late 5,7-DHT lesions made by the intracisternal route. They suggest that recovery mechanisms did not occur or failed to reverse the neurochemical or behavioral consequences of early 5,7-DHT lesions.


Splenic artery embolization: An alternative approach in a critically ill patient with autoimmune hemolytic anemia.
Assessment of general health status and hematological parameters usually precedes the use of invasive diagnostic and therapeutic procedures in critically ill patients. Angiography can be effective and safe as a substitute for major surgical procedures, or as a bridging therapy in such cases. We present a critically ill patient with hemolytic anemia that underwent splenic artery embolization as a bridging therapy. We aimed to emphasize that minimally invasive approaches and multidisciplinary care can be utilized in the treatment of critically ill patients with accompanying hematological disease.


In vivo and in vitro effects of cholecystokinin octapeptide on the release of growth hormone in rats.
The effect of cholecystokinin octapeptide (CCK-8) on the release of growth hormone (GH) in rats was studied in vivo and in vitro. Intravenous injection of 5 micrograms/100 g BW of CCK-8 resulted in significant increase in the plasma GH level after 10 and 20 min. CCK-8 at concentrations of 10(-11)M to 10(-7)M also caused dose-dependent stimulation of GH release from dispersed cells of rat anterior pituitary. On the other hand, somatostatin (SRIF) inhibited GH release from dispersed cells of rat anterior pituitary in a dose-related manner at concentrations of 10(-7)M to 10(-9)M. Release of GH from the cells was increased by addition of K+ at high concentration (50 mM) in a Ca++-dependent manner. Addition of 10(-3)M verapamil to the incubation medium inhibited CCK-8-induced GH release from the cells. Addition of SRIF (10(-7)M) to the incubation medium inhibited GH release from the cells induced by CCK-8 or high K+ (50 mM). These results indicate that CCK-8 acts directly on the anterior pituitary cells to stimulate GH release and that calcium ion is involved in the mechanism of this effect.


Seroepidemiology of hepatitis A virus infection in southern Taiwan.
Hepatitis A virus infection was common in Taiwan. Most of the Taiwan data on the prevalence of Hepatitis A virus antibody (anti-HAV), however have derived from the Taipei area and few reports are available on the age-specific prevalence in other parts of Taiwan. Sera of 738 healthy inhabitants in Tainan District, a rural southern Taiwan, were collected from January to December, 1992, and screened the anti-HAV IgG by radioimmunoassay. The prevalence rate of anti-HAV among infants was 64.6%, which decreased to 3.3% in preschool and school-age children up to 12 years old. The prevalence rate of anti-HAV antibodies was over 92% in adult subjects beyond 30 years of age, and 82.4% among 34 pregnant women. Compared to the data obtained from the children living in Taipei City, our results showed that the prevalence rate of anti-HAV in age group 1 to 10 years in Tainan area was higher than Taipei City (2.3-3.7% vs. 0-0.5%, 0.03 < P < 0.09). The data also indicated that the age of primary infection in children has extended to an older age group. The rarity of HAV infection in Taiwan has created a large growing population of susceptible young adults. Mass vaccination for this population should be considered in the preventive program of public health.


[Influence of continuous high-volume hemofiltration on IRAK-4 protein expression in severe acute pancreatitis].
To investigate the influence of continuous high-volume hemofiltration (CHVHF) on interleukin 1 receptor-associated kinase-4 (IRAK-4) and tumor necrosis factor-alpha (TNF-alpha) levels in patients with severe acute pancreatitis (SAP). Forty-one patients with SAP were randomly divided into two groups to receive treatment with CHVHF plus conventional therapy (21 patients) and conventional therapy only (20 patients). Venous blood samples were taken before and 12, 24, and 72 h after the treatment for evaluation of APACHE II scores. The mRNA and protein levels of IRAK-4 in the monocytes were determined by real-time PCR and Western blotting, respectively, and serum TNF-alpha levels was detected using enzyme-linked immunosorbent assay (ELISA). Among the 21 patients receiving CHVHF, 18 survived and 3 died, and in the conventional therapy group, death occurred in 5 cases. In the surviving patients of CHVHF group, the APACHE II scores, IRAK-4 mRNA and protein levels and TNF-alpha levels were all significantly lowered after the treatment, and these indices were also significantly lower than those in the conventional group after treatment (P<0.05). CHVHF is effective in reducing monocyte IRAK-4 levels and serum TNF-alpha level in SPA patients, and thus alleviates the symptoms and improves the prognosis of SAP, possibly by reducing the level of the activators that induce monocyte activation via the Toll-like receptor.


Simulating Signal Aberration and Ranging Error for Ultrasonic Indoor Positioning.
Increasing efforts toward the development of positioning techniques testify the growing interest for indoor position-based applications and services. Many applications require accurate indoor positioning or tracking of people and assets, and some market sectors are starting a rapid growth of products based on these technologies. Ultrasonic systems have already been demonstrating their effectiveness and to possess the desired positioning accuracy and refresh rates. In this work, it is shown that a typical signal used in ultrasonic positioning systems to estimate the range between the target and reference points-namely, the linear chirp-due to the effects of acoustic diffraction, in some cases, undergoes a shape aberration, depending on the shape and size of the transducer and on the angle under which the transducer is seen by the receiver. In the presence of such signal shape aberrations, even one of the most robust ranging techniques, which is based on cross-correlation, provides results affected by a much greater error than expected. Numerical simulations are carried out for a typical ultrasonic chirp, ultrasonic emitter, and range technique based on cross-correlation and for a typical office room, obtained using the academic acoustic simulation software Field II. Spatial distributions of the ranging error are provided, clearly showing the favorable low error regions. The work demonstrates that particular attention must be paid to the design of the acoustic section of the ultrasonic positioning systems, considering both the shape and size of the ultrasonic emitters and the shape of the acoustic signal used.


