Mycobacterium abscessus infections in lung transplant recipients: the international experience.
The clinical significance of Mycobacterium abscessus infection in the lung transplant population is not well understood. An international survey was performed to determine the incidence and clinical outcomes of M abscessus infections before and after lung transplantation. Thirty-one (50%) of the 62 transplant centers affiliated with the International Society of Heart and Lung Transplantation responded to the survey. Of 5,200 transplants performed, 17 patients (0.33%) (M/F, 12:5) were identified with M abscessus after transplantation. Two patients had respiratory colonization before lung transplantation. Post-transplantation M abscessus infections occurred in the pulmonary allograft in 12, in skin/soft tissue in 3, or both in 2. Median time to diagnosis after transplantation was 18.5 months (range, 1-111 months). Therapies included multiple antibiotics in 16, surgical débridement in 2, interferon-gamma in 1, or no therapy owing to presumed colonization in 1. Eleven (73%) of 16 treated patients had a radiologic or microbiologic response to treatment. Concurrent infections were common, with Aspergillus (n = 8) and Pseudomonas aeruginosa (n = 5) most frequently seen. Death in 2 patients was attributed to M abscessus. Ten of 17 patients are alive and considered cured. M abscessus infection in the lung transplant recipient is uncommon and challenging; however, successful treatment can occur. Prolonged combination anti-microbial therapy is required for pulmonary involvement, and surgical débridement is recommended for cutaneous lesions. Concurrent infections are common and may contribute to mortality in this immunosuppressed population.


Nonparametric Bayesian inference for mean residual life functions in survival analysis.
Modeling and inference for survival analysis problems typically revolves around different functions related to the survival distribution. Here, we focus on the mean residual life (MRL) function, which provides the expected remaining lifetime given that a subject has survived (i.e. is event-free) up to a particular time. This function is of direct interest in reliability, medical, and actuarial fields. In addition to its practical interpretation, the MRL function characterizes the survival distribution. We develop general Bayesian nonparametric inference for MRL functions built from a Dirichlet process mixture model for the associated survival distribution. The resulting model for the MRL function admits a representation as a mixture of the kernel MRL functions with time-dependent mixture weights. This model structure allows for a wide range of shapes for the MRL function. Particular emphasis is placed on the selection of the mixture kernel, taken to be a gamma distribution, to obtain desirable properties for the MRL function arising from the mixture model. The inference method is illustrated with a data set of two experimental groups and a data set involving right censoring. The supplementary material available at Biostatistics online provides further results on empirical performance of the model, using simulated data examples.


Natural antioxidants and atherosclerosis.
The precursors of fibrous atherosclerotic plaques are fatty streaks, characterized by accumulation of fat laden macrophages beneath an intact endothelium. These macrophages are derived from monocytes in the circulating blood and the lipid is derived from plasma low density lipoprotein (LDL). But LDL is poorly taken up by monocytes/macrophages in vitro unless it has been oxidatively modified. Hence the phypothesis has developed that one determinant of atherosderosis is whether LDL becomes oxidized by free radicals in the subendothelial space. An epidemiological study of 12 European sub-populations which all have about the same plasma cholesterol concentration but quite different incidences of coronary heart disease (CHD) showed a significant inverse correlation of plasma a -tocopherol with CHD. In several animal models, vitamin E or some other antioxidants attenuate experimental atherosclerosis. Each particle of LDL contains about 8-12 molecules of tocopherol, 0.5 to 1 molecule of ubiquinol-10 and small amounts of carotenoids but other antioxidants in the extracellular fluid, notably (water-soluble) ascorbate protect against oxidative damage in in vitro experiments with human blood plasma. The ascorbate presumably acts by regeneration a -tocopherol from its one-electron oxidation product, the a-tocopheroxyl radical. The author found that the small amounts of ubiquinol present in LDL offer important protection against oxidation. Unlike vitamins C and E, ubiquinol is biosynthesized by humans but it is also obtained from the diet (some fatty fish are the richest sources). The ubiquinol content of plasma LDL was increased 4-fold by giving volunteers ubiquinone. Their plasma LDL was subsequently found more resistant against oxidation.


[The value of surgery in the treatment of invasive pulmonary aspergillosis in neutropenic patients].
The aim of the study is to specify the indication for surgery in the treatment of invasive pulmonary aspergillosis (API). From January 1991 to October 1996 nineteen patients who had been treated with chemotherapy and associated marrow aplasia and suffering from API were operated on. At the time of the surgical intervention all of the patients were treated with antifungal drugs. The delay between the start of their symptoms and the start of treatment was 2.6 days (range: 0-17 days). 1. The risk of a massive haemoptysis by contact between the fungal infection and the pulmonary artery led to eight urgent surgical operations: six lobectomies and two lobectomies associated with segmentectomy. The mean level of polymorphonuclear neutrophils was 296 cell/mm3 (0-1,000). Plastic surgery on the pulmonary artery was carried out in three patients. One patient died after the operation with progression of the API. The duration of postoperative stay was 13 days (6-18). 2. Planned surgery consisted of a resection of the residual mass after antifungal treatment and a diagnostic approach to the intraparenchymatous mass of indeterminate aetiology. A resection of the residual masses (in spite of antifungal treatment) was carried out in seven patients: before further haematological therapy in six cases and in one case for a superinfected lesion. The type of resection was: a lobectomy (n = 4), a lingulectomy (n = 1) and an atypical resection (n = 2). No postoperative deaths were reported. The patients left the surgical service between the seventh and twentieth day postoperatively. The surgery was used in four patients as the diagnostic approach in view of intraparenchymal masses of unknown aetiology and had enabled a fungal mycelium to be isolated at the centre of persisting inflammation. Antifungal treatment sometimes associated with surgery allowed for a better prognosis in patients suffering from invasive pulmonary aspergillosis.


Is oxygen therapy beneficial for normoxemic patients with acute heart failure? A propensity score matched study.
The clinical efficiency of routine oxygen therapy is uncertain in patients with acute heart failure (AHF) who do not have hypoxemia. The aim of this study was to investigate the association between oxygen therapy and clinical outcomes in normoxemic patients hospitalized with AHF using real-world data. Normoxemic patients diagnosed with AHF on ICU admission from the electronic ICU (eICU) Collaborative Research Database were included in the current study, in which the study population was divided into the oxygen therapy group and the ambient-air group. Propensity score matching (PSM) was applied to create a balanced covariate distribution between patients receiving supplemental oxygen and those exposed to ambient air. Linear regression and logistic regression models were performed to assess the associations between oxygen therapy and length of stay (LOS), and all-cause in-hospital as well as ICU mortality rates, respectively. A series of sensitivity and subgroup analyses were conducted to further validate the robustness of our findings. A total of 2922 normoxemic patients with AHF were finally included in the analysis. Overall, 42.1% (1230/2922) patients were exposed to oxygen therapy, and 57.9% (1692/2922) patients did not receive oxygen therapy (defined as the ambient-air group). After PSM analysis, 1122 pairs of patients were matched: each patient receiving oxygen therapy was matched with a patient without receiving supplemental oxygen. The multivariable logistic model showed that there was no significant interaction between the ambient air and oxygen group for all-cause in-hospital mortality [odds ratio (OR) 1.30; 95% confidence interval (CI) 0.92-1.82; P = 0.138] or ICU mortality (OR 1.39; 95% CI 0.83-2.32; P = 0.206) in the post-PSM cohorts. In addition, linear regression analysis revealed that oxygen therapy was associated with prolonged ICU LOS (OR 1.11; 95% CI 1.06-1.15; P < 0.001) and hospital LOS (OR 1.06; 95% CI 1.01-1.10; P = 0.009) after PSM. Furthermore, the absence of an effect of supplemental oxygen on mortality was consistent in all subgroups. Routine use of supplemental oxygen in AHF patients without hypoxemia was not found to reduce all-cause in-hospital mortality or ICU mortality.


Alternating 5,5-Dimethylcyclopentadiene and Diketopyrrolopyrrole Copolymer Prepared at Room Temperature for High Performance Organic Thin-Film Transistors.
We report that the inclusion of nonaromatic 5,5-dimethylcyclopentadiene monomer into a conjugated backbone is an attractive strategy to high performance semiconducting polymers. The use of this monomer enables a room temperature Suzuki copolymerization with a diketopyrrolopyrrole comonomer to afford a highly soluble, high molecular weight material. The resulting low band gap polymer exhibits excellent photo and thermal stability, and despite a large π-π stacking distance of 4.26 Å, it demonstrates excellent performance in thin-film transistor devices.


Heat shock proteins and arthritis--new readers start here.
The possible roles of heat shock proteins in the pathogenesis of inflammatory arthritis have been discussed for a number of years, and investigated intensively in both animal models and human disease. This review surveys evidence which has pointed, on the one hand, to hsp as targets of a pathogenic immune response, and on the other, to an immunoregulatory role for T cell recognition of self hsp. The extent to which findings in experimental animals have led to further insights applicable to human disease is also emphasised.


Social support, coping, and psychological distress in mothers and fathers of pediatric transplant candidates: a pilot study.
Both parents and children report significant psychological difficulties and family disruption prior to transplantation; however, there have been fewer studies examining predictors of distress in both mothers and fathers and across multiple transplant groups. Thirty-four mothers and 22 fathers participated in this pilot study. Parents completed measures during a routine tertiary pretransplant psychological evaluation. Paired sample t-test results indicated that mothers and fathers differed significantly on specific coping strategies employed, with fathers less likely to use engagement strategies than mothers. Correlation analyses demonstrated strong associations between engagement coping strategies and less psychological distress and the reverse with disengagement coping strategies for both mothers and fathers. Social support was associated with less psychological distress for mothers, but was unrelated to distress for fathers. Using regression analyses, for mothers, lack of social support, and disengagement coping predicted poor psychological outcomes. Taken together, these results suggest that assessing specific coping strategies employed by both mothers and fathers is an essential component of the pretransplant evaluation process. This study delineates areas for intervention that impact adjustment in parents of pediatric transplant candidates.


