Early endocrine, metabolic, and sonographic characteristics of polycystic ovary syndrome (PCOS): comparison between nonobese and obese adolescents.
Approximately half of all women with polycystic ovary syndrome (PCOS) are overweight or obese, and studies have reported endocrine and metabolic differences between lean and obese women with PCOS. PCOS has not been as extensively investigated in the adolescent population. The objectives of our study were to further characterize early endocrine and metabolic alterations in adolescents with PCOS and to determine whether differences between nonobese and obese women with PCOS are present early in its course. We studied an ethnically heterogeneous group of 48 adolescents: 11 nonobese with PCOS [age, 16.1 +/- 1.9 yr; body mass index (BMI), 22.5 +/- 1.5 kg/m(2)], 22 obese with PCOS (age, 15.5 +/- 1.4 yr; BMI, 35.9 +/- 6.2 kg/m(2)), and 15 obese controls (age, 14.4 +/- 1.5 yr; BMI, 35.8 +/- 7.1 kg/m(2)). Fasting levels of glucose, insulin, proinsulin, hemoglobin A1c, testosterone, SHBG, Delta4-androstenedione (Delta4-A), dehydroepiandrosterone sulfate (DHEAS), LH, FSH, IGF-I, IGF binding protein-1, free IGF-I, and lipids were measured. Six of the 11 nonobese PCOS subjects, 11 of the 22 obese PCOS subjects, and six of the 15 controls underwent standard oral glucose tolerance testing. The insulin response to the oral glucose tolerance test was measured by the insulin area under the curve (I(AUC120)). Measures of insulin sensitivity were calculated as the fasting glucose to insulin ratio, quantitative insulin sensitivity check index, and composite insulin sensitivity index. The nonobese adolescents with PCOS demonstrated higher levels of LH, SHBG, Delta4-A, DHEAS, dihydrotestosterone, free IGF-I, and high-density lipoprotein, and lower low-density lipoprotein, compared with the obese PCOS group. Fasting levels of insulin and proinsulin, I(AUC120), and log I(AUC120) were higher, and the fasting glucose to insulin ratio, quantitative insulin sensitivity check index, and composite insulin sensitivity index were lower in the obese compared with the nonobese PCOS subjects. Greater levels of LH and androgens, including total and free testosterone, Delta4-A, and DHEAS, and lower SHBG levels were found in the obese PCOS group compared with the obese controls. Adolescents with PCOS manifest clinical, metabolic, and endocrine features similar to those of adult women, and differences between nonobese and obese women with PCOS may be detected in adolescence. Our findings indicate a more pronounced alteration in the hypothalamo-pituitary-adrenal axis in nonobese adolescents with PCOS and a more marked dysregulation of insulin levels and impairment of insulin sensitivity in their obese counterparts. Our data also suggest differences in the IGF system between nonobese and obese adolescents with PCOS.


[Metabolism of fibrinogen].
Fibrinogen metabolism was studied with the use of coagulation and enzyme immunoassay techniques for measuring its concentrations and the levels of fibrinogen (fibrin) degradation products and of monomer fibrin soluble complexes in adults and children in health and disease. The detected age-associated and nosologic changes in fibrinogen and its metabolites' concentrations are discussed, as is the practical value of the methods employed.


HCG contamination of alglucerase: clinical implications in low-dose regimen.
Alglucerase (Ceredase) is currently the treatment of choice for patients with symptomatic Gaucher disease. The contamination of this placental enzyme with human chorionic gonadotropin (hCG) has raised concern regarding possible endocrinological complications. We examined 32 patients treated with low-dose alglucerase and 27 untreated patients as controls, and found no significant clinical differences between the two groups: no prepubertal children were affected, no menstrual irregularities were reported, and all hCG levels were well within normal range. Conversely, our finding of a statistically significant difference between the groups underscores the importance of initiating parallel studies of hCG contamination in patients receiving high-dose protocol.


