Metabolomics Study of Resina Draconis on Myocardial Ischemia Rats Using Ultraperformance Liquid Chromatography/Quadrupole Time-of-Flight Mass Spectrometry Combined with Pattern Recognition Methods and Metabolic Pathway Analysis.
Resina draconis (bright red resin isolated from Dracaena cochinchinensis, RD) has been clinically used for treatment of myocardial ischemia (MI) for many years. However, the mechanisms of its pharmacological action on MI are still poorly understood. This study aimed to characterize the plasma metabolic profiles of MI and investigate the mechanisms of RD on MI using ultraperformance liquid chromatography/quadrupole time-of-flight mass spectrometry-based metabolomics combined with pattern recognition methods and metabolic pathway analysis. Twenty metabolite markers characterizing metabolic profile of MI were revealed, which were mainly involved in aminoacyl-tRNA biosynthesis, phenylalanine, tyrosine, and tryptophan biosynthesis, vascular smooth muscle contraction, sphingolipid metabolism, and so forth. After RD treatment, however, levels of seven MI metabolite markers, including phytosphingosine, sphinganine, acetylcarnitine, cGMP, cAMP, L-tyrosine, and L-valine, were turned over, indicating that RD is likely to alleviate MI through regulating the disturbed vascular smooth muscle contraction, sphingolipid metabolism, phenylalanine metabolism, and BCAA metabolism. To our best knowledge, this is the first comprehensive study to investigate the mechanisms of RD for treating MI, from a metabolomics point of view. Our findings are very valuable to gain a better understanding of MI metabolic profiles and provide novel insights for exploring the mechanisms of RD on MI.


Pitfalls of adverse event reporting in paediatric cardiac intensive care.
To evaluate the pitfalls of incident reporting in a complex medical environment. Retrospective review of 211 incident reports in a paediatric cardiac intensive care unit (CICU). Two adverse event reporting databases were compared: database A (DA), the hospital's official reporting system, is non-anonymous and reports are predominantly made by nurses; database B (DB) is anonymous and reports are submitted by a CICU consultant who collects data from daily ward rounds. Both databases classify adverse events into incident type (drug errors, ventilation, cannulae/indwelling lines, chest drains, blood transfusion, equipment, operational) and severity (0 = no, 1 = minor, 2 = major, 3 = life threatening consequences). Between 1 April 1998 and 31 July 2001 there were 211 adverse events involving 178 patients (11.87%), among 1500 patients admitted to CICU. A total of 112 incidents were reported in DA, 143 in DB, and 44 in both. In isolation, both databases gave an unrepresentative picture of the true frequency and severity of adverse events. Under-reporting was especially notable for less severe events (grade 0, or near misses) Incident reporting in the medical field is highly variable, and is heavily influenced by profession of the reporters as well as anonymity. When adverse event reporting is based predominantly on the observations of a single professional group, the data are grossly inaccurate.


Effects of Parkinson's disease on visuomotor adaptation.
Visuomotor adaptation to a kinematic distortion was investigated in Parkinson's disease (PD) patients and age-matched controls. Participants performed pointing movements in which the visual feedback of hand movement, displayed as a screen cursor, was normal (pre-exposure condition) or rotated by 90 degrees counterclockwise (exposure condition). Aftereffects were assessed in a post-exposure condition in which the visual feedback of hand movement was set back to normal. In pre- and early-exposure trials, both groups showed similar initial directional error (IDE) and movement straightness (RMSE, root mean square error), but the PD group showed reduced movement smoothness (normalized jerk, NJ) and primary submovement to total movement distance ratios (PTR). During late-exposure the PD subjects, compared with controls, showed larger IDE, RMSE, NJ, and smaller PTR scores. Moreover, PD patients showed smaller aftereffects than the controls during the post-exposure condition. Overall, the PD group showed both slower and reduced adaptation compared with the control group. These results are discussed in terms of reduced signal-to-noise ratio in feedback signals related to increased movement variability and/or disordered kinesthesia, deficits in movement initiation, impaired selection of initial movement direction, and deficits in internal model formation in PD patients. We conclude that Parkinson's disease impairs visuomotor adaptation.


Effectiveness of programmes as part of primary prevention demonstrated on the example of cardiovascular diseases and the metabolic syndrome.
The HTA-report (HTA = Health Technology Assessment) deals with the primary prevention of cardiovascular diseases and diabetes mellitus type 2. In 2009 approximately 356,000 people died in Germany due to cardiovascular diseases. According to estimations about 6.3 million people are suffering from diabetes mellitus type 2. The interventions that are subsidized by the public health insurance are mainly focused on sufficient physical activities, healthy nutrition, stress management and the reduction of the consumption of addictive drugs and luxury food. Which lifestyle-related measures and/or programmes for primary prevention of cardiovascular diseases and of the metabolic syndrome are effective? To what extent will the health status be improved by these offers? To what extent will existing health resources and skills be strengthened by these offers? Are there any differences regarding the effectiveness among the interventions with respect to different settings or subgroups? Which lifestyle-related interventions and/or programmes for primary prevention of cardiovascular diseases and of the metabolic syndrome are sustainable and cost-effective? Which outcome parameters are in the view of the contributors decisive for the evaluation of the effectiveness? In the view of the contributor are there different values between the outcome parameters? In the view of the payers and other actors are there different values between the outcome parameters? Which ethical and juridical factors have to be considered? Which social and/or socio-economic parameters influence the use of the services and effectiveness? A systematic literature research is done in 35 databases. For the period 2005 to 2010, reviews, epidemiological and clinical studies as well as economical evaluations which deal with primary prevention programmes regarding cardiovascular diseases or the metabolic syndrome are included. 44 publications meet the inclusion criteria. These studies confirm the effectiveness of the primary prevention programmes. Physical activity programs seem to have a stronger effect than nutrition programmes. Psychological programmes prove as well effectiveness, if they include cognitive behaviour therapy. The identified economical studies indicate that programmes for cardiovascular prevention can be conducted cost-effectively. Interventions that focus on the general population turn out to be particularly cost-effective and sustainable. There is a wide range of primary preventive effective lifestyle-related interventions with high evidence. The outcomes and results are consistent with the recommendations of the two identified evidence-based guidelines regarding the recommendations on lifestyle and healthy nutrition. Furthermore, the cost-effectiveness of primary prevention services is proven. With regard to the economical studies it is however worth noting that this result is based on very few publications. The transferability has to be critically assessed as the studies mainly originate from the American health system. On the whole a comprehensive setting approach with educative, somatic, psychosocial and activity therapeutic components is recommended. The sustainability of a prevention intervention must be ensured from programme to programme. Long-term studies are necessary to make valid statements regarding the sustainable effectiveness: There is an essential deficit in the current practiced evaluation of the use of primary prevention services provided by the health insurance - mainly regarding the comprehensive setting approach - regarding the evidence-based evaluation of the prescribed preventive interventions. With regard to the ethical, social and economical evaluation the research situation is deficient. The situation has to be particularly analyzed for the socially deprived and one has to respond to their specific needs for prevention.


Reduction of GAG storage in MPS II mouse model following implantation of encapsulated recombinant myoblasts.
Hunter syndrome, mucopolysaccharidosis type II (MPS II), is a X-linked inherited disorder caused by the deficiency of the enzyme iduronate-2-sulfatase (IDS), involved in the lysosomal catabolism of the glycosaminoglycans (GAG) dermatan and heparan sulfate. Such a deficiency leads to the intracellular accumulation of undegraded GAG and eventually to a progressive severe clinical pattern. Many attempts have been made in the last two to three decades to identify possible therapeutic strategies for the disorder, including gene therapy and somatic cell therapy. In this study we evaluated the intraperitoneal implantation of allogeneic myoblasts over-expressing IDS, enclosed in alginate microcapsules, in the MPS II mouse model. Animals were monitored for 8 weeks post-implantation, during which plasma and tissue IDS levels, as well as tissue and urinary GAG contents, were measured. Induced enzyme activity occurred both in the plasma and in the different tissues analyzed. A significant decrease in urinary undegraded GAG between the fourth and the sixth week of treatment was observed. Moreover, a biochemical reduction of GAG deposits was measured 8 weeks after treatment in the liver and kidney, on average 30 and 38%, respectively, while in the spleen GAG levels were almost normalized. Finally, the therapeutic effect was confirmed by histolochemical examination of the same tissues. Such effects were obtained following implantation of about 1.5 x 10(6) recombinant cells/animal. Taken together, these results represent a clear evidence of the therapeutic efficacy of this strategy in the MPS II mouse model, and encourage further evaluation of this approach for potential treatment of human beings.


[Regional differences in fertility rates in real generations in Russia (according to the 2020 population census)].
Studies on birth rate regularities in Russia in the context of the task of ensuring reproduction of the population remain relevant. Assessment of the scale and trends in regional differentiation using the method of calculating birth rates in real generations of women makes it possible to obtain a more reliable picture of the ongoing processes, to assess the reproductive potential and target groups for the most effective implementation of demographic policy measures. The article presents results of calculations of fertility rates in real generations of women for all regions of the Russian Federation in line with the 2020 population census. The analysis has identified significant differences in the scale and patterns of fertility in the generations of women in the Russian regions. In 34 constituent entities of the Russian Federation, the difference (in one direction or another) between places in rows in terms of the average number of children born to women aged 40-44 (according to the 2020 population census) and the total fertility rate (2021 data) exceeds 10 places. The potential is best realized in the national republics, while in the regions of Central Russia small families prevail. The prognostic possibilities of using the expected numbers of children are proved, and the use of the total fertility rate indicator as a target for the Russian average indicators was validated. Interregional differentiation is significantly higher for the third birth, which is confirmed by the calculated coefficient of variation.