Effect of exogenous estradiol Benzoate on uterine blood flow in postpartum dairy cows.
The objective of this study was to assess the uterine blood flow following estradiol benzoate administration in Holstein-Friesian dairy cows by trans-rectal color Doppler ultrasonography. Six healthy lactating Holstein-Friesian cows were examined daily for 10 days starting at 4 weeks postpartum. All the cows, which were clinically healthy based on vaginal mucus scoring and endometrial cytology, were examined by trans-rectal Doppler ultrasonography to measure pulsatility index (PI), resistance index (RI), time average maximum velocity (TAMAX), blood flow volume (BFV) and diameter in the uterine arteries ipsilateral and contralateral to the previously pregnant uterine horn. On the third day of the experiment, the six cows were administered 10 mg intramuscular injection of estradiol-17β (E2).Blood samples were collected at the time of daily examination for the assessment ofE2concentrations.The PI and RI values decreased while TAMAX, BFV and diameter of uterine arteries increased in response toE2 administration (P < 0.05).There was a high correlation between both the ipsilateral and contralateral uterine arteries for all variables that were studied(r = 0.860, P < 0.0001, r = 0.922, P < 0.0001, r = 0.651, P < 0.0001, r = 0.879, P < 0.0001, r = 0.861, P < 0.0001 for the PI, RI, TAMAX, BFV and uterine arteries diameter, respectively).In conclusion, the greater blood concentrations ofE2may be responsible for the greater TAMAX, BFV, increased diameters and decreased PI and RI of the uterine arteries during the puerperium in dairy cows.


Design, synthesis, and metal binding of novel Pseudo- oligopeptides containing two phosphinic acid groups.
Phosphinic compounds have potential as amide-bond mimetics in the development of novel peptidomimetics, enzyme inhibitors, and metal-binding ligands. Novel pseudo-oligopeptides with two phosphinic acid groups embedded in the peptide backbone serving as amide-bond surrogates, Psi[P(O,OH)--CH(2)], were targeted. A series of linear and cyclic pseudo-oligopeptides with two phosphinic acid groups arrayed at different positions in the peptide sequence were designed, including Ac--Phe--{(R,S)--AlaPsi[P(O,OH)--CH(2)]Gly}(2)--NH(2) (P2), Ac--NH--(R,S)--AlaPsi[P(O,OH)--CH(2)]Gly--Phe--(R,S)--AlaPsi[P(O,OH)--CH(2)]Gly--NH(2) (P3), Ac--NH--(R,S)--AlaPsi[P(O,OH)--CH(2)]Gly--Phe--Phe--(R,S) --AlaPsi[P(O,OH)--CH(2)]Gly--NH(2) (P4), cyclo{NH--(R,S)--AlaPsi[P(O,OH)--CH(2)]Gly--Phe}(2) (P5), and cyclo[NH--(R,S)--AlaPsi[P(O,OH)--CH(2)]Gly--Phe--Phe](2) (P6). They were synthesized via conventional Fmoc chemistry on solid support utilizing Fmoc-protected phosphinic acid-containing pseudo-dipeptide fragment, i.e. Fmoc--(R,S)--AlaPsi[P(O,OCH(3))--CH(2)]Gly--OH. The pseudo-peptides containing two phosphinic acid groups exhibited the highest binding affinity and selectivity for Fe(III) among the 10-metal ions screened by ESI-MS analysis--Cu(II), Zn(II), Co(II), Ni(II), Mn(II), Fe(II), Fe(III), Al(III), Ga(III), and Gd(III). P4 and P6 with 11-atom linkages between the two phosphinic acids preferred intramolecular metal binding to form 1:1 ligand/metal complexes. As revealed by competition experiments, P4 showed the highest relative binding affinity among the six compounds tested. Noteworthy, P4 also showed higher relative binding affinity than similar dihydroxamate-containing pseudo-peptides reported previously. The novel structural prototype and facile synthesis along with selective and potent Fe(III) binding strongly suggest that pseudo-peptides containing the two or more phosphinic groups as amide-bond surrogates deserve further exploration in medicinal chemistry.


The S100 Protein Family as Players and Therapeutic Targets in Pulmonary Diseases.
The S100 protein family consists of over 20 members in humans that are involved in many intracellular and extracellular processes, including proliferation, differentiation, apoptosis, Ca2 + homeostasis, energy metabolism, inflammation, tissue repair, and migration/invasion. Although there are structural similarities between each member, they are not functionally interchangeable. The S100 proteins function both as intracellular Ca2+ sensors and as extracellular factors. Dysregulated responses of multiple members of the S100 family are observed in several diseases, including the lungs (asthma, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, cystic fibrosis, pulmonary hypertension, and lung cancer). To this degree, extensive research was undertaken to identify their roles in pulmonary disease pathogenesis and the identification of inhibitors for several S100 family members that have progressed to clinical trials in patients for nonpulmonary conditions. This review outlines the potential role of each S100 protein in pulmonary diseases, details the possible mechanisms observed in diseases, and outlines potential therapeutic strategies for treatment.


Presentation and Management Outcome of Glomus Tumors of the Hand.
To document the clinical presentation of glomus tumors of the hand and evaluate the outcome of complete surgical excision in terms of relief of symptoms, any postoperative nail deformities and tumor recurrence over a period of one year. This descriptive case series spanned over a period of twelve years. All patients of either gender and all ages who had histologically confirmed glomus tumors of the hands were included. All of them underwent surgical excision under local anesthesia. Out of 17 patients, majority (n=12; 70.58%) were females. The mean age was 41.17±13.7 years. The dominant hand was involved in 11 (64.70%) patients. There were 14 patients (82.35%) with subungual tumors whereas 3(17.64%) had volar pulp glomus tumors. The mean diagnostic delay was 18.88±9.3 months. The tumor size ranged from 2 mm to 1.1cm with a mean of 4.05±4.3mm. All the patients (n=17,100%) experienced complete symptomatic relief within 2-4 weeks after surgical excision. There were no postoperative nail deformities. There was no recurrence over a period of one year. Glomus tumors of the hands were more frequently found among women in their fourth and fifth decades. Dominant hand, index finger and distal phalanx represented the commonest affected anatomic locales. Majority of the tumors were subungual. Majority of the patients suffered over 12 months in distressful pain before being diagnosed. Complete surgical excision under local anesthesia provided rapid relief of the symptoms. Creation of awareness about the tumor among doctors as well as public would help to ensure early presentation to plastic surgeon, prompt diagnosis and hence avoidance of the prolonged periods of agonizing misery.


Reevaluation of the direct method of calculating Fresnel and other linear canonical transforms.
The linear canonical transform may be used to simulate the effect of paraxial optical systems on wave fields. Using a recent definition of the discrete linear canonical transform, phase space diagram analyses of the sampling requirements of the direct method of calculating the Fresnel and other linear canonical transforms are more favorable than previously thought. Thus the direct method of calculating these transforms may be used with fewer samples than previously reported simply by making use of an appropriate reconstruction filter on the samples output by the algorithm.


LC-ESI/MS/MS analysis of neonicotinoids in urine of very low birth weight infants at birth.
Neonicotinoid insecticides are widely used systemic pesticides with nicotinic acetylcholine receptor agonist activity that are a concern as environmental pollutants. Neonicotinoids in humans and the environment have been widely reported, but few studies have examined their presence in fetuses and newborns. The objective of this study is to determine exposure to neonicotinoids and metabolites in very low birth weight (VLBW) infants. An analytical method for seven neonicotinoids and one neonicotinoid metabolite, N-desmethylacetamiprid (DMAP), in human urine using LC-ESI/MS/MS was developed. This method was used for analysis of 57 urine samples collected within 48 hours after birth from VLBW infants of gestational age 23-34 weeks (male/female = 36/21, small for gestational age (SGA)/appropriate gestational age (AGA) = 6/51) who were admitted to the neonatal intensive care unit of Dokkyo Hospital from January 2009 to December 2010. Sixty-five samples collected on postnatal day 14 (M/F = 37/22, SGA/AGA = 7/52) were also analyzed. DMAP, a metabolite of acetamiprid, was detected in 14 urine samples collected at birth (24.6%, median level 0.048 ppb) and in 7 samples collected on postnatal day 14 (11.9%, median level 0.09 ppb). The urinary DMAP detection rate and level were higher in SGA than in AGA infants (both p<0.05). There were no correlations between the DMAP level and infant physique indexes (length, height, and head circumference SD scores). These results provide the first evidence worldwide of neonicotinoid exposure in newborn babies in the early phase after birth. The findings suggest a need to examine potential neurodevelopmental toxicity of neonicotinoids and metabolites in human fetuses.


Seroprevalence of antibodies against SARS-CoV-2 virus in Northern Serbia (Vojvodina): A four consecutive sentinel population-based survey study.
Monitoring changes of seroprevalence over time is important at the beginning and during of COVID-19 outbreak to anticipate its dynamics and plan an adequate public health response. We conducted a repeated cross-sectional investigation among asymptomatic outpatient subjects and covered 0.1% of total population of Northern Serbia (Autonomous Province of Vojvodina). Each participant was tested for anti-SARS-CoV-2 antibodies using an immunochromatographic qualitative test (point-of-care rapid test). In the last round of survey IgG antibodies targeting the S1 subunit of the spike protein and the nucleocapsid protein of SARS-CoV-2 virus were assessed. During the four rounds of survey (between the end of April and the end of September), anti-SARS-CoV-2 seropositivities based on immunochromatographic test results were 2.60% (95% CI 1.80-3.63), 3.93% (95% CI 2.85-5.28), 6.11% (95% CI 4.72-7.77) and 14.60% (95% 12.51-16.89), respectively. After adjusting with results obtained from the Line immunoassay test, the estimated overall seroprevalence increased to 16.67% (95% CI 14.45-19.08) corresponding to 322,033 infections in total by the end of September 2020 in Vojvodina's population. Throughout the course of the study, for every RT-PCR confirmed case of COVID-19, there were 39-87 additional infections in Vojvodina. No significant difference (p>0.05) in SARS-CoV-2 seropositivity regarding gender and between age subgroups was observed over the course of the survey. The population prevalence of SARS-CoV-2 antibodies implies much more widespread infection in Vojvodina than indicated by the number of confirmed cases. However, our results suggest that the population of Vojvodina has not reached a desirable level of protection from SARS-CoV-2 virus by the end of September 2020.