Computer simulations on aggregation of acetic acid in the gas phase, liquid phase, and supercritical carbon dioxide.
Computer simulations including semiempirical molecular orbital and Monte Carlo methods were employed to investigate the aggregation of acetic acid in the gas phase, liquid phase, and supercritical carbon dioxide. The binary vapor-liquid coexistence curves of the CO(2)/acetic acid mixtures were calculated at 313.2, 333.2, and 353.2 K and are in excellent agreement with experimental measurements. Two sets of rigorous hydrogen-bonding criteria were established for the hydrogen bonding at the hydroxyl oxygen and carbonyl oxygen, respectively. With the criteria, detailed statistics of hydrogen bonding states and distribution of aggregate sizes and structures were fully investigated and compared in the three phases, which will shed light on the development of more rigorous and accurate real associated solution models in the future.


Variations in properties of virus released from morphologically different cell lines transformed in vitro by Friend leukemia virus.
The properties of the virus synthesized by each of three morphologically different cell lines originating from DBA/2J fetal liver cells transformed by the anemic strain of Friend leukemia virus in vitro were analyzed. The cells of line G-1 are malignant in syngeneic DBA/2 mice, grow in suspension, and are erythroid in origin. Cells of lines G-2 and G-3 are adherent, are epithelial in appearance, and produce no tumors in DBA/2J mice. Higher reverse transcriptase activity was detected in the culture fluid of lines G-2 and G-3, although virus from G-1 cells was more leukemogenic. Differences were also found in the virion density and size of the viral genome. RNA from the virions produced by G-2 and G-3 cells sedimented at 75 S in a sucrose gradient; virion RNA from G-1 cells sedmiented at 60 S. However, when subjected to polyacrylamide gel electrophoresis, all three virus strains showed identical RNA subunits with an estimated molecular weight of 2.6 X 10(6). Analysis of virion proteins by slab gel electrophoresis showed differences in envelope protein (gp71) components but not in the major core protein (p30). The properties of these viruses are stable and remain unchanged after passage in 3T3 cells.


Diarrhoea and constipation.
Drug-induced constipation is mostly caused by changes in gut motility, whilst diarrhoea is more frequently caused by an increase in intestinal fluid secretion. In both instances the drug has to reach the enteric nervous system or the enterocyte, either via the blood or from the lumen, in sufficient concentrations to affect the mediators that regulate motility and fluid transport. Diarrhoea and constipation are frequently mentioned as side-effects of drugs, and therapeutic agents for almost all organ systems have been implicated. However, both these side-effects are usually mild or moderate, and rarely necessitate interruption of drug treatment. An exception to this rule is the antibiotic-associated colitis seen in patients treated with antibiotics such as lincomycin or clindamycin; in principle almost all antibiotics may cause this severe and potentially life-threatening complication. Other rare forms of severe, drug-induced colitis and diarrhoea result from toxic or anaphylactic reactions against gold preparations, cytostatic agents and sulphonamides. Ischaemic colitis due to vascular complications has been described in some women taking oral contraceptives, and in patients treated with vasopressin or digitalis.


Identification of CD4 and major histocompatibility complex functional peptide sites and their homology with oligopeptides from human immunodeficiency virus type 1 glycoprotein gp120: role in AIDS pathogenesis.
CD4 molecules interact with class II major histocompatibility complex molecules as a critical costimulatory signal in CD4+ cell immune activation. CD4 also recognizes a specific region of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp120 forming a binding site for early stages of HIV-1 infection. We designed two software packages, AUTOMAT and CRITIC, which allowed us to identify similarities between regions of HIV-1 proteins and immunoregulatory protein sequences stored in data banks. In this report we have characterized (i) a pentapeptide, SLWDQ, found in both CD4 and HIV-1 gp120, which surprisingly had remained undetected in these two well-studied molecules until now, and (ii) an HLA sequence corresponding to the putative functional site of H2 I-A. We found that a region of gp120 (residues 254-263) known to be similar to a sequence in HLA class II beta chain overlaps this functional region. We showed experimentally that these two CD4 and HLA peptide segments inhibit CD4+ cell immune activation. There is strong inhibition (50% up to 80%) of immune activation by SLWDQ-containing gp120 segments and a lesser inhibition by the gp120 HLA-homologous segment. In addition, we found that SLWDQ induced in HIV-1-infected individuals a humoral (antibody) and cellular (cytotoxic T lymphocyte) immune reaction. We propose that these HIV-1 gp120 segments, together with the known CD4-binding region, may contribute to the HIV-1-induced immunosuppression by two mechanisms affecting CD4-HLA interaction during T-cell immune activation: autoimmune reaction toward CD4 and direct interference with the CD4-HLA costimulatory signal inducing CD4+ cell anergy with, as a consequence, generation of immunosuppression.