Adverse events associated with encorafenib plus binimetinib in the COLUMBUS study: incidence, course and management.
Dual inhibition of the mitogen-activated protein kinase pathway with BRAF/MEK inhibitor (BRAFi/MEKi) therapy is a standard treatment for BRAFV600-mutant metastatic melanoma and has historically been associated with grade III pyrexia or photosensitivity depending on the combination used. The objective of this study was to fully describe adverse events from the COLUMBUS study evaluating the most recent BRAF/MEK inhibitor combination encorafenib+binimetinib. Patients with locally advanced, unresectable or metastatic BRAFV600-mutant melanoma were randomised to receive encorafenib 450 mg once daily plus binimetinib 45 mg twice daily, encorafenib 300 mg once daily or vemurafenib 960 mg twice daily. Adverse events that represent known effects of available BRAFi and/or MEKi were evaluated. The safety population included a total of 570 patients (encorafenib+binimetinib = 192; encorafenib = 192; vemurafenib = 186). Median duration of exposure was longer with encorafenib+binimetinib (51 weeks) than with encorafenib (31 weeks) or vemurafenib (27 weeks). Common BRAFi/MEKi toxicities with encorafenib+binimetinib were generally manageable, reversible and infrequently associated with discontinuation. Pyrexia was less frequent with encorafenib+binimetinib (18%) and encorafenib (16%) than with vemurafenib (30%) and occurred later in the course of therapy with encorafenib+binimetinib (median time to first onset: 85 days versus 2.5 days and 19 days, respectively). The incidence of photosensitivity was lower with encorafenib+binimetinib (5%) and encorafenib (4%) than with vemurafenib (30%). The incidence of serous retinopathy was higher with encorafenib+binimetinib (20%) than with encorafenib (2%) or vemurafenib (2%), but no patients discontinued encorafenib+binimetinib because of this event. Encorafenib+binimetinib is generally well tolerated and has a low discontinuation rate in patients with BRAFV600-mutant melanoma, with a distinct safety profile as compared with other anti-BRAF/MEK targeted therapies. ClinicalTrials.gov (Identifier: NCT01909453) and with EudraCT (number 2013-001176-38).


Ginsenoside Rg3 Protects against Diabetic Cardiomyopathy and Promotes Adiponectin Signaling via Activation of PPAR-γ.
Ginsenoside Rg3 extracted from Panax notoginseng has therapeutic effects on diabetes and heart diseases. However, the underlying mechanism of ginsenoside Rg3 on diabetic cardiomyopathy (DCM) remains unclear. 24-week-old diabetic db/db mice were treated with ginsenoside Rg3 for 12 weeks, then body weight, serum lipids, adiponectin levels, as well as cardiac function and pathological morphology, were measured. The targets of ginsenoside Rg3 and its regulation of the adiponectin pathway were also evaluated on 3T3-L1 or H9c2 cells. Ginsenoside Rg3 directly bound to PPAR-γ, improving adiponectin secretion and promoting adiponectin signaling. Significantly attenuated overweight, hyperglycemia, and hyperlipidemia, as well as alleviated lipid accumulation and dysfunction in adipose, liver, and heart tissues, were observed in the ginsenoside Rg3-treated group. Ginsenoside Rg3 could be a promising drug targeting PPAR-γ to treat diabetic cardiomyopathy.


Comparison of near fusional vergence ranges with rotary prisms and with prism bars.
Common methods for determination of fusional vergence ranges make use of rotary prisms in the phoropter or prism bars out of the phoropter. This study compared near fusional vergence ranges with rotary prisms with those with prism bars. Fifty young adults served as subjects. Odd-numbered subjects had rotary prism vergences performed before prism bar vergences. For even-numbered subjects, prism bar vergences were done first. Base-in (BI) vergences were done before base-out (BO) vergences with both rotary prisms and prism bars. A coefficient of agreement was calculated by multiplying the standard deviation of the individual subject differences between rotary prisms and prism bars by 1.96, to approximate the range within which the 2 tests would agree 95% of the time. The lowest coefficient of agreement was 7.3Δ for the BI recovery. The others were high, ranging from 15.4Δ for the BO recovery to 19.5Δ for the BO break. Fusional vergence ranges determined by prism bars out of the phoropter cannot be used interchangeably with those determined by phoropter rotary prisms for the purpose of follow-up on individual patients or for the purpose of comparison with norms.


[The kinetics of the urinary excretion of mexidol and its glucuronate conjugate in patients].
Using HPLC with fluorescence detector we studied elimination kinetics of the antioxidant drug mexidol and its glucuronoconjugated metabolite in 16 patients suffering from neurosis and traumatic CNS injury after receiving mexadol (in a dose of 500 mg, in tablets). It is found that mexidol undergoes rapid glucuronoconjugation and is excreted with urine (0.31% and 49.6% of the received dose in the form of mexidol and its glucuronoconjugate, respectively) within 11.5-h period of examination. A substantial variability in the rate and degree of mexidol and glucuronoconjugate elimination with urine is observed. A trend to intensive glucuronoconjugation is observed in patients aged up to 40.


Role of a ZF-HD Transcription Factor in miR157-Mediated Feed-Forward Regulatory Module That Determines Plant Architecture in Arabidopsis.
In plants, vegetative and reproductive development are associated with agronomically important traits that contribute to grain yield and biomass. Zinc finger homeodomain (ZF-HD) transcription factors (TFs) constitute a relatively small gene family that has been studied in several model plants, including Arabidopsis thaliana L. and Oryza sativa L. The ZF-HD family members play important roles in plant growth and development, but their contribution to the regulation of plant architecture remains largely unknown due to their functional redundancy. To understand the gene regulatory network controlled by ZF-HD TFs, we analyzed multiple loss-of-function mutants of ZF-HD TFs in Arabidopsis that exhibited morphological abnormalities in branching and flowering architecture. We found that ZF-HD TFs, especially HB34, negatively regulate the expression of miR157 and positively regulate SQUAMOSA PROMOTER BINDING-LIKE 10 (SPL10), a target of miR157. Genome-wide chromatin immunoprecipitation sequencing (ChIP-Seq) analysis revealed that miR157D and SPL10 are direct targets of HB34, creating a feed-forward loop that constitutes a robust miRNA regulatory module. Network motif analysis contains overrepresented coherent type IV feedforward motifs in the amiR zf-HD and hbq mutant background. This finding indicates that miRNA-mediated ZF-HD feedforward modules modify branching and inflorescence architecture in Arabidopsis. Taken together, these findings reveal a guiding role of ZF-HD TFs in the regulatory network module and demonstrate its role in plant architecture in Arabidopsis.


Prevalence of DSM-IV disorders in a population-based sample of 5- to 8-year-old children: the impact of impairment criteria.
This study determined the impact of impairment criteria on the prevalence and patterns of comorbidity of child DSM-IV disorders. The validity of these impairment criteria was tested against different measures of mental health care referral and utilization. We interviewed parents of 1,154 children aged 5-8 years in-depth using the Diagnostic Interview Schedule for Children in Rotterdam, the Netherlands, to establish DSM-IV diagnosis. These children were randomly selected or oversampled based on Child Behavior Checklist ratings from a large population-based study (N = 6,172). Referral data were extracted from the psychiatric interview as well as from a follow-up questionnaire. The results showed an overall prevalence of DSM-IV disorders of 31.1 % when impairment was not considered. This rate declined to 22.9 % when mild impairment was required and declined even further, to 10.3 %, for more severe levels of impairment. Similarly, the overall comorbidity rate declined from 8.5 to 6.7 and 2.7 % when mild and severe impairment were required, respectively. Virtually all children who attained symptom thresholds for a specific disorder, and had been referred to a mental health care professional because of the associated symptoms, also had mild impairment. The requirement of severe impairment criteria significantly increased diagnostic thresholds, but for most disorders, this definition captured only half of the clinically referred cases. In conclusion, prevalence was highly dependent upon the criteria used to define impairment. If severe impairment is made a diagnostic requirement, many children with psychiatric symptoms and mild impairment seeking mental health care will be undiagnosed and possibly untreated.


Coordinated induction of inducible nitric oxide synthase and GTP-cyclohydrolase I is dependent on inflammatory cytokines and interferon-gamma in HaCaT keratinocytes: implications for the model of cutaneous wound repair.
Recently we demonstrated a strong expression of inducible nitric oxide synthase (iNOS) and GTP-cyclohydrolase I (GTP-CH I) in the basal keratinocytes of the epidermis adjacent to the wound and of the hyperproliferative epithelium during wound healing. To identify possible mediators of iNOS and GTP-CH I expression during this process, we analyzed the regulation of iNOS and GTP-CH I expression in cultured human keratinocytes. We found a large and long lasting coinduction of iNOS and GTP-CH I expression upon simultaneous treatment of quiescent cells with inflammatory cytokines interleukin-1beta, tumor necrosis factor-alpha, and interferon-gamma, but not with serum growth factors. The stimulatory effect of interleukin-1beta, tumor necrosis factor-alpha, and interferon-gamma is strongly synergistic on iNOS and GTP-CH I expression, because these factors alone stimulated GTP-CH I expression, although to a much lesser extent. Furthermore, iNOS mRNA levels are not influenced at all by stimulation with IL-1beta and revealed only a weak induction after treatment with tumor necrosis factor-alpha and interferon-gamma. Induction of iNOS and GTP-CH I gene expression upon cytokine and interferon-gamma exposure is independent of de novo protein synthesis. Because these cytokines are present at the wound site, they might be responsible for iNOS and GTP-CH I induction during cutaneous repair. Serum, which is released upon hemorrhage, is likely to play no stimulatory role in iNOS and GTP-CH I induction during wound healing.


[Health status of workers contacting chrysotile asbestos waste on railway objects].
Asbestos dust associated with other factors induces more hazardous effects, than if acting solely. That is seen especially in women whose morbidity grows 1.5-2.0 times higher than in men of the same occupations. Further studies are recommended for better knowledge asbestos dust influence under provocative action of other hazards.


Gestational diabetes and offspring birth size at elevated environmental pollutant exposures.
Gestational diabetes mellitus (GDM) is associated with increased availability of glucose and macronutrients in fetal circulation and macrosomia. Therefore, the role of GDM in the association between metabolism-disrupting chemicals and birth size deserves attention. We examined whether GDM may mediate or modify the associations between maternal environmental pollutant exposures and offspring birth size measures. We analyzed 604 Faroese pregnant women and their offsprings born in 1997-2000. Maternal pregnancy serum concentrations of organochlorine compounds (OCs: polychlorinated biphenyl (PCB) congeners and dichlorodiphenyldichloroethylene (DDE)), and five perfluoroalkyl substances (PFASs), and hair and cord blood mercury concentrations were measured. We used regression (single-pollutants) and structural equation models (SEMs) (multiple-pollutant analyses using latent constructs of OCs, PFASs and mercury) to estimate the associations with GDM and birth size measures, accounting for mediation and/or effect modification by GDM. Serum-DDE and hair-mercury concentrations were associated with GDM (adjusted OR per concentration doubling: 1.29; 95% CI: 0.94, 1.77 for DDE, and 0.79; 95% CI: 0.62, 0.99 for mercury), but in multiple pollutant-adjusted SEMs only a positive association between OC exposure and GDM remained significant (change in GDM odds per OC doubling: 0.45; 95% CI: 0.05, 0.86). PCB and overall OC exposure were positively associated with head circumference (SEM; mean change per OC doubling: 0.13cm; 95% CI, 0.01. 0.25). Overall PFAS exposure was inversely associated with birth weight (SEM; mean change per PFAS doubling: -169g; 95% CI: -359, 21), and for many single-PFASs we found a pattern of inverse associations with birth weight and head circumference in boys, and positive or null associations in girls. None of the environmental pollutants was associated with offspring length. GDM neither modified nor mediated the associations with birth size measures. We found associations with GDM and offspring birth size to be specific to the environmental pollutant or pollutant group. Associations with birth size measures appear to be independent of GDM occurrence.