The use of clinical databases in disease outcomes research: Is the ethics of IRB review keeping up?
There is a perceived tension in research ethics between protecting the interests of participants and promoting good research as a societal good. The challenge of balancing the potential benefits of large clinical databases for disease outcomes research while protecting patients' privacy and confidentiality is an example of this dynamic. What is new about this tension in the context of "data warehousing" is the conflation of many differing interpretations of relevant ethics terminology, the proliferation of different kinds of databases, as well as the growth of research on a global level without the requisite harmonization of regulatory frameworks. The evolution of electronic medical records, the blurring of lines between clinical care and research in some rare orphan diseases, the growing trend to advocate for patient-centered research, and the advent of "open science" to facilitate global research initiatives have also contributed to challenging the existing norms for degrees of consent to this kind of research.


TOPAS-imaging: extensions to the TOPAS simulation toolkit for medical imaging systems.
Objective. The TOol for PArticle Simulation (TOPAS) is a Geant4-based Monte Carlo software application that has been used for both research and clinical studies in medical physics. So far, most users of TOPAS have focused on radiotherapy-related studies, such as modeling radiation therapy delivery systems or patient dose calculation. Here, we present the first set of TOPAS extensions to make it easier for TOPAS users to model medical imaging systems.Approach. We used the extension system of TOPAS to implement pre-built, user-configurable geometry components such as detectors (e.g. flat-panel and multi-planar detectors) for various imaging modalities and pre-built, user-configurable scorers for medical imaging systems (e.g. digitizer chain).Main results. We developed a flexible set of extensions that can be adapted to solve research questions for a variety of imaging modalities. We then utilized these extensions to model specific examples of cone-beam CT (CBCT), positron emission tomography (PET), and prompt gamma (PG) systems. The first of these new geometry components, the FlatImager, was used to model example CBCT and PG systems. Detected signals were accumulated in each detector pixel to obtain the intensity of x-rays penetrating objects or prompt gammas from proton-nuclear interaction. The second of these new geometry components, the RingImager, was used to model an example PET system. Positron-electron annihilation signals were recorded in crystals of the RingImager and coincidences were detected. The simulated data were processed using corresponding post-processing algorithms for each modality and obtained results in good agreement with the expected true signals or experimental measurement.Significance. The newly developed extension is a first step to making it easier for TOPAS users to build and simulate medical imaging systems. Together with existing TOPAS tools, this extension can help integrate medical imaging systems with radiotherapy simulations for image-guided radiotherapy.


Identifying students at risk for mental health problems.
Almost one-quarter of school-age children in the United States meet criteria for serious mental illness. School nurses can identify children at risk or suffering from undetected mental illness through observation, consultation with teachers and parents, interview techniques, and simple written tools. Valid and reliable tools that are in the public domain and can be accessed via the Internet are included. Referral to mental health providers within the school system or community is necessary for students at risk.


Preparation of oriented and aligned H(2) and HD by stimulated Raman pumping.
Stimulated Raman pumping has been used to prepare oriented and aligned samples of H(2)(nu=1,J=1,2,3) and HD(nu=1,J=2) under collision-free conditions using the (1,0) S(0), S(1), Q(1), Q(2), and O(3) lines. The M-sublevel anisotropies were interrogated by polarized [2+1] resonance-enhanced multiphoton ionization via the (0,1) O(2), O(3), and S(1) lines of the E,F (1)Sigma(g) (+)-X (1)Sigma(g) (+) system. The optical excitation schemes employed in this study generate highly oriented and aligned molecular ensembles. We show that the H(2)(nu=1,J=2,M=0) and H(2)(nu=1,J=2,M=2) samples retain their initial polarization for greater than 100 ns and are therefore suitable candidates for targets or projectiles in future scattering experiments.


From club drug to orphan drug: sodium oxybate (Xyrem) for the treatment of cataplexy.
Narcolepsy, a rare disease with a prevalence of 0.05% in the general population, affects an estimated 140,000 patients in the United States. Patients have been able to lead fuller personal and professional lives since the Food and Drug Administration approved sodium oxybate (Xyrem) in 2002 for treatment of cataplexy in patients with narcolepsy. Previously, gamma-hydroxybutyrate (GHB), the active ingredient of sodium oxybate, had been a substance of abuse, most notoriously as a date-rape drug. Public Law 106-172, the date-rape prohibition act enacted in 2000, was modified to allow the drug to be legally administered for medical purposes. Because of the apprehension regarding the risk of possible drug diversion after the approval of sodium oxybate and concerns about safety, the Xyrem Risk Management Program was created. This program has been successful in satisfying the needs of patients and physicians while ensuring responsible distribution of the drug.


[Contribution to nursing care for patients with mitral valve disease].
The purpose of this study was to define: the profile of patients with mitral valve dysfunction (stenosis and/or insufficiency) who were assisted at the University Outpatients' Clinic, the knowledge that these patients had concerning their disorder and the main difficulties and limitations resulting from it. The necessary data were obtained by interviewing 29 patients from November 1997 to February 1998. An analysis was conducted through the Content Analysis Technique. The results obtained helped to understand the problem under the individual's and his family's viewpoint, which helped to elaborate a nursing care program with an educational focus.


Role of the substrate field inhomogeneities in coherent resonant Raman scattering.
The peculiar role of the substrate field on the nonlinear optical response of a molecular adsorbate experiencing a resonant Raman scattering process is analyzed. The description of the internal dynamics is done in terms of the renormalized normal mode coordinates that account for the conformational changes induced in the adsorbate by the substrate field. This analytical description, well-adapted to weak substrate fields, points out the underlying mechanisms that are responsible for the enhancement of the resonant Raman signal observed in some molecules. They involve elementary processes bringing additional intermediate vibrational states into play, depending on the nature of the field inhomogeneities. Also, according to the relative values of the unperturbed equilibrium positions of the modes, their displacements, and frequency changes due to the substrate field, enhancement as well as decrease of the signal can possibly be observed and are evaluated. Of course, for a strong substrate field, the number of intermediate vibrational levels participating in the Raman process becomes very large, and a complete numerical evaluation is required.