[Pulmonary alveolar proteinosis].
Pulmonary alveolar proteinosis (PAP) is a rare, diffuse infiltrative lung disease of unknown etiology characterized by accumulation of abnormal lung surfactant in the alveoli and distal airways. Although it was first described in 1958, few large scale studies have been published. The diagnosis is conventionally based on lung biopsy and the value of less invasive procedures such as bronchoalveolar lavage (BAL) remains controversial. A multi-center retrospective study was conducted in an attempt to update epidemiological, clinical and long term outcome and to assess the usefulness of chest CT scan and BAL in the management of a large homogeneous series of 41 patients. Inclusion criteria required a clinical picture compatible with PAP and either histological confirmation, or a BAL with a milky macroscopic appearance coupled with positive staining to PAS. Mean age was 48.8 years with a 4: 1 male predominance. The prevalence of smokers (80%) and occupational exposure to various inhaled dusts (39%) was high. The clinical, roentgenographic and functional features were in keeping with previous series. Worsening dyspnea was the most common symptom. Other common manifestations were dry cough, recurrent lung infections, weight loss, finger clubbing, crackles and cyanosis. LDH serum levels were increased in 51% of cases. Lung function tests usually showed a mild restrictive ventilatory defect with hypoxemia and reduced DLCO. Chest X ray revealed bilateral ground glass opacities with consolidation or air bronchogram involving peri-hilar or lower lobes. Chest CT scan, performed in 38 patients, revealed a similar pattern in most of them with diffuse intra-alveolar ground glass opacities (33/38) and interlobular thickening (35/38), resulting in a crazy paving appearance in the typical geographic pattern (32/38). This latter aspect was highly suggestive of the diagnosis. Segmental BAL led to a definitive diagnosis in 62% and lung biopsy was only required in 38% of cases. These data suggest that careful BAL analysis can be sufficient to provide a diagnosis without the need for a lung biopsy. During follow-up, spontaneous remission or improvement was reported in 26%. Segmental (n=3) or whole lung lavage (n=22) was required in 62.5% with a favorable course (complete remission 37%, improvement 34%, stable course 21%) in 92% of the cases. In this series the overall prognosis for PAP remained good, although unpredictable.


Nitrogen availability from composts for humid region perennial grass and legume-grass forage production.
Perennial forages may be ideally suited for fertilization with slow N release amendments such as composts, but difficulties in predicting N supply from composts have limited their routine use in forage production. A field study was conducted to compare the yield and protein content of a binary legume-grass forage mixture and a grass monocrop cut twice annually, when fertilized with diverse composts. In all three years from 1998-2000, timothy (Phleum pratense L.)-red clover (Trifolium pratense L.) and timothy swards were fertilized with ammonium nitrate (AN) at up to 150 and 300 kg N ha(-1) yr(-1), respectively. Organic amendments, applied at up to 600 kg N ha(-1) yr(-1) in the first two years only, included composts derived from crop residue (CSC), dairy manure (DMC), or sewage sludge (SSLC), plus liquid dairy manure (DM). Treatments DM at 150 kg N ha(-1) yr(-1) and CSC at 600 kg N ha(-1) yr(-1) produced cumulative timothy yields matching those obtained for inorganic fertilizer. Apparent nitrogen recovery (ANR) ranged from 0.65% (SSLC) to 15.1% (DMC) for composts, compared with 29.4% (DM) and 36.5% (AN). The legume component (approximately 30%) of the binary mixture acted as an effective "N buffer" maintaining forage yield and protein content consistently higher, and within a narrower range, across all treatments. Integrating compost utilization into livestock systems that use legume-grass mixtures may reduce the risk of large excesses or deficits of N, moderate against potential losses in crop yield and quality, and by accommodating lower application rates of composts, reduce soil P and K accumulation.