Quercetin supplementation does not alter antioxidant status in humans.
This study measured the influence of ingesting quercetin on plasma measures for oxidative stress and antioxidant capacity. Male and female subjects (n = 1002) varying in age (18-85 years) and body mass index (BMI) (16.7-52.7 kg/m(2)) were studied. Subjects were randomized to one of three groups using double-blinded methods: placebo, 500 mg or 1000 mg quercetin/day with 125 mg or 250 mg vitamin C/day, respectively. Pre- and post-study fasting blood samples show that plasma quercetin increased in a dose-responsive manner. The pattern of change in plasma F(2)-isoprostanes, oxidized low density lipoprotein, reduced glutathione, ferric reducing ability of plasma (FRAP) and oxygen radical absorbance capacity (ORAC) did not differ between supplementation groups or after adjustment for gender, age, BMI and disease status. In summary, quercetin supplementation over 12 weeks in doses of 500 mg or 1000 mg/day significantly increased plasma quercetin levels, but had no influence on several measures of oxidative stress and antioxidant capacity.


Economic evaluation of the HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) randomized controlled trial: an exercise training study of patients with chronic heart failure.
Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION) assigned 2331 outpatients with medically stable heart failure to exercise training or usual care. We compared medical resource use and costs incurred by these patients during follow-up. Extensive data on medical resource use and hospital bills were collected throughout the trial for estimates of direct medical costs. Intervention costs were estimated using patient-level trial data, administrative records, and published unit costs. Mean follow-up was 2.5 years. There were 2297 hospitalizations in the exercise group and 2332 in the usual care group (P=0.92). The mean number of inpatient days was 13.6 (standard deviation [SD], 27.0) in the exercise group and 15.0 (SD, 31.4) in the usual care group (P=0.23). Other measures of resource use were similar between groups, except for trends indicating that fewer patients in the exercise group underwent high-cost inpatient procedures. Total direct medical costs per participant were an estimated $50,857 (SD, $81,488) in the exercise group and $56,177 (SD, $92,749) in the usual care group (95% confidence interval for the difference, $-12,755 to $1547; P=0.10). The direct cost of exercise training was an estimated $1006 (SD, $337). Patient time costs were an estimated $5018 (SD, $4600). The cost of exercise training was relatively low for the health care system, but patients incurred significant time costs. In this economic evaluation, there was little systematic benefit in terms of overall medical resource use with this intervention. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00047437.


A Scoping Review of Respirator Literature and a Survey among Dental Professionals.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus was discovered in China in late 2019 and subsequently triggered a global pandemic. Dentists, like many other health professionals, are at an increased risk of contracting the virus as they work in close proximity to patients, especially when performing aerosol-generating procedures. Thus, in order for dentists to protect themselves and their patients, it is recommended that practitioners wear filtering facepiece 2 (FFP2) respirators. The prolonged use of these FFP2 respirators has been linked to several side effects. The aim of this paper is to assess the perceived experience associated with N95/FFP2 respirators based on the available literature and data collected through an online survey completed by Italian dental professionals. Articles were included up to May 2020 and literature searches were conducted through The National Library of Medicine, Cochrane Central Register of Controlled Trials, and Embase databases. The search terms included COVID-19, respirators, masks, and discomfort. An online survey was administered to 256 Italian dentists. The results from this survey were in agreement with the available literature. The findings concurred that the prolonged use of respirators was associated with headaches (47.5%), severe exertion and discomfort (50.8%), moderate concentration problems (54.3%), moderate breathing difficulties (63.5%), and consequently, an impaired work ability (85.5%). These findings were not influenced by the number of hours spent wearing the respirator. Despite several side effects, FFP2 respirators are fundamental in protecting dentists and their importance was acknowledged.


Hierarchical Flower-like Sulfides with Increased Entropy for Electromagnetic Wave Absorption.
The concept of high entropy is considered promising to enhance electromagnetic wave absorption properties. However, preparing high-entropy sulfides with unique structures for high-performance electromagnetic absorption remains a challenge. In this study, hierarchical porous flower-like dual-phase sulfides were designed with increased entropy and fabricated using a versatile approach. The porous flower configuration enhanced the scattering of electromagnetic waves and the impedance-matching characteristics. Additionally, the effect of high entropy induced diverse defects that were favorable for electromagnetic wave dissipation in dual-phase sulfides. The design of the dual-phase structure generated strong interface polarization, and the composition and content of the phases exhibited clear changes with the increase in the number of metal elements. Interestingly, apparent lattice distortions, defects, and shear strains were directly observed near the dual-phase interface of millerite (102) and pyrite (220) planes, facilitating the occurrence of dipole polarization. Consequently, the developed dual-phase high-entropy sulfide exhibited outstanding microwave absorption properties. The minimum reflection loss value of (FeCoNiCuZn)S was -45.8 dB at a thickness of 1.5 mm, and the optimal effective absorption bandwidth was 3.8 GHz at a thickness of 1.4 mm thickness. Thus, the design of high-entropy sulfides brings meaningful guidance for tuning the wave absorption properties in sulfides.


Protective roles of gamma delta T cells and interleukin-15 in Escherichia coli infection in mice.
The number of gamma delta T cells in the peritoneal cavity was increased after an intraperitoneal (i.p.) infection with Escherichia coli in lipopolysaccharide (LPS)-responsive C3H/HeN mice but not in LPS-hyporesponsive C3H/HeJ mice. The gamma delta T cells preferentially expressed invariant Vgamma6 and Vdelta1 chains and proliferated to produce a large amount of gamma interferon in the presence of LPS. Mice depleted of gamma delta T cells by T-cell receptor delta gene mutation showed impaired resistance against E. coli as assessed by bacterial growth. Macrophages from C3H/HeN mice infected with E. coli expressed higher levels of interleukin-15 (IL-15) mRNA than those from the infected C3H/HeJ mice. Administration of anti-IL-15 monoclonal antibody inhibited, albeit partially, the appearance of gamma delta T cells in C3H/HeN mice after E. coli infection and diminished the host defense against the infection. These results suggest that LPS-stimulated gamma delta T cells play an important role in the host defense against E. coli infection and that IL-15 may be partly involved in the protection via an increase in the gamma delta T cells.


When and why women might suspend PrEP use according to perceived seasons of risk: implications for PrEP-specific risk-reduction counselling.
Oral pre-exposure prophylaxis (PrEP) using the antiretroviral drug emtricitabine/tenofovir disoproxil fumarate (Truvada) has been shown to dramatically reduce the risk of HIV acquisition for women at higher risk of infection if taken daily. Understanding when and why women would intentionally stop using an efficacious oral PrEP drug within the context of their 'normal' daily lives is essential for delivering effective PrEP risk-reduction counselling. As part of a larger study, we conducted 60 qualitative interviews with women at higher risk of HIV in Bondo, Kenya, and Pretoria, South Africa. Participants charted their sexual contacts over the previous six months, indicated whether they would have taken PrEP if available and discussed whether and why they would have suspended PrEP use. Nearly all participants said they would have used PrEP in the previous six months; half indicated they would have suspended PrEP use at some point. Participants' reasons for an extended break from PrEP were related to partnership dynamics (e.g., perceived low risk of a stable partner) and phases of life (e.g., trying to conceive). Life events (e.g., holidays and travel) could prompt shorter breaks in PrEP use. These circumstances may or may not correspond to actual contexts of lower risk, highlighting the importance of tailored PrEP risk-reduction counselling.


Clinical longevity of ceramic laminate veneers bonded to teeth with and without existing composite restorations up to 40 months.
This study evaluated the survival rate of ceramic laminate veneers bonded to teeth with and without existing composite restorations (ECR). Twenty patients (mean age: 49.7 years) received 92 feldspathic ceramic laminate veneers (Shofu Vintage AL) on the maxillary teeth (intact teeth: n = 26; teeth with ECR: n = 66). Preparations with incisal overlap were made, and ECR of good quality were not removed but conditioned using silica coating (CoJet) and silanization (ESPE-Sil). Enamel and dentin were etched with 38% H3PO4 for 15-30 s and rinsed 30 s; adhesive resin (Excite) was applied, and laminate veneers were then cemented (Variolink Veneer). Restorations were evaluated at baseline and thereafter every 6 months using modified United States Public Health Service criteria. Mean observation period was 21.6 months. Overall, five absolute failures were encountered (fractures: n = 3; chipping: n = 1; debonding: n = 1), resulting in a survival rate of 94.6% (Kaplan-Meier). Survival rates of the laminates bonded to teeth without (96%) and with ECR (93.5%) did not show significant differences (p > 0.05). Slight marginal defects (16 of 87 laminates) and slight marginal discoloration at the margins were noted (12 of 87 laminates) until the final recall. Secondary caries and endodontic complications were not detected in any of the teeth. The clinical survival of ceramic laminate veneers up to 40 months was not significantly influenced when they were bonded onto intact teeth or onto teeth with ECR. When no caries is present, it may not be necessary to replace existing composite restorations prior to cementation of ceramic laminate veneers.


C8orf46 homolog encodes a novel protein Vexin that is required for neurogenesis in Xenopus laevis.
Neural basic helix-loop helix (bHLH) transcription factors promote progenitor cell differentiation by activation of downstream target genes that coordinate neuronal differentiation. Here we characterize a neural bHLH target gene in Xenopus laevis, vexin (vxn; previously sbt1), that is homologous to human c8orf46 and is conserved across vertebrate species. C8orf46 has been implicated in cancer progression, but its function is unknown. Vxn is transiently expressed in differentiating progenitors in the developing central nervous system (CNS), and is required for neurogenesis in the neural plate and retina. Its function is conserved, since overexpression of either Xenopus or mouse vxn expands primary neurogenesis and promotes early retinal cell differentiation in cooperation with neural bHLH factors. Vxn protein is localized to the cell membrane and the nucleus, but functions in the nucleus to promote neural differentiation. Vxn inhibits cell proliferation, and works with the cyclin-dependent kinase inhibitor p27Xic1 (cdkn1b) to enhance neurogenesis and increase levels of the proneural protein Neurog2. We propose that vxn provides a key link between neural bHLH activity and execution of the neurogenic program.