Isopentenyl pyrophosphate-reactive Vgamma9Vdelta 2 T helper 1-like cells are the major gammadelta T cell subset recovered from lesions of patients with genital herpes.
Herpes simplex virus (HSV)-specific T cells are essential to control and resolve genital herpes (GH). To investigate the potential involvement of gamma delta T cells in GH, T cells were recovered and expanded, by mitogenic stimulation, to T cell lines from the genital lesions of 17 patients with GH and 5 control subjects who had other diseases. Relatively high numbers of gamma delta T cells--predominantly, V gamma 9V delta 2 T cells--were detected only in the T cell lines of the patients with GH. Intralesional V gamma 9V delta 2 T cell clones did not recognize HSV-infected cells, but they showed reactivity to isopentenyl pyrophosphate and Daudi cells. The T cell clones secreted interferon- gamma, tumor necrosis factor- alpha, interleukin (IL)-8, macrophage inflammatory protein-1 alpha, and RANTES (regulated on activation, normally T cell expressed or secreted), but they secreted no or limited IL-4. The results of the present study suggest the infiltration and putative involvement of isopentenyl pyrophosphate-reactive V gamma 9V delta 2 T helper 1-like cells in individuals with GH.


Traditional foods and physical activity patterns and associations with cultural factors in a diverse Alaska Native population.
To determine the prevalence of traditional food and physical activity use and associations with cultural factors among 3,830 Alaska Native and American Indian (AN/AI) people enrolled in the Education and Research Towards Health (EARTH) Study in 3 regions of Alaska. Cross-sectional analysis of baseline data from a cohort study. Participants (2,323 women and 1,507 men) completed a computer-assisted self-administered questionnaire that included information on diet, physical activity, life-style and cultural factors. Over 92% of participants reported eating at least 1 traditional food in the past year. The top 3 traditional foods reported were fish, moose and agutaq (a mixture of berries and fat). The percentage of people who consumed traditional foods varied by region and age but not by sex (p < 0.01). Almost 70% of participants engaged in at least one traditional harvesting physical activity. Picking berries or greens, cutting/smoking fish or meat and fishing were the most common activities. Participation in traditional physical activity was highest in south-west Alaska and was higher among men than women, but did not differ by age (p < 0.01). Both traditional food and physical activity were associated with greater tribal self-identification, speaking a Native language at home, using traditional remedies and participating in or attending traditional events (p < 0.05). The EARTH Study found relationships between traditional food use, physical activities, cultural activities and behaviours. Consumption of a variety of traditional foods and participation in traditional physical activities remain an important part of the contemporary Alaska Native life-style. Efforts to promote and sustain these foods and activities in AN/AI populations may lead to improved health outcomes.


[IMPLEMENTATION OF A NATIONAL SCREENING PROGRAM FOR DETECTION OF MALIGNANT AND PRE-MALIGNANT CERVICAL MORBIDITY IN ISRAEL].
The natural development of cervical cancer, which takes many years, is mostly initiated by infection with human papillomavirus (HPV) and is characterized by the development of precancerous lesions, cervical intraepithelial neoplasia 3 (CIN3), which are defined as abnormal changes in epithelial cells that cover the cervix surface. Since the pre-cancerous process is microscopic and asymptomatic, early detection is based on cytological screening, the Pap test. In Israel, Pap tests are performed based on selfreferral for testing and not within the framework of a national screening program because of the low incidence rate of cervical cancer in Israel. The current program is characterized by low coverage rates, redundancy checks conducted on a small and selective group of women and therefore, lower efficacy in comparison to an organized, national program. In recent decades, the incidence rates of pre-malignant and malignant cervical morbidity showed increasing trends in Israel, an increase which can be stopped. Launching a national, organized program for the early detection of cervical cancer using Pap test and raising the awareness of women and physicians in Israel regarding the importance of this test, will increase the test uptake and decrease its current selectiveness. Furthermore, this will, in the short run, improve serious cervical morbidity, and in the long run, also reduce the incidence of precancerous and cancerous cervical lesions, as has been described in many countries in the world.


Effects of an 8-week multimodal program on thoracic posture, glenohumeral range of motion and serve performance in competitive young tennis players.
Intensive tennis practice is known to generate sport-specific adaptations at the shoulder region and influence the sagittal spinal curvature. However, increased thoracic kyphosis decreases the shoulder functional capacity, which could limit tennis performance. Therefore, the aim of this study was to investigate the effects of an 8-week multimodal program on thoracic posture, glenohumeral range of motion, and serve performance in competitive young tennis players. Eighteen male and four female players (age: 16.0 ± 2.4 years, height: 170.7 ± 11.0 cm; mass: 62.1 ± 11.5 kg; International Tennis Number: 3-4) performed their regular training during 8 weeks, which was used as a reference period, and implemented a multimodal program including stretching, strengthening, and myofascial release exercises, four times per week during 8 additional weeks, which corresponded to the intervention period. The thoracic curvature angle and mobility, the biacromial and interscapular distances, the glenohumeral range of motion and the tennis serve performance were assessed three times, i.e., before and after the regular training and after the 8-week multimodal program. The results showed that the 8-week regular training had no significant effects on thoracic curvature angle [effect size (ES) = 0.02-0.36, p = 0.06-0.46] and mobility (ES = 0.05-0.26, p = 0.13-0.42), biacromial (ES = 0.05, p = 0.18) and interscapular distances (ES = 0.03, p = 0.45), ranges of motion in glenohumeral internal (ES = 0.04, p = 0.43) and external rotation (ES = 0.43, p = 0.06), and tennis serve accuracy (ES = 0.33, p = 0.07) and velocity (ES = 0.09, p = 0.35). The 8-week multimodal program increased moderately the thoracic mobility (ES = 0.55, p = 0.01), moderately to strongly the serve accuracy and velocity (ES = 0.65, p = 0.003, for both), strongly decreased the interscapular distance (ES = 1.02, p < 0.001), and strongly increased the range of motion in glenohumeral internal (ES = 0.90, p < 0.001) and external rotation (ES = 1.49, p < 0.001). These findings indicated that an 8-week multimodal program, including spine and glenohumeral mobility and shoulder girdle strength exercises, performed four times per week during 8 weeks, is moderately relevant to rectify the sagittal thoracic curvature in competitive tennis players, while such a program may help regain the range of motion in glenohumeral rotation without tennis serve performance impairment.


