Altered compartmentalization of transforming growth factor-beta in asthmatic airways.
Asthma is characterized by alterations of the bronchial epithelium associated with inflammatory cell infiltrates and sub-epithelial fibrosis. Transforming Growth Factor-beta (TGF-beta) is an anti-inflammatory and fibrosing cytokine normally present in bronchial epithelial cells and also potentially produced by inflammatory cells. Thus, TGF-beta could play a role in the asthmatic process, and its expression could be modified in asthmatic airways. To test this latter hypothesis, we studied the bronchial distribution of TGF-beta in asthmatic patients. TGF-beta 1, 2, 3 distribution was studied by immunohistochemistry in bronchial biopsies from 12 asthmatic patients and 10 non-asthmatic subjects. Bronchial epithelial cells from asthmatics were negative or faintly positive while a bright staining was detected in these from non-asthmatics (P < 0.01). In both groups, when inflammatory cells were present beneath the basement membrane, they were stained by the anti-TGF-beta antibody. This study shows an altered compartimentalization of TGF-beta in asthma. (a) TGF-beta is scarse in asthmatic bronchial epithelial cells, which could favour the perennization of the bronchial inflammation, and (b) TGF-beta is present in inflammatory cells beneath the basement membrane, where it could be involved in the frequent sub-epithelial fibrosis.


Hepaticojejunostomy in benign and malignant high bile duct stricture: approaches to the left hepatic ducts.
Biliary-enteric anastomosis for relief of biliary obstruction caused by benign or malignant disease at the confluence of the bile ducts can be difficult. An approach by dissection at the confluence has to be performed directly into an area of scarring or at the site of a neoplastic lesion; exposure of an adequate duct for anastomosis is often difficult and may appear impossible. This paper describes an alternative approach to the hepatic ducts by dissection of the left hepatic ductal system. The method has been used with success in thirty-six patients.


[Family planning and tubal ligation: analysis of the work of a team of health providers].
This article presents partial results from a study aimed at recognizing the work of members of a public health team who regularly perform tubal ligations. Empirical data were obtained through interviews and observation of routine activities by nine team members. The principal analytical categories were health work concepts. The team was basically characterized as hierarchical, but the specific decision on surgical sterilization tended to become more horizontal, with a tendency towards a multidisciplinary approach. This situation tends to involve the ethical dimension, with a shift from scientific and biomedical knowledge to the social sciences and humanities. On the other hand, and in a contradictory way, in the actual decision to perform surgical sterilization, technical criteria are supported by biomedical knowledge, and comprehensive knowledge is relegated to a secondary role.


Program Evaluation to Aid Choice of Aripiprazole or Risperidone for Hospitalized Adolescents with Cannabis Use Disorder and Psychosis.
Introduction: Co-occurring cannabis use and psychosis is an increasing problem. No single behavioral or pharmacologic treatment has emerged as clearly superior. To address the gap, this nonrandomized, quality improvement project compares outcomes for adolescents with co-occurring cannabis use disorder and psychosis prescribed risperidone or aripiprazole. Materials and Methods: This project is a retrospective chart review of 110 adolescents (ages 13-21 years) hospitalized for psychosis and co-occurring cannabis use disorder. The primary outcomes are length of stay and length of stay index. Results: Adolescents prescribed risperidone compared with aripiprazole had a significantly greater length of stay (9.7 days vs. 5.8 days, p = 0.002) and length of stay index (1.4 vs. 0.79, p = 0.004). Conclusions: Adolescents hospitalized for co-occurring psychosis and cannabis use disorder had a significantly longer length of stay and length of stay index. These data are consistent with a more rapid reduction in acute psychotic symptoms for aripiprazole compared with risperidone in the context of co-occurring cannabis use disorder.


Population pharmacokinetics of vancomycin in Japanese adult patients.
Population pharmacokinetic parameters of vancomycin (VCM) in Japanese adult patients infected with methicillin-resistant Staphylococcus aureus (MRSA) were estimated using 1253 items of serum concentration data from 190 patients obtained in routine drug monitoring. The two-compartment linear model was adopted, and VCM clearance (CL) was correlated with the creatinine clearance (CLcr), which was observed or estimated by the Cockcroft-Gault equation. The population pharmacokinetic analysis program NONMEM with first-order conditional estimation method was used. The results showed VCM clearance to be linearly correlated with CLcr (CL [ml/min] = 0.797 x CLcr) when the estimated CLcr was <85 ml/min, but no linear relationship at higher than this level because of the lack of accuracy in the CLcr estimates. The interindividual variability of CL was 38.5%; K12 and K21 were 0.525 hr(-1) and 0.213 hr(-1), respectively. The distribution volume at steady state (V[SS]) was 60.71, with no significant dependence on the actual body weight. The interindividual variability of Vss was 25.4%. The calculated half-life (t1/2,beta) in a typical patient with CLcr of 85 ml/minute was 12.8 hours. Residual variability was 23.7%. These results were compared to those of healthy volunteers, and guidelines for dosage adjustment in VCM therapy are discussed.


Role of H-2 and non-H-2 genes in control of bacterial clearance from the spleen in Salmonella typhimurium-infected mice.
The ability of mice to clear Salmonella typhimurium from their spleens in the late phase of infection was studied after inoculation with a temperature-sensitive mutant. Clearance of bacteria was delayed in C57BL/6 mice compared with BALB/c, C3H/HeJ, DBA/2, A/J, and CBA mice. The responses of F1 hybrids, backcrosses, and recombinant inbred strains derived from C57BL/6 and BALB/c (both Itys) and of H-2 congenic mice were analyzed. The results showed that the low rate of bacterial clearance was recessive, that the rate of clearance was under polygenic control, and that an H-2-linked gene(s) plays a major role. Among H-2 congenic mice with a C57BL/10 background, three phenotypes of bacterial clearance could be distinguished: high (H-2j, H-2q, and H-2u), intermediate (H-2d, H-2f, H-2k, H-2p, H-2r, H-2s, and H-2v), and low (H-2b) rates. The effect of the H-2 complex was apparent with different genetic backgrounds (Itys and Ityr). In recombinant inbred strains derived from C57BL/6 (Itys) and A/J (Ityr) mice, the effect of the H-2b haplotype on bacterial clearance appeared to be fully expressed only in strains carrying the Itys allele.


Personalizing interventions using real-world interactions: Improving symptoms and social functioning in schizophrenia with tailored metacognitive therapy.
When clients' lives are not reflected in therapy, they struggle to apply the skills learned in treatment to everyday situations. In this pilot study, we determined if using clients' real-world interactions in therapy could effectively target metacognitive capacity-yielding improved symptoms and social functioning-by tailoring treatment to focus on issues faced by clients in daily life. Using a randomized controlled trial design, schizophrenia subjects with metacognitive deficits completed 24 sessions of: (a) Standard Metacognitive Reflection and Insight Therapy (MERIT); or (b) Tailored MERIT. Real-world interactions were captured via the Electronically Activated Recorder (EAR), a smartphone application that passively records audio in daily life. All subjects wore the EAR; however, real-world interactions were only used to personalize sessions in Tailored MERIT. Feasibility and acceptability were shown; those in Tailored MERIT wore the EAR 84% of their waking hours and reported minimal burden. When compared to Standard MERIT, Tailored MERIT participants showed large pre-post reductions in negative metacognitive beliefs and disorganized symptoms. Small, but nonsignificant, improvements in social functioning were also observed. Compared to an evidence-based benchmark, we observed that real-world interactions can be used to tailor metacognitive therapy and improve outcomes in schizophrenia. Tailored MERIT has the potential to impact practice by personalizing treatment to account for individual variations in environment and lifestyle-aligning with the Precision Medicine Initiative-in a way that is not possible with current therapy. This is particularly salient in schizophrenia, where limited insight and cognitive deficits often make subjective reporting unreliable. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Sex-Specific Development in Haplodiploid Honeybee Is Controlled by the Female-Embryo-Specific Activation of Thousands of Intronic LncRNAs.
Embryonic development depends on a highly coordinated shift in transcription programs known as the maternal-to-zygotic transition (MZT). It remains unclear how haploid and diploid embryo coordinate their genomic activation and embryonic development during MZT in haplodiploid animals. Here, we applied a single-embryo RNA-seq approach to characterize the embryonic transcriptome dynamics in haploid males vs. diploid females of the haplodiploid insect honeybee (Apis mellifera). We observed typical zygotic genome activation (ZGA) occurred in three major waves specifically in female honeybee embryos; haploid genome activation was much weaker and occurred later. Strikingly, we also observed three waves of transcriptional activation for thousands of long non-coding transcripts (lncRNA), 73% of which are transcribed from intronic regions and 65% were specific to female honeybee embryos. These findings support a model in which introns encode thousands of lncRNAs that are expressed in a diploid-embryo-specific and ZGA-triggered manner that may have potential functions to regulate gene expression during early embryonic development in the haplodiploid insect honeybee.


High Betrayal Child Sexual Abuse and Hallucinations: A Test of an Indirect Effect of Dissociation.
Though hallucinations traditionally have been conceptualized as a central feature of psychosis, some hallucinations may be dissociative, with dissociation potentially contributing to hallucinations. Childhood trauma has been linked with dissociation and hallucinations. Betrayal trauma theory distinguishes abusive experiences based on closeness to the perpetrator. In the current study, we examined the indirect effect of dissociation on the relationship between high betrayal child sexual abuse (perpetrated by a close other) and hallucinations. Participants (N = 192) from a northwestern university in the United States completed self-report measures online assessing history of high betrayal child sexual abuse and current dissociation and hallucinations. Bootstrapping analyses indicated a significant indirect effect of high betrayal child sexual abuse on hallucinations through dissociation, 95% Confidence Interval (.16, .66). Through betrayal trauma theory, this study provides a non-pathologizing framework for understanding how dissociation and hallucinations may develop as natural reactions to the harm inherent in child sexual abuse perpetrated by a close other. These findings have clinical implications for relational models of healing for trauma survivors who are distressed by dissociation and hallucinations.