Chloride channels in the apical membrane of a distal nephron A6 cell line.
In this report, single-channel recording methods were used to determine whether there are Cl- conductive pathways in the apical membrane of cultured renal distal nephron cells (A6). Two different types of single Cl- channels were observed. In cell-attached patches, one had a unit conductance of 3 pS, whereas the unit conductance of the other was 8 pS. In cell-attached patches, the currents associated with the 3-pS Cl- channel outwardly rectified, whereas the current voltage relationship for the 8-pS Cl-channel was linear. The 3-pS Cl- channel has one open and one closed state; the 8-pS Cl- channel has one open and two closed states. The open probability of the 3-pS Cl- channel was voltage dependent (increasing with depolarization of the membrane) but even at very depolarized potentials (+140 mV) remained small (always less than 0.1). On the other hand, the open probability of the 8-pS Cl- channel was large (approximately 0.8) and voltage independent. The closing rate of the 3-pS Cl- channel was decreased when the patch membrane was depolarized, whereas the opening rate was increased. In contrast, the closing rate of the 8-pS Cl- channel decreased with depolarization, but the opening rates were voltage independent. The outward rectification of the 3-pS channel was markedly reduced in inside-out patches when high calcium concentrations (10-800 microM) were present on the intracellular surface. The open probability of the 3-pS Cl- channel is increased by membrane permeable analogues of adenosine 3',5'-cyclic monophosphate primarily by decreasing the mean closed time.


The role of child-keyworker attachment in burnout among Saudi residential staff.
Research on the impact of the keyworker-child relationship on residential staff is scarce. This longitudinal study investigated the potential moderating effects of child and keyworker attachment styles on the link between child behavioural problems and staff burnout and the moderating effects of child attachment style on the link between keyworker attachment style and keyworker burnout. Participants included 261 children and 59 residential child care workers, from 5 orphanages in Saudi Arabia. Five self-report measures were utilised: The Strengths and Difficulties Questionnaire, the Security Scale, the Coping Strategies Questionnaire, the Maslach Burnout Inventory and the Experiences in Close Relationships Questionnaire. Keyworkers caring for relatively non-avoidant children and those with an avoidant attachment style themselves experienced relatively high burnout a year later. Relatively high burnout was also reported by avoidant keyworkers who cared for avoidant and generally insecure children, while anxiously attached keyworkers reported relatively high burnout when they cared for children with any type of insecure attachment style. The present findings highlight essential interpersonal processes involved in the development of burnout in residential child care workers and call for the employment of attachment-focused interventions as measures of burnout prevention.


Comprehensive HRMS Chemical Characterization of Pomegranate-Based Antioxidant Drinks via a Newly Developed Suspect and Target Screening Workflow.
Antioxidants play a significant role in human health, protecting against a variety of diseases. Therefore, the development of products with antioxidant activity is becoming increasingly prominent in the human lifestyle. New antioxidant drinks containing different percentages of pomegranate, blackberries, red grapes, and aronia have been designed, developed, and manufactured by a local industry. The comprehensive characterization of the drinks' constituents has been deemed necessary to evaluate their bioactivity. Thus, LC-qTOFMS has been selected, due to its sensitivity and structure identification capability. Both data-dependent and -independent acquisition modes have been utilized. The data have been treated according to a novel, newly designed workflow based on MS-DIAL and MZmine for suspect, as well as target screening. The classical MS-DIAL workflow has been modified to perform suspect and target screening in an automatic way. Furthermore, a novel methodology based on a compiled bioactivity-driven suspect list was developed and expanded with combinatorial enumeration to include metabolism products of the highlighted metabolites. Compounds belonging to ontologies with possible antioxidant capacity have been identified, such as flavonoids, amino acids, and fatty acids, which could be beneficial to human health, revealing the importance of the produced drinks as well as the efficacy of the new in-house developed workflow.


Metaproteomic analysis of biocake proteins to understand membrane fouling in a submerged membrane bioreactor.
Metaproteomic analyses, including two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) separation and matrix-assisted laser desorption/ionization (MALDI)-time-of-flight (TOF)/TOF mass spectrometer (MS) detection, were used to trace and identify biocake proteins on membranes in a bench-scale submerged membrane bioreactor (MBR). 2D-PAGE images showed that proteins in the biocake (S3) at a low transmembrane pressure (TMP) level (i.e., before the TMP jump) had larger gray intensities in the pH 5.5–7.0 region regardless of the membrane flux, similar to soluble microbial product (SMP) proteins. However, the biocake (S2 and S4) at a high TMP level (i.e., after the TMP jump) had many more proteins in the pH range of 4.0–5.5, similar to extracellular polymeric substance (EPS) proteins. Such similarities between biocake proteins and SMP or EPS proteins can be useful for tracing the sources of proteins resulting in membrane fouling. In total, 183 differentially abundant protein spots were marked in the three biocakes (S2, S3, and S4). However, only 32 protein spots co-occurred in the 2D gels of the three biocakes, indicating that membrane fluxes and TMP evolution levels had significant effects on the abundance of biocake proteins. On the basis of the MS and MS/MS data, 23 of 71 protein spots were successfully identified. Of the 23 proteins, outer membrane proteins (Omp) were a major contributor (60.87%). These Omps were mainly from potential surface colonizers such as Aeromonas, Enterobacter, Pseudomonas, and Thauera. Generally, the metaproteomic analysis is a useful alternative to trace the sources and compositions of biocake proteins on the levels of molecules and bacteria species that can provide new insight into membrane fouling.


[Clinical practice guidelines for precision diagnosis and treatment of complex liver tumor guided by three-dimensional visualization technology (version 2019)].
Virtual resection of liver structures guided by three-dimensional visualization technology (3DVT) has been extensively used in China. This technique provides a safe and effective method for accurate diagnosis of liver tumors and has important applications in preoperative evaluation, surgical planning and intraoperative guidance of liver cancer surgeries. The technical advantages and clinical significance of 3DVT in the diagnosis and treatment of complex liver tumors have been recognized. In order to standardize the application of 3DVT in the precision diagnosis and treatment of complex liver tumors, this guideline provides explanations and recommendations in the following aspects: (1) the establishment of homogenization processing and quality control system of 3D reconstruction; (2) the establishment of 3D reconstructed models of abdominal organs and lesions; (3) the individualized classification and quantitative analysis of blood vessels based on 3DVT; (4) 3DVT-based classification and grading of hepatic vessels in complex hepatic tumors; (5) evaluation system for surgery evaluation after reconstruction of the 3D visualization model; (6) application of 3D printing in complex hepatectomy; (7) virtual reality technology; (8) ICG fluorescence imaging; (9) multi-modal images for real-time navigation; (10) three-dimensional visualization to guide the preoperative surgical planning of precision hepatectomy; (11) application of 3DVT guidance in other therapeutic methods of hepatocellular carcinoma; (12) application of 3DVT in follow-up evaluation of the patients after liver cancer surgeries. 3DVT for visualization of the liver structures has important clinical values for accurate preoperative evaluation, preoperative planning and surgical navigation of complex liver tumors, and it facilitates precision surgeries to improve the outcomes and promote postoperative recovery of the patients.


Dystonic movements following thalamonal and alfentanil induction--a case report.
A 62 year old woman developed dystonic movements following induction of anesthesia with thalamonal and alfentanil. The patient remained awake during the episode. A small dose of thiopental sodium followed by succinylcholine aborted the unpleasant state. The case is being presented to emphasize the point that even small doses of opioid narcotic can cause tonic movements and frank seizures in some patients.


Elucidating the redox-driven dynamic interactions between arsenic and iron-impregnated biochar in a paddy soil using geochemical and spectroscopic techniques.
Iron (Fe)-modified biochar, a renewable amendment that synthetizes the functions of biochar and Fe materials, demonstrates a potential to remediate arsenic (As)-contaminated soils. However, the effectiveness of Fe-based biochar to immobilize As in paddy soils under varying redox conditions (Eh) has not been quantified. We tested the capability of the raw (RBC) and Fe-impregnated (FeBC) biochars to immobilize As in a paddy soil under various Eh conditions (from -400 to +300 mV) using a biogeochemical microcosm system. In the control, As was mobilized (686.2-1535.8 μg L-1) under reducing conditions and immobilized (61.6-71.1 μg L-1) under oxidizing conditions. Application of FeBC immobilized As at Eh < 0 mV by 32.6%-81.1%, compared to the control, because of the transformation of As-bound Fe (hydro)oxides (e.g., ferrihydrite) and the formation of complexes (e.g., ternary As-Fe-DOC). Application of RBC immobilized As at Eh < -100 mV by 16.0%-41.3%, compared to the control, due to its porous structure and oxygen-containing functional groups. Mobilized As at Eh > +200 mV was caused by the increase of pH after RBC application. Amendment of the Fe-modified biochar can be a suitable approach for alleviating the environmental risk of As under reducing conditions in paddy soils.


Preference for gel over suppository as delivery vehicle for a rectal microbicide: results of a randomised, crossover acceptability trial among men who have sex with men.
To assess whether men who have sex with men (MSM) prefer a gel or a suppository as a delivery vehicle for a rectal microbicide. 77 HIV-negative MSM with a recent history of inconsistent condom use during receptive anal intercourse (RAI) who acknowledged being at risk of contracting HIV were enrolled in a randomised, crossover acceptability trial. They compared 35 ml placebo gel with 8 g placebo rectal suppositories used on up to three RAI occasions each. Participants preferred the gel over the suppository (75% versus 25%, p<0.001) and so did their partners (71% versus 29%, p<0.001). The gel received more favourable ratings overall and on attributes such as colour, smell, consistency, feeling in rectum immediately after insertion and/or 30 minutes after insertion and application process. The gel resulted in less negative ratings in terms of participants being bothered by leakage, soiling, bloating, gassiness, stomach cramps, urge to have bowel movement, diarrhoea, pain or trauma. Participants liked the gel more in terms of feelings during anal sex, sexual satisfaction, partners' sexual satisfaction and liking the product when condoms were used and when condoms were not used. In this sample taken from one of the populations most likely to benefit from rectal microbicide availability, gel had greater acceptability than a suppository as a potential microbicide vehicle.


Comprehending Sentences With the Body: Action Compatibility in British Sign Language?
Previous studies show that reading sentences about actions leads to specific motor activity associated with actually performing those actions. We investigate how sign language input may modulate motor activation, using British Sign Language (BSL) sentences, some of which explicitly encode direction of motion, versus written English, where motion is only implied. We find no evidence of action simulation in BSL comprehension (Experiments 1-3), but we find effects of action simulation in comprehension of written English sentences by deaf native BSL signers (Experiment 4). These results provide constraints on the nature of mental simulations involved in comprehending action sentences referring to transfer events, suggesting that the richer contextual information provided by BSL sentences versus written or spoken English may reduce the need for action simulation in comprehension, at least when the event described does not map completely onto the signer's own body.