Emergent laparoscopic surgical intervention for perforated hemorrhagic cholecystitis with hemodynamic instability.
Hemorrhagic cholecystitis is a rare diagnosis that closely mimics acute cholecystitis. Physical examination, laboratory studies and, in particular, computed tomography imaging allow for rapid diagnosis, stabilization and emergent surgical intervention. We describe our experience with three patients requiring emergent surgical intervention for hemorrhagic cholecystitis with unique clinical features including decreased platelet function due to liver cirrhosis, dual antiplatelet therapy and intraoperative finding of cholecystohepatic communication. Furthermore, we provide video recordings of two cases highlighting the severity of the disease. All presented patients were hemodynamically unstable and showed peritoneal signs on exam. Laboratory studies revealed moderate anemia and leukocytosis, while computed tomography suggested hemorrhage in the gallbladder. All patients required blood transfusions during their care and underwent laparoscopic cholecystectomy. Hemoperitoneum and gallbladder perforation were confirmed intraoperatively. Patients fully recovered without significant postoperative complications due to expedited operative management.


Reliable and sensitive detection of glycosaminoglycan chains with immunoblots.
Complex glycans play vital roles in many biological processes, ranging from intracellular signaling and organ development to tumor growth. Glycan expression is routinely assessed by the application of glycan-specific antibodies to cells and tissues. However, glycan-specific antibodies quite often show a large number of bands on immunoblots and it is hard to interpret the data when reliable controls are lacking. This limits the scope of glycobiology studies and poses challenges for replication. We sought to resolve this issue by developing a novel strategy that utilizes an immunoreaction enhancing technology to vastly improve the speed and quality of glycan-based immunoblots. As a representative case study, we used chondroitin sulfate glycosaminoglycan (CS-GAG) chains as the carbohydrate target and a monoclonal antibody, CS-56, as the probe. We discovered that preincubation of the antibody with its antigenic CS-GAG chain distinguishes true-positive signals from false-positive ones. We successfully applied this strategy to 10E4, a monoclonal anti heparan sulfate GAGs (HS-GAGs) antibody, where true-positive signals were confirmed by chemical HS-GAG depolymerization on the membrane. This evidence that glycan-specific antibodies can generate clear and convincing data on immunoblot with highly replicable results opens new opportunities for many facets of life science research in glycobiology.


Omega 3 polyunsaturated fatty acids supplementation and blood pressure levels in hypertriglyceridemic patients with untreated normal-high blood pressure and with or without metabolic syndrome: a retrospective study.
Recent evidence suggests that at least a part of the polyunsaturated fatty acids (PUFAs) heart protective effect is mediated by a relatively small but significant decrease in blood pressure level. We retrospectively evaluated the long-term effect of a PUFA supplementation on the blood pressure level of 111 hypertriglyceridemic subjects with untreated normal-high blood pressure that were prescribed a 2 grams PUFA supplementation in order to improve their plasma lipid pattern. After 12 months of treatment, systolic blood pressure (SBP) meanly decreased by 2.7 +/- 2.5 mmHg (p = 0.001) and diastolic blood pressure (DBP) by 1.3 +/- 3.3 mmHg (p < 0.001), while basal heart rate decreased by 4.0 +/- 4.4 bpm (p < 0.001). Both SBP and DBP reduction were significantly related to the baseline SBP (p < 0.001) and DBP (p < 0.001), respectively. Diastolic blood pressure change was also inversely related to the patient's age (p = 0.004). No significant difference was perceived in the metabolic syndrome subgroup. In our retrospective study, highly purified omega-3 PUFA long-term supplementation is associated with a significant reduction in SBP, DBP, Pulse pressure (PP), and basal heart rate in hypertriglyceridemic patients with normal-high blood pressure. No significant difference was perceived in the metabolic syndrome subgroup. The main determinants of the PUFA anti-hypertensive effect appear to be the basal blood pressure level and age.


Circulating microRNAs as potential diagnostic biomarkers and therapeutic targets in prostate cancer: Current status and future perspectives.
Prostate cancer (PCa) is one of the most common malignancies among men. Despite advancement in technology and medicine over past decades, late diagnosis remains a critical milestone in effective treatment. Therefore, it is necessary to identify novel and reliable biomarkers which are specifically sensitive and specific for prognosis and prediction of clinical outcomes. MicroRNAs (miRNAs) play important roles in posttranslational regulations of genes. Circulating and exosomal miRNAs can be applied as useful diagnostic markers for a different type of malignancies, including PCa. Herein, we summarized various roles of miRNAs (diagnostic, therapeutic, and prognostic) in PCa. Moreover, we highlighted exosomal miRNAs as a new candidate in diagnosis and monitoring response to therapy in patients with PCa.


EcdGHK are three tailoring iron oxygenases for amino acid building blocks of the echinocandin scaffold.
The echinocandins are a small group of fungal N-acylated cyclic hexapeptides that are fungicidal for candida strains and fungistatic for aspergilli by targeting cell wall 1,3-β-glucan synthases. The side chains of all six amino acid building blocks have hydroxyl groups, including the nonproteinogenic 4R,5R-dihydroxy-Orn1, 4R-OH-Pro3, 3S,4S-dihydroxy-homoTyr4, and 3S-OH-4S-Me-Pro6. The echinocandin (ecd) gene cluster contains two predicted nonheme mononuclear iron oxygenase genes (ecdG,K) and one encoding a P450 type heme protein (ecdH). Deletion of the ecdH gene in the producing strain Emericella rugulosa generates an echinocandin scaffold (echinocandin D) lacking both hydroxyl groups on Orn1. Correspondingly, the ΔecdG strain failed to hydroxylate C3 of the homoTyr residue, and purified EcdG hydroxylated free L-homoTyr at C3. The ΔecdK strain failed to generate mature echinocandin unless supplemented with either 4R-Me-Pro or 3S-OH-4S-Me-Pro, indicating blockage of a step upstream of Me-Pro formation. Purified EcdK is a Leu 5-hydroxylase, acting iteratively at C5 to yield γ-Me-Glu-γ-semialdehyde in equilibrium with the cyclic imine product. Evaluation of deshydroxyechinocandin scaffolds in the in vitro anticandidal assays revealed up to a 3-fold loss of potency for the ΔecdG scaffolds, but a 3-fold gain of potency for the ΔecdH scaffold, in line with prior results on deoxyechinocandin homologues.