Viscoelasticity breaks the symmetry of impacting jets.
A jet of a Newtonian liquid impacting on a wall at right angle spreads as a thin liquid sheet which preserves the radial symmetry of the jet. We report that for a viscoelastic jet (solution of polyethylene glycol in water) this symmetry can break; close to the wall, the jet cross section becomes faceted and radial steady liquid films (wings) form, which connect the cross-section vertices to the sheet. The number of wings increases with increasing the viscoelastic relaxation time of the solution, but also with increasing jet velocity and decreasing distance from the jet nozzle to the wall. We propose a mechanism for this surprising destabilization of the jet shape, which develops perpendicularly to the direction expected for a buckling mechanism, and explain these dependencies. We also discuss the large-scale consequences of the jet destabilization on the sheet spreading and fragmentation, which show through the faceting of hydraulic jumps and of suspended (Savart) sheets.


High prevalence of Cryptosporidium in young children with prolonged diarrhea.
A prospective study was done to identify Cryptosporidium in the stools of young children, aged 2 months to 3 years, admitted to hospital. Of a total of 387 stool samples from 387 individuals, 131 stool specimens forming the control group were from children with non-diarrheal, respiratory tract infections, 200 and 56 stool samples were from children with acute diarrhea and prolonged diarrhea, respectively. No Cryptosporidium was discovered in the control group. Only 1 sample positive for Cryptosporidium was found in the group with acute diarrhea, whereas 4 samples of Cryptosporidium were found in the group with prolonged diarrhea. The prevalence of Cryptosporidium in the group with prolonged diarrhea was significantly higher than the other two groups (p < 0.05). In those children with prolonged diarrhea, Cryptosporidium should always be included in the differential diagnosis.


Non-destructive detection of large molecules without mass limitation.
The problem for molecular identification knows many solutions, which include mass spectrometers whose mass sensitivity depends on the performance of the detector involved. The purpose of this article is to show by means of molecular dynamics simulations how a laser-cooled ion cloud, confined in a linear radio-frequency trap, can reach the ultimate sensitivity providing the detection of individual charged heavy molecular ions. In our simulations, we model the laser-cooled Ca+ ions as two-level atoms, confined thanks to a set of constant and time oscillating electrical fields. A singly charged molecular ion with a mass of 106 amu is propelled through the ion cloud. The induced change in the fluorescence rate of the latter is used as the detection signal. We show that this signal is due to a significant temperature variation triggered by the Coulomb repulsion and amplified by the radio-frequency heating induced by the trap itself. We identify the optimum initial energy for the molecular ion to be detected, and furthermore, we characterize the performance of the detector for a large range of confinement voltages.


Outcome of incisional hernia repair in patients with Inflammatory Bowel Disease.
Incisional Hernia (IH) repair in patients with Inflammatory Bowel Disease (IBD) has not been well studied. Outcomes of 170 patients with IBD who underwent IH repair were included in the study. The incidence of recurrence after IH repair in IBD is 27%. Patients with Crohn's disease (CD) had larger defects at the time of repair, higher proportion of bowel resection and a longer postoperative stay when compared to Ulcerative colitis (UC). The only significant predictor of recurrence after IH repair was the number of previous bowel resections prior to hernia repair (HR 1.59, p < 0.01). Three cases (10%) of late onset enterocutaneous fistulas were identified in patients who underwent IH repair with synthetic mesh inlay. Surgical repair results in a recurrence of IH in 27% of patients with IBD. The number of previous bowel resections is the only factor that correlates with development of recurrent IH in IBD.


Relative bioavailability of iron from two different iron tablets used in the Indonesian Iron Supplementation Program.
The relative bioavailability of two different iron tablets which are used in the Indonesian iron supplementation program was determined, because low bioavailability of iron might decrease the impact of the program. In two studies volunteers (n = 12, n = 6) received 120 mg elemental iron either as two iron tablets, each containing 60 mg elemental iron, or as an aqueous Fe(II)-sulphate solution in a randomized cross-over design. Plasma iron concentrations were measured before, and 1, 2, 4, 6, 8 and 10 hours after dosing. For each of the tablets and solutions, the positive area under the concentration/time curve (AUC+), the peak plasma level (Cmax), the time to reach the peak plasma level (tmax) and the relative bioavailability were determined. Relative bioavailability of both tablets was high (106.9 +/- 24.3%) and 116.3 +/- 43.1%). This indicates a good therapeutical efficacy of both tablets. In case where low effectiveness of iron supplementation programs is recorded, factors other than low bioavailability of iron in the tablets must be responsible.


Managing colonic inflammation associated gut derangements by systematically optimised and targeted ginger extract-Lactobacillus acidophilus loaded pharmacobiotic alginate beads.
Presently, we explore a cobiotic-ginger extract (GE; antioxidant-antiinflammatory) and Lactobacillus acidophilus (LAB, probiotic), for control of oxidative-stress, inflammation and dysbiosis mediated gut ailments. Since orally administered LAB looses viability while GE is a gastric irritant with poor ADME, we encapsulated them into calcium-alginate beads. Water-loving, viscolysing, and osmotic-building effects of polyethylene glycol were used to address poor probiotic encapsulation (≤10%) by effective sealing of numerous fine voids formed in the alginate gel. Beads were systematically optimized for maximum entrapment (92±2.3% for GE, and 30±1.2% for LAB) and sustained release, and were coated with eudragit-S100 for colonic-targetability, as established by in-vitro release. In-vivo evaluation in DMH-DSS induced colitis and precancerous lesions, in rats, indicated attenuation of oxidative stress (catalase, SOD, LPO) and inflammatory burden (IL-6 and TNF-α), and downregulation of COX-2, iNOS, and c-Myc by both GE and LAB; restoration of colonic permeability by GE; and modulation of gut bacteria and SCFAs by LAB as the mechanisms of action. Complementing activities of GE and LAB in cobiotic beads lead to better reversals. Histology (H&E and toluidine blue) confirmed healing of precancerous lesions.


CD15s/CD62E Interaction Mediates the Adhesion of Non-Small Cell Lung Cancer Cells on Brain Endothelial Cells: Implications for Cerebral Metastasis.
Expression of the cell adhesion molecule (CAM), Sialyl Lewis X (CD15s) correlates with cancer metastasis, while expression of E-selectin (CD62E) is stimulated by TNF-α. CD15s/CD62E interaction plays a key role in the homing process of circulating leukocytes. We investigated the heterophilic interaction of CD15s and CD62E in brain metastasis-related cancer cell adhesion. CD15s and CD62E were characterised in human brain endothelium (hCMEC/D3), primary non-small cell lung cancer (NSCLC) (COR-L105 and A549) and metastatic NSCLC (SEBTA-001 and NCI-H1299) using immunocytochemistry, Western blotting, flow cytometry and immunohistochemistry in human brain tissue sections. TNF-α (25 pg/mL) stimulated extracellular expression of CD62E while adhesion assays, under both static and physiological flow live-cell conditions, explored the effect of CD15s-mAb immunoblocking on adhesion of cancer cell-brain endothelium. CD15s was faintly expressed on hCMEC/D3, while high levels were observed on primary NSCLC cells with expression highest on metastatic NSCLC cells (p < 0.001). CD62E was highly expressed on hCMEC/D3 cells activated with TNF-α, with lower levels on primary and metastatic NSCLC cells. CD15s and CD62E were expressed on lung metastatic brain biopsies. CD15s/CD62E interaction was localised at adhesion sites of cancer cell-brain endothelium. CD15s immunoblocking significantly decreased cancer cell adhesion to brain endothelium under static and shear stress conditions (p < 0.001), highlighting the role of CD15s-CD62E interaction in brain metastasis.


CCAAT/enhancer binding protein alpha (C/EBP alpha) undifferentiated protein: a developmentally regulated nuclear protein that binds to the C/EBP alpha gene promoter.
During differentiation of 3T3-L1 preadipocytes into adipocytes, transcription of the C/EBP alpha (CCA-AT/enhancer binding protein alpha) gene is activated. The promoter of the C/EBP alpha gene contains a bipartite cis element with binding sites for C/EBP alpha undifferentiated protein (CUP) and an Sp1-like GT box binding protein. Binding of CUP to this element is markedly enhanced by its interaction with the Sp1-like protein. CUP, purified approximately 100,000-fold from HeLa cell nuclear extracts, appears to be composed of at least two types of subunit. Evidence is presented that a CUP-containing protein complex bridges between the CUP/Sp1-like GT box element and a downstream cis element, which contains a C/EBP binding site. During differentiation of 3T3-L1 preadipocytes into adipocytes, CUP activity or expression decreases as expression of C/EBP alpha increases. It is suggested that bridging by the CUP-containing protein complex may play a role in transcriptional regulation of the C/EBP alpha gene.


Assessment of the risk for broad sensitization by blood transfusions.
The risk factors associated with the production of lymphocyte antibodies were studied by evaluating the conditions of sensitization in 73 renal failure patients and by searching for lymphocyte antibodies by flow cytometry before the induction of overt sensitization by blood transfusions. In 14 patients the lymphocytotoxic antibodies were not broadly reactive and became undetectable within 5 months. These patients were mostly first transplant candidates who received transfusions prior to the rise of panel antibody reactivity. The remaining 59 patients developed broadly reactive antibodies that persisted for longer than 5 months, regardless of whether or not they were given subsequent blood transfusions. This group was made up almost exclusively of multiparous women or patients who had previously lost a kidney graft. There were 13 patients having no lymphocytotoxic antibodies who developed broad sensitization after blood transfusions. These patients were also multiparous women or previously transplanted patients, suggesting that previous exposure to alloantigens by transplants or pregnancies appeared to be a precondition for blood transfusions to induce broad sensitization. This was confirmed by detecting lymphocyte antibodies by flow cytometry in the pretransfusion serum of 9 of the 13 patients. In contrast, patients who did not make antibodies after transfusions, or those who developed temporary responses, did not have lymphocyte antibodies in their pretransfusion specimens. These findings suggest that patients with low levels of lymphocyte antibodies, not detectable by standard cytotoxicity, are at high risk of developing broadly reactive cytotoxic antibodies after blood transfusions.


Intra-abdominal fluid collections after liver transplantation.
Fluid collections are commonly seen following orthotopic liver transplantation. The majority of these collections are not infected and resolve spontaneously. However, infected collections are associated with significant morbidity and mortality and usually require drainage. Clinical signs of infection are frequently masked following transplantation due to immunosuppression. Intrahepatic collections usually represent abscesses or bilomas and invariably require intervention. Altered anatomical relationships result in signs that frequently help to differentiate these from loculated fluid within hepatic fissures. Other imaging features indicating infection include the presence of gas where none was seen previously, the development of a discrete wall and changes in the surrounding liver.