A Distinct Genetic Cluster in Cultivated Chickpea as Revealed by Genome-wide Marker Discovery and Genotyping.
The accurate description of plant biodiversity is of utmost importance to efficiently address efforts in conservation genetics and breeding. Herein, we report the successful application of a genotyping-by-sequencing (GBS) approach in chickpea ( L.), resulting in the characterization of a cultivated germplasm collection with 3187 high-quality single nucleotide polymorphism (SNP) markers. Genetic structure inference, principal component analysis, and hierarchical clustering all indicated the identification of a genetic cluster corresponding to black-seeded genotypes traditionally cultivated in Southern Italy. Remarkably, this cluster was clearly distinct at both genetic and phenotypic levels from germplasm groups reflecting commercial chickpea classification into and seed types. Fixation index estimates for individual polymorphisms pointed out loci and genomic regions that might be of significance for the diversification of agronomic and commercial traits. Overall, our findings provide information on genetic relationships within cultivated chickpea and highlight a gene pool of great interest for the scientific community and chickpea breeding, which is limited by the low genetic diversity available in the primary gene pool.


[Perioperative fluid therapy].
Physiologic balance between fluids and electrolytes should remain stable during the perioperative period. Gaps in our understanding of how this balance is maintained has given rise to inappropriate management practices. Both failure to replace lost fluids and the infusion of excessive amounts can lead to serious consequences for the patient. There is currently renewed interest in studying the best use of fluids and/or blood products during and after surgery. This update of perioperative fluid therapy is based on a review of indexed literature retrieved by means of a PubMed search for the period of January 1999 through December 2009.


Amorphous Hole-Transporting Material based on 2,2'-Bis-substituted 1,1'-Biphenyl Scaffold for Application in Perovskite Solar Cells.
Perovskite solar cells are considered a promising technology for solar-energy conversion, with power conversion efficiencies currently exceeding 20 %. In most of the reported devices, Spiro-OMeTAD is used for positive-charge extraction and transport layer. Although a number of alternative hole-transporting materials with different aromatic or heteroaromatic fragments have already been synthesized, a cheap and well-performing hole-transporting material is still in high demand. In this work, a two-step synthesis of a carbazole-based hole-transporting material is presented. Synthesized compounds exhibited amorphous nature, good solubility and thermal stability. The perovskite solar cells employing the newly synthesized material generated a power conversion efficiency of 16.5 % which is slightly lower than that obtained with Spiro-OMeTAD (17.5 %). The low-cost synthesis and high performance makes our hole-transport material promising for applications in perovskite-based optoelectronic devices.


Lipoproteins Cause Bone Resorption in a Mouse Model of Staphylococcus aureus Septic Arthritis.
Septic arthritis, most often caused by Staphylococcus aureus, is a rapidly progressive and destructive joint disease with substantial mortality and morbidity. Staphylococcus aureus lipoproteins (Lpps) are known to induce arthritis and bone destruction. Here, we aimed to investigate the bone resorptive effect of S. aureus Lpps in a murine arthritis model by intra-articular injection of purified S. aureus Lpps, synthetic lipopeptides, and live S. aureus strains. Analyses of the bone mineral density (BMD) of the distal femur bone were performed. Intra-articular injection of both live S. aureus and purified S. aureus Lpps were shown to significantly decrease total- and trabecular BMD. Liquid chromatography-mass spectrometry analyses revealed that the Lpps expressed by S. aureus SA113 strain contain both diacyl and triacyl lipid moieties. Interestingly, synthetic diacylated lipopeptide, Pam2CSK4, was more potent in inducing bone resorption than synthetic triacylated lipopeptide, Pam3CSK4. Modified lipoproteins lacking the lipid moiety were deprived of their bone resorptive abilities. Monocyte depletion by clodronate liposomes fully abrogated the bone resorptive capacity of S. aureus lipoproteins. Our data suggest that S. aureus Lpps induce bone resorption in locally-induced murine arthritis, an effect mediated by their lipid-moiety through monocytes/macrophages.


Evaluation of assays for quantification of DNA in canine plasma as an indirect marker of NETosis.
Neutrophil extracellular traps (NET), consisting of a filamentous DNA/chromatin-histone scaffold originating from neutrophils are part of the innate immune response, may be released under a variety of inflammatory conditions and are associated with an increased risk for thrombosis. The purpose of this study was to evaluate a SYTOX green fluorescence assay and a histone-DNA complex (hisDNA) ELISA for quantification of NET-related DNA in canine plasma. The influence of variations in blood sample handling on assay results was tested. Accuracy of the SYTOX green fluorescence and the hisDNA ELISA was evaluated with dilutional linearity using serial dilutions. Interference was assessed by addition of purified bilirubin or hemoglobin. Precision was determined by calculating the intra- and inter-assay CV. Preanalytic sample handling did not influence DNA measurements by either assay. Citrate and EDTA plasma samples were equivalent. For the DNA fluorescence assay, dilutional linearity was poor due to autofluorescence, which was corrected by addition of canine plasma to the diluent. The presence of bilirubin and hemoglobin also increased autofluorescence, and resulted in falsely low concentrations of DNA. On the hisDNA ELISA, pigmentemia had no effect. Both assays as modified in this study are suitable for measuring DNA in canine EDTA or citrate plasma. However, performance of the fluorescence assay was impacted by pigmentemia, and it was less sensitive than the ELISA in detecting the presence of nucleosome material in the plasma.


Characterization of cuticular proteins in CPR family in the wolf spider, Pardosa pseudoannulata, and the response of one subfamily genes to environmental stresses.
Cuticular protein (CP) plays an essential role in the construction and function of exoskeleton in arthropods. CPR family, CP with Rebers and Riddiford (R&R) Consensus, is the largest CP family in insects, but it lacks systematic research in non-insect arthropods. In this study, we explored CPRs in the wolf spider, Pardosa pseudoannulata, a predator to many insect pests. We totally identified 152 CPRs in P. pseudoannulata genome, which were divided into two subgroups based on R&R Consensus sequences, with 12 CPRs in RR-1 and 140 in RR-2. All RR-2 members presented a novel Consensus with 34 amino acids, G-x(8)-G-x(6)-Y-x-A-x(3)-G-x(7)-N-E-x-G, which was a common characteristic for RR-2 CPRs in chelicerates. Transcriptome data was used to document the expression patterns of CPR genes in different tissues and ecdysis processes. The specific expressions were found for part CPR genes, such as five RR-2 genes that were specifically expressed in male genital bulbs and eleven RR-1 genes that were highly expressed in the integument. Due to the limited number and integument-specific expression of RR-1 genes, we further analyzed their responses to different environmental stresses at the transcriptional level. Except for PapsCPR11, ten RR-1 genes responded to at least one environmental stress, among with the expression of PapsCPR12 was significantly changed by three stresses (dryness, low temperature and imidacloprid treatments). Silencing PapsCPR12 increased the tolerance of P. pseudoannulata to imidacloprid. Overall, the results presented novel Consensus characteristics of CPRs in P. pseudoannulata, which was helpful for the identification and evolution analysis of CPRs in non-insect arthropods.


Multiple genes encode the human Na+,K+-ATPase catalytic subunit.
A human genomic library was constructed and screened with hybridization probes derived from sheep and rat cDNAs encoding the alpha and alpha(+) isoforms, respectively, of the Na+,K+-ATPase catalytic subunit. Genomic sequences spanning 150 kilobases were isolated. Four genes, designated alpha A, alpha B, alpha C, and alpha D, each 20-25 kilobases in length, were identified by restriction mapping, Southern blot hybridization analysis, and limited DNA sequencing. We present evidence that two of these genes, alpha A and alpha B, encode the alpha and alpha(+) isoforms, respectively. The other genes, alpha C and alpha D, one of which is physically linked to the alpha(+) gene, exhibit nucleotide and amino acid homology to Na+,K+-ATPase catalytic subunit cDNA sequences but do not correspond to any previously identified isoforms.


The antioxidants--vitamin C,vitamin E, selenium, and carotenoids.
This is the second in a series of articles reviewing the recent revisions of the Recommended Dietary Allowances (RDA) and the resulting Dietary Reference Intakes (DRI). In April of 2000, the Food and Nutrition Board of the National Academy of Sciences released Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. The central premise of the report did not perpetuate the prevailing popular thought that large doses of antioxidants will prevent chronic diseases. Instead the panel concluded that at this time, insufficient scientific evidence exists to sustain claims that ingesting megadoses of dietary antioxidants can prevent certain chronic illnesses such as cardiovascular disease or cancer. In some instances recommended nutrient levels were reduced from the previous report in 1989; e.g., for the first time upper tolerable levels of ingestion (UL) were established to prevent the harmful effects of over consumption of essential nutrients, such as vitamin C, vitamin E, and selenium. Although dietary recommendations do exist for vitamin A, the panel did not set recommendations for beta-carotene or the other carotenoids due to lack of sufficient research to support recommended intakes or upper tolerable levels of intake. However, the panel advises the public to avoid intakes of provitamin A compounds, such as the numerous carotenoids, beyond the levels required to prevent vitamin A deficiency. Changes were also made with regard to estimating the amount of provitamin A carotenoids required to make a unit of retinal. The revised estimate suggests a twofold higher conversion rate than previously believed. Although this comprehensive report on the dietary reference intakes for vitamin C, vitamin E, selenium, and the carotenoids did not decisively confirm the role of antioxidants for the prevention of chronic diseases in humans, many research studies have generated new data to support this concept. Additional research is needed to define the attributes of antioxidants as studies progress from in vitro and animal studies to human nutrition.


A Murine Model to Study Epilepsy and SUDEP Induced by Malaria Infection.
One of the largest single sources of epilepsy in the world is produced as a neurological sequela in survivors of cerebral malaria. Nevertheless, the pathophysiological mechanisms of such epileptogenesis remain unknown and no adjunctive therapy during cerebral malaria has been shown to reduce the rate of subsequent epilepsy. There is no existing animal model of postmalarial epilepsy. In this technical report we demonstrate the first such animal models. These models were created from multiple mouse and parasite strain combinations, so that the epilepsy observed retained universality with respect to genetic background. We also discovered spontaneous sudden unexpected death in epilepsy (SUDEP) in two of our strain combinations. These models offer a platform to enable new preclinical research into mechanisms and prevention of epilepsy and SUDEP.