Language development in children of clinically depressed mothers in remission: Early experience effects.
We compared language comprehension and production across the second year of life in children of clinically depressed mothers who later remitted with children of nondepressed mothers. Altogether, 157 mother-child dyads participated: 46 with mothers diagnosed at infant age 5 months as having major, minor, or other depressive disorders who fully remitted by 15 and 24 months and 111 with nondepressed mothers. The majority of mothers (mean [M] age = 32.8 years) were married, European American, and college educated. The groups did not differ on most sociodemographic indices, and analyses controlled for residual group differences in maternal education and child birth order. Children of early clinically depressed mothers understood fewer words at 15 months (by maternal report on the MacArthur Communicative Development Inventory [MCDI]) and 24 months (by experimenter-administered Reynell Developmental Language Scales [RDLS]) than children of nondepressed mothers. Children of nondepressed mothers increased in language comprehension from 15 to 24 months, whereas children of early clinically depressed mothers did not. Aggregating over 15 and 24 months, nondepressed mothers reported that their children expressed more words than clinically depressed mothers reported their children expressed; experimenter assessment revealed no difference between the two groups. Maternal clinical depression in the first 5 months is related to reduced language comprehension and production during the second year of life even in children whose mothers remit, indicating an early experience effect of maternal clinical depression in muting child language development. Future research should identify the mechanisms by which this early experience effect occurs to inform targeted early preventative interventions for at-risk children. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Commentary on "Being on time for appointments.
In "Being on time for appointments," Sharon Schwarze addresses an important issue -- the tendency for doctors to keep patients waiting for their appointments. Let me state categorically that I agree that this is a deplorable situation that warrants discussion and warrants a serious attempt to correct the practice. I do believe, however, that this is an issue more appropriately considered under the rubric of etiquette rather than ethics, though clearly it is subsumed in the category of respect for persons....


Mutation of TRPM6 causes familial hypomagnesemia with secondary hypocalcemia.
Familial hypomagnesemia with secondary hypocalcemia (OMIM 602014) is an autosomal recessive disease that results in electrolyte abnormalities shortly after birth. Affected individuals show severe hypomagnesemia and hypocalcemia, which lead to seizures and tetany. The disorder has been thought to be caused by a defect in the intestinal absorption of magnesium, rather than by abnormal renal loss of magnesium. Restoring the concentrations of serum magnesium to normal values by high-dose magnesium supplementation can overcome the apparent defect in magnesium absorption and in serum concentrations of calcium. Life-long magnesium supplementation is required to overcome the defect in magnesium handling by these individuals. We previously mapped the gene locus to chromosome 9q in three large inbred kindreds from Israel. Here we report that mutation of TRPM6 causes hypomagnesemia with secondary hypocalcemia and show that individuals carrying mutations in this gene have abnormal renal magnesium excretion.


Regulation of the rhodopsin-transducin interaction by a highly conserved carboxylic acid group.
Rhodopsin is a member of a family of G protein-coupled receptors which share structural and functional homologies. A tripeptide sequence (Glu or Asp/Arg/Tyr) at the cytoplasmic border of the third transmembrane segment is conserved among most of these receptors. This region is involved in G protein activation in rhodopsin as well as in other receptors. The role of the conserved Glu-134 was studied by site-specific mutagenesis of rhodopsin in combination with a real-time fluorescence assay of G protein (transducin) activation. Assay conditions were chosen under which the transducin activation rate was determined either by rhodopsin-transducin complex formation or by GTP gamma S-induced complex dissociation. Glu-134 was replaced by Gln in order to mimic the protonated state of the carboxylic acid group. This mutation caused the pH dependency of complex formation to extend to the alkaline range as compared with rhodopsin. Replacement of Glu-134 by Asp had an opposite but less pronounced effect on the pH dependency and lowered the overall efficiency of transducin activation. The acidity constant (pKa) of the residue at position 134 did not directly determine the pH sensitivity of complex formation, indicating that other amino acid residues contribute to a titratable binding domain that includes Glu-134. In contrast, the pH sensitivity of GTP gamma S-induced complex dissociation was not changed by the mutations, although absolute rates were affected. The data suggest that the protonated state of Glu-134 favors binding of rhodopsin to transducin and that Glu-134 is not titratable in the rhodopsin-transducin complex.


Use of Casein Amorphous Calcium Phosphate (CPP-ACP) on White-spot Lesions: Randomised Clinical Trial.
To evaluate the efficacy of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) in the remineralisation of white-spot lesions in 80 anterior teeth of children aged 5-13 years enrolled in public schools of the city of Botucatu, São Paulo, Brazil. The study sample consisted of 36 individuals divided into 4 groups: G1. control (placebo paste); G2. fluoride gel; G3. CPP-ACP; G4: CPP-ACP + fluoride. Each product was applied twice by a calibrated examiner with a week of interval between. Lesions were monitored with a DIAGNOdent Pen before the first application, before the second application, and 1 and 3 months after the first application. To evaluate the lesion intensity, the Friedman test was applied, and to compare experimental groups, the Kruskal-Wallis test was applied. The analyses were complemented with the Dunn test and the level of significance was 5%. At the end of the 90-day trial, the use of CPP-ACP and fluoride showed comparable results in terms of remineralisation. The best white-spot lesion remineralisation was observed when CPP-ACP and fluoride were combined. The use of CPP-ACP is a good alternative for the remineralisation of white-spot lesions. The effect can be improved when this product is applied in combination with fluoride.