Effects of Rider Experience Level on Horse Kinematics and Behavior.
There is little information on behavioral and physical effects of lesson horses being used multiple times a day or ridden by riders of varying levels of skill, leaving lesson program managers with limited information to support horse management and welfare decisions. This study used video analysis to evaluate whether horses exhibited different limb kinematics or patterns of behavior under riders with differing levels of experience, factors that could impact physical effort by the horse. Riders (n = 8) were sorted by skill level (four beginner and four advanced), and horses (n = 8) were sorted by sensitivity level (four reactive and four nonreactive). Then pairs of horses (one reactive and one nonreactive in each pair) and pairs of riders (one beginner and advanced in each pair) were created. The pairs were then used in a repeated 2 × 2 Latin square design. Data were collected at the posting trot, using an English saddle, during the stance phase of single fore and hind footfalls. Multivariate analysis of variance of the kinematic variables revealed no overall trends across the kinematic variables, with only a small number of joints showing near-significant effects. Behaviors were quantified based on a study-specific ethogram and willingness scale, but no differences related to rider skill level or horse sensitivity were identified. Although our data suggest no differences in horse kinematics or behavior between beginner and advanced rider groups of horses ridden at the trot, further trials would be required to test for effects during other portions of the stride cycle, other gaits, or longer durations of locomotion.


The Athlete Biological Passport: How to Personalize Anti-Doping Testing across an Athlete's Career?
For decades, drug testing has been the main instrument at the disposal of anti-doping authorities. The availability in the 1980s of substances identical to those produced by the human body, including the "big 3" (erythropoietin, testosterone, and growth hormone), necessitated a new paradigm in anti-doping. The athlete biological passport (ABP) is a new paradigm, complementary to traditional drug testing, based on the personalized monitoring of doping biomarkers. Athletes who abuse doping substances do so to trigger physiological changes that provide performance enhancement. The ABP aims to detect these changes through its 3 hematological, steroidal, and endocrine modules. Any deviation of a biomarker from what is expected in a healthy physiological condition can be attributable to doping or a medical condition, which, interestingly, is also the criterion used to define a banned substance. Recent advances in proteomics and metabolomics offer immense opportunities to enhance the ABP. The ABP shares multiple aspects with the present customization of health care and personalized medicine.


Correlation between serogroup and susceptibility to chloramphenicol, clindamycin, erythromycin, rifampicin and tetracycline among 308 isolates of Clostridium difficile.
The susceptibility to chloramphenicol, clindamycin, erythromycin, rifampicin and tetracycline of 308 isolates of Clostridium difficile from various origins was determined by a disc diffusion susceptibility testing and the results were compared with the serogroup of the strains. For the five antimicrobials, there was a clear-cut separation between susceptible and resistant strains. Some correlation between resistance and serogroup was found. Almost all of the 161 isolates of serogroups A, F, G, H and X were susceptible to all antibiotics. The 32 toxigenic isolates of serogroup C were characterized by a typical resistance pattern which could be used for typing purposes. Other serogroups showed variable patterns. The review of 64 cases of antibiotic associated diarrhoea showed that these differences in susceptibility could have clinical implications: all seven cases due to clindamycin were caused by a clindamycin resistant strain of serogroup C, whereas cases associated with other antibiotics were distributed among various serogroups.


SHPS-1 deficiency induces robust neuroprotection against experimental stroke by attenuating oxidative stress.
Src homology 2 domain-containing protein tyrosine phosphatase substrate-1 (SHPS-1), also known as Signal-regulatory protein alpha (SIRPα) or SIRPA is a transmembrane protein that is predominantly expressed in neurons, dendritic cells, and macrophages. This study was conducted to investigate the role of SHPS-1 in the oxidative stress and brain damage induced by acute focal cerebral ischemia. Wild-type (WT) and SHPS-1 mutant (MT) mice were subjected to middle cerebral artery occlusion (60 min) followed by reperfusion. SHPS-1 MT mice had significantly reduced infarct volumes and improved neurological function after brain ischemia. In addition, neural injury and oxidative stress were inhibited in SHPS-1 MT mice. The mRNA and protein levels of the antioxidant genes nuclear factor-E2-related factor 2 (Nrf2) and heme oxygenase 1 were up-regulated in SHPS-1 MT mice. The SHPS-1 mutation suppressed the phosphorylation of SHP-1 and SHP-2 and increased the phosphorylation of Akt and GSK3β. These results provide the first demonstration that SHPS-1 plays an important role in the oxidative stress and brain injury induced by acute cerebral ischemia. The activation of Akt signaling and the up-regulation of Nrf2 and heme oxygenase 1 likely account for the protective effects that were observed in the SHPS-1 MT mice.


Physical fitness and functional ability of children with intellectual disability: effects of a short-term daily treadmill intervention.
Persons with intellectual disability (ID) and associated multiple disabilities have been found by many researchers to be a population with deficient physical fitness measures, which can be explained by an inactive lifestyle, a result of lack of awareness of the positive physical effects of physical exercise, or lack of motivation for any motor activity. Various plans for physical exercise have been put forward, but many are found impractical in nonresearch-based intervention. In this study, 15 children with ID on a motor functioning level of 7-14 months used a treadmill daily for 2 months. Our findings indicated a most significant improvement in the level of physical fitness of the participants (p < 0.005), as measured by pulse at rest and during effort. The improvement in physical fitness modestly (r = 0.5), but significantly (p < 0.05), correlated with a significant (p < 0.0007) improvement in functional ability of the participating children. Further examination a year after intervention terminated showed a return to preintervention pulse-at-rest values. The research examined the treadmill training method and found that it can be operated with the support of an unskilled staff person under the supervision of a physiotherapist. The research was performed under real-life conditions, enabling relatively easy implementation in the existing conditions of special education centers. This method is a type of exercise that is easy to operate without entailing long-term budgetary expenses and might improve the health status of children with ID, who are a population at risk for developing heart-related diseases at a young age.


Knowledge, Fear, and Anxiety Levels Among Pregnant Women During the COVID-19 Pandemic: A Cross-Sectional Study.
This study aimed to evaluate pregnant women's knowledge, fear, and anxiety levels during the coronavirus outbreak. This cross-sectional study was conducted on 170 pregnant women between May 20 and July 10, 2020. Data collection form for demographics and obstetric details, questionnaire on knowledge, attitudes, and practice toward COVID-19, and State-Trait Anxiety Inventory-I were used. The vast majority of pregnant women were afraid of being infected with the COVID-19 and causing mother-to-baby transmission. A positive correlation was found between fear of coronavirus transmission and the level of anxiety (p < .05). Risk perceptions regarding COVID-19 have affected the anxiety and knowledge levels of pregnant women. Based on the findings, knowledge levels, concerns, and fears about the risk of COVID-19 exposure have implications on the anxiety levels of pregnant women. Pregnant women experienced high stress and anxiety levels due to increased risk of COVID-19 transmission during face-to-face antenatal visits.


Reaction-path dynamics and theoretical rate constants for the CH(n)F(4-n) + O3 --> HOOO + CH(n-1)F(4-n) (n = 2,3) reactions.
We present a theoretical study of the hydrogen abstraction reactions from CH(3)F and CH(2)F(2) by an ozone molecule. The geometries and harmonic vibrational frequencies of all stationary points are calculated at the MPW1K, BHandHLYP, and MPWB1K levels of theory. The energies of all of the stationary points were refined by using both higher-level (denoted as HL) energy calculations and QCISD(T)/6-311++G(2df,2pd) calculations based on the optimized geometries at the MPW1K/6-31+G(d,p) level of theory. The minimum energy paths (MEPs) were obtained by the MPW1K/6-31+G(d,p) level of theory. Energetic information of the points along the MEPs is further refined by the HL method. The rate constants were evaluated on the basis of the MEPs from the HL level of theory in the temperature range 200-2500 K by using the conventional transition-state theory (TST), the canonical variational transition-state theory (CVT), the microcanonical variational transition-state theory (microVT), the CVT coupled with the small-curvature tunneling (SCT) correction (CVT/SCT), and the microVT coupled with the Eckart tunneling correction (microVT/Eckart) based on the ab initio calculations. A general agreement was found among the TST, CVT, and microVT theories. The fitted three-parameter Arrhenius expressions of the calculated forward CVT/SCT and microVT/Eckart rate constants of the ozonolysis of fluoromethane are k(CVT/SCT)(T) = 2.76 x 10(-34)T(5.81)e((-13975/)(T)) and k(microVT/Eckart)(T) = 1.15 x 10(-34)T(5.97)e((-14530.7/)(T)), respectively. The fitted three-parameter Arrhenius expressions of the calculated forward CVT/SCT and microVT/Eckart rate constants of the ozonolysis of difluoromethane are k(CVT/SCT)(T) = 2.29 x 10(-36)T(6.42)e((-15451.6/)(T)) and k(microVT/Eckart)(T) = 1.31 x 10(-36)T(6.45)e((-15465.8/)(T)), respectively.


Gas-liquid chromatographic determination of 3-trifluoromethyl-4-nitrophenol in natural waters.
A procedure for the analysis of 3-trifluoromethyl-4-nitrophenol (TFM) in natural waters is described. The lampricide is extracted from acidified water samples on the macroreticular resin XAD-7 and eluted from the column with ethyl ether. The ether extract is dried, concentrated, and partitioned with potassium carbonate. TFM is acetylated in the aqueous alkaline solution and the acetate derivative is extracted into benzene for analysis by electron capture gas-liquid chromatography. Recoveries of TFM from natural waters exceeded 90% and as little as 0.01 mug TFM can be quantitated in a 1 L sample.


Grazing-incidence neutron-induced fluorescence probes density profiles of labeled molecules at solid/liquid interfaces.
We report on the use of characteristic prompt γ-fluorescence after neutron capture induced by an evanescent neutron wave to probe densities and depth profiles of labeled molecules at solid/liquid interfaces. In contrast to classical scattering techniques and X-ray fluorescence, this method of "grazing-incidence neutron-induced fluorescence" combines direct chemical specificity, provided by the label, with sensitivity to the interface, inherent to the evanescent wave. We demonstrate that the formation of a supported lipid membrane can be quantitatively monitored from the characteristic fluorescence of (157)Gd(3+) ions bound to the headgroup of chelator lipids. Moreover, we were able to localize the (157)Gd(3+) ions along the surface normal with nanometer precision. This first proof of principle with a well-defined model system suggests that the method has a great potential for biology and soft matter studies where spatial resolution and chemical sensitivity are required.