Studies on cardiac myofibrillogenesis with antibodies to titin, actin, tropomyosin, and myosin.
Cardiac myofibrillogenesis was examined in cultured chick cardiac cells by immunofluorescence using antibodies against titin, actin, tropomyosin, and myosin. Primitive cardiomyocytes initially contained stress fiber-like structures (SFLS) that stained positively for alpha actin and/or muscle tropomyosin. In some cases the staining for muscle tropomyosin and alpha actin was disproportionate; this suggests that the synthesis and/or assembly of these two isoforms into the SFLS may not be stoichiometric. The alpha actin containing SFLS in these myocytes could be classified as either central or peripheral; central SFLS showed developing sarcomeric titin while peripheral SFLS had weak titin fluorescence and a more uniform stain distribution. Sarcomeric patterns of titin and myosin were present at multiple sites on these structures. A pair of titin staining bands was clearly associated with each developing A band even at the two or three sarcomere stage, although occasional examples of a titin band being associated with a half sarcomere were noted. The appearance of sarcomeric titin patterns coincided or preceded sarcomere periodicity of either alpha actin or muscle tropomyosin. The early appearance of titin in myofibrillogenesis suggests it may have a role in filament alignment during sarcomere assembly.


Intracorporeal lithotripsy: which modality is best?
A large number of related articles published within the last year were reviewed. Different types of intracorporeal lithotripter devices were compared according to their advantages, disadvantages, efficacy, safety and clinical applications. General directions of future developments are discussed. Ultrasound lithotripters employed through rigid endoscopes provide high fragmentation rates (97-100%) and stone free rate (94%). Clinical evaluation of a new combination ultrasound and pneumatic lithotripter reported an overall stone free rate of 80-89.7%. No major complications were observed. The holmium:YAG (Yttrium-Aluminum-Garnet) laser lithotripter is able to destroy all compositions of stone. The stone free rate for ureteral stones is close to 100%. Complications are rare and minimal. Newer wavelengths such as erbium:YAG are currently impractical. There are limited clinical data regarding frequency-doubled double-pulse neodymium:YAG laser lithotripsy. Ultrasound lithotripsy is still the preferable modality applied through rigid endoscopes. A new combination of ultrasound and pneumatic impactor includes the advantages of each mode. The holmium:YAG laser lithotripter is the method of choice for flexible endoscopic procedures. Further development of new lithotripters with different energy sources and their combination is necessary.


Augmented surveillance of antimicrobial resistance with high-throughput robotics detects transnational flow of fluoroquinolone-resistant Escherichia coli strain into poultry.
Food animal AMR surveillance programs assess only small numbers of Escherichia coli (from 100 to 600 per animal class) nationally each year, severely limiting the evaluation of public health risk(s). Here we demonstrate an affordable approach for early detection of emerging resistance on a broad scale that can also accurately characterize spatial and temporal changes in resistance. Caecal samples (n = 295) obtained from 10 meat poultry were screened using high-throughput robotics. Initial screening via agar dilution (5310 plates) quantified AMR carriage (cfu/g) for each sample. Ciprofloxacin-resistant isolates (n = 91) proceeded to downstream broth microdilution susceptibility testing. A subset of 28 ciprofloxacin-resistant isolates underwent WGS and phylogenetic analysis. Intra- and inter-flock carriage of resistance varied with drug class. Ampicillin and tetracycline resistance was ubiquitous to most birds in all flocks with an average carriage rate of 5.8 log10 cfu/g. Gentamicin and ciprofloxacin-resistant E. coli colonized fewer birds, and had an average carriage rate of 1.2 log10 cfu/g and 1.0 log10 cfu/g of faeces, respectively. Resistance to extended-spectrum cephalosporins was absent. ST354 was the dominant ST among the WGS isolates, but they demonstrated markedly lower resistance gene carriage than their international counterparts. These data amply demonstrate the ineffectiveness of commonly relied-on approaches to AMR surveillance for achieving early detection of emergence, or for measuring spatial and temporal resistance trends. Genetic analysis suggested there has been transnational flow of a ciprofloxacin-resistant strain into Australian poultry flocks, explaining their detection in a nation that prohibits fluoroquinolone use in poultry.


Peripapillary vessel density in healthy people, primary open-angle glaucoma, and normal-tension glaucoma.
To compare peripapillary vessel density using optical coherence tomography angiography (OCT-A) in eyes of healthy people, primary open-angle glaucoma (POAG), and normal-tension glaucoma (NTG). Thirty patients with POAG, 27 patients with NTG, and 29 healthy individuals in the control group were assessed. Capillary vessels in peripapillary retinal nerve fiber layer (RNFL) represented by whole image RPC (radial peripapillary capillary) density in an AngioDisc scan 4.5 × 4.5 mm centered on the optic disc, and ONH morphological variables (disc area, rim area, cup to disc area ratio (CDR)), and average peripapillary RNFL thickness were measured. Differences in mean RPC, RNFL, disc area, rim area, and CDR between the groups were statistically significant (P < 0.05). The difference in RNFL thickness and rim area was not significant between NTG and healthy groups, while RPC and CDR showed a statistically significant difference between all pairs. The vessel density in the POAG group was 8.25% and 11.7% lower compared to the NTG and healthy groups, respectively; while the mean difference was less (2.97%) for the NTG and healthy group. In the POAG group, 67.2% of the variation in RPC can be explained by a model containing CDR and RNFL thickness, and in normal eyes 38.8% of the changes using a model containing RNFL. The peripapillary vessel density is reduced in both types of glaucoma. The vessel density in NTG was significantly lower than in the healthy eyes, despite the lack of significant difference in RNFL thickness and neuroretinal rim area between them.


Phase contrast imaging reveals low lung volumes and surface areas in the developing marsupial.
Marsupials are born with immature lungs when compared to eutherian mammals and rely, to various extents, on cutaneous gas exchange in order to meet metabolic requirements. Indeed, the fat-tailed dunnart is born with lungs in the canalicular stage of development and relies almost entirely on the skin for gas exchange at birth; consequently undergoing the majority of lung development in air. Plane radiographs and computed tomography data sets were acquired using phase contrast imaging with a synchrotron radiation source for two marsupial species, the fat-tailed dunnart and the larger tammar wallaby, during the first weeks of postnatal life. Phase contrast imaging revealed that only two lung sacs contain air after the first hour of life in the fat-tailed dunnart. While the lung of the tammar wallaby was comparatively more developed, both species demonstrated massive increases in air sac number and architectural complexity during the postnatal period. In addition, both the tammar wallaby and fat-tailed dunnart had lower lung volumes and parenchymal surface areas than were expected from morphometrically determined allometric equations relating these variables to body mass during the neonatal period. However, lung volume is predicted to scale with mass as expected after the neonatal marsupial reaches a body mass of ∼1 g and no longer relies on the skin for gas exchange. Decreased lung volume in the marsupial neonate further supports the maxim that cutaneous gas exchange occurs in the marsupial neonate because the respiratory apparatus is not yet capable of meeting the gas exchange requirements of the newborn.


Multistage selection for genetic gain by orthogonal transformation.
An exact transformed culling method for any number of traits or stages of selection with explicit solution for multistage selection is described in this paper. This procedure does not need numerical integration and is suitable for obtaining either desired genetic gains for a variable proportion selected or optimum aggregate breeding value for a fixed total proportion selected. The procedure has similar properties to multistage selection index and, as such, genetic gains from use of the procedure may exceed ordinary independent culling level selection. The relative efficiencies of transformed to conventional independent culling ranged from 87% to over 300%. These results suggest that for most situations one can chose a multistage selection scheme, either conventional or transformed culling, which will have an efficiency close to that of selection index. After considering cost savings associated with multistage selection, there are many situations in which economic returns from use of independent culling, either conventional or transformed, will exceed that of selection index.


Chalkley Estimates of Angiogenesis in Early Breast Cancer - Relevance to Prognosis.
The aim of this study was to investigate whether Chalkley estimates of angiogenesis add new knowledge regarding prediction of prognosis in 455 consecutive early breast carcinomas, both node-positive (52%) and node-negative (48%). Median follow-up was 101 months. Intense vascularization indicated poor disease-specific (p=0.003) and overall (p=0.004) survival. In node-negative patients, Chalkley counts were not associated with prognosis, whereas in node-positive patients, high Chalkley scores indicated poor disease-specific (p=0.0006) and overall (p=0.0008) survival. A multivariate analysis showed that positive lymph nodes, high histopathological grades, and negative oestrogen receptors were independent markers of cancer-related death. A high histopathological grade was associated with cancer-related death in node-negative patients, whereas in node-positive patients, many lymph nodes, high malignancy grade, negative oestrogen receptor, and increasing Chalkley counts (both tertiles and continuous) were independent markers of disease-specific death. Thus, in a univariate analysis it was found that high Chalkley estimates of angiogenesis indicated a poor prognosis, but high Chalkley estimates were independent prognostic markers only in node-positive patients.


Low temperature-acclimation impairs cellular migration in the adult cerebral cortex of the tropical lizard, Tropidurus hispidus (Spix, 1825) (Squamata: Tropiduridae).
The effects of different temperature-acclimations on cellular proliferation and migration were studied in the cerebral cortex of the tropical lizard, Tropidurus hispidus. Lizards were divided in two groups: warm-acclimated lizards (WALs), maintained at the temperature and photoperiod conditions of their natural habitat (mean temperature 26°C; 12:12 light:dark) and the cold-acclimated lizards (CALs), maintained at the same cycle of illumination and a mean temperature of 16°C. Animals were injected with the proliferative marker 5-bromodeoxyuridine (BrdU) and euthanized fifteen or thirty days later for the immunostaining. There was no difference in the number of BrdU-positive nuclei between the experimental groups in any of the cortical layers. In CALs, the positive nuclei were found mostly close to the ependyma, whereas in WALs many positive nuclei were also found in the plexiform and cellular layers of the cortex. In CALs, BrdU-positive nuclei appeared grouped (of 2-3 nuclei), a characteristic not seen in the other group. These data suggest that temperature affects the migrating capability of the newly generated neurons in the lizard cortex, but appears not to interfere with its generation.