[Psychological causative factors in postpartum depression amongst women with normal and high-risk pregnancies].
The study presented in the following article was based on the assumption a state of mind of a mother-to-be directly influences her state of mind after giving birth. The aim of the study was to determine whether a case of a high-risk pregnancy, and the related stress, can be significant causative factors in postpartum depression, in case of pregnancies with a normal course, as well as whether incidences of postpartum depression among women with normal and high-risk pregnancies are correlated with the level of stress and depression experienced during pregnancy. 70 women were examined in the study: 35 women with normal pregnancies represented the control group and 35 women with high-risk pregnancies represented the study group. The following methods were used to find answers to the posed research questions: a demographic survey, Perceived Stress Scale, the Beck Depression Scale and the Edinburgh Postnatal Depression Scale. Women with high-risk pregnancies demonstrated a significantly much higher level of stress and related negative emotions; also they handled the stress and emotions worse than women with normal pregnancies. Also, higher intensity of depression symptoms during pregnancy were observed in the study group of women with high-risk pregnancies. In both groups, higher intensity of symptoms of post-childbirth depression was correlated with higher level of stress and more severe depression during pregnancy. Pregnancy--especially high-risk pregnancy, which is associated with health difficulties and complications, and consequently, higher stress level, feelings of uncertainty and depression--is an additional risk factor of postpartum depression. There exists a necessity to create therapeutic programs aimed at psychological support for suffering women.


Myo-Spain: Spanish Registry of patients with idiopathic inflammatory myopathy. Methodology.
To describe the methods of the Spanish Registry of patients with idiopathic inflammatory myopathy (IIM) (Myo-Spain), as well as its strengths and limitations. The main objective of the project is to analyse the evolution and clinical management of a cohort of patients with IIM. Observational, longitudinal, ambispective and multicentre study of a cohort of patients with IIM seen in rheumatology units in Spain. All patients with a diagnosis of IMM will be included in the regular follow-up of the participating centres, regardless of age on initiation of the process. Incident cases will be all patients who at the beginning of the study have been diagnosed for less than 12 months and prevalent cases for more than 12 months. The registry will include data from the visit at baseline, one year and two years. Socio-demographic, clinical, analytical variables, complications, comorbidities, association with other rheumatic diseases, hospital admissions, mortality and treatments will be collected. In addition, indices, scales and questionnaires of activity, muscle involvement, damage, disability, and quality of life will be determined. The recruitment period will be 23 months. The purpose is to obtain a cohort of 400 patients with IMM. Myo-Spain registry provides the opportunity to develop a cohort of incident and prevalent patients with IMM in Spain. Myo-Spain will be able to assess in detail the clinical characteristics of the disease at different times. The comprehensive information collected during the visits is expected to provide a broad source of data for future analysis.


Toxoplasma gondii seroprevalence in dairy and beef cattle: Large-scale epidemiological study in Estonia.
Toxoplasma gondii is a zoonotic protozoan parasite that thrives in Estonia. In this nationwide cross-sectional study, we tested sera from 3991 cattle, collected from 228 farms in 2012-2013, for anti-T. gondii immunoglobulin G antibodies using a commercial direct agglutination test. Titer of 100 was set as cut-off: samples that tested positive at the dilution 1:100 were defined as positive. The apparent animal-level seroprevalence was 18.62%. At least one seropositive animal was found on 68.86% of the farms, and seropositive cattle were detected in all counties. The seroprevalence appeared to increase with age until five years (60-71 months) of age, but had no obvious pattern in the older animals. Animals of the local Estonian Red breed had higher odds to test seropositive than did animals of the Estonian Holstein breed. Whether the farm focused on dairy or beef cattle was not associated with an animal testing T. gondii seropositive nor with finding at least one T. gondii seropositive animal on the farm. The odds of finding at least one T. gondii seropositive animal on the farm were higher if the herd size was above median (105 in dairy and mixed dairy farms; 35 in beef and mixed beef farms). The results indicate that T. gondii is endemic within the agricultural setting in Estonia and present on the majority of cattle farms.