Combined high thoracic and lumbar epidural block for a patient with severe peripheral vascular disease undergoing axillo bifemoral bypass surgery.
A 63 years old patient with severely impaired pulmonary function presented with bilateral lower limb vascular blockade and was operated for emergency aortobifemoral bypass. The patient was considered to be at very high risk for general anesthesia but doing the case under regional anesthesia was also challenging because of the multiple dermatomal levels needed to be anesthetized and because of the potential of adverse effects with such extensive block. There are only a few reported cases of using combination of central neuraxial blocks. The procedure was successfully performed using combined high thoracic and lumbar epidural blockade with two different local anesthetics to minimizing toxicity and observing no adverse effects related to anesthesia technique.


Assisted bicycle training delays functional deterioration in boys with Duchenne muscular dystrophy: the randomized controlled trial "no use is disuse".
Physical training might delay the functional deterioration caused by disuse in boys with Duchenne muscular dystrophy (DMD). The "No Use Is Disuse" study is the first explorative, randomized controlled trial in boys with DMD to examine whether assisted bicycle training is feasible, safe, and beneficial. Ambulatory and recently wheelchair-dependent boys with DMD were allocated to the intervention or control group. The intervention group received assisted bicycle training of the legs and arms during 24 weeks. The control group received the same training after a waiting period of 24 weeks. The primary study outcomes were the Motor Function Measure (MFM) and the Assisted 6-Minute Cycling Test (A6MCT). Group differences were examined by an analysis of covariance. Thirty boys (mean age 10.5 ± 2.6 years, 18 ambulant and 12 wheelchair-dependent) were allocated to the intervention (n = 17) or the control (n = 13) group. All boys in the intervention group (except one) completed the training. After 24 weeks, the total MFM score remained stable in the intervention group, whereas it had significantly decreased in the control group (Δ = 4.9, 95% confidence interval = 2.2-7.6). No significant group differences were found for the A6MCT. No serious adverse events were observed. Our results suggest that assisted bicycle training of the legs and arms is feasible and safe for both ambulant and wheelchair-dependent children and may decline the deterioration due to disuse. Progressive deterioration, however, may compromise the design of trials for DMD.


Broiler diet modification and litter storage: impacts on phosphorus in litters, soils, and runoff.
Modifying broiler diets to mitigate water quality concerns linked to excess phosphorus (P) in regions of intensive broiler production has recently increased. Our goals were to evaluate the effects of dietary modification, using phytase and reduced non-phytate phosphorus (NPP) supplementation, on P speciation in broiler litters, changes in litter P forms during long-term storage, and subsequent impacts of diets on P in runoff from litter-amended soils. Four diets containing two levels of NPP with and without phytase were fed to broilers in a three-flock floor pen study. After removal of the third flock, litters were stored for 440 d at their initial moisture content (MC; 24%) and at a MC of 40%. Litter P fractions and orthophosphate and phytate P concentrations were determined before and after storage. After storage, litters were incorporated with a sandy and silt loam and simulated rainfall was applied. Phytase and reduced dietary NPP significantly reduced litter total P. Reducing dietary NPP decreased water-extractable inorganic phosphorus (IP) and the addition of dietary phytase reduced NaOH- and HCl-extractable organic P in litter, which correlated well with orthophosphate and phytic acid measured by 31P nuclear magnetic resonance (NMR), respectively. Although dry storage caused little change in P speciation, wet storage increased concentrations of water-soluble IP, which increased reactive P in runoff from litter-amended soils. Therefore, diet modification with phytase and reduced NPP could be effective in reducing P additions on a watershed scale. Moreover, efforts to minimize litter MC during storage may reduce the potential for dissolved P losses in runoff.


Economic evaluation of four angiotensin II receptor blockers in the treatment of hypertension.
To evaluate the cost effectiveness of achieving JNC 7 blood pressure goals with angiotensin II receptor blockers (ARBs). Cost effectiveness of olmesartan, losartan, valsartan, and irbesartan was compared with real world patient chart and claims data from a large US health plan. Patients 18 and older with >or=2 claims for an ARB between May 1, 2002 and December 31, 2005 were identified from the claims database. Patients with a diagnosis of hypertension in the 6-month baseline period before the first (index) ARB claim and ARB-free during baseline were included. Medical charts were randomly sampled from the cohort of identified patients; effectiveness data were obtained from charts and linked to healthcare claims and costs. These data were used to populate the decision analytic model. All-cause and hypertension-attributable costs to achieve JNC 7 goals were measured. Comparisons were made within low and high-dose strata and pooled across ARB doses. 121 472 patients were identified, and charts were randomly abstracted for 1600. Of these, 1293 patients were hypertensive at index. Baseline patient characteristics for the chart group were modestly different from the larger cohort. More patients treated with olmesartan (77.8%) than with losartan (66.5%), valasartan (68.8%), or irbesartan (68.8%) achieved JNC 7 BP goals. In pooled-dose comparisons, cost per patient reaching BP goal was $8964 (all-cause) and $2704 (hypertension-attributable) for olmesartan; compared with $10 848 and $3291 for losartan; $10 557 and $3577 for valsartan; and $13395 and $4325 for irbesartan, respectively. The trend was similar for the dose stratification analysis, except in the comparison between high-dose losartan and olmesartan, where losartan had a lower cost-effectiveness ratio. Overall olmesartan was the most effective and cost-saving treatment option compared to losartan, valsartan, and irbesartan for the achievement of JNC 7 BP goals in this managed-care population.


Mechanisms in muscle atrophy in immobilization and aging.
The purpose of this report was to study the effects of four weeks of hindlimb immobilization on acid phosphatase activity of old rats in comparison with the profile obtained after similar treatment in young rats.


Triangular flap for atypical cleft lip. A modification in design.
Standardized steps or criteria for designing a triangular flap do not always fit for all types of cleft lip repair. Some compromise among the criteria is required, especially for atypical cases, such as those with a long vertical height on the noncleft side and a short lateral lip element. In order to secure symmetry in the horizontal length of vermilion, or in the distance from the peak of the cupid's bow to the mouth corner, E' should be located as high as allowable. The ratio of the length of the vertical incision to that of the triangular base affects the final shape of the repaired lip in many ways. Since the bottom of the cupid's bow is generally gradual, slight horizontal asymmetry in the cupid's bow is usually acceptable, as compared with that of the other components.


Dextran-induced release of serotonin from isolated rat peritoneal mast cells.
Dextran (9 mg/ml incubate) was found to induce a serotonin (5-HT) release from isolated rat peritoneal mast cells of about 10% within an incubation period of 5 min. at 37 degrees. The extent of release was not increased by using higher concentrations of dextran or by increasing the incubation period from 5 to 20 min. The dextran-induced release of 5-HT was increased to 50-60% when the mast cells were preincubated with phosphatidylserine (PS) in doses of 2.6-4.3 microgram/ml incubate. Higher concentrations of PS alone induced a rapid 5-HT release of approximately 50-60%. The 5-HT release process studied was found to possess both similarities and dissimilarities with the previously described dextran-induced release process of histamine, also studied in isolated rat peritoneal mast cells. The results supported previous indirect evidence of a 5-HT release from mast cells in the early phase of the dextran-induced anaphylactoid reaction in the rat.


MUSIC APPRECIATION AND TRAINING FOR COCHLEAR IMPLANT RECIPIENTS: A REVIEW.
In recent years, there has been increasing interest in music perception of cochlear implant (CI) recipients, and a growing body of research conducted in this area. The majority of these studies have examined perceptual accuracy for pitch, rhythm, and timbre. Another important, but less commonly studied aspect of music listening is appreciation, or appraisal. Despite the ongoing research into potential technological improvements that may improve music perception for recipients, both perceptual accuracy and appreciation generally remain poor for most recipients. Whilst perceptual accuracy for music is important, appreciation and enjoyment also warrants research as it also contributes to clinical outcomes and perceived benefits. Music training is being shown to offer excellent potential for improving music perception and appreciation for recipients.Therefore, the primary topics of this review are music appreciation and training. However, a brief overview of the psychoacoustic, technical, and physiological factors associated with a recipient's perception of music is provided, as these are important factors in understanding the listening experience for CI recipients. The purpose of this review is to summarize key papers that have investigated these issues, in order to demonstrate that i) music enjoyment and appraisal is an important and valid consideration in evaluating music outcomes for recipients, and ii) that music training can improve music listening for many recipients, and is something that can be offered to persons using current technology.


Epigenetic regulation of the TRAIL/Apo2L apoptotic pathway by histone deacetylase inhibitors: an attractive approach to bypass melanoma immunotherapy resistance.
TNF-related apoptosis-inducing ligand (TRAIL/Apo2L) is a major cytotoxic mechanism employed by cytotoxic T lymphocytes (CTL) and natural killer (NK) cells to eradicate malignant cells. TRAIL/Apo2L interacts with its cognate receptors located on tumor cell surface namely, TRAIL-R1 (DR4), TRAIL-R2 (DR5), TRAIL-R3 (DcR1), TRAIL-R4 (DcR2) and osteoprotegerin (OPG). The exact function of DcR1 and DcR2 remains elusive. TRAIL/Apo2L or agonistic monoclonal antibodies directed against TRAIL/Apo2L death-inducing receptors (DR4, DR5) have become an attractive immunological therapeutic tools in clinical oncology due to their selective killing of tumors and lack of affinity towards healthy cells. Though a potent anti-cancer modality, some cancer cells exhibit inherent or acquired resistance to TRAIL/Apo2L. Postulated resistance mechanisms include up-regulation of c-FLIP, down-regulation of caspase-8, down-regulation/shedding of death receptors and an imbalanced ratio of pro- to anti-apoptotic genes due to aberrant activity of cellular survival signal transduction pathways. The development of resistance has spurred the use of combination therapy, in particular using small molecule sensitizing agents, to restore apoptosis sensitivity. A novel category of such compounds is histone deacetylase inhibitors (HDACi), which block HDACs from removing acetyl groups from histone tails thereby preventing silencing of pro-apoptotic genes and regulating the expression of non-histone proteins (i.e., apoptosis-associated genes), are effective agents in some malignancies. Some HDACi, such as Suberoylanilide Hydroxamic Acid (SAHA), have received FDA approval for cancer treatment. In various melanoma preclinical models, HDACi in conjunction with TRAIL/Apo2L, via modulation of apoptotic machinery, have proven to overcome acquired/inherent resistance to either agent. Here, we discuss recent findings on the role of TRAIL/Apo2L and its agonistic mAbs in melanoma immunotherapy with discussions on potential cellular and molecular events by which HDACi can sensitize metastatic melanoma to TRAIL/Apo2L-mediated immune-therapy, thereby, overcoming resistance.