Ultra-thin parylene-aluminium hybrid coatings on nanocellulose films to resist water sensitivity.
Non-sustainable single-use plastics used for food packaging needs to be phased out. Films made from cellulose nanofibrils (CNFs) are suitable candidates for biodegradable and recyclable packaging materials as they exhibit good mechanical properties, excellent oxygen barrier properties and high transparency. Yet, their poor water vapour barrier properties have been a major hindrance in their commercialisation. Here, we describe the preparation of 25 μm thick CNF films with significantly improved water vapour barrier properties after deposition of ultrathin polymeric and metallic coatings, parylene C and aluminium, respectively. When first adding a 40 nm aluminium layer followed by an 80 nm parylene layer, i.e. with a combined thickness of less than one percent of the CNF film, a water vapour transmission rate of 2.8 g m-2 d-1 was achieved at 38 °C and 90 % RH, surpassing a 25 μm polypropylene film (4-12 g m-2 d-1). This is an improvement of more than 700 times compared to uncoated CNF films, under some of the harshest possible conditions a packaging material will need to endure in commercial use. The layers showed a good and even coverage, as assessed by atomic force microscopy, and the parylene-coated surfaces were hydrophobic with a contact angle of 110°, providing good water repellency.


Carbonic anhydrase inhibitory properties of novel benzylsulfamides using molecular modeling and experimental studies.
In this study, a series of sulfamoyl carbamates and sulfamide derivatives were synthesized. Six commercially available benzyl amines and BnOH were reacted with chlorosulfonyl isocyanate (CSI) to give sulfamoyl carbamates. Pd-C catalyzed hydrogenolysis reactions of carbamates afforded sulfamides. The inhibition effects of novel benzylsulfamides on the carbonic anhydrase I, and II isoenzymes (CA I, and CA II) purified from fresh human blood red cells were determined by Sepharose-4B-L-Tyrosine-sulfanilamide affinity chromatography. In vitro studies were shown that all of novel synthesized benzylsulfamide analogs inhibited, concentration dependently, both hCA isoenzyme activities. The novel benzylsulfamide compounds investigated here exhibited nanomolar inhibition constants against the two isoenzymes. Ki values were in the range of 28.48±0.01-837.09±0.19nM and 112.01±0.01-268.01±0.22nM for hCAI and hCA II isoenzymes, respectively. Molecular modeling approaches were also applied for studied compounds.


Full-Duplex Cooperative Sensing for Spectrum-Heterogeneous Cognitive Radio Networks.
In cognitive radio networks (CRNs), spectrum sensing is critical for guaranteeing that the opportunistic spectrum access by secondary users (SUs) will not interrupt legitimate primary users (PUs). The application of full-duplex radio to spectrum sensing enables SU to carry out sensing and transmission simultaneously, improving both spectrum awareness and CRN throughput. However, the issue of spectrum sensing with full-duplex radios deployed in heterogeneous environments, where SUs may observe different spectrum activities, has not been addressed. In this paper, we give a first look into this problem and develop a light-weight cooperative sensing framework called PaCoSIF, which involves only a pairwise SU transmitter (SU-Tx) and its receiver (SU-Rx) in cooperation. A dedicated control channel is not required for pairwise cooperative sensing with instantaneous feedback (PaCoSIF) because sensing results are collected and fused via the reverse channel provided by full-duplex radios. We present a detailed protocol description to illustrate how PaCoSIF works. However, it is a challenge to optimize the sensing performance of PaCoSIF since the two sensors suffer from spectrum heterogeneity and different kinds of interference. Our goal is to minimize the false alarm rate of PaCoSIF given the bound on the missed detection rate by adaptively adjusting the detection threshold of each sensor. We derive an expression for the optimal threshold using the Lagrange method and propose a fast binary-searching algorithm to solve it numerically. Simulations show that, with perfect signal-to-interference-and-noise-ratio (SINR) information, PaCoSIF could decrease the false alarm rate and boost CRN throughput significantly against conventional cooperative sensing when SUs are deployed in spectrum-heterogeneous environments. Finally, the impact of SINR error upon the performance of PaCoSIF is evaluated via extensive simulations.


Early liver transplantation is essential for familial amyloidotic polyneuropathy patients' quality of life.
Nineteen patients, who had undergone liver transplantation for familial amyloidotic polyneuropathy, had answered a quality of life questionnaire including 61 questions on somatic and mental symptoms, social aspects of life, confidence and satisfaction before, one year, and two years after transplantation. We found that patient satisfaction was generally good two years or more after the transplantation. Most of the patients were very or quite satisfied with the result. All of them had the drive to go on and felt hopeful about the future. However, on the second follow-up, 37% of the patients noted that they felt more insecure in their everyday life and there was a significant difference between the two assessments. The diarrhea score became worse between one and two years after the transplantation and was closely related to the duration of the gastrointestinal symptoms and to the duration of the disease before transplantation. The mental symptoms also increased significantly between the evaluations and this related to the severity of the somatic symptoms. Our conclusion is that liver transplantation should be performed before advanced somatic symptoms start to develop in order to improve the patients' chances of a good quality of life following liver transplantation.


Risk-Based Approach for Analytical Comparability and Comparability Protocols.
Chemistry, manufacturing, and control postapproval changes are an intrinsic part of the life cycle of pharmaceutical products. In this paper, the authors examined the potential impact of such changes on the product quality, safety, and efficacy of biologics. Comparability studies and more specifically analytical comparability are introduced as one of the tools that can support both biomanufacturers and health agencies in ensuring that patient safety and product safety and efficacy is maintained through the proposed changes. Together with a scientific risk-based review approach based on product and process knowledge and the definition of acceptance criteria that will ensure that the product is "essentially similar", what constitutes a holistic comparability study is detailed. ICH Guidelines principles and definitions are used throughout the paper to aid the reader with other appropriate references. Finally, two case studies are presented: change to the manufacturing facility of the drug substance, and change to the manufacturing process of a drug substance intermediate and manufacturing facility.


Catalytic HF Shuttling between Fluoroalkanes and Alkynes.
In this paper, we report BF3•OEt2 as a catalyst to shuttle equivalents of HF from a fluoroalkane to an alkyne. Reactions of terminal and internal aliphatic alkynes led to formation of difluoroalkane products, while diarylalkynes can be selectively converted into fluoroalkenes. The method tolerates numerous sensitive functional groups including halogen, protected amine, ester and thiophene substituents. Mechanistic studies (DFT, probe experiments) suggest the catalyst is involved in both the defluorination and fluorination steps, with BF3 acting as a Lewis acid and OEt2 a weak Lewis base that mediates proton transfer. In certain cases, the interconversion of fluoroalkene and difluoroalkane products was found to be reversible. The new catalytic system was applied to demonstrate proof-of-concept recycling of poly(vinylidene difluoride).


A comparative study on the hepatoprotective effect of selenium-nanoparticles and dates flesh extract on carbon tetrachloride induced liver damage in albino rats.
Exposure to environmental pollutants such as carbon tetrachloride (CCL4) causes liver damage. This study aimed to compare the ameliorative activity of the dates flesh extract (DFE) and selenium-nanoparticles (SeNPs) on CCL4-induced hepatotoxicity and if DFE could be a useful alternative supplement. Twenty-four male albino rats were enrolled and randomly divided into four equal groups (6 rats in each group): control group received only basal diet with no medications. Group II received CCL4 in a dose of 0.5 mg/kg intraperitoneal injection twice weekly for four weeks. Group III rats were pretreated with SeNPs in a dose of 2.5 mg/kg once a day orally three times/wk for four weeks alone then combined with the previously described dose of CCL4 for another four weeks. Group IV rats were pretreated with DFE in a dose of 8 ml of the aqueous extract/kg/d orally for four weeks alone then combined with the previously described dose of CCL4 for another four weeks. The liver damage was assessed by estimation of plasma concentration of albumin and enzymes activities of alanine aminotransferase and tissue genes expression. Liver oxidation levels were assessed by measuring the tissue concentration of the malondialdehyde, superoxide dismutase, and the total glutathione. Additionally, inflammatory mediators tumour necrosis factor--α and interleukin-6 were estimated. Detecting the liver's cellular structural damage was done by histopathological and immunohistochemical examination. This study suggests that CCL4-induced liver damage in rats can be protected by administration whether the costly SeNPs or the economical DFE.


Associations among work-related stress, cortisol, inflammation, and metabolic syndrome.
This cross-sectional study examined the relationship between work-related stress, cortisol, and C-reactive protein (CRP) in predicting metabolic syndrome (MtS). Self-reported work stress measured by the effort reward imbalance ratio (ERI), anthropometric data, CRP, and saliva cortisol were collected from 204 healthy Jordanian male workers. ERI and cortisol were significantly associated with the presence of MtS (OR = 4.74, 95% CI: 2.13-10.55; OR = 3.03, 95% CI: 2.08-4.40; OR = 11.50, 95% CI: 2.16-59.14, respectively). The odds of MtS in men with high ERI and high cortisol were significantly higher than that of men with low ERI and low cortisol (OR = 11.50, 95% CI: 2.16-59.14). CRP was significantly associated with MtS (OR = 2.51, 95% CI: 1.50-4.20). The odds of MtS were significantly higher in centrally obese men with both high ERI and CRP level. Thus, high ERI along with high cortisol or high CRP increases the risk for MtS, especially among centrally obese men.


Speech errors reflect newly learned phonotactic constraints.
Speech errors reveal the speaker's implicit knowledge of phonotactic constraints, both languagewide constraints (e.g., /K/ cannot be a syllable onset when one is speaking English) and experimentally induced constraints (e.g., /k/ cannot be an onset during the experiment). Four experiments investigated the acquisition of novel 2nd-order constraints, in which the allowable position of a consonant depends on some other property of the syllable (e.g., /k/ can only be an onset if the vowel is /I/). Participants recited strings of syllables that exhibited the novel constraints throughout a 4-day experiment. Their errors reflected the newly learned constraints but not until the 2nd day of training. This contrasts with previous research showing that errors become sensitive to 1st-order constraints almost immediately. A model that learns to assign phonemes to syllable positions is presented. It attributes the relative slowness of the acquisition of 2nd-order constraints to the self-interfering property of these constraints.