[What advantages does volar plate fixation have over K-wire fixation for distal radius extension fractures in the elderly?].
The purpose of this retrospective study was to compare the outcome of open reduction and internal fixation (ORIF) followed immediately by physiotherapy and of percutaneous K-wire-fixation and casting for unstable distal radius fractures in elderly patients, considering the results both in general, for all such fractures, and selectively for A3 and C2 fractures. Follow-up examinations were performed 26 (18-48) months after surgery in 43 patients (median age 67 (60-83) years) treated with K-wire fixation and 9 (5-17) months after surgery in 46 patients (median age 76 (60-90) years) treated with ORIF, and the outcome of each was recorded as Disabilities of the Arm, Shoulder and Hand (DASH), Gartland-Werley and Castaing scores; the radiological loss of correction was also assessed. Statistical analysis was performed first without reference to the specific type of fracture for the K-wire- and the total ORIF -groups, and then selectively for A3 and C2 -fractures only; in the second analysis the patients were divided into three groups: KD, ORIF with and ORIF without angular stability. The Garland-Werley and Castaing scores do not indicate any significant difference between the procedures specified. According to the Garland-Werley score 37 patients (86%) treated by K-wire fixation and 39 (85%) treated by ORIF achieved "excellent" and "good" results; according to the Castaing score there were 33 (77%) "good" results after K-wire fixation and 34 (74%) good results after ORIF. The radiological loss of correction (K-wire fixation/ORIF) as measured by the radial inclination (median 2/2.5 degrees), the palmar tilt (median 3/5 degrees) and the radial shortening (median 1/1 degrees mm) do not differ significantly. Suboptimal radiological results do not always correlate with results that are only "fair" or "poor". The non-fracture-specific DASH score suggests a higher degree of patient satisfaction after K-wire fixation (7 [0-87] points) than after ORIF (17 [0-82] points), which is not confirmed by fracture-specific evaluation. There is a significantly earlier return to the "activities of daily living" (4 as against 8 weeks) after ORIF. All the treatments compared are suitable for the treatment of A3 and C2 fractures. The important advantages of ORIF are the early functional physiotherapy without casting and without obligatory second surgery and the earlier return to "activities of daily living", which are all of decisive importance for older patients, who are the ones most frequently affected.


Changes in sick leave rates and the use of pregnancy-associated social benefits among pregnant Swedish women: an outcomes study.
We attempted to determine if an amended social security system has lessened the rate of sickness absence during pregnancy in Sweden over the period 1978-1989. We studied the records of 3998 women who gave birth in 1978, 1986, 1988, and 1989 at the University Hospital in Linköping and the Värnamo County Hospital. Retrospective collection of all data concerning the rates and durations of sickness absence during pregnancy, drawing of parental benefit, and use of granted pregnancy benefit was performed from Sweden's standardized social security files. Obstetric variables concerning the course and outcome of pregnancy and delivery, as well as the health status of the newborns, were obtained from standardized and antenatal care and delivery files. Between 1978 and 1989, the rate of sickness absenteeism during pregnancy increased by almost 100% for periods of absence not supported by a doctor's certificate and by about 50% for those with a doctor's certificate. During the same time, the average number of days of sick leave per pregnant woman more than doubled. The changes were most apparent among younger pregnant women. During the decade studied, no significant differences were found with regard to antenatal care, modes of delivery, or the health status of the newborns. In spite of the introduction within the Swedish social security system of more generous rules for pregnant women, the changes in the rates of registered sick leave during pregnancy observed over time were most unfavorable. The present study indicates that the rate of sick leave during pregnancy reflects a complex social phenomenon and cannot be explained solely by an increase in the rate of actual illness or sickness. Such a rate is also likely to depend on general attitudes and expectations among pregnant women, which may vary over time. When amendments in social benefits for pregnant women are considered to improve the health status of the pregnant population, society ought to clearly define the precise aim pursued and the consequences expected to escape unintended socioeconomic results.


Gene analysis of the calcium channel 1 subunit and clinical studies for two patients with hypokalemic periodic paralysis.
Hypokalemic periodic paralysis (HypoPP) is a skeletal muscle disorder in which episodic attacks of muscle weakness occur; they are associated with decreased serum potassium (K+) levels. Recent molecular approaches have clarified that the condition is caused by mutations in the skeletal muscle voltage-gated calcium channel 1 subunit (CACNA1S). We describe two unrelated patients with HypoPP, followed by their relevant clinical studies and gene analysis. Clinical studies included an oral glucose tolerance test (OGTT), food-loading and insulin tolerance tests (ITT). For Case 1, serum K+ levels were extremely decreased following insulin tolerance testing compared with levels for controls. These results support the hypothesis that no efflux of K+ ion occurs in patients because of low activity of adenosine triphosphate (ATP)-sensitive K+ channel (KATP) channels. Mutational analysis of the CACNA1S gene showed a duplicate insertion of 14 base pairs (bp) from 52 to 65 in intron 26, present in the heterozygous state in both patients. No other mutations were detected in the CACNA1S gene, the muscle sodium channel gene (SCN4A) or the voltage-gated K+ channel gene (KCN3) of either patient. Further analysis showed that this duplicate insertion of 14 bp in intron 26 of the CACNA1S gene was found in 23.7% of healthy subjects. K+ dynamics studies are useful for confirming this syndrome, while further gene analysis for various ion channels using amplification and direct sequencing are required to evaluate the molecular basis of the disorder in the individual patient.


Anti-Sm B cell tolerance and tolerance loss in systemic lupus erythematosus.
Autoimmunity is a serious health problem and understanding the maintenance and loss of tolerance to self-antigens are key issues in developing new therapeutic strategies to treat these diseases. Despite considerable progress toward understanding B cell tolerance and tolerance loss, much remains unknown, particularly regarding B cells specific for antigens targeted in disease. Our interest in systemic lupus erythematosus (SLE), a B cell-mediated autoimmune disease characterized by the production of autoantibodies to numerous nuclear antigens, is focused on understanding B cell tolerance and tolerance loss to the SLE-specific autoantigen Sm in mice and humans. Our work aims to provide the cellular and molecular underpinnings for the development of rational therapies to target autoreactive B cells in human SLE.


Matsutakone and Matsutoic Acid, Two (Nor)steroids with Unusual Skeletons from the Edible Mushroom Tricholoma matsutake.
Matsutakone (1), a novel sterol with an unprecedented polycyclic ring system, together with a new norsteroid matsutoic acid (2) were isolated from the fruiting bodies of Tricholoma matsutake. Their structures and absolute configurations were assigned by extensive spectroscopic analyses and computational methods. Bioassay results showed that compounds 1 and 2 exhibited inhibitory activities against acetylcholinesterase (IC50 20.9 μM for 1).


Both hair cortisol levels and perceived stress predict increased symptoms of depression: an exploratory study in young adults.
Depressive symptoms are a common mental health problem among young adults, but the physiological mechanisms that mediate between stress and depressive symptoms remain unclear. Accordingly, this exploratory study (1) examined how hair cortisol concentrations were associated with self-perceived stress and depressive symptoms in a sample of young adults and (2) tested whether hair cortisol could explain variance in depressive symptoms beyond perceived stress before and after controlling for levels of vigorous physical activity (VPA). The sample consisted of 42 exercise and health science university students (20 males, 22 females; mean age = 21.2 years). Cortisol concentrations were extracted from hair strands close to the scalp. Participants completed self-rating questionnaires about depressive symptoms and perceived stress. Students with elevated hair cortisol levels tended to report lower depressive symptoms and lower perceived stress. Increased perceived stress was associated with higher depressive symptoms, and both hair cortisol and perceived stress predicted depressive symptoms after controlling for VPA. The present data suggest that elevated hair cortisol levels do not necessarily constitute a health risk. Hair cortisol measurement can serve as a noninvasive and painless biomarker of chronic stress and mental disorders; however, additional research is needed.


Atrial Lesions in a Pedigree With PRKAG2 Cardiomyopathy: Involvement of Disrupted AMP-Activated Protein Kinase Signaling.
PRKAG2 cardiomyopathy is a rare progressive disease characterized by increased ventricular wall thickness and preexcitation. Dysfunction of the protein 5'-AMP-activated protein kinase (AMPK) plays a decisive role in the progression of ventricular lesions. Although patients with the PRKAG2-R302Q mutation have a high incidence of atrial fibrillation (AF), the molecular mechanism contributing to the disease remains unclear. We carried out whole-genome sequencing with linkage analysis in three affected members of a family. Atrial samples were obtained from the proband via surgical intervention. Control atrium biopsies were obtained from patients with persistent AF. Pathological changes were analyzed using the hematoxylin and eosin (H&E), Masson, and periodic acid-Schiff (PAS) staining. The AMPK signaling pathway was investigated by western blot. A murine atrial cardiomyocyte cell line (HL-1) and human induced pluripotent stem derived atrial cardiomyocytes (hiPSC-ACMs) were transfected with an adenovirus carrying the same mutation. We used enzyme linked immunosorbent assay (ELISA) to determine the AMPK activity in HL-1 cells and hiPSC-ACMs overexpressing PRKAG2-R302Q. Pathological results showed a large quantity of glycogen accumulation and vacuolization in cardiomyocytes from the proband atrial tissue. Western blot analysis revealed that the AMPK activity was significantly downregulated compared with that of the controls. Furthermore, remarkable glycogen deposition and impairment of AMPK activity were reproduced in HL-1 cells overexpressing PRKAG2-R302Q. Taken together, PRKAG2-R302Q mutation directly impair atrial cardiomyocytes. PRKAG2-R302Q mutation lead to glycogen deposition and promote the growth of atrial lesions by disrupting the AMPK pathway.


[Molecular and immunological methods applied in diagnosis of mycoses].
The diagnosis of fungal infections remains a problem for the management of fungal diseases, particularly in the immunocompromised patients. Systemic Candida infections and invasive aspergillosis can be a serious problem for individuals who need intensive care. Traditional methods used for the identification and typing of medically important fungi, such as morphological and biochemical analysis, are time-consuming. For the diagnosis of mycoses caused by pathogenic fungi faster and more specific methods, especially after the dramatic increase in nosocomial invasive mycoses are needed. New diagnostic tools to detect circulating fungal antigens in biological fluids and PCR-based methods to detect species or genus-specific DNA or RNA have been developed. Antigen detection is limited to searching only one genus. Molecular genetic methods, especially PCR analysis, are becoming increasingly important as a part of diagnostics in the clinical mycology laboratory. Various modifications of the PCR method are used to detect DNA in clinical material, particularly multiple, nested and real-time PCR. Molecular methods may be used to detection of nucleic acids of fungi in clinical samples, to identify fungal cultures at the species level or to evaluate strain heterogeneity differences within the species. This article reviews some of the recent advances in the possibility of molecular diagnosis of fungal infections.