Mono-ADP-Ribosylhydrolase Assays.
Despite substantial progress in ADP-ribosylation research in recent years, the identification of ADP-ribosylated proteins, their ADP-ribose acceptors sites, and the respective writers and erasers remains challenging. The use of recently developed mass spectrometric methods helps to further characterize the ADP-ribosylome and its regulatory enzymes under different conditions and in different cell types. Validation of these findings may be achieved by in vitro assays for the respective enzymes. In the below method, we describe how recombinant ADP-ribosylated proteins are demodified in vitro with mono-ADP-ribosylhydrolases of choice to elucidate substrate and potentially also site specificity of these enzymes.


Reassembled Vacuoles for Drug Delivery Carriers Using Yeast Vacuoles for Enhanced Antibacterial Activity.
In this study, we aimed to develop an efficient drug delivery system by reassembling vacuoles isolated from Saccharomyces cerevisiae. Initially, we assessed the impact of vacuolar enzymes on the efficacy of the loaded antibiotic polymyxin B (PMB), by conducting antibacterial activity tests using Shigella flexneri and Salmonella enteritidis. The results showed that vacuolar enzymes inhibited the effectiveness of PMB, highlighting the limitations of using natural vacuoles as drug carriers. To overcome this, we proposed a new drug delivery system called reassembled vacuoles (ReV). ReV particles were created by removing vacuolar enzymes and reassembling the vacuolar membrane through extrusion. ReV demonstrated improved structural stability, a more uniform size, and enhanced PMB release compared to natural vacuoles. Encapsulation efficiency tests revealed high loading efficiency for both normal vacuoles (NorV) and ReV, with over 80% efficiency at concentrations up to 600 μg/mL. The antibacterial activity of PMB-loaded ReV showed comparable results to PMB alone, indicating the potential of ReV as a drug delivery system. In conclusion, reassembled vacuoles offer a promising approach for drug delivery, addressing the limitations of natural vacuoles and providing opportunities for targeted and efficient drug release.


Colony formation in vitro as a prognostic indicator for primary breast cancer.
Cells from some, but not all, tumor biopsy samples form colonies when cultured in semi-solid media. The possibility that colony formation by progenitor cells in these tumors may reflect a more "aggressive" phenotype bearing clinical implications was examined in a series of 61 patients with primary breast cancer. Tumor cells from 32 samples formed colonies in vitro. There was no correlation between colony formation and any of the standard clinical parameters such as tumor size, nodal status, metastatic spread, or hormone receptor levels. Eighteen patients had inflammatory, locally advanced and/or detectable metastatic breast cancer at the time of surgery. Sixteen of these patients have progressed and 15 have died, with no relationship between colony formation and survival. For the 43 remaining patients, 23 had a tissue sample that gave rise to colonies in vitro; 14 of these have relapsed, with a median relapse-free survival (RFS) of 37.6 months, and eight have died with a median survival time of 46.8 months. This is compared with four relapses (median RFS not reached, P = .0043, Peto-Pike), and four deaths (median not reached, P = .1175) in the group without growth of the tumor specimen. These results indicate that colony formation is an independent prognostic parameter for breast cancer, which may be useful for selecting patients who would benefit from more intensive therapy.


[Development and clinical approval of a micromodification of the human leukocyte migration inhibition reaction].
The author suggests a new modification of the human blood leukocyte migration inhibition test. The results of the clinical approval of the test permit it to be recommended for the investigation in dynamics of the cellular immunity and the humoral factors in ptients with different immunopathological state. This modification permits to carry out 10-15 parallel investigations using small quantitites of the blood.


The influence of nasal abnormalities in adherence to continuous positive airway pressure device therapy in obstructive sleep apnea patients.
The few studies that examine the effect of nasal abnormalities on continuous positive airway pressure device (CPAP) adherence are controversial. The aim of this study was to evaluate the contribution of nasal abnormalities in CPAP adherence. We included patients with moderate to severe OSA. The patients were submitted to rhinoscopy, nasofibroscopy, nasal inspiratory peak flow, and acoustic rhinometry. The patients who used a CPAP for 4 h or more per night for at least 70 % of the nights over a 6-month period were considered to have good adherence. Thirty-four patients finished the study. Eleven (33.4 %) were female and 23 (67.6 %) were male. Sixteen (47.1 %) patients had good adherence. The body mass index (p = 0.030), neck circumference (p = 0.006), and apnea-hypopnea index (p = 0.032) were higher, and the oxyhemoglobin saturation minimum was lower (p = 0.041) in the good adherence group. Nasal parameters showed no differences between good and poor adherence groups. In Spearman's correlation, surprisingly, there was a negative correlation between the highest number of hours of CPAP use with smaller values of nasal minimal cross-sectional areas in the supine position (r, 0.375; p = 0.029). In the linear regression model, the nasal findings that predicted increased of the CPAP use were the following: lower scores of nasal symptoms (p = 0.007) and lower nasal volume in supine position (p = 0.001). The majority of the nasal parameters evaluated in this study did not influence CPAP adherence.