Radical scavenging activities of peels and pulps from cv. Golden Delicious apples as related to their phenolic composition.
The relationship between phenolic composition and radical scavenging activity of apple peel and pulp was investigated in fruit produced according to both organic and integrated agricultural methods. Apple tissue extracts were subjected to high-performance liquid chromatography separation, which showed that as compared with pulps, peels are richer in almost all of the quantified phenolics. Flavonols, flavanols, procyanidins, dihydrochalcones, and hydroxycinnamates were the identified phenolic classes in peel tissue, and the most abundant compounds were epicatechin, procyanidin B2, and phloridzin. Pulps were poorer in phytochemicals. Their major phenolics were procyanidins and hydroxycinnamates. Flavonols in amounts <20 mg kg(-1) fresh weight (fw) were also found. In both peels and pulps, integrated production samples were richer in polyphenols. Among the 14 compounds identified, only phloridzin had a tendency to appear higher in organic peels. The total antioxidant capacities (TAC) of extracts were evaluated using the 1,1-diphenyl-2-picrylhydrazyl radical assay and were expressed as Trolox equivalents. Integrated peels gave the highest TAC (18.56 mM kg(-1) fw), followed by organic peels (TAC = 14.96), integrated pulps (TAC = 7.12), and organic pulps (TAC = 6.28). In peels, the top contributors to the antioxidant activity were found to be flavonols, flavanols, and procyanidins, which accounted for about 90% of the total calculated activity whereas in pulps, the TAC was primarily derived from flavanols (monomers and polymers) together with hydroxycinnamates. A good correlation between the sum of polyphenols and the radical scavenging activities was found. Among the single classes of compounds, procyanidins (in peels and pulps) and flavonols (in peels) were statistically correlated to the TAC.


Screening and optimization of phage display cyclic peptides against the WDR5 WBM site.
Of the various WD40 family proteins, WDR5 is a particularly important multifunctional adaptor protein that can bind to several protein complexes to regulate gene activation, so it was considered as a promising epigenetic target in anti-cancer drug development. Despite many inhibitors having been discovered directing against the arginine-binding cavity in WDR5 called the WIN site, the side hydrophobic cavity called the WBM site receives rather scant attention. Herein, we aim to obtain novel WBM-targeted peptidic inhibitors with high potency and selectivity. We employed two improved biopanning approaches with a disulfide-constrained cyclic peptide phage library containing 7 randomized residues and identified several peptides with micromole binding activity by docking and binding assay. To further optimize the stability and activity, 9 thiol-reactive chemical linkers were utilized in the cyclization of the candidate peptide DH226027, which had good binding affinity. This study provides an effective method to discover potent peptides targeting protein-protein interactions and highlights a broader perspective of peptide-mimic drugs.


Octave-spanning supercontinuum generation in hybrid silver metaphosphate/silica step-index fibers.
We reveal the potential of step-index fibers consisting of a metaphosphate glass core and a silica cladding as an ultrafast octave-spanning supercontinuum source. The hybrid waveguide was fabricated by pressure-assisted melt filling and possesses a sophisticated dispersion behavior with two zero-dispersion points in the proximity of the Erbium laser bands. The fiber generates an octave-spanning supercontinuum from 0.7 to 2.4 μm if pumped at 1.56 μm with 30 fs pulses and energies as low as 300 pJ. Numerical simulations reveal soliton fission and double dispersive wave generation as the dominant broadening effect. This study highlights phosphate glasses as a promising new candidate for the next generation of broadband photonic devices, as they allow for high rare earth-doping levels and dispersion posttuning via plasmonic nanoparticle growth.


Self-association of beta-lactoglobulin c in acetate buffers.
The self-association of beta-lactoglobulin C at pH 4.65 (23 degrees C) in acetate buffer has been studied at various temperatures, 10, 16, 20 and 25 degrees C, by a series of sedimentation equilibrium experiments. Two different buffers were used. Buffer I with an ionic strength of 0.1 consisted of 0.1M acetic acid and 0.1M sodium acetate; buffer II had 0.1M KCl in addiation so that its ionic strength was 0.2. The variation of the apparent weight average molecular weight, Mwa, with the total solute concentration, c, was characteristic of a self-association. In contrast to the behavior of beta-lactoglobulin A in acetate buffer, the association of beta-lactoglobulin C did not proceed beyond dimer. Furthermore, within the experimental error, the self-association of beta-lactoglobulin C was independent of temperature and ionic strength; all experimental data could be put on the same Mwa (or M1/Mwa) vs. c plot! Several models were used to test the self-association, and a monomer--dimer association with K2 = 2.10 X 10(3) dl/g and BM1 =- 1.2 X 10(-2) dl/g seemed to give a good description of the M1/Mwa vs. c curve.


Foley catheter or prostaglandin E2 inserts for induction of labour at term: an open-label randomized controlled trial (PROBAAT-P trial) and systematic review of literature.
To assess the safety and effectiveness of a transcervical Foley catheter compared to vaginal prostaglandin E2 inserts for term induction of labour. We conducted an open-label randomized controlled trial in five hospitals in the Netherlands. Women with a singleton term pregnancy in cephalic presentation, intact membranes, unfavourable cervix, and no prior caesarean section were enrolled. Participants were randomly allocated by a web-based randomization system to induction of labour with a 30 ml Foley catheter or 10mg slow-release vaginal prostaglandin E2 inserts in a 1:1 ratio. Due to the nature of the intervention this study was not blinded. The primary outcome was the caesarean section rate. Secondary outcomes were maternal and neonatal morbidity and time from intervention to birth. Additionally, we carried out a systematic review and meta-analysis of similar studies. We analyzed 226 women: 107 received a Foley catheter and 119 inserts. Caesarean section rates were comparable (20% versus 22%, RR 0.90, 95% CI 0.54-1.50). Secondary outcomes showed no differences. We observed no serious maternal or neonatal morbidity. Meta-analysis showed comparable caesarean section rates, but significantly fewer cases of hyperstimulation during the ripening phase when a Foley catheter was used. We found, in this relatively small study, no differences in effectiveness and safety of induction of labour with a Foley catheter and 10mg slow release vaginal prostaglandin E2 inserts. Meta-analysis confirmed a comparable caesarean section rate, and showed fewer cases of hyperstimulation when a Foley catheter was used.


e-Health Interventions Targeting Pain-Related Psychological Variables in Fibromyalgia: A Systematic Review.
There is growing evidence to support the potential benefit of e-Health interventions targeting psychosocial outcomes and/or pain-related psychological variables for chronic pain conditions, including fibromyalgia syndrome (FMS). This systematic review aims at providing an in-depth description of the available e-Health psychological and/or multicomponent interventions for patients with FMS. Searches were made in PubMed, Cochrane, Web of Science, and PsycINFO up to 15 May 2023, finally including twenty-six articles. The quality of the included articles was medium-high (average quality assessment score of 77.1%). 50% of studies were randomized controlled trials (RCTs) (n = 13), and the majority of them focused exclusively on adult patients with FMS (n = 23) who were predominantly female. Four categories of e-Health modalities were identified: web-based (n = 19), mobile application (m-Health) (n = 3), virtual reality (VR) (n = 2), and video consulting (n = 2). Interventions were mainly based on the cognitive behavioral therapy (CBT) approach (n = 14) and mostly involved contact with a healthcare professional through different digital tools. Overall, a growing number of psychological and multicomponent interventions have been created and delivered using digital tools in the context of FMS, showing their potentiality for improving psychosocial outcomes and pain-related psychological variables. However, some digital tools resulted as underrepresented, and the literature on this topic appears highly heterogeneous precluding robust conclusions.


Microbial colonization and infectious complications in bone marrow transplant recipients treated in strict protective isolation.
Bone marrow transplantation was carried out in 10 patients (5 with acute leukemia and 5 with aplastic anaemia). Protection against endogenous and exogenous infection was attempted by a rigorous sterile protective isolation regimen, comprising laminar-air-flow cabinets, daily decontamination of skin, mucous membranes and intestines. All supplies of food, fluids, medicine and equipment were sterilized. In all patients a heavy suppression of the normal bacterial flora was obtained after approximately 1 week and 85% of a total of 1026 days of decontamination revealed only scanty growth in one or a few regions of the patients. The surviving microorganisms were Candida albicans and non-pathogenic commensals (mainly Staphylococcus albus). In 1 patient only an exogenic microorganism was introduced possibly by transfusion or staff. 16 febrile episodes were recorded in the patients during decontamination covering 21% of the period. Four episodes were caused by bacteria (Klebsiella pneumoniae, Pseudomonas aeruginosa and mixed). In most of the remaining episodes the etiology was not established. The results thus show that endogenous pathogenic bacteria can be eradicated by the regimen, and that systemic antimicrobial chemotherapy can be restricted and guided by the results of the previous and contemporary cultures. However, viral infections remain a major problem in these patients. Efforts should be maintained to avoid entrance of exogenic bacteria by staff and supplies.


Wintertime organic aerosols in Christchurch and Auckland, New Zealand: contributions of residential wood and coal burning and petroleum utilization.
Wintertime PM10 samples from two New Zealand cities (Christchurch and Auckland) have been characterized using gas chromatography - mass spectrometry for biomass burning tracers, hopanes, n-alkanes, fatty acids, n-alkanols and sugars. The aerosol samples of Christchurch, which were heavily influenced by residential wood and coal burning, showed substantially higher ambient concentrations for most of the organic compounds than those of Auckland, where major sources of aerosols were vehicular emissions and sea-salt. Mass ratios between the biomass burning tracers studied were found to be significantly different (e.g., beta-sitosterol to nssK+ ratios were more than three times higher in Christchurch than in Auckland), although levoglucosan to nssK+ ratios were similar at the both sites. We also estimated, for the first time using stereochemical configurations of hopanes, that 60% of fossil fuel emissions came from petroleum utilization with the remaining 40% being from coal burning in Christchurch. In contrast, contribution of coal burning was negligible in Auckland. Moreover, contributions of most biomass burning tracers to organic carbon (OC) were significantly higher in Christchurch than in Auckland. On the other hand, saccharides (excluding levoglucosan) and hopanes accounted for larger fractions of OC in Auckland. This study demonstrates that intensive wood and coal burning can significantly affect organic aerosol composition in an urban environment.