Role of p16/INK4a and Ki-67 as specific biomarkers for cervical intraepithelial neoplasia: An institutional study.
P16/INK4a and Ki-67 have emerged as important biomarkers for the detection of high-risk human papilloma virus (HR-HPV) associated dysplastic changes in the cervical biopsy samples. The increasing inter- and intra-observer variability in the diagnosis of dysplastic lesions and immature squamous metaplasia on histopathology has led to the advent of these biomarkers. This study was taken up with an aim to study their role in increasing the diagnostic accuracy in equivocal cases on histopathology. Fifty cervical biopsy specimens were stained with p16/INK4a and Ki-67 consisting of 10 cases each of cervical intraepithelial neoplasia (CIN I/II/III) along with five cases of squamous metaplasia. Histopathological diagnosis was considered as the gold standard. Statistical analysis was done by kappa statistics, and P value was calculated. The sensitivity and specificity of p16/INK4a and Ki-67 were 76.2%, 87.5%, 90.5%, and 87.5%, respectively. The overall agreement of both the immunostains with histopathological diagnosis was statistically significant (P < 0.05) and the diagnostic accuracy improved when both the stains were used in conjunction. Ki-67 and p16/INK4a can be used as complimentary tests in differentiating dysplastic and nondysplastic lesions and help in confirming the histopathological diagnosis. They aid in recognition of dysplasias caused by HR-HPV, which have higher tendency to progress to neoplasia. However, further research is advocated before the widespread use of these markers for screening of dysplasias.


Digoxin serum concentration measurement in patients with suspected digitalis-induced arrhythmias.
The serum digoxin concentration (SDC) was measured in 100 consecutive patients with suspected digitalis-induced arrhythmias. In 24 (toxic group) of these subjects arrhythmias disappeared after glycoside withdrawal. The mean (+/- SD) SDC was 2.88 +/- 1.89 ng/ml in the toxic group and 1.00 +/- 0.61 in the nontoxic group (p less than 0.0001). With respect to digitoxicity, the SDC showed a predictive accuracy rate of 88%, a specificity rate of 89%, and a sensitivity rate of 62%. Since our results were obtained from symptomatic patients, we observed a better predictive accuracy rate than other authors, who studied symptomatic and asymptomatic subjects. The high percentage of false-negatives makes it impossible to consider the SDC by itself a diagnostic test for digitoxicity. However, the SDC is a useful test since all other parameters are less sensitive and/or less rapid indicators of probable digitalis intoxication.


Alcohol norms, expectancies, and reasons for drinking and alcohol use in a U.S. versus a Japanese college sample.
Two hundred eighty-two students at Arizona State University in the U.S. and 339 students at Okayama University in Japan completed a questionnaire on their alcohol use, expectancies of the effects of alcohol on their own and others' moods and behaviors, the desirability of these effects, norms of significant others for levels of alcohol use and the subject's desire to comply with these norms, and reasons for drinking and not drinking alcohol. Although frequencies of current drinkers versus abstainers did not differ between the two samples, the U.S. students began regular alcohol use at a significantly earlier age, currently drank more alcohol, had higher alcohol expectancies for emotional responses, and endorsed more celebratory reasons for drinking than their Japanese counterparts. U.S. students, however, had lower expectancies for flushing and lower perceived norms for drinking. Hierarchical multiple regressions performed using data from the current drinkers indicated that expectancies of disinhibition and especially aggressiveness after alcohol use, alcohol norms, celebratory (but not pathological) reasons for drinking, and reasons for not drinking were more predictive of reported levels of alcohol use among the U.S. students as compared with the Japanese students.


Clinical features of adult-relapse asthma in comparison with those of child-onset asthma and adult-onset asthma.
Clinical features of adult-relapse asthma (group B, n = 15) were compared with those of child-onset asthma (group A, n = 18) and adult-onset asthma (group C, n = 34) in terms of allergic component and bronchial hypersensitivity. The percentage of patients with high levels of serum IgE (> 300 U/ml) in groups A, B, and C was 83%, 73%, and 50%, respectively, and the percentage of patients with positive IgE RAST for house dust was 87.5%, 78.6%, and 46.7%, and that for mite was 93.3%, 92.9%, and 58.6% in groups A, B, and C, respectively. The histamine concentration of PC20 for the bronchial hypersensitivity test in groups A, B, and C was 196 micrograms/ml, 500 micrograms/ml, and 724 micrograms/ml, respectively. Thus, the adult-relapse asthma was closer to the child-onset asthma type in allergic state and closer to the adult-onset asthma type in bronchial hypersensitivity state. The classification employed here seemed to provide some merits in delineating the features of adulthood asthma.


Real-time monitoring of an endogenous Fgf8a gradient attests to its role as a morphogen during zebrafish gastrulation.
Morphogen gradients impart positional information to cells in a homogenous tissue field. Fgf8a, a highly conserved growth factor, has been proposed to act as a morphogen during zebrafish gastrulation. However, technical limitations have so far prevented direct visualization of the endogenous Fgf8a gradient and confirmation of its morphogenic activity. Here, we monitor Fgf8a propagation in the developing neural plate using a CRISPR/Cas9-mediated EGFP knock-in at the endogenous fgf8a locus. By combining sensitive imaging with single-molecule fluorescence correlation spectroscopy, we demonstrate that Fgf8a, which is produced at the embryonic margin, propagates by diffusion through the extracellular space and forms a graded distribution towards the animal pole. Overlaying the Fgf8a gradient curve with expression profiles of its downstream targets determines the precise input-output relationship of Fgf8a-mediated patterning. Manipulation of the extracellular Fgf8a levels alters the signaling outcome, thus establishing Fgf8a as a bona fide morphogen during zebrafish gastrulation. Furthermore, by hindering Fgf8a diffusion, we demonstrate that extracellular diffusion of the protein from the source is crucial for it to achieve its morphogenic potential.


[Late amaurotic familial idiocy with curvilinear bodies and finger prints. Report of a case studied using electron microscopy].
A case of late amaurotic family idiocy of "curvilinear bodies" and "finger prints" is presented. The patient was a .7 year-old non-Jewish boy with convulsions and mental deterioration. A male sibling died at age 12 with a similar picture and a younger brother is starting also with the same symptoms. Biopsy of the brain disclosed a PAS, Sudan black and oil red O positive granular material in the cytoplasm of a large population of cortical neurons. An electron microscopy study disclosed that the stored lipid was composed of masses of so-called "curvilinear bodies" and "finger prints". The same material was found within the cytoplasm of a ganglion cell as well as in endothelial cells of mucosa of the rectum obtained by biopsy. This new variety of amaurotic family idiocy does not occur in Jewish people and the stored lipid is not a ganglioside. It is emphasized that rectal biopsies, as well as the electronmicroscope are useful tools for a more precise diagnosis of the form of storage disease.


Is consolidation chemotherapy after concurrent chemo-radiotherapy beneficial for patients with locally advanced non-small-cell lung cancer? A pooled analysis of the literature.
The purpose of this study was to evaluate whether consolidation chemotherapy (CCT) after concurrent chemo-radiotherapy is beneficial for patients with locally advanced non-small-cell lung cancer (LA-NSCLC). We systematically searched PubMed for phase II/III trials published before December 31, 2011, examining survival of LA-NSCLC treated with concurrent chemo-radiotherapy. Median overall survival and other study characteristics were collected from each study and pooled. We extracted log-transformed hazards and standard errors under the assumption that survival follows an exponential distribution, and computed a pooled median overall survival and a 95% confidence interval (CI) using random-effects model. Collected trial arms were categorized as having CCT or not having it, CCT+ and CCT-, respectively. Forty-one studies were identified including seven phase III studies and 34 phase II studies with 45 arms (CCT+: 25; CCT-: 20). Clinical data were comparable for clinical stage, performance status, cancer histology, sex, and median age between the two groups. There was no statistical difference in pooled mOS between CCT+ (19.0 month; 95% CI, 17.3-21.0) and CCT- (17.9 month; 95% CI, 16.1-19.9). Predicted hazard ratio of CCT+ to CCT- was 0.94 (95% CI, 0.81-1.09; p = 0.40). There were no differences between the two groups with regard to grade 3-5 toxicities in pneumonitis, esophagitis, and neutropenia. These models estimated that addition of CCT could not lead to significant survival prolongation or risk reduction in death for LA-NSCLC patients. The pooled analysis based on a publication basis failed to provide evidence that CCT yields significant survival benefit for LA-NSCLC.


Characterization of beta 1- and beta 2-adrenoceptors in rat skeletal muscles.
Binding studies with (-)-[125I]cyanopindolol (ICYP) were conducted to characterize beta-adrenoceptors in plantaris and soleus muscles of rats (male, 250-300 g). The distribution of beta 1- and beta 2-adrenoceptors in different muscle fiber types, identified in serial sections by succinic dehydrogenase (SDH) staining, was studied by autoradiography. The densities of binding sites (Bmax, fmol/mg protein) were 5.4 +/- 0.9 (mean +/- SEM) in plantaris and 11.5 +/- 2.0 in soleus muscle. In plantaris muscle, monophasic competition curves were observed when binding experiments were performed using CGP20712A (50 pM to 0.5 mM), a beta 1-adrenoceptor selective antagonist, or ICI 118,551 (50 pM to 20 microM), a beta 2-adrenoceptor selective antagonist, to compete for ICYP binding. Analysis with LIGAND revealed a single binding site with a KD value of 2.41 +/- 0.56 nM (mean +/- SEM) for ICI 118,551 and 8.93 +/- 3.00 microM for CGP 20712A, indicating the presence of a homogeneous population of beta 2-adrenoceptors. In soleus muscle, competition curves were biphasic with 16-21% beta 1-adrenoceptors. Autoradiographic studies supported the findings from binding studies with membrane homogenates. The ICYP binding pattern was associated closely with the muscle fiber types identified by SDH staining. Propranolol-resistant binding sites were observed, and these sites were associated with muscle fibers positive to SDH staining.