Emerging role of regulatory T cells in gene transfer.
Induction and maintenance of immune tolerance to therapeutic transgene products are key requirements for successful gene replacement therapies. Gene transfer may also be used to specifically induce immune tolerance and thereby augment other types of therapies. Similarly, gene therapies for treatment of autoimmune diseases are being developed in order to restore tolerance to self-antigens. Regulatory T cells have emerged as key players in many aspects of immune tolerance, and a rapidly increasing body of work documents induction and/or activation of regulatory T cells by gene transfer. Regulatory T cells may suppress antibody formation and cytotoxic T cell responses and may be critical for immune tolerance to therapeutic proteins. In this regard, CD4(+)CD25(+) regulatory T cells have been identified as important components of tolerance in several gene transfer protocols, including hepatic in vivo gene transfer. Augmentation of regulatory T cell responses should be a promising new tool to achieve tolerance and avoid immune-mediated rejection of gene therapy. During the past decade, it has become obvious that immune regulation is an important and integral component of tolerance to self-antigens and of many forms of induced tolerance. Gene therapy can only be successful if the immune system does not reject the therapeutic transgene product. Recent studies provide a rapidly growing body of evidence that regulatory T cells (T(reg)) are involved and often play a crucial role in tolerance to proteins expressed by means of gene transfer. This review seeks to provide an overview of these data and their implications for gene therapy.


Carriers in cell-based therapies for neurological disorders.
There is a pressing need for long-term neuroprotective and neuroregenerative therapies to promote full function recovery of injuries in the human nervous system resulting from trauma, stroke or degenerative diseases. Although cell-based therapies are promising in supporting repair and regeneration, direct introduction to the injury site is plagued by problems such as low transplanted cell survival rate, limited graft integration, immunorejection, and tumor formation. Neural tissue engineering offers an integrative and multifaceted approach to tackle these complex neurological disorders. Synergistic therapeutic effects can be obtained from combining customized biomaterial scaffolds with cell-based therapies. Current scaffold-facilitated cell transplantation strategies aim to achieve structural and functional rescue via offering a three-dimensional permissive and instructive environment for sustainable neuroactive factor production for prolonged periods and/or cell replacement at the target site. In this review, we intend to highlight important considerations in biomaterial selection and to review major biodegradable or non-biodegradable scaffolds used for cell transplantation to the central and peripheral nervous system in preclinical and clinical trials. Expanded knowledge in biomaterial properties and their prolonged interaction with transplanted and host cells have greatly expanded the possibilities for designing suitable carrier systems and the potential of cell therapies in the nervous system.


Using transmission properties to determine blood glucose levels.
A non-intrusive technique based on modeling the body as a transmission channel was tested in vitro and was shown to perform equally with a commercial OTS glucose meter on saline-glucose solutions of concentrations of glucose from 30 to 300 mg/dL. The technique uses an initial frequency sweep to locate a frequency where a resonant response occurs. At that position the phase is changing rapidly and can therefore be used more easily to measure a phase difference. This sweet spot can be natural or assisted. Present efforts are toward a system which uses a feedback amplifier with a low phase margin in order to easily find the the region of rapid phase change. Initial tests measuring known glucose concentrations with an OTS glucose meter and then using the proposed technique were shown to correlate with the actual concentrations with an R(2) = 0.9879 and R(2) = 0.9952 respectively (with one outlier data point removed). Further tests are being conducted in vitro on whether other interfering agents may disrupt results. The ultimate goal of the development of this technique is to fabricate a device that is worn externally on the upper arm and does not require blood for testing. A device is being built and is scheduled for human subject testing in Summer 2013. Some results of human testing may be available at the EMBC conference. Human testing will involve measurements done with our device against an OTS glucose meter and results compared. The future goal is to refine the device so that it can be worn 24 hours a day and will automatically test the wearer at a user specified interval such as 10 or 20 minutes by transmitting a low power signal for a few microseconds. Power levels are still being determined but, in simulation, nano-watts was sufficient for the distance needed to travel which is orders of magnitude less than present day cell phones. To evaluate safety of the system, 3D electromagnetic simulations are being carried out with the device positioned strapped to the upper arm. Simulations show transmission along the targeted paths which suggests that affective glucose sensing is possible with this device.


Activation of Stat3 in renal tumors.
Signal transducer and activator of transcription 3 (Stat3) plays a vital role in signal transduction pathways that mediate transformation and inhibit apoptosis. Oncogenic Stat3 is persistently activated in several human cancers and transformed cell lines. Previous studies indicate activation of Stat3 in renal cell carcinoma (RCC). However, the detailed characterization of the Stat3 expression pattern in different histologic types of RCC is lacking. We have analyzed the immunoprofile of activated or phosphorylated Stat3 (pStat3) in a tissue microarray of renal tumors of different histologic types, including 42 cases of conventional clear cell type, 24 chromophobe, and 7 papillary, 15 oncocytoma, 7 urothelial carcinoma and 21 normal kidney tissues using an anti-pStat3 antibody (recognizes only activated STAT3). pStat3 nuclear staining was observed in 25 of 42 conventional clear cell RCC (59.5 %), 8 of 24 chromophobe RCC (33.3%), 4 of 7 papillary RCC (57.1%). In the other tumor groups, 4 of 15 oncocytomas (26.7%) and 6 of 7 urothelial carcinomas (85.7%) showed positive nuclear staining. Weak nuclear immunoreactivity for pStat3 was seen in 4 of 21 cases of non-neoplastic kidney tissue (19.0%). The extent of Stat3 activation as determined by nuclear expression of its phosphorylated form is increased in histologic types of renal tumors with greater malignant potential, specifically conventional clear cell RCC, papillary RCC and urothelial carcinoma, only slightly increased in chromophobe RCC, and not increased in oncocytoma. These results suggest a role of Stat3 activation in different types of renal neoplasia, possibly serving as a prognostic marker or therapeutic target.


Visual corticopontine and tectopontine projections in the macaque.
We studied projections from extrastriate visual areas and the superior colliculus to the pontine nuclei of monkeys using degeneration staining and transport of wheatgerm agglutinin horseradish peroxidase, and 3H amino acids. The superior colliculus and the extrastriate cortical visual areas both project to the ipsilateral dorsolateral region of the pontine nuclei. The projections from extrastriate visual cortex occupy a much larger territory within the pontine nuclei than those from the superior colliculus. The superficial laminae of the superior colliculus project only to the ipsilateral pontine nuclei. The projection to the contralateral nucleus reticularis tegmenti pontis arises from cells in deeper laminae within the superior colliculus.


Gluconeogenesis measured with [U-13C]glucose and mass isotopomer analysis of apoB-100 amino acids in pigs.
Infant pigs (8.5 kg) were fasted for 16 h and infused for 6 h with [U-13C]glucose. The fractional abundances of all 13C mass isotopomers of plasma glucose, lactate, and pyruvate and of plasma, hepatic, and very low density lipoprotein apolipoprotein B-100 (apoB-100) alanine, glutamate, and aspartate were measured. The ratios of [13C3]aspartate. [13C3]glutamate, and [13C3]alanine in apoB-100 were used to estimate the positional equilibrium of [13C3]oxaloacetate, the fractional contribution of pyruvate carboxylase to the hepatic oxaloacetate flux, and the activity of hepatic pyruvate dehydrogenase. The values were compared with those based on glucose labeling and previously published equations. The two methods [Katz and Lee method (J. Katz, P.A. Wals., and W.-N. P. Lee. J. Biol. Chem. 264: 12994-13001, 1989) and apoB method] gave similar estimates of the positional equilibrium of [13C3]oxaloacetate (0.59, Katz and Lee method; 0.61, apoB method) but slightly different estimates of the contribution of pyruvate carboxylase to the oxaloacetate flux (0.36, Katz and Lee; 0.31 apoB). Gluconeogenesis apparently contributed between 71 (Katz and Lee method) and 80% (apoB method) of the glucose entry rate (25 mumol.kg-1.min-1), and pyruvate dehydrogenase contributed 20% of the hepatic acetyl-CoA. We conclude that the labeling of aspartate in apoB-100 provides a good estimate of the isotopomer distribution in hepatic oxaloacetate but may underestimate the absolute isotopic enrichment by 50%.


Inducible Fgf13 ablation enhances caveolae-mediated cardioprotection during cardiac pressure overload.
The fibroblast growth factor (FGF) homologous factor FGF13, a noncanonical FGF, has been best characterized as a voltage-gated Na+ channel auxiliary subunit. Other cellular functions have been suggested, but not explored. In inducible, cardiac-specific Fgf13 knockout mice, we found-even in the context of the expected reduction in Na+ channel current-an unanticipated protection from the maladaptive hypertrophic response to pressure overload. To uncover the underlying mechanisms, we searched for components of the FGF13 interactome in cardiomyocytes and discovered the complete set of the cavin family of caveolar coat proteins. Detailed biochemical investigations showed that FGF13 acts as a negative regulator of caveolae abundance in cardiomyocytes by controlling the relative distribution of cavin 1 between the sarcolemma and cytosol. In cardiac-specific Fgf13 knockout mice, cavin 1 redistribution to the sarcolemma stabilized the caveolar structural protein caveolin 3. The consequent increase in caveolae density afforded protection against pressure overload-induced cardiac dysfunction by two mechanisms: (i) enhancing cardioprotective signaling pathways enriched in caveolae, and (ii) increasing the caveolar membrane reserve available to buffer membrane tension. Thus, our results uncover unexpected roles for a FGF homologous factor and establish FGF13 as a regulator of caveolae-mediated mechanoprotection and adaptive hypertrophic signaling.