Permeation of macromolecules into polyelectrolyte microcapsules.
Polyelectrolyte microcapsules (PEMCs) have been prepared by coating red blood cells with the polyelectrolytes poly(styrenesulfonate), poly(allylamine hydrochloride), and dextran sulfate applying the layer-by-layer technique with subsequent dissolution of the core. The capsule permeability for human serum albumin (HSA) was studied as a function of the ionic strength and pH by means of confocal microscopy. PEMCs produced with dextran sulfate and poly(allylamine hydrochloride) show a significant increase in permeability for HSA at salt concentrations over 1 mM. For PEMCs prepared with poly(styrenesulfonate) and poly(allylamine hydrochloride) the limiting salt concentration is 5 mM. No pH dependence for permeation was observed. A correlation between the permeation and adsorption of HSA on the PEMC walls was investigated. Finally, a mechanism for the permeability, combining electrostatic interactions, and the presence of pores in the polymer layers is presented confirmed by the considerable increase of permeation of charged molecules in the presence of salt and the permeation of neutral molecules regardless of the ionic strength.


A high-sensitivity ELISA for detection of human FGF18 in culture supernatants from tumor cell lines.
Fibroblast growth factor 18 (FGF18) is elevated in several human cancers, such as gastrointestinal and ovarian cancers, and stimulates the proliferation of tumor cells. This suggests that FGF18 may be a promising candidate biomarker in cancer patients. However, the lack of a high-sensitivity enzyme-linked immunosorbent assay (ELISA) does not permit testing of this possibility. In this study, we generated monoclonal antibodies against human FGF18 and developed a high-sensitivity ELISA to measure human FGF18 at concentrations as low as 10 pg/mL. Of the eight tumor cell lines investigated, we detected human FGF18 in culture supernatants from four tumor cell lines, including HeLa, OVCAR-3, BxPC-3, and SW620 cells, albeit the production levels were relatively low in the latter two cell lines. Moreover, the in-house ELISA could detect murine FGF18 in sera from mice overexpressing murine Fgf18 in hepatocytes, although the sensitivity in detecting murine FGF18 was relatively low. This FGF18 ELISA could be a valuable tool to validate FGF18 as a potential biomarker for cancer patients and to test the contribution of FGF18 for various disease models invivo and in vitro.


[Choristoma of the middle ear].
Choristoma is one of the varieties of congenital developmental anomalies, where one or another normal tissue of the body is located in an atypical place for itself. The short literary review of choristoma of middle ear is presented in article. A rare clinical cases of salivary gland choristoma of the middle ear (5-year-old girl with left-sided conductive hearing loss of III degree) and glial choristoma of the mastoid (19-year-old man with signs of chronic suppurative otitis media of the right ear) are described.


How to consider implant-prosthetic rehabilitation in elderly patients: a narrative review.
With the beginning of the twenty-first century, population aging has emerged as a major worldwide phenomenon. The dentist must respond to this demographic change by taking into consideration the possibility of restoring oral function in the elderly patient with the use of dental implants. This article aims to provide a narrative review of the literature regarding the implant survival rate in geriatric patients and the relative importance and advantages of implant-prosthetic rehabilitation through a scientific analysis of the literature through online databases and dental journals. Tooth loss can have a significant impact on patients' oral function and significantly affects quality of life, self-esteem, and nutritional status. Although many studies in the past have reported that implant success is age-dependent, more recent studies suggest that they are safe and predictable for geriatric patients, improving quality of life, with similar results to those of younger age groups. Advanced age does not necessarily represent a contraindication for implant placement and osseointegration and success is influenced by patient and site-specific factors. Aging is a process that affects each patient differently, consequently, there should be a specific therapeutic approach for everyone, which must consider the functional and cognitive status of the patient, his medical condition, and his social situation-economic and motivational.


Epilepsy in KCNH1-related syndromes.
KCNH1 mutations have been identified in patients with Zimmermann-Laband syndrome and Temple-Baraitser syndrome, as well as patients with uncharacterized syndromes with intellectual disability and overlapping features. These syndromes include dysmorphic facial features, nail hypo/aplasia, thumb and skeletal anomalies, intellectual disability, and seizures. We report the epilepsy phenotype in patients with KCNH1 mutations. Demographic data, electroclinical features, response to antiepileptic drugs, and results of significant diagnostic investigations of nine patients carrying mutations in KCNH1 were obtained from referring centres. Epilepsy was present in 7/9 patients. Both generalized and focal tonic-clonic seizures were observed. Complete seizure control was achieved with pharmacological treatment in 2/7 patients; polytherapy was required in 4/7 patients. Status epilepticus occurred in 4/7 patients. EEG showed a diffusely slow background in 7/7 patients with epilepsy, with variable epileptiform abnormalities. Cerebral folate deficiency and an increase in urinary hypoxanthine and uridine were observed in one patient. Epilepsy is a key phenotypic feature in most individuals with KCNH1-related syndromes, suggesting a direct role of KCNH1 in epileptogenesis, although the underlying mechanism is not understood.


New amino acid polymorphism, Ala/Val4058, in exon 45 of the polycystic kidney disease 1 gene: evolution of alleles.
The PKD1 gene, which is responsible for the most common form of autosomal dominant polycystic kidney disease, has recently been cloned and sequenced. Many disease-causing mutations have been characterized in this gene, most of them resulting in premature protein termination. However, mutation analysis not routinely implemented for family investigations in a clinical setting, because of the large size and complexity of the gene. Instead, genetic linkage analysis using highly polymorphic CA dinucleotide repeats that map around the gene is still the method of choice. Recently, a few intragenic polymorphisms have been described that are also useful for linkage studies. Here, a new diallelic polymorphism is described for amino acid residue 4058, Ala/Val4058, with allelic frequencies of 0.88 and 0.12, respectively, and a heterozygosity of 0.23, in the Greek and Greek-Cypriot populations. Interestingly, this polymorphism and Ala4091-A/G, which has previously been described in Caucasians, were not detected in DNA from 44 Japanese samples tested. This is particularly important when allelic frequencies in a particular population are used for linkage analysis of families of different ethnic origin. Also, observation of the two polymorphisms together as haplotypes suggests that the Ala/Val4058 polymorphism occurred more recently than the establishment of the Ala4091-A/G polymorphism, and specifically on the G allele.


Insomnia symptoms and mortality: a register-linked study among women and men from Finland, Norway and Lithuania.
Evidence on the association between insomnia symptoms and mortality is limited and inconsistent. This study examined the association between insomnia symptoms and mortality in cohorts from three countries to show common and unique patterns. The Finnish cohort comprised 6605 employees of the City of Helsinki, aged 40-60 years at baseline in 2000-2002. The Norwegian cohort included 6236 participants from Western Norway, aged 40-45 years at baseline in 1997-1999. The Lithuanian cohort comprised 1602 participants from the City of Palanga, aged 35-74 years at baseline in 2003. Mortality data were derived from the Statistics Finland and Norwegian Cause of Death Registry until the end of 2012, and from the Lithuanian Regional Mortality Register until the end of 2013. Insomnia symptoms comprised difficulties initiating sleep, nocturnal awakenings, and waking up too early. Covariates were age, marital status, education, smoking, alcohol, physical inactivity, obesity, diabetes, cardiovascular diseases, depression, shift work, sleep duration, and self-rated health. Cox regression analysis was used. Frequent difficulties initiating sleep were associated with all-cause mortality among men after full adjustments in the Finnish (hazard ratio 2.51; 95% confidence interval 1.07-5.88) and Norwegian (hazard ratio 3.42; 95% confidence interval 1.03-11.35) cohorts. Among women and in Lithuania, insomnia symptoms were not statistically significantly associated with all-cause mortality after adjustments. In conclusion, difficulties initiating sleep were associated with mortality among Norwegian and Finnish men. Variation and heterogeneity in the association between insomnia symptoms and mortality highlights that further research needs to distinguish between men and women, specific symptoms and national contexts, and focus on more chronic insomnia.


Effects of resveratrol on the pharmacokinetics of diltiazem and its major metabolite, desacetyldiltiazem, in rats.
The purpose of this study was to investigate the effects of resveratrol, an antioxidant, on the pharmacokinetics of diltiazem and its active metabolite, desacetyldiltiazem, in rats. The pharmacokinetic parameters of diltiazem and desacetyldiltiazem were determined after an oral administration of diltiazem (15 mg/kg) to rats in the presence and absence of resveratrol (0.5, 2.5, and 10 mg/kg). Compared to the control group, the presence of resveratrol significantly (P < 0.05) increased the area under the plasma concentration-time curve (AUC) of diltiazem, except for resveratrol 0.5 mg/kg. Consequently, the absolute bioavailability (AB) of diltiazem in the presence of resveratrol (2.5 and 10 mg/kg) was significantly (P < 0.05) higher (10.2-11.1%) than that of the control (6.9%). The relative bioavailability (RB) of diltiazem in the presence of resveratrol (2.5 and 10 mg/kg) was increased by 1.48- to 1.60-fold. Resveratrol did not alter absorption rate constant (K(a)) and the time to reach the peak concentration (T(max)) of diltiazem. The AUC of desacetyldiltiazem was increased significantly (P < 0.05) in the presence of 10 mg/kg of resveratrol. The metabolite-parent AUC ratio (MR) in the presence of resveratrol was decreased but did not show significant change. In conclusion, resveratrol significantly increased the bioavailability of diltiazem due to the inhibition of both the cytochrome P450 (CYP) 3A4-mediated metabolism and the efflux pump P-glycoprotein (P-gp) in the intestine and/or liver. Based on these results, if these results would be confirmed in clinical experiments, the dosage of diltiazem should be readjusted when diltiazem is used concomitantly with resveratrol.


Japanese pediatric patient with moderately active ulcerative colitis successfully treated with ustekinumab: A case report.
Ustekinumab is effective in the treatment of adult Crohn disease (CD) and ulcerative colitis (UC). However, data on its efficacy and safety in pediatric CD and UC are limited. To the best of our knowledge, there are no reports of Japanese children with UC treated with ustekinumab in the long-term. A 14-year-old man with diarrhea and bloody stools was referred to our hospital. Colonoscopy revealed total colitis-type UC. His pediatric UC activity index score was 50, indicating moderately active UC. Ulcerative colitis. Infliximab was introduced because of steroid-resistant refractory UC; however, secondary ineffectiveness was observed 17 months later. Therefore, ustekinumab was administered along with prednisolone (16 years of age). The patient achieved UC remission after ustekinumab treatment, leading to maintained remission without side effects. To the best of our knowledge, this is the first pediatric case of moderately active UC successfully treated with ustekinumab in Japan. Ustekinumab combined with steroids is an effective and safe induction therapy for UC.