Carbohydrate metabolism in African women with twin pregnancy.
Carbohydrate metabolism was evaluated in 21 twin pregnancies and in 21 women with singleton pregnancies. The groups were matched for age, weight, parity, and period of gestation. A 100-g oral glucose tolerance test was performed on all 42 subjects. No significant differences in venous plasma glucose responses were found between singleton and twin pregnancies. The only significant difference between the insulin responses of the two groups was a lower plasma insulin concentration at 60 min in the twin group (P less than 0.03).


[Localised vasculitis - an uncommon cause of an unilateral persistent blepharoedema].
To report on the rare case of a localised small-vessel vasculitis causing persistent blepharoedema. A 58-year old woman presented with sudden occurrence of a severe, unilateral blepharoedema. Extended serological examination, orbital CT, and MRI were normal; sonography showed slight thickening of the lateral rectus muscle. Under treatment with higher dosed steroids, the swelling of the lid vanished, but relapsed when the therapy was gradually reduced. Biopsy revealed florid vasculitis of the small vessels in the orbital soft tissue. No signs of systemic manifestation were found. Our patient presented with a localised, eosinophilic vasculitis of the small orbita vessels, a very rare cause of blepharoedema. In the literature only three cases with a localised eosinophilic vasculitis have been reported previously. Early diagnostic biopsy is recommended in such cases of persistent blepharoedema.


Treatment of Degenerative Lumbar Spondylolisthesis by Tongdu Bushen Acupuncture, Intradermal Acupuncture, and Moxibustion Integrated Therapy Combined with Core Muscle Training Program: Study Protocol for a Randomized Controlled Clinical Trial.
Degenerative lumbar spondylolisthesis (DLS), one of the most common causes of low back pain, is defined as the displacement of a vertebral body over the lower vertebral body with degenerative changes and the absence of fracture or defect in the vertebral ring. This disease is a common and frequently occurring disease. Currently, there are many clinical treatment methods, but there is no specific method, and most of them have the characteristics of slow effect and easy recurrence. The objective of this study is to summarize and analyze the effects of treatment of degenerative lumbar spondylolisthesis by Tongdu Bushen acupuncture, intradermal acupuncture, and moxibustion integrated therapy combined with core muscle training program (CMT) on the improvement of pain degree and dysfunction index, as well as the gait characteristics. 120 patients with DLS will be recruited and randomly divided into two groups using electroacupuncture combined with the CMT group as the control group. Visual Analogue Scale (VAS), Oswestry Disability Index (ODI), and Japanese Orthopedic Association score (JOA) will be used for evaluation. The spatiotemporal and kinematics parameters in gait analysis, as well as the ability of lumbar muscle contraction, fatigue resistance, relaxation, and coordination of lumbar muscle in surface electromyography (sEMG), will be used as objective observation indexes to observe the effectiveness of Tongdu Bushen acupuncture, intradermal acupuncture, and moxibustion integrated therapy combined with CMT. Discussion. Tongdu Bushen acupuncture, intradermal acupuncture, and moxibustion integrated therapy is a traditional Chinese medicine treatment for DLS. Our results will provide evidence to determine whether the integrated therapy can effectively treat DLS, as well as its advantages and safety, and lay a foundation for further research. This trial is registered with ChiCTR2100050409.


Complementing theory with practice to enhance Students' learning.
Combining cognitive skills teaching related to the techniques leads to better understanding in a skill training course; but still there a substantial disagreement in curriculum on such combinations. This study aims to help guide the designers in making the outline of instructional plan for a Clinical Skills Module (CSM) for the undergraduates. Objectives were to assess performance of students on a clinical skill after training by two different models of (hands-on only or with cognitive skills) instructions and explore their perception on the employment of educational strategies through Focus Group Discussions (FGD) through a Sequential mixed method study design: (1) Quantitative (Pre- and post-assessments and comparing their results (2) Qualitative (Exploration of perspectives through constructivist approach using qualitative phenomenological design) The study was conducted during the month of September, 2015 at Rabigh Medical College, King Abdul Aziz University, Jeddah. Students entering fourth year were randomized to two groups to participate in pre-post OSCE using global rating scale and their scores were compared. The examiners were kept blinded to the randomization of students undergoing two separate training methods. The test group (group A) was trained for both procedural as well as cognitive skills whereas the control group (Group-B) was trained only with hands-on practice. Later their perception about the addition of cognitive skills to improve of procedural skills was explored through focus group discussions. The recorded audio tapes of FGDs were transcribed and analysed thematically. Triangulation of themes and trends was achieved by relating the content analysis to the relevant frequency of quotes. Auditing of the data verification was done by all the authors separately.. A total of 42 students completed both pre- and post-tests. As a result, student performance in OSCE significantly increased from pre- to post-test (p<0.001) in both the groups; on the other hand no statistically significant difference was found in the pre- and posttest scores between groups A and B (p=0.108). Five themes (1) advantages, (2) disadvantages of combining theory with practice, (3) time balance in teaching a skill, (4) training on skills, (5) skillsassessment, were found prevalent on thematic analysis of the FGDs. Students' ability to grasp the procedural skills was not significantly different when they acquire the cognitive skills in addition to the practical sessions. Students were more convinced to adopt combination of the two in the learning of procedural skills.


A comparative assessment of West Virginia's financial incentive programs for rural physicians.
Financial incentive programs are increasingly being used as a strategy to recruit physicians to underserved rural areas. Critical evaluation of state-supported programs is often lacking but is necessary to determine their efficacy and to improve outcomes. The purpose of this study was to assess 4 service-contingent programs in West Virginia, a state with critical physician shortages. Survey instruments were developed to evaluate the effectiveness of these programs and to document the practice environments and career paths of obligated allopathic and osteopathic physicians compared with a control group of nonobligated rural practitioners. Data were also collected from physicians who were recipients of multiple incentive programs and from obligated physicians who had defaulted. Responses from more than 60% of surveyed physicians indicated that the typical respondent was a married white male who was a midcareer family practice physician. Obligated physicians were more likely than nonobligated physicians to have graduated from a West Virginia medical school and residency program, to be influenced by financial factors in their career decisions, to provide care to uninsured patients, and to work in offices that offered sliding fee scales. Both groups of physicians demonstrated similar retention patterns, reported a high degree of job satisfaction, and expressed a need for more practice management training. Although these financial incentive programs were found to be effective in recruiting primary care physicians to medically underserved areas of the state, the financial support of these programs was found to be too modest, and improved marketing of the programs was indicated.


Tyrosine hydroxylase-immunoreactive boutons in synaptic contact with identified striatonigral neurons, with particular reference to dendritic spines.
Tyrosine hydroxylase-immunoreactive fibres in the rat neostriatum were studied in the electron microscope in order to determine the nature of the contacts they make with other neural elements. The larger varicose parts of such fibres contained relatively few vesicles and rarely displayed synaptic membrane specializations; however, thinner parts of axons (0.1-0.4 micron) contained many vesicles and had symmetrical membrane specializations, indicative of en passant type synapses. By far the most common postsynaptic targets of tyrosine hydroxylase-immunoreactive boutons were dendritic spines and shafts, although neuronal cell bodies and axon initial segments also received such input. Six striatonigral neurons in the ventral striatum were identified by retrograde labelling with horseradish peroxidase and their dendritic processes were revealed by Golgi impregnation using the section-Golgi procedure. The same sections were also developed to reveal tyrosine hydroxylase immunoreactivity and so we were able to study immunoreactive boutons in contact with the Golgi-impregnated striatonigral neurons. Each of the 280 immunoreactive boutons examined in the electron microscope displayed symmetrical synaptic membrane specializations: 59% of the boutons were in synaptic contact with the dendritic spines, 35% with the dendritic shafts and 6% with the cell bodies of striatonigral neurons. The dendritic spines of striatonigral neurons that received input from immunoreactive boutons invariably also received input, usually more distally, from unstained boutons that formed asymmetrical synaptic specializations. A study of 87 spines along the dendrites of an identified striatonigral neuron showed that the most common type of synaptic input was from an individual unstained bouton making asymmetrical synaptic contact (53%), while 39% of the spines received one asymmetrical synapse and one symmetrical immunoreactive synapse. It is proposed that the spatial distribution of presumed dopaminergic terminals in synaptic contact with different parts of striatonigral neurons has important functional implications. Those synapses on the cell body and proximal dendritic shafts might mediate a relatively non-selective inhibition. In contrast, the major dopaminergic input that occurs on the necks of dendritic spines is likely to be highly selective since it could prevent the excitatory input to the same spines from reaching the dendritic shaft. One of the main functions of dopamine released from nigrostriatal fibres might thus be to alter the pattern of firing of striatal output neurons by regulating their input.


Shoulder girdle neoplasms mimicking frozen shoulder syndrome.
Shoulder pain and immobility comprise a multifactorial disorder apparently affected by pain inhibiting joint motion. As the syndrome is very common, many patients do not undergo detailed imaging studies before treatment. This study compared a series of 7 patients in whom a neoplasm was the underlying cause for the stiff shoulder with a series of 50 patients with primary or secondary frozen shoulder. In addition to a detailed history being taken, the Disabilities of the Arm, Shoulder, and Hand (DASH) upper limb outcomes data collection questionnaire was completed and physical examination, radiography, ultrasonography, and bone scanning were performed in all cases. In the cases of tumor, the presenting symptom was a stiff shoulder without radiographic abnormality in 7 of 67 patients with shoulder girdle neoplasms who were seen at our musculoskeletal oncology clinic. The tumors included osteoid osteoma, osteoblastoma, metastatic carcinoma, chondrosarcoma, periosteal lipoma, and acute lymphoblastic lymphoma. The diagnosis was established in all cases by an area of focal isotope uptake demonstrated by a routine technetium 99 methylene diphosphonate bone scan. In a single case of metastatic colon carcinoma, the diagnosis could only be established by magnetic resonance imaging, as the radiographs were normal and the bone scan demonstrated diffuse uptake over the proximal humerus. The patients whose frozen shoulder was caused by an underlying tumor were significantly younger and had a lower fatigue/energy dimension score on the RAND Short Form-36 health survey. The most useful diagnostic test appears to be a discrete area of bony tenderness, present in 7 of 7 patients with tumor and in only 5 of 50 patients in the control group. Although an underlying tumor is a rare cause of frozen shoulder syndrome, the potential grave consequences of misdiagnosis and the possibility of performing an unnecessary and ineffective invasive procedure should prompt physicians to increased vigilance. In patients with discrete bony tenderness elicited by light tapping, a bone scan should be ordered and magnetic resonance imaging should be considered.