Pattern of allergic rhinitis among children in Ekiti, Nigeria.
Allergic rhinitis is a chronic and recurrent nasal condition. It is often neglected in children with late presentation. This study aimed at determining the prevalence, sociodemographic features, comorbid illnesses, complications and quality of life in children with allergic rhinitis in the study institution. This is a prospective hospital based study of children with allergic rhinitis in Ekiti state university teaching hospital, Ado Ekiti. The study was carried out in ENT department over a period of two years (between June 2015 to May 2017). Informed consent was obtained from the parents/guardian/patients and consented patients were enrolled into the study. Data were obtained by pretested interviewers assisted questionnaire. Details of their history, physical examination and investigations were carried out and findings were documented. All data obtained were descriptively analysed using SPSS version 18.0 and presented in simple tables and charts. Ethical clearance was sought for and obtained from the ethical committee of the hospital. A total of 4341 patients were seen out of which 265 were children with allergic rhinitis. Prevalence of allergic rhinitis in children in this study was 6.1%. There were 63.0% males with male to female ratio of 2:1. Allergic rhinitis was peaked at preschool age group (1-5 years) accounted for 47.9%. A total of 42.3% participants were living in urban setting while 57.7% were from rural setting. Majorities (40.4%) of the patients were in nursery and parent's major occupation was mainly farming in 27.2%. There was positive family history of allergy in 54.7% patients. Perennial allergic rhinitis were noted in 63.8% patients while seasonal allergic rhinitis were noted in 36.2% patients. Major form of allergens was inhalant 81.8% and the least form of allergen was ingestant 5.7%. The commonest identified trigger factors among the study population were as follows: dust, cold weather and smoke which were accounted for 59.6%, 37.4% and 18.9% of the study patients respectively. Other noted triggering factors were soap and perfume which accounted for 4.2% and 1.1% respectively. Major associated comorbid illnesses among the patients were tonsils hypertrophy, adenoid hypertrophy and inferior turbinate hypertrophy which accounted for 55.5%, 46.4% and 40.4% respectively. Clinical presentations of allergic rhinitis in this study were mainly 75.8% nasal blockage, 65.3% runny nose and 8.5% recurrent sneezing. Commonest complications of allergic rhinitis were 35.1% pharyngitis, 32.1% otitis media and 28.3% headache. Treatment of allergic rhinitis leads to improvement on the clinical features in 90.1% patients. No significant improvement in clinical features were noticed in 9.8% patients. None of the studied patients reported worse clinical condition after treatment of allergic rhinitis. No mortality was recorded from allergic rhinitis in this study. Allergic rhinitis affect all paediatric age group and there were delayed presentation in the participants. There were associated comorbid illnesses, complications and affectation of quality of life at presentation in majority of the patients.


Molecular approaches to the study of atrial natriuretic factor.
Application of recombinant DNA technology to the study of atrial natriuretic factor (ANF) has significantly increased our understanding of the biochemistry and physiology of this cardiac hormone. Molecular characterization of the ANF gene and mRNA has yielded structural details about this peptide, and provided tools to investigate maturation, storage, and secretion of a cardiac hormone. Genetic probes have facilitated analyses of the role of a natriuretic and vasorelaxant hormone in pathophysiologic states. Furthermore, studies on the regulation of this cardiac gene have begun to provide data on the molecular basis for biochemical changes in the heart that occur in response to physiologic and pathologic processes.


Role of nitric oxide in Salmonella typhimurium-mediated cancer cell killing.
Bacterial targeting of tumours is an important anti-cancer strategy. We previously showed that strain SL7838 of Salmonella typhimurium targets and kills cancer cells. Whether NO generation by the bacteria has a role in SL7838 lethality to cancer cells is explored. This bacterium has the mechanism for generating NO, but also for decomposing it. Mechanism underlying Salmonella typhimurium tumour therapy was investigated through in vitro and in vivo studies. NO measurements were conducted either by chemical assays (in vitro) or using Biosensors (in vivo). Cancer cells cytotoxic assay were done by using MTS. Bacterial cell survival and tumour burden were determined using molecular imaging techniques. SL7838 generated nitric oxide (NO) in anaerobic cell suspensions, inside infected cancer cells in vitro and in implanted 4T1 tumours in live mice, the last, as measured using microsensors. Thus, under these conditions, the NO generating pathway is more active than the decomposition pathway. The latter was eliminated, in strain SL7842, by the deletion of hmp- and norV genes, making SL7842 more proficient at generating NO than SL7838. SL7842 killed cancer cells more effectively than SL7838 in vitro, and this was dependent on nitrate availability. This strain was also ca. 100% more effective in treating implanted 4T1 mouse tumours than SL7838. NO generation capability is important in the killing of cancer cells by Salmonella strains.


Cortical thickness and prosocial behavior in school-age children: A population-based MRI study.
Prosocial behavior plays an important role in establishing and maintaining relationships with others and thus may have important developmental implications. This study examines the association between cortical thickness and prosocial behavior in a population-based sample of 6- to 9-year-old children. The present study was embedded within the Generation R Study. Magnetic resonance scans were acquired from 464 children whose parents had completed the prosocial scale of the Strengths and Difficulties Questionnaire. To study the association between cortical thickness and prosocial behavior, we performed whole-brain surface-based analyses. Prosocial behavior was related to a thicker cortex in a cluster that covers part of the left superior frontal and rostral middle frontal cortex (p < .001). Gender moderated the association between prosocial behavior and cortical thickness in a cluster including the right rostral middle frontal and superior frontal cortex (p < .001) as well as in a cluster covering the right superior parietal cortex, cuneus, and precuneus (p < .001). Our results suggest that prosocial behavior is associated with cortical thickness in regions related to theory of mind (superior frontal cortex, rostral middle frontal cortex cuneus, and precuneus) and inhibitory control (superior frontal and rostral middle frontal cortex).


Natural cholera infection-derived immunity in an endemic setting.
Live oral cholera vaccines may protect against cholera in a manner similar to natural cholera infections. However, information on which to base these vaccines is limited. The study was conducted in a cholera-endemic population in Bangladesh. Patients with cholera (index patients) detected between 1991 and 2000 were age-matched to 4 cholera-free controls and then followed up during the subsequent 3 years. El Tor cholera was associated with a 65% (95% confidence interval [CI], 37%-81%; P < .001) lower risk of a subsequent El Tor episode. Reduction of the risk of subsequent El Tor cholera was similar for children < 5 years and for older persons and was sustained during all 3 years of follow-up. Having El Tor Inaba cholera was associated with lower risks of both El Tor Inaba and El Tor Ogawa cholera, but having El Tor Ogawa cholera was associated only with a reduced risk of El Tor Ogawa cholera. O139 cholera was associated with a 63% (95% CI, -61% to 92%; P = .18) lower risk of subsequent O139 cholera, but there was no evidence of cross-protection between the O1 and O139 serogroups. Live oral cholera vaccines designed to protect against the O1 and O139 serogroups should contain at least the Inaba serotype and strains of both serogroups.


Distinct roles for sodium, chloride, and calcium in excitotoxic dendritic injury and recovery.
The postsynaptic neuronal dendrite is selectively vulnerable to hypoxic-ischemic brain injury and glutamate receptor overactivation. We explored the glutamate receptor pharmacology and ionic basis of rapid, reversible alterations in dendritic shape which occur in cultured neurons exposed to glutamate. Dendrite morphology was assessed with the fluorescent membrane tracer, DiI, or immunofluorescence labeling of the somatodendritic protein, MAP2. Cortical cultures derived from 15-day-old mouse embryos underwent segmental dendritic beading when exposed to NMDA, AMPA, or kainate, but not to metabotropic glutamate receptor agonists. Varicosity formation in response to NMDA or kainate application was substantially attenuated in reduced sodium buffer (substituted with N-methyl-D-glucamine). Furthermore, veratridine-induced sodium entry mimicked excitotoxic alterations in dendrites and additionally caused varicosity formation in axons. Solutions deficient in chloride (substituted with Na methylsulfate) and antagonists of chloride-permeable GABA/glycine receptors reduced NMDA- or kainate-induced varicosity formation. An increase in dendrite volume was observed as varicosities formed, and varicosity formation was attenuated in sucrose-supplemented hypertonic media. Despite marked structural changes affecting virtually all neurons, dendrite shape returned to normal within 2 h of terminating glutamate receptor agonist application. Neurons exposed to kainate recovered more rapidly than those exposed to NMDA, and neurons exposed to NMDA in calcium-free buffer recovered more rapidly than cells treated with NMDA in normal buffer. While sodium, chloride, and water entry contribute to excitotoxic dendritic injury acutely, calcium entry through NMDA receptors results in lasting structural changes in damaged dendrites.


Hepatitis C virus double-stranded RNA is the predominant form in human liver and in interferon-treated cells.
Hepatitis C virus (HCV) is unique among RNA viruses in its ability to establish chronic infection in the majority of exposed adults. HCV persists in the liver despite interferon (IFN)-stimulated gene (ISG) induction; robust induction actually predicts treatment failure and viral persistence. It is unclear which forms of HCV RNA are associated with ISG induction and IFN resistance during natural infections. To thoroughly delineate HCV RNA populations, we developed conditions that fully separate the strands of long double-stranded RNA (dsRNA) and allow the released RNAs to be quantified in reverse transcription/polymerase chain reaction assays. These methods revealed that dsRNA, a pathogen-associated molecular pattern (PAMP), comprised 52% (standard deviation, 28%) of the HCV RNA in the livers of patients with chronic infection. HCV dsRNA was proportionally higher in patients with the unfavorable IL28B TT (rs12979860) genotype. Higher ratios of HCV double-stranded to single-stranded RNA (ssRNA) correlated positively with ISG induction. In Huh-7.5 cells, IFN treatment increased the total amount of HCV dsRNA through a process that required de novo viral RNA synthesis and shifted the ratio of viral dsRNA/ssRNA in favor of dsRNA. This shift was blocked by ribavirin (RBV), an antiviral drug that reduces relapse in HCV patients. Northern blotting established that HCV dsRNA contained genome-length minus strands. HCV dsRNA is the predominant form in the HCV-infected liver and has features of both a PAMP and a genomic reservoir. Interferon treatment increased rather than decreased HCV dsRNA. This unexpected finding suggests that HCV produces dsRNA in response to IFN, potentially to antagonize antiviral defenses. (Hepatology 2017;66:357-370).


Long-chain acylcarnitines activate cell stress and myokine release in C2C12 myotubes: calcium-dependent and -independent effects.
Acylcarnitines, important lipid biomarkers reflective of acyl-CoA status, are metabolites that possess bioactive and inflammatory properties. This study examined the potential for long-chain acylcarnitines to activate cellular inflammatory, stress, and death pathways in a skeletal muscle model. Differentiated C2C12 myotubes treated with l-C14, C16, C18, and C18:1 carnitine displayed dose-dependent increases in IL-6 production with a concomitant rise in markers of cell permeability and death, which was not observed for shorter chain lengths. l-C16 carnitine, used as a representative long-chain acylcarnitine at initial extracellular concentrations ≥25 μM, increased IL-6 production 4.1-, 14.9-, and 31.4-fold over vehicle at 25, 50, and 100 μM. Additionally, l-C16 carnitine activated c-Jun NH2-terminal kinase, extracellular signal-regulated kinase, and p38 mitogen-activated protein kinase between 2.5- and 11-fold and induced cell injury and death within 6 h with modest activation of the apoptotic caspase-3 protein. l-C16 carnitine rapidly increased intracellular calcium, most clearly by 10 μM, implicating calcium as a potential mechanism for some activities of long-chain acylcarnitines. The intracellular calcium chelator BAPTA-AM blunted l-C16 carnitine-mediated IL-6 production by >65%. However, BAPTA-AM did not attenuate cell permeability and death responses, indicating that these outcomes are calcium independent. The 16-carbon zwitterionic compound amidosulfobetaine-16 qualitatively mimicked the l-C16 carnitine-associated cell stress outcomes, suggesting that the effects of high experimental concentrations of long-chain acylcarnitines are through membrane disruption. Herein, a model is proposed in which acylcarnitine cell membrane interactions take place along a spectrum of cellular concentrations encountered in physiological-to-pathophysiological conditions, thus regulating function of membrane-based systems and impacting cell biology.