Use of extracorporeal membrane oxygenation in a patient with diffuse alveolar hemorrhage.
Extracorporeal membrane oxygenation (ECMO) was developed as a supportive therapy for severe respiratory failure. It has been shown to be life-saving in neonates and children with isolated respiratory failure, however, its usefulness in adults remains controversial. We report the successful use of ECMO in an adult patient with severe hypoxemic respiratory failure secondary to diffuse alveolar hemorrhage from Wegener granulomatosis.


Creating Genome Modifications in C. elegans Using the CRISPR/Cas9 System.
The clustered, regularly interspaced, short, palindromic repeat (CRISPR)-associated (CAS) nuclease Cas9 has been used in many organisms to generate specific mutations and transgene insertions. Here we describe a method using the S. pyogenes Cas9 in C. elegans that provides a convenient and effective approach for making heritable changes to the worm genome.


The Mechanism of Action of Ghrelin and Motilin in the Pacemaker Potentials of Interstitial Cells of Cajal from the Murine Small Intestine.
Interstitial cells of Cajal (ICCs) are pacemaker cells that exhibit periodic spontaneous depolarization in the gastrointestinal (GI) tract and generate pacemaker potentials. In this study, we investigated the effects of ghrelin and motilin on the pacemaker potentials of ICCs isolated from the mouse small intestine. Using the whole-cell patch-clamp configuration, we demonstrated that ghrelin depolarized pacemaker potentials of cultured ICCs in a dose-dependent manner. The ghrelin receptor antagonist [D-Lys] GHRP-6 completely inhibited this ghrelin-induced depolarization. Intracellular guanosine 5'-diphosphate-β-S and pre-treatment with Ca2+free solution or thapsigargin also blocked the ghrelin-induced depolarization. To investigate the involvement of inositol triphosphate (IP3), Rho kinase, and protein kinase C (PKC) in ghrelin-mediated pacemaker potential depolarization of ICCs, we used the IP3 receptor inhibitors 2-aminoethoxydiphenyl borate and xestospongin C, the Rho kinase inhibitor Y-27632, and the PKC inhibitors staurosporine, Go6976, and rottlerin. All inhibitors except rottlerin blocked the ghrelin-induced pacemaker potential depolarization of ICCs. In addition, motilin depolarized the pacemaker potentials of ICCs in a similar dose-dependent manner as ghrelin, and this was also completely inhibited by [D-Lys] GHRP-6. These results suggest that ghrelin induced the pacemaker potential depolarization through the ghrelin receptor in a G protein-, IP3-, Rho kinase-, and PKC-dependent manner via intracellular and extracellular Ca2+ regulation. In addition, motilin was able to depolarize the pacemaker potentials of ICCs through the ghrelin receptor. Therefore, ghrelin and its receptor may modulate GI motility by acting on ICCs in the murine small intestine.


Impact of an Asha intervention on depressive symptoms among rural women living with AIDS in India: comparison of the Asha-Life and Usual Care program.
The purpose of this randomized pilot study is to conduct an intervention with 68 rural women living with AIDS to compare the effectiveness of two different programs on depressive symptoms. The trial was designed to assess the impact of the Asha-Life intervention engaging with an HIV-trained village woman, Asha (Accredited Social Health Activist), to participate in the care of women living with AIDS (WLA), along with other health care providers compared to a Usual Care group. Two high prevalence HIV/AIDS villages in rural Andhra Pradesh, which were demographically alike and served by distinct Public Health Centers, were selected randomly from a total of 16 villages. The findings of this study demonstrated that the Asha-Life participants significantly reduced their depressive symptom scores compared to the Usual Care participants. Moreover, women living with AIDS who demonstrated higher depressive symptom scores at baseline had greater reduction in their depressive symptoms than women with lower scores.


How do great bowerbirds construct perspective illusions?
Many animals build structures to provide shelter, avoid predation, attract mates or house offspring, but the behaviour and potential cognitive processes involved during building are poorly understood. Great bowerbird (Ptilinorhynchus nuchalis) males build and maintain display courts by placing tens to hundreds of objects in a positive size-distance gradient. The visual angles created by the gradient create a forced perspective illusion that females can use to choose a mate. Although the quality of illusion is consistent within males, it varies among males, which may reflect differences in how individuals reconstruct their courts. We moved all objects off display courts to determine how males reconstructed the visual illusion. We found that all individuals rapidly created the positive size-distance gradient required for forced perspective within the first 10 objects placed. Males began court reconstruction by placing objects in the centre of the court and then placing objects further out, a technique commonly used when humans lay mosaics. The number of objects present after 72 h was not related to mating success or the quality of the illusion, indicating that male skill at arranging objects rather than absolute number of objects appears to be important. We conclude that differences arise in the quality of forced perspective illusions despite males using the same technique to reconstruct their courts.


Incorporating machine learning and social determinants of health indicators into prospective risk adjustment for health plan payments.
Risk adjustment models are employed to prevent adverse selection, anticipate budgetary reserve needs, and offer care management services to high-risk individuals. We aimed to address two unknowns about risk adjustment: whether machine learning (ML) and inclusion of social determinants of health (SDH) indicators improve prospective risk adjustment for health plan payments. We employed a 2-by-2 factorial design comparing: (i) linear regression versus ML (gradient boosting) and (ii) demographics and diagnostic codes alone, versus additional ZIP code-level SDH indicators. Healthcare claims from privately-insured US adults (2016-2017), and Census data were used for analysis. Data from 1.02 million adults were used for derivation, and data from 0.26 million to assess performance. Model performance was measured using coefficient of determination (R2), discrimination (C-statistic), and mean absolute error (MAE) for the overall population, and predictive ratio and net compensation for vulnerable subgroups. We provide 95% confidence intervals (CI) around each performance measure. Linear regression without SDH indicators achieved moderate determination (R2 0.327, 95% CI: 0.300, 0.353), error ($6992; 95% CI: $6889, $7094), and discrimination (C-statistic 0.703; 95% CI: 0.701, 0.705). ML without SDH indicators improved all metrics (R2 0.388; 95% CI: 0.357, 0.420; error $6637; 95% CI: $6539, $6735; C-statistic 0.717; 95% CI: 0.715, 0.718), reducing misestimation of cost by $3.5 M per 10,000 members. Among people living in areas with high poverty, high wealth inequality, or high prevalence of uninsured, SDH indicators reduced underestimation of cost, improving the predictive ratio by 3% (~$200/person/year). ML improved risk adjustment models and the incorporation of SDH indicators reduced underpayment in several vulnerable populations.


Retrieving autobiographical memories of painful events activates the anterior cingulate cortex and inferior frontal gyrus.
Patients will often reflect on the meaning of a painful episode, as, for example, when completing questionnaire measures of subjective pain experience or in clinical interviews. Neuroimaging studies of the human cortical and subcortical physical pain response have identified a neural network consistently referred to as the "pain matrix." We used functional magnetic resonance imaging to investigate whether the pain matrix could be activated through the retrieval of memories relating to previously painful events, in the absence of any direct peripheral noxious input. Fourteen pain-free participants were explicitly instructed to recall autobiographical memories of painful episodes in response to pain-related words and non-painful episodes in response to equally salient but non-pain words. Memories triggered by pain-related words produced significantly greater activation of left caudal anterior cingulate cortex (BA32'), and left inferior frontal gyrus (BA44, extending to BA47/45) more than memories triggered by equally salient but non-pain words. We suggest that these activations demonstrate a semantic retrieval process for pain-related memories, which may provide a means of cognitively reappraising the memory of the painful episode, thus allowing the person to elaborate on the circumstances surrounding the event, without physically re-experiencing it. The present study reveals a putative neural mechanism for the retrieval of autobiographical memories of previously painful events, which may provide a means of cognitively reappraising a painful episode, without physically re-experiencing it. This finding has implications for understanding disease mechanisms of chronic pain and their impact on subsequent treatment.


Monophasic sarcomatoid eccrine porocarcinoma. Report of a case and literature review.
Sarcomatoid porocarcinoma (SP) is a rare subtype of porocarcinoma composed of both malignant epithelial and sarcoma-like components. To our knowledge, only eight cases of this neoplasm have been published, all of them biphasic. A 42-year-old man presented with a latero-cervical nodule that had been noted for about five months. Histopathological study revealed an infiltrative tumor within the dermis and hypodermis without connection to epidermis, whose diagnosis was monophasic sarcomatoid eccrine porocarcinoma (SEP). The study of nine cases de SP, including the present, revealed that the ages of the patients ranged from 42 to 89 years (mean 72.3 years). There was no clear difference in the incidence with respect to gender. The location of the tumor was most common in the head and neck, followed by lower extremity. The size ranged from 2.5 cm to 3.5 cm (mean 3 cm). At the time of diagnosis, six (66.7%) lesions were ulcerated. No case was clinically diagnosed. Residual poroma was present in six (66.7%) cases. Only one case showed apocrine differentiation. Mitoses and comedonecrosis were frequent. Of the cases published, only four had a follow-up of at least 16 months. One patient succumbed to the tumor. We report for the first time a case of monophasic SEP without epidermal connection. The patient presented a regional lymph node metastasis three months after excision. The main differential diagnosis includes primary dermal melanoma and other rare variants of cutaneous melanoma, primary cutaneous clear cell sarcoma, primary cutaneous synovial sarcoma, and cutaneous metastasis from visceral sarcomatoid carcinoma.


Enantioselectivity of basic analytes in CZE enantioseparation under reversed-polarity mode using sulfated beta-cyclodextrins as chiral selectors: An unusual temperature effect.
Temperature effects on the enantioselectivity of basic analytes in CZE enantioseparation were studied under reversed-polarity mode using randomly sulfate-substituted beta-CDs (MI-S-beta-CD) as chiral seletors. Two catecholamines (epinephrine and isoproterenol) and two structurally related compounds (octopamine and norephedrine) were selected as test compounds in an electrophoretic system at low pH. The mobility differences between the (+)-enantiomers and the (-)-enantiomers of the two catecholamines and dopamine at 40 degrees C are greater than those at 25 degrees C with MI-S-beta-CD, even at a concentration as low as 0.3% w/v. Thus the enantioselectivity of these three basic analytes increases with increasing temperature. This phenomenon results from the inequality of the temperature effect on the mobility of the two enantiomers. In contrast, norephedrine behaves differently. The (+)-enantiomers of these basic analytes were found to migrate faster than the (-)-enantiomers. Consequently, the unusual temperature effect on the enantioselectivity can be observed when the mobility difference of the (+)-enantiomer between 40 and 25 degrees C is greater than that of the (-)-enantiomer using MI-S-beta-CD at a concentration greater than about 0.7% w/v for enantioseparation of isoproterenol, 0.4% w/v for epinephrine, and 0.3% w/v for octopamine. This unusual temperature effect offers the advantages to enhance enantioselectivity, to improve enantioseparation, and to reduce migration times.