Extinction rates under nonrandom patterns of habitat loss.
Most models that examine the effects of habitat conversion on species extinctions assume that habitat conversion occurs at random. This assumption allows predictions about extinction rates based on the species-area relationship. We show that the spatially aggregated nature of habitat conversion introduces a significant bias that may lead species-loss rates to exceed those predicted by species-area curves. Correlations between human activity and major compositional gradients, or species richness, also alter predicted species extinction rates. We illustrate the consequences of nonrandom patterns of habitat conversion by using a data set that combines the distribution of native vascular plants with human activity patterns in California.


Prognostic factors in HIV-related diffuse large-cell lymphoma: before versus after highly active antiretroviral therapy.
To compare the prognostic factors for survival and the validity of the International Prognostic Index (IPI) in patients with HIV-related diffuse large-cell lymphoma (HIV-DLCL) treated with curative intent in the pre-highly active antiretroviral therapy (HAART) era versus the HAART era. We retrospectively reviewed 192 patients with HIV-DLCL diagnosed from 1982 to 2003. Pre-HAART era included 120 patients who did not receive HAART, whereas the HAART era included 72 patients diagnosed after January 1997 who received HAART. There were no statistically significant differences in terms of either lymphoma or HIV-related characteristics in the two time periods. The complete response rate improved from 32% in the pre-HAART to 57% in the HAART era (P = .0006), and median survival time improved from 8.3 to 43.2 months (P = .0005). In groups with low-, low-intermediate-, and high-intermediate-risk IPI disease, 3-year overall survival rates were 20%, 22%, and 5% in the pre-HAART era and 64%, 64%, and 50% in the HAART era, respectively. On multivariate analysis, factors independently associated with decreased survival in both periods were increasing IPI scores and failure to attain complete remission, whereas CD4 less than 100 cells/microL predicted shorter survival in only the pre-HAART era. Prognostic factors and overall survival of patients with HIV-DLCC have changed. Clinical outcomes in patients with HIV-DLCL are now approaching the outcomes of patients with de novo lymphoma.


GENOTYPE-ENVIRONMENT INTERACTION AND THE EVOLUTION OF PHENOTYPIC PLASTICITY.
Studies of spatial variation in the environment have primarily focused on how genetic variation can be maintained. Many one-locus genetic models have addressed this issue, but, for several reasons, these models are not directly applicable to quantitative (polygenic) traits. One reason is that for continuously varying characters, the evolution of the mean phenotype expressed in different environments (the norm of reaction) is also of interest. Our quantitative genetic models describe the evolution of phenotypic response to the environment, also known as phenotypic plasticity (Gause, 1947), and illustrate how the norm of reaction (Schmalhausen, 1949) can be shaped by selection. These models utilize the statistical relationship which exists between genotype-environment interaction and genetic correlation to describe evolution of the mean phenotype under soft and hard selection in coarse-grained environments. Just as genetic correlations among characters within a single environment can constrain the response to simultaneous selection, so can a genetic correlation between states of a character which are expressed in two environments. Unless the genetic correlation across environments is ± 1, polygenic variation is exhausted, or there is a cost to plasticity, panmictic populations under a bivariate fitness function will eventually attain the optimum mean phenotype for a given character in each environment. However, very high positive or negative correlations can substantially slow the rate of evolution and may produce temporary maladaptation in one environment before the optimum joint phenotype is finally attained. Evolutionary trajectories under hard and soft selection can differ: in hard selection, the environments with the highest initial mean fitness contribute most individuals to the mating pool. In both hard and soft selection, evolution toward the optimum in a rare environment is much slower than it is in a common one. A subdivided population model reveals that migration restriction can facilitate local adaptation. However, unless there is no migration or one of the special cases discussed for panmictic populations holds, no geographical variation in the norm of reaction will be maintained at equilibrium. Implications of these results for the interpretation of spatial patterns of phenotypic variation in natural populations are discussed.


'We usually just start dancing our Indian dances': urban American Indian (AI) female youths' negotiation of identity, health and the body.
In this article, we utilise qualitative research techniques to explore how 14 urban American Indian (AI) females (aged 11-17) living in the state of Maryland discursively construct and experience health and the body, as well as how/if traditional culture shapes their understandings. In doing so, we address a significant gap in the knowledge base concerning the health beliefs of urban AI youth, and build upon research utilising a decolonising approach. Using a two-step process of thematic analysis and poststructuralist discourse analysis, we arrived at three key findings: (1) while youths are taught (and learn) mainstream lessons about health and bodily norms (mostly at school), they negotiate these lessons in complex and at times contradictory ways; (2) they do not view their AI status as conferring more or less risk upon them or their community; and (3) AI identity appears to be fluid in nature, becoming more salient, even a resource, in certain situations. We conclude with a discussion of the importance of spaces within the urban context in shaping youths' embodied subjectivities, and in particular, contrast the space of the school with that of the urban AI community centre.


Advanced glycation endproduct induces ROS accumulation, apoptosis, MAP kinase activation and nuclear O-GlcNAcylation in human cardiac myocytes.
Accumulation of advanced glycation endproduct (AGE) has been implicated in the pathogenesis of diabetic complications. However, the precise role and mechanism behind AGE-associated diabetic heart injury are not fully clear. This study was designed to evaluate the effect of AGE on accumulation of reactive oxygen species (ROS), apoptosis, mitogen-activated protein kinase (MAPK) activation and nuclear O-GlcNAcylation in fetal human cardiac myocytes. Myocytes were maintained for 24-72 h in a defined culture medium containing high glucose, the AGE carbon precursor methylglyoxal (MG), and MG-AGE derived from MG and bovine serum albumin (BSA). Generation of ROS was detected by 5-(6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate. Apoptosis was evaluated by caspase-3 activity and quantitative DNA fragmentation. Both high glucose (25.5 mM) and MG (200 microM) significantly enhanced ROS and AGE formation with greater effects elicited by MG. Both high glucose and MG-AGE significantly facilitated apoptosis with a more predominant effect from MG-AGE. In addition, phosphorylation of MAPK cascade [extracellular signal-regulated kinase-1/2 (ERK1/2) and p38] and nuclear O-GlcNAcylation were enhanced in MG-AGE-treated myocytes, similar to those elicited by high glucose. MG-AGE-induced phosphorylation of ERK1/2 and p38 was nullified by neutralizing AGE with specific anti-AGE antibody but not nonspecific antiserum. Collectively, these results indicated that AGE or its precursor MG may trigger ROS generation, apoptosis, MAPK activation and nuclear O-GlcNAcylation in human cardiac myocytes, in a manner reminiscent of high extracellular glucose.


A prospective longitudinal cohort study of the effectiveness of 25% xylitol toothpaste on mutans streptococci in high caries-risk young children.
To compare the prevalence of mutans streptococci (SM) prevalence and categorical distribution in the saliva of high caries-risk children after their 24 months exposure to 25% xylitol toothpaste applied twice a day. To also examine the early caries susceptibility at baseline. An observational design with two times of collection. A total of 270 mother-infant dyads (mean age of infant 6.7 months) were initially recruited. At baseline, a dental exam looked for any early clinical signs of caries, and saliva collections were performed to assess SM prevalence. Two years later, other saliva collections were performed on a residual sample of 102 young children at the endpoint. Two hundred four saliva samples were analysed with Dentocult, a commercial kit estimating in four categories, the SM distribution, expressed as the number of colonies forming units per milliliter of saliva (CFU/ml). The dental exam used the ICDAS system to include initial carious lesions (d1-2). The dentist administrated a maternal socio-economic questionnaire as the study collector. A domestic strategy using a natural toothpaste containing 25% of xylitol as a vehicle, and tooth brushing as a habit, showed a promising antibacterial cariogenic effect. This approach could be a relevant alternative to in-home care to prevent ECC and early SM contamination.


Bio-mimicking of proline-rich motif applied to carbon nanotube reveals unexpected subtleties underlying nanoparticle functionalization.
Here, we report computational studies of the SH3 protein domain interacting with various single-walled carbon nanotubes (SWCNT) either bare or functionalized by mimicking the proline-rich motif (PRM) ligand (PPPVPPRR) and compare it to the SH3-PRM complex binding. With prolines or a single arginine attached, the SWCNT gained slightly on specificity when compared with the bare control, whereas with multi-arginine systems the specificity dropped dramatically to our surprise. Although the electrostatic interaction provided by arginines is crucial in the recognition between PRM and SH3 domain, our results suggest that attaching multiple arginines to the SWCNT has a detrimental effect on the binding affinity. Detailed analysis of the MD trajectories found two main factors that modulate the specificity of the binding: the existence of competing acidic patches at the surface of SH3 that leads to "trapping and clamping" by the arginines, and the rigidity of the SWCNT introducing entropic penalties in the proper binding. Further investigation revealed that the same "clamping" phenomenon exits in the PRM-SH3 system, which has not been reported in previous literature. The competing effects between nanoparticle and its functionalization components revealed by our model system should be of value to current and future nanomedicine designs.


Role of vitamin D in risk factors of patients with type 2 diabetes mellitus.
Previous observational studies have suggested that low vitamin D status is associated with high circulating C-reactive protein levels, as well as other plasma inflammatory cytokines. However, there is no study to explore the relationship between vitamin D status and Lp-PLA2, a new biomarker of vascular-specific inflammation. The aim of this study was to examine the association between vitamin D status and circulating Lp-PLA2 levels in subjects with type 2 diabetes mellitus. This descriptive cross-sectional study enrolled diabetic subjects who underwent physical examination at Taizhou People's Hospital between August 2016 and January 2017. Blood pressure, anthropometry, metabolic profiles, serum 25(OH)D levels and Lp-PLA2 mass levels were measured in all participants. A total of 196 participants were recruited into this study. The vitamin D insufficiency group had higher serum LP-PLA2 levels than the vitamin D sufficiency group (t=-2.765, p=.005). A significant negative correlation was noted between Lp-PLA2 and 25(OH)D in the vitamin D insufficiency group (r=-0.364, p=0.009). However, no significant relationship between serum Lp-PLA2 concentration and 25(OH)D levels was observed in subjects with vitamin D sufficiency. From this cohort of patients with type 2 diabetes, regardless of traditional cardiovascular risk factors, we observed a statistically significant inverse relation between Lp-PLA2 and 25(OH)D at levels <30ng/mL.