The 5p12 breast cancer susceptibility locus affects MRPS30 expression in estrogen-receptor positive tumors.
Genome-wide association studies have identified numerous loci linked to breast cancer susceptibility, but the mechanism by which variations at these loci influence susceptibility is usually unknown. Some variants are only associated with particular clinical subtypes of breast cancer. Understanding how and why these variants influence subtype-specific cancer risk contributes to our understanding of cancer etiology. We conducted a genome-wide expression Quantitative Trait Locus (eQTL) study in a discovery set of 287 breast tumors and 97 normal mammary tissue samples and a replication set of 235 breast tumors. We found that the risk-associated allele of rs7716600 in the 5p12 estrogen receptor-positive (ER-positive) susceptibility locus was associated with elevated expression of the nearby gene MRPS30 exclusively in ER-positive tumors. We replicated this finding in 235 independent tumors. Further, we showed the rs7716600 risk genotype was associated with decreased MRPS30 promoter methylation exclusively in ER-positive breast tumors. In vitro studies in MCF-7 cells carrying the protective genotype showed that estrogen stimulation decreased MRPS30 promoter chromatin availability and mRNA levels. In contrast, in 600MPE cells carrying the risk genotype, estrogen increased MRPS30 expression and did not affect promoter availability. Our data suggest the 5p12 risk allele affects MRPS30 expression in estrogen-responsive tumor cells after tumor initiation by a mechanism affecting chromatin availability. These studies emphasize that the genetic architecture of breast cancer is context-specific, and integrated analysis of gene expression and chromatin remodeling in normal and tumor tissues will be required to explain the mechanisms of risk alleles.


Commercially available probiotic drinks containing Lactobacillus casei DN-114001 reduce antibiotic-associated diarrhea.
To investigate the effect of Lactobacillus-containing commercially available probiotic formulations in Germany during antibiotic treatment with an analysis of cost-efficiency. In an observational study, we analyzed the frequency of bowel movements from 258 patients with infections in a primary care hospital in western Germany; 107 of the patients were offered a probiotic drink containing at least 10 billion cultures of Lactobacillus casei DN 114001 b.i.d. The economic analysis was based on the costs of patient isolation vs preventive intake of probiotics. In a second pilot study, two commercially available probiotic drinks with different Lactobacillus casei strains were directly compared in 60 patients in a randomized controlled fashion. In the first study, the incidence of antibiotic-associated diarrhea (AAD) was significantly reduced in the intervention group (6.5% vs 28.4%), and the duration of AAD in days was significantly shorter (1.7 ± 1.1 vs 3.1 ± 2.1). Higher age and creatinine and lower albumin were identified as risk factors for AAD. Ampicillin was the antibiotic with the highest rate of AAD (50%) and with the greatest AAD reduction in the probiotic group (4.2%, relative risk reduction 92%). The economic analysis showed a cost advantage of nearly 60000 €/year in a department of this size. The second study confirmed the preventive effect of the drink with Lactobacillus casei DN114001; however, there were no advantages found for the other tested probiotic drink containing Lactobacillus casei Shirota. In contrast to a drink containing Lactobacillus casei Shirota, a commercially available probiotic drink containing Lactobacillus casei DN 114001 cost-efficiently reduces the prevalence of AAD during antibiotic treatment.


Signatures of DNA target selectivity by ETS transcription factors.
The ETS family of transcription factors is a functionally heterogeneous group of gene regulators that share a structurally conserved, eponymous DNA-binding domain. DNA target specificity derives from combinatorial interactions with other proteins as well as intrinsic heterogeneity among ETS domains. Emerging evidence suggests molecular hydration as a fundamental feature that defines the intrinsic heterogeneity in DNA target selection and susceptibility to epigenetic DNA modification. This perspective invokes novel hypotheses in the regulation of ETS proteins in physiologic osmotic stress, their pioneering potential in heterochromatin, and the effects of passive and pharmacologic DNA demethylation on ETS regulation.


Comparative Effectiveness of Medication Therapy Management Eligibility Criteria Across Racial/Ethnic Groups.
Previous research indicates that eligibility criteria for medication therapy management (MTM) services in Medicare prescription drug (Part D) plans, defined under the Medicare Modernization Act (MMA), are associated with racial/ethnic disparities and ineffective in identifying individuals with medication utilization issues. Our study's objective was to determine the comparative effectiveness of MTM eligibility criteria under MMA and in the Affordable Care Act (ACA) in identifying patients with medication utilization issues across racial/ethnic groups. ACA and MMA MTM eligibility criteria were compared on proportions of eligible individuals among patients with medication utilization issues. Multinomial logistic regression was conducted to control for patient/community characteristics. Need-based and demand-based analyses were used to determine disparities due to need and demand for healthcare. Main/sensitivity analyses were conducted for the range of eligibility thresholds. Medicare data (2012-2013) linked to Area Health Resources Files. A total of 964 610 patients 65 years or older. Medication safety/adherence measures, developed primarily by the Pharmacy Quality Alliance, were used to determine medication utilization issues. Higher proportions of patients were eligible based on ACA than MMA MTM eligibility criteria. For example, in 2013, proportions based on ACA and MMA MTM eligibility criteria would be 99.7% and 26.2%, respectively, in the main analysis (p < .001); in the demand-based main analysis, ACA criteria were associated with 13.6% and 9.8%, respectively, higher effectiveness than MMA criteria among non-Hispanic blacks and Hispanics than non-Hispanic whites. ACA MTM eligibility criteria are more effective than MMA criteria in identifying older patients needing MTM, particularly among minorities. J Am Geriatr Soc 67:581-587, 2019.


The influence of the victim on shock induced aggression in rats.
In two studies, free-roaming male rats (aggressors) were shocked in the presence of male target rats restrained in either an upright or a supine posure. In addition, in Experiment II, two levels of aggressor shock intensity (0.8 mA or 2.0 mA) were used while targets received one of three levels of shock (0.5 mA, 1.5 mA, or 2.5 mA). In both studies, upright targets were attacked less than supine targets. Frequency of aggression was directly related to level of aggressor shock intensity in Experiment II. Also, attack by 0.8-mA aggressors against supine targets was inversely related to level of target shock intensity. The low level of attack against upright targets was interpreted in terms of a threat diaplay. Similarily, it was concluded that the target shock-intensity effect in Experiment II was due to specific threat behaviors displayed by those supine rats that received the highest-intensity shocks.