Engineering yeast for the production of breviscapine by genomic analysis and synthetic biology approaches.
The flavonoid extract from Erigeron breviscapus, breviscapine, has increasingly been used to treat cardio- and cerebrovascular diseases in China for more than 30 years, and plant supply of E. breviscapus is becoming insufficient to satisfy the growing market demand. Here we report an alternative strategy for the supply of breviscapine by building a yeast cell factory using synthetic biology. We identify two key enzymes in the biosynthetic pathway (flavonoid-7-O-glucuronosyltransferase and flavone-6-hydroxylase) from E. breviscapus genome and engineer yeast to produce breviscapine from glucose. After metabolic engineering and optimization of fed-batch fermentation, scutellarin and apigenin-7-O-glucuronide, two major active ingredients of breviscapine, reach to 108 and 185 mg l-1, respectively. Our study not only introduces an alternative source of these valuable compounds, but also provides an example of integrating genomics and synthetic biology knowledge for metabolic engineering of natural compounds.


Determinants of the receipt of the 9-valent human papillomavirus vaccine in the first year after introduction in North Carolina.
The objective of this study was to describe the transition from bi- and quadrivalent HPV vaccines to 9vHPV in aggregate and identify determinants of the receipt of 9vHPV among youth following the introduction of 9vHPV in North Carolina. The study used a retrospective cohort design with data from the North Carolina Immunization Registry (NCIR). Our sample included all doses of HPV vaccine administered between July 2015 and October 2016 to age-eligible youth (ages 9-17). We used a logistic regression model to associate individual child-level and ZIP Code Tabulation Area (ZCTA)-level characteristics with an indicator variable for receiving 9vHPV (vs. other HPV vaccines). Youth receiving the HPV vaccine were more likely to receive 9vHPV if they lived in a ZCTA with a larger age-eligible (i.e., 9-17) population, a health professional shortage area, or a higher number of annual outpatient visits per capita. They were less likely to receive 9vHPV if they were older, received a publicly-funded dose, or lived in a ZCTA with a higher percentage of the population with less than a high-school education or a higher number of religious organizations. While the transition from other HPV vaccines to 9vHPV was relatively quick, there were disparities in the diffusion of 9vHPV across North Carolina.


Postbiotics as the new frontier in food and pharmaceutical research.
Food is the essential need of human life and has nutrients that support growth and health. Gastrointestinal tract microbiota involves valuable microorganisms that develop therapeutic effects and are characterized as probiotics. The investigations on appropriate probiotic strains have led to the characterization of specific metabolic byproducts of probiotics named postbiotics. The probiotics must maintain their survival against inappropriate lethal conditions of the processing, storage, distribution, preparation, and digestion system so that they can exhibit their most health effects. Conversely, probiotic metabolites (postbiotics) have successfully overcome these unfavorable conditions and may be an appropriate alternative to probiotics. Due to their specific chemical structure, safe profile, long shelf-life, and the fact that they contain various signaling molecules, postbiotics may have anti-inflammatory, immunomodulatory, antihypertensive properties, inhibiting abnormal cell proliferation and antioxidative activities. Consequently, present scientific literature approves that postbiotics can mimic the fundamental and clinical role of probiotics, and due to their unique characteristics, they can be applied in an oral delivery system (pharmaceutical/functional foods), as a preharvest food safety hurdle, to promote the shelf-life of food products and develop novel functional foods or/and for developing health benefits, and therapeutic aims. This review addresses the latest postbiotic applications with regard to pharmaceutical formulations and commercial food-based products. Potential postbiotic applications in the promotion of host health status, prevention of disease, and complementary treatment are also reviewed.


[Arrhythmia due to mitral valve prolapse].
Mitral valve prolapse (MVP) a common condition easily recognised by echocardiography with, however, strict criteria to avoid diagnosis by excess, may be complicated by arrhythmias. Two very different situations oppose severe decompensated mitral regurgitation due to myxoid dystrophy and quasi-asymptomatic MVP with a good prognosis and a low risk of complications. The important question is therefore to detect risk criteria of sudden death in patients with few symptoms. Unfortunately, no isolated factor or association of factors resolves this problem in a given patient. However, it is usually young women without severe mitral regurgitation but with thickened valves and, sometimes, a long QT interval, who are involved. Programmed ventricular stimulation and the detection of later ventricular potentials do not seem to be useful in the present state of our knowledge.


Potential of gold nanoparticles for oxidation in fine chemical synthesis.
In recent years supported gold nanoparticles have emerged as efficient catalysts with considerable synthetic potential for liquid-phase oxidation reactions based on molecular oxygen as oxidant. Here we critically review the most attractive applications related to the selective oxidation of functional groups containing O, N, or Si heteroatoms. The reactions include the oxidation of alcohols, aldehydes, and organosilanes; the diverse transformations of amines; benzylic oxidations; and some one-pot multistep reactions starting with alcohol or amine oxidation. In complex liquid-phase transformations relying on bifunctional catalysis, appropriate choice of the support is frequently more important than the size of the gold particles. In some oxidation reactions gold nanoparticles outperform the traditional platinum-group metal catalysts, but the latest results indicate the superiority of bimetallic particles containing gold and platinum, palladium, or rhodium. The environmentally benign nature of the transformations is discussed.


Review: Endocrine regulation of placental phenotype.
Hormones have an important role in regulating fetal development. They act as environmental signals and integrate tissue growth and differentiation with relation to nutrient availability. While hormones control the developmental fate of resources available to the fetus, the actual supply of nutrients and oxygen to the fetus depends on the placenta. However, much less is known about the role of hormones in regulating placental development, even though the placenta has a wide range of hormone receptors and produces hormones itself from early in gestation. The placenta is, therefore, exposed to hormones by autocrine, paracrine and endocrine mechanisms throughout its lifespan. It is known to adapt its phenotype in response to environmental cues and fetal demand signals, particularly when there is a disparity between the fetal genetic drive for growth and the nutrient supply. These adaptive responses help to maintain fetal growth during adverse conditions and are likely to depend, at least in part, on the hormonal milieu. This review examines the endocrine regulation of placental phenotype with particular emphasis on the glucocorticoid hormones. It focuses on the availability of placental hormone receptors and on the effects of hormones on the morphology, transport capacity and endocrine function of the placenta.


Identification of a protein product of the myotonic dystrophy gene using peptide specific antibodies.
In order to identify the protein product of the recently characterised myotonic dystrophy gene, we have raised an antibody (DMAP1) to a peptide sequence of the predicted gene product. This antibody identifies a novel 52 kDa protein in a range of mouse tissues, and in addition a related 42 kDa protein in brain and heart. A second antibody raised to a different peptide from the same predicted sequence, also identifies the 52 kDa protein, which strongly implies that this 52 kDa protein is a major translation product of the myotonic dystrophy gene.


Scrotal approach for inguinal hernia and hydrocele repair in boys.
The scrotal approach to repairing inguinal hernias and hydroceles in boys is a relatively new approach, which offers the paediatric surgeon the choice of leaving a more cosmetically acceptable scar. This paper reports the experience of one centre using this approach. 195 consecutive repairs in 176 boys were studied. The operative technique is described. With an average follow-up of 13 months, there was one recurrence. There were no wound infections. Testicular size was equal or larger than the contralateral testicle in all but two cases. All boys had an excellent cosmetic result. The scrotal approach for inguinal hernia or hydrocele repair is a safe procedure without added morbidity and with excellent cosmetic results.


Exercise training and endothelial dysfunction in coronary artery disease and chronic heart failure. From molecular biology to clinical benefits.
Endothelial dysfunction (ED) has been documented in patients with both coronary artery disease (CAD) and chronic heart failure (CHF)-being responsible for exercise-induced myocardial ischemia in the former and increased afterload in the latter. In the last two decades exercise training has assumed a major role in both cardiovascular disorders. In CAD exercise training has established positive effects on myocardial perfusion. Recently, exercise training has been shown to attenuate paradoxical vasoconstriction in CAD. The improved ED after training explains the improvement of myocardial perfusion in the absence of changes in baseline coronary artery diameter. Since ED has been identified as a predictor of coronary events exercise may contribute to long-term reductions of cardiovascular mortality. In CHF the increased peripheral vascular resistance - especially during exercise - is more important. ED contributes to the peripheral vasoconstriction. Training programs have shown to improve ED in CHF. A long-term study of hemodynamic effects of training in CHF revealed a significant reduction of total peripheral resistance (TPR) that after 6 months with a concomitant increase in stroke volume. In a subgroup analysis a significant correlation between changes in TPR and changes in peripheral ED was observed. Cell culture and animal experiments suggest that shear stress increases the endothelial L-arginine uptake, enhances NO synthase activity and expression, and upregulates the production of extracellular superoxide dismutase, which prevents premature NO breakdown. All these molecular effects converge on a reduction of myocardial ischemic events in CAD and a decrease of afterload in CHF.


From achiral to helical bilayer self-assemblies of a 1,3,5-triazine-2,4,6-triphenol-grafted polyanionic cluster: countercation and solvent modulation.
A triazine derivative with two short alkyl chains was covalently grafted onto a disk-like polyoxometalate cluster on both sides, and an amphiphilic polyanionic cluster was obtained. The linear cluster complex showed phase separation in polar and non-polar solutions and self-assembled into spherical, planar, and helical aggregates in turn with the solution polarity decreasing from the methanol/water to the chloroform/n-hexane mixture. Accompanied by morphological changes, the self-assembled bilayer structure varied from a regular bilayer structure either partially or fully, to an over interdigitated bilayer structure and finally to a partially inverse interdigitated bilayer structure. Moreover, induced chirality took place and was amplified in the helical assembly via the modulation of counter-cations and solvent polarity.