Alcohol and drugs in drivers fatally injured in traffic accidents in Sweden during the years 2000-2002.
During the years 2000-2002, alcohol, pharmaceuticals and illicit drugs were analysed in blood samples from fatally injured drivers in Sweden. The total number of drivers was 920 and in 855 of these, corresponding to 93%, a toxicological investigation was performed. About 85% of the drivers were men and 15% were women. All but three women (96%) were car drivers while the corresponding figure for men was about 78% and about 13% were motorcyclists. The number of positive cases increased from 38.9% in year 2000 to 45.9% in year 2002 and alcohol was the most common drug with frequencies of 19.8%, 25.0% and 21.8% for the studied years 2000, 2001 and 2002, respectively. The median blood alcohol concentration ranged from 1.6 to 2.0mg/mL for men and from 1.2 to 1.8 mg/mL for women. There was a decrease in cases where alcohol was the only drug detected, from 52 out of 58 cases (90%) in year 2000 to 41 out of 61 cases (67%) in 2002. At the same time there was an increase, from 5.4% to 10.0% of illicit drugs, mainly amphetamine, and the cases with multiple drug intake increased from 10% to 26%. The prevalence of pharmaceuticals as the only drug or drugs detected decreased from 14.0% to 10.4% and in the majority of these cases the drug concentrations were within the therapeutic range.


Bacterial vaginosis a "broad overview".
Bacterial vaginosis (BV) was first reported in 1995 by Gardner and Dukes, who described the unique clinical signs and symptoms and the distinctive nature of the vaginal discharge associated with it. They also described a "new" causative organism, which they named "Haemophilus vaginalis", subsequently renamed Gardnerella vaginalis. BV is currently the most prevalent cause of infectious vaginitis among women attending for genitourinary diseases. BV has a complex microbiology. Lactobacillus populations, which are usually dominant in healthy women, are replaced by a polymicrobial group of organisms that includes G. vaginalis, anaerobic Gram-negative rods such as Prevotella species, Peptostreptococcus species, Mycoplasma hominis, Ureaplasma urealyticum, and often Mobiluncus species. Anaerobic bacteria produce enzymes, aminopeptidases, that degrade protein and decarboxylases that convert amino acids and other compounds to amines. Those amines contribute to the signs and symptoms associated with the syndrome, raising the vaginal pH and producing a discharge odor. The excessive amounts of bacteria characteristic of the syndrome attach to epithelial cell surfaces, resulting in "clue cell". Nearly half the patients report no noticeable symptoms, but many develop a characteristic copious, malodorous discharge if untreated. Results from epidemiologic studies have associated BV with serious upper genital tract infections and adverse pregnancy outcome. In particular, the presence of BV in pregnant women increases the risk of preterm delivery, and evidence is now compelling that BV is a cause of preterm delivery. The interest in potential invasiveness of G. vaginalis has increased. However, virulence determinants have not been studied enough. The most important therapy includes clindamycin and metronidazole.


Stirring up the mud: using a community-based participatory approach to address health disparities through a faith-based initiative.
This case study provides a mid-course assessment of the Bronx Health REACH faith-based initiative four years into its implementation. The study uses qualitative methods to identify lessons learned and to reflect on the benefits and challenges of using a community-based participatory approach for the development and evaluation of a faith-based program designed to address health disparities. Key findings concern the role of pastoral leadership, the importance of providing a religious context for health promotion and health equality messages, the challenges of creating a bilingual/bi-cultural program, and the need to provide management support to the lay program coordinators. The study also identifies lessons learned about community-based evaluation and the importance of addressing community concern about the balance between evaluation and program. Finally, the study identifies the challenges that lie ahead, including issues of program institutionalization and sustainability.


Effects of single intravenous doses of dexamethasone on baseline plasma cortisol concentrations and responses to synthetic ACTH in healthy dogs.
The duration of adrenocortical suppression resulting from a single IV dose of dexamethasone or dexamethasone sodium phosphate was determined in dogs. At 0800 hours, 5 groups of dogs (n = 4/group) were treated with 0.01 or 0.1 mg of either agent/kg of body weight or saline solution (controls). Plasma cortisol concentrations were significantly (P less than 0.01) depressed in dogs given either dose of dexamethasone or dexamethasone sodium phosphate by posttreatment hour (PTH) 2 and concentrations remained suppressed for at least 16 hours. However, by PTH 24, plasma cortisol concentrations in all dogs, except those given 0.1 mg of dexamethasone/kg, returned to control values. Adrenocortical suppression was evident in dogs given 0.1 mg of dexamethasone/kg for up to 32 hours. The effect of dexamethasone pretreatment on the adrenocortical response to ACTH was studied in the same dogs 2 weeks later. Two groups of dogs (n = 10/group) were tested with 1 microgram of synthetic ACTH/kg given at 1000 hours or 1400 hours. One week later, half of the dogs in each group were given 0.01 mg of dexamethasone/kg at 0600 hours, whereas the remaining dogs were given 0.1 mg of dexamethasone/kg. The ACTH response test was then repeated so that the interval between dexamethasone treatment and ACTH injection was 4 hours (ACTH given at 1000 hours) or 8 hours (ACTH given at 1400 hours). Base-line plasma cortisol concentrations were reduced in all dogs given dexamethasone 4 or 8 hours previously.(ABSTRACT TRUNCATED AT 250 WORDS)


[Limits of impregnated bednets for malaria control in tropical Africa].
There is no direct relationship between malaria transmission intensity and the burden of the disease. Due to acquired immunity there is little difference both in potential malaria mortality and the total number of malaria attacks over an entire lifetime between individuals bitten by infected anophelines a few times a year and those bitten by infected anophelines hundreds of times a year: It is only for low levels of transmission that there exists a relation between the entomological inoculation rate, the disease incidence rate and potential malaria mortality. Even if impregnation by insecticides improves bednet efficiency the vector capacity of Anopheles gambiae, An. arabiensis and An. funestus is too high for impregnated bednets to be an efficient means of malaria control in most rural areas of tropical Africa. The reduction of malaria mortality observed during several pilot projects is probably a short term effect. We propose focussing vector control on low and/or unstable malaria transmission areas, i.e. where these activities have proved crucial for the reduction or even eradication of malaria. In moderate or high transmission areas, better access to health care and improvement of malaria case management are currently the only means for reducing durably the burden of malaria.


Health-related quality of life among Syrian refugees resettled in Sweden.
The main purpose of this study was to assess health-related quality of life (HRQoL) among Syrian refugees resettled in Sweden. Further, we wanted to investigate whether sex, age, education, area of residence, cohabitation and social support were associated with HRQoL in this population. This is a cross-sectional study including 1215 Syrian refugees from a randomly selected sample frame resettled in Sweden between the years 2011 and 2013. HRQoL was measured by the EQ-5D-5L descriptive system, and EQ-5D-5L index values were calculated. Associations between sex, age, education, area of residence, cohabitation, social support and EQ-5D-5L were investigated using multiple linear regression analysis. Depression/anxiety was the most commonly (61.9%) reported EQ-5D-5L problem among the group of Syrian refugees. The mean EQ-5D-5L index value was found to be 0.754. Male sex, younger age, cohabitation and social support were found associated with a higher EQ-5D-5L index score. Our results concerning long-lasting health problems among the study population indicate that there is a profound need for policies and interventions promoting refugees' health. Our results also show that social support, a modifiable factor, is relevant to refugees' overall health, pointing to the importance of public health interventions and policies targeting the facilitation, mobilization and enhancing of refugees' social support.


Environmental stressors as a driver of the trait composition of benthic macroinvertebrate assemblages in polluted Iberian rivers.
We used the trait composition of macroinvertebrate communities to identify the effects of pesticides and multiple stressors associated with urban land use at different sites of four rivers in Spain. Several physical and chemical stressors (high metal pollution, nutrients, elevated temperature and flow alterations) affected the urban sites. The occurrence of multiple stressors influenced aquatic assemblages at 50% of the sites. We hypothesized that the trait composition of macroinvertebrate assemblages would reflect the strategies that the assemblages used to cope with the respective environmental stressors. We used RLQ and fourth corner analysis to address the relationship between stressors and the trait composition of benthic macroinvertebrates. We found a statistically significant relationship between the trait composition and the exposure of assemblages to environmental stressors. The first RLQ dimension, which explained most of the variability, clearly separated sites according to the stressors. Urban-related stressors selected taxa that were mainly plurivoltine and fed on deposits. In contrast, pesticide impacted sites selected taxa with high levels of egg protection (better egg survival), indicating a potentially higher risk for egg mortality. Moreover, the trait diversity of assemblages at urban sites was low compared to that observed in pesticide impacted sites, suggesting the homogenization of assemblages in urban areas.


Chemosensory input from mouthparts in response to sexually dimorphic cuticular wax mediates male sexual discrimination in Galerucella grisescens (Coleoptera: Chrysomelidae).
The surface of the insect body is covered with a hydrophobic layer called cuticular wax (CW). In addition to functioning as an anti-desiccation agent, CW is critical for chemical communication. It has been reported that in Chrysomelidae, males discriminate between sexes based on the sex-specific CW. However, little is known regarding the underlying sensory basis. Herein, we demonstrate that chemosensory input from mouthparts mediates sexual discrimination in male Galerucella grisescens (Chrysomelidae). Observations of mating behaviour, bioassays for CW, and chemical analyses revealed that G. grisescens possess qualitatively sexually dimorphic CW, and such compositional differences allow males to distinguish between sexes. Using electron microscopy, blocking male chemosensory organs, and electrophysiological experiments, we showed that male mouthparts bear chemosensory sensilla tuned to female CW components, and sensory input from them induces male aedeagal insertion, a common male behavioural response to females. Thus, detecting CW via mouthparts is essential for males to distinguish between sexes, consistent with the fact that males inspect conspecific individuals by licking their body surfaces. To our best knowledge, this is the first report describing the detailed functional roles of mouthparts in sexual discrimination in Coleoptera. We believe that this study will promote further studies on insect chemical communication.