Monoclonal Invariant NKT (iNKT) Cell Mice Reveal a Role for Both Tissue of Origin and the TCR in Development of iNKT Functional Subsets.
Invariant NKT (iNKT) cell functional subsets are defined by key transcription factors and output of cytokines, such as IL-4, IFN-γ, IL-17, and IL-10. To examine how TCR specificity determines iNKT function, we used somatic cell nuclear transfer to generate three lines of mice cloned from iNKT nuclei. Each line uses the invariant Vα14Jα18 TCRα paired with unique Vβ7 or Vβ8.2 subunits. We examined tissue homing, expression of PLZF, T-bet, and RORγt, and cytokine profiles and found that, although monoclonal iNKT cells differentiated into all functional subsets, the NKT17 lineage was reduced or expanded depending on the TCR expressed. We examined iNKT thymic development in limited-dilution bone marrow chimeras and show that higher TCR avidity correlates with higher PLZF and reduced T-bet expression. iNKT functional subsets showed distinct tissue distribution patterns. Although each individual monoclonal TCR showed an inherent subset distribution preference that was evident across all tissues examined, the iNKT cytokine profile differed more by tissue of origin than by TCR specificity.


Bone regeneration materials and their application over 20 years: A bibliometric study and systematic review.
Bone regeneration materials (BRMs) bring us new sights into the clinical management bone defects. With advances in BRMs technologies, new strategies are emerging to promote bone regeneration. The aim of this study was to comprehensively assess the existing research and recent progress on BRMs, thus providing useful insights into contemporary research, as well as to explore potential future directions within the scope of bone regeneration therapy. A comprehensive literature review using formal data mining procedures was performed to explore the global trends of selected areas of research for the past 20 years. The study applied bibliometric methods and knowledge visualization techniques to identify and investigate publications based on the publication year (between 2002 and 2021), document type, language, country, institution, author, journal, keywords, and citation number. The most productive countries were China, United States, and Italy. The most prolific journal in the BRM field was Acta Biomaterialia, closely followed by Biomaterials. Moreover, recent investigations have been focused on extracellular matrices (ECMs) (370 publications), hydrogel materials (286 publications), and drug delivery systems (220 publications). Research hotspots related to BRMs and extracellular matrices from 2002 to 2011 were growth factor, bone morphogenetic protein (BMP)-2, and mesenchymal stem cell (MSC), whereas after 2012 were composite scaffolds. Between 2002 and 2011, studies related to BRMs and hydrogels were focused on BMP-2, in vivo, and in vitro investigations, whereas it turned to the exploration of MSCs, mechanical properties, and osteogenic differentiation after 2012. Research hotspots related to BRM and drug delivery were fibroblast growth factor, mesoporous materials, and controlled release during 2002-2011, and electrospinning, antibacterial activity, and in vitro bioactivity after 2012. Overall, composite scaffolds, 3D printing technology, and antibacterial activity were found to have an important intersection within BRM investigations, representing relevant research fields for the future. Taken together, this extensive analysis highlights the existing literature and findings that advance scientific insights into bone tissue engineering and its subsequent applications.


Nursing work environment, patient safety and quality of care in pediatric hospital.
Objectives To describe the characteristics of the nursing work environment, safety attitudes, quality of care, measured by the nursing staff of the pediatric units, as well as to analyze the evolution of quality of care and hospital indicators. Methods Descriptive study with 136 nursing professionals at a paediatric hospital, conducted through personal and professional characterization form, Nursing Work Index - Revised, Safety Attitudes Questionnaire - Short Form 2006 and quality indicators. Results The professionals perceive the environment as favourable to professional practice, and consider good quality care that is also observed by reducing the incidence of adverse events and decreased length of stay. The domain job satisfaction was considered favourable to patient safety. Conclusions The work environment is favourable to nursing practice, the professionals nursing approve the quality of care and the indicators tended reducing adverse events and length of stay.


Adult IDH wild-type lower-grade gliomas should be further stratified.
Astrocytoma of the isocitrate dehydrogenase (IDH) wild-type gene is described as a provisional entity within the new World Health Organization (WHO) classification. Some groups believe that IDH wild-type lower-grade gliomas, when interrogated for other biomarkers, will mostly turn out to be glioblastoma. We hypothesize that not all IDH wild-type lower-grade gliomas have very poor outcomes and the group could be substratified prognostically. Seven hundred and eighteen adult WHO grades II and III patients with gliomas from our hospitals were re-reviewed and tested for IDH1/2 mutations. One hundred and sixty-six patients with IDH wild-type cases were identified for further studies, and EGFR and MYB amplifications, mutations of histone H3F3A, TERT promoter (TERTp), and BRAF were examined. EGFR amplification, BRAF, and H3F3A mutations were observed in 13.8%, 6.9%, and 9.5% of patients, respectively, in a mutually exclusive pattern in IDH wild-type lower-grade gliomas. TERTp mutations were detected in 26.8% of cases. Favorable outcome was observed in patients with young age, oligodendroglial phenotype, and grade II histology. Independent adverse prognostic values of older age, nontotal resection, grade III histology, EGFR amplification, and H3F3A mutation were confirmed by multivariable analysis. Tumors were further classified into "molecularly" high grade (harboring EGFR, H3F3A, or TERTp) (median overall survival = 1.23 y) and lower grade (lacking all of the 3) (median overall survival = 7.63 y) with independent prognostic relevance. The most favorable survival was noted in molecularly lower-grade gliomas with MYB amplification. Adult IDH wild-type lower-grade gliomas are prognostically heterogeneous and do not have uniformly poor prognosis. Clinical information and additional markers, including MYB, EGFR, TERTp, and H3F3A, should be examined to delineate discrete favorable and unfavorable prognostic groups.


Poor nutrition and alcohol consumption are related to high serum homocysteine level at post-stroke.
Increased serum homocysteine (Hcy) levels have been reported to be related to the occurrence of cardio- and cerebrovascular diseases. High serum Hcy levels are also related to the development of secondary stroke and all-cause mortality. The purpose of this study was to investigate the prevalence of high serum homocysteine level and relating factors, and the change over the 10 month period post-stroke. Consecutive stroke patients who were admitted to the Asan Medical Center were enrolled. Ten months after the onset of stroke, an interview with a structured questionnaire was performed and blood samples were obtained for the biochemical parameters. Nutritional status was determined using the mini nutritional assessment (MNA) score and dietary nutrient intakes were also obtained using a 24 hour recall method. Out of 203 patients, 84% were malnourished or at risk of malnutrition, and 26% had high homocysteine levels at 10 months post-stroke. Using logistic regression, the factors related with high homocysteine levels at 10 months post-stroke included heavy alcohol consumption (P = 0.020), low MNA scores (P = 0.026), low serum vitamin B12 (P = 0.021) and low serum folate levels (P = 0.003). Of the 156 patients who had normal homocysteine levels at admission, 36 patients developed hyperhomocysteinemia 10 months post-stroke, which was related to heavy alcohol consumption (P = 0.013). Persistent hyperhomocysteinemia, observed in 22 patients (11%), was related to male sex (P = 0.031), old age (P = 0.042), low vitamin B6 intake (P = 0.029), and heavy alcohol consumption (P = 0.013). Hyperhomocysteinemia is common in post-stroke, and is related to malnutrition, heavy alcohol drinking and low serum level of folate and vitamin B12. Strategies to prevent or manage high homocysteine levels should consider these factors.


Hepatitis B virus s protein enhances sperm apoptosis and reduces sperm fertilizing capacity in vitro.
Studying the impact of Hepatitis B virus S protein (HBs) on early apoptotic events in human spermatozoa and sperm fertilizing capacity. Spermatozoa were exposed to HBs (0, 25, 50, 100 µg/ml) for 3 h, and then fluo-4 AM calcium assay, Calcein/Co(2+) assay, protein extraction and ELISA, ADP/ATP ratio assay, sperm motility and hyperactivation and sperm-zona pellucida (ZP) binding and ZP-induced acrosome reaction (ZPIAR) tests were performed. The results showed that in the spermatozoa, with increasing concentration of HBs, (1) average cytosolic free Ca(2+) concentration ([Ca(2+)]i) rose; (2) fluorescence intensity of Cal-AM declined; (3) average levels of cytochrome c decreased in mitochondrial fraction and increased in cytosolic fraction; (4) ADP/ATP ratios rose; (5) average rates of total motility and mean hyperactivation declined; (6) average rate of ZPIAR declined. In the above groups the effects of HBs exhibited dose dependency. However, there was no significant difference in the number of sperms bound to ZP between the control and all test groups. HBs could induce early events in the apoptotic cascade in human spermatozoa, such as elevation of [Ca(2+)]i, opening of mitochondrial permeability transition pore (MPTP), release of cytochrome c (cyt c) and increase of ADP/ATP ratio, but exerted a negative impact on sperm fertilizing capacity.


Determination of vitamin B6 vitamers and pyridoxic acid in plasma: development and evaluation of a high-performance liquid chromatographic assay.
Marginal deficiency of vitamin B6 has recently been related to cardiovascular diseases. Because of that there is an increasing interest in a suitable and reliable method for quantifying this vitamin in routine laboratory medicine. We have developed a HPLC-based method able to quantify the B6 vitamers pyridoxal 5'-phosphate (PLP), pyridoxal (PL), pyridoxamine 5'-phosphate (PMP), pyridoxine (PN), and pyridoxamine (PM) and the degradation product 4-pyridoxic acid (4-PA). The separation was accomplished using a C18 (ODS) analytical column and an ion-pair reversed-phase chromatography. B6 vitamers were eluted with a gradient of acetonitrile (0.5-15%) in a potassium phosphate buffer with 1-octanesulfonic acid and triethylamine, pH 2.16. The concentration of the vitamers was determined with fluorescence detector (328 nm excitation, 393 nm emission) after postcolumn derivatization with phosphate buffer containing 1 g/L sodium bisulfite. The performance of the assay was evaluated by analyzing six plasma samples with interrelated concentration and two control samples (unspiked and vitamer spiked) over a 3-months period. The HPLC method was able to identify PLP, 4-PA, PM, PL, PN, and PMP from all other compounds in plasma in an analytical run of 46 min. The imprecisions and mean values (presented in parenthesis in nmol/L) were (unspiked and spiked sample) 9-8% (41-65) for PLP, 12-7% (18-40) for 4-PA, 67-28% (4-19) for PL, 15% (21) for PN, 10% (27) for PM, and 27% (17) for PMP. All three B6 vitamers (PLP, 4-PA, and PL) present in unspiked plasma showed an excellent linearity within the range of (nM) 8-60 (4-PA), 1-19 (PL), and 11-99 (PLP). In conclusion, we report a HPLC-based method that separates and detects nanomolar quantities of six B6 vitamers and demonstrate that the method will be suitable for routine quantitation of PLP and 4-PA in human plasma.


Using auditory-visual speech to probe the basis of noise-impaired consonant-vowel perception in dyslexia and auditory neuropathy.
Both dyslexics and auditory neuropathy (AN) subjects show inferior consonant-vowel (CV) perception in noise, relative to controls. To better understand these impairments, natural acoustic speech stimuli that were masked in speech-shaped noise at various intensities were presented to dyslexic, AN, and control subjects either in isolation or accompanied by visual articulatory cues. AN subjects were expected to benefit from the pairing of visual articulatory cues and auditory CV stimuli, provided that their speech perception impairment reflects a relatively peripheral auditory disorder. Assuming that dyslexia reflects a general impairment of speech processing rather than a disorder of audition, dyslexics were not expected to similarly benefit from an introduction of visual articulatory cues. The results revealed an increased effect of noise masking on the perception of isolated acoustic stimuli by both dyslexic and AN subjects. More importantly, dyslexics showed less effective use of visual articulatory cues in identifying masked speech stimuli and lower visual baseline performance relative to AN subjects and controls. Last, a significant positive correlation was found between reading ability and the ameliorating effect of visual articulatory cues on speech perception in noise. These results suggest that some reading impairments may stem from a central deficit of speech processing.