Legacies of Pre-1960s Municipal Waste Incineration in the Pb of City Soils.
A 1937 street map of Durham, North Carolina, located four city-run waste incinerators that we recognized to be sites of contemporary city parks. We obtained city permission to sample three park's soils, developed a sampling design for geospatial mapping of hypothetical incinerator-ash contamination of park soils, and queried online Durham newspapers to understand histories of incinerator operations, ash disposal, and incinerator-to-park conversions. In 2021-2022, seven decades after parks were created, two parks had soil-Pb > 400 mgPb/kg, EPA's threshold for safe soil in play areas. At Walltown Park, six of 97 surface samples ranged from 416 to 1338 mg Pb/kg within meters of a basketball court and a park path. East Durham Park had a hectare-sized area where 12 samples averaged 1294 mgPb/kg (median 1335 mg/kg). Engineering surveys of United States and Canadian cities in 1941 and 1958 suggest that half incinerated solid wastes. Many records describe how incinerator ash was dumped with little regard for health or environmental hazards. Legacy soil contaminations of incinerator ash can be identified, as we have done in Durham, from historical records of city-waste incinerator operations, online access to newspaper archives that describe incinerator-to-park conversions, and a XRF to screen for soil-Pb contamination.


[Cognitive function in patients with systemic sclerosis].
Central nervous system involvement is seldom reported in patients with systemic sclerosis (SSc). Cognitive functions were determined in 21 patients with definite SSc and 42 healthy controls. Thyroid function was also measured in order to eliminate the effect of hypothyroidism on cognitive functioning. It was found that the SSc patients with normal thyroid function showed defective long-term and recent memory, learning ability, criticism, perception and visuo-perceptual skills, their simple reaction time was prolonged. Similar but less advanced cognitive defects were shown in the SSc patients with overt or latent hypothyroidism. The obtained results indicate that the central nervous system involvement is more common in patients with SSc than it has been reported earlier.


Mitral valve surgery in patients with systemic lupus erythematosus.
Valvular heart disease is the common cardiac manifestation of systemic lupus erythematosus (SLE) with a tendency for mitral valve regurgitation. In this study we report a case of mitral valve replacement for mitral stenosis caused by Libman-Sacks endocarditis in the setting of SLE. In addition, we provide a systematic review of the literature on mitral valve surgery in the presence of Libman-Sacks endocarditis because its challenge on surgical options continues. Surgical decision depends on structural involvement of mitral valve and presence of active lupus nephritis and antiphospholipid antibody syndrome. Review of the literature has also shown that outcome is good in most SLE patients who have undergone valvular surgery, but association of antiphospholipid antibody syndrome with SLE has negative impact on the outcome.


Acid hydrolysis conditions for quantification of meningococcal X polysaccharide in a pentavalent vaccine using HPAEC-PAD/ESI-MS.
A selective and sensitive method was evaluated for quantitation of meningococcal X (Men X) polysaccharide in pentavalent meningococcal A, C, W, Y and X conjugate vaccine using different acid hydrolysis conditions like HCl, TFA, HF, HF-TFA, and HF-HCl. High-performance anion exchange chromatography with pulsed amperometric detection (HPAEC-PAD) using CarboPac PA10 column was used to identify the hydrolyzed products based on retention time and its comparison with monosaccharide standards. Complete release of glucosamine (GlcN) from Men X in monovalent bulk and pentavalent vaccine samples was achieved using HF hydrolysis at 80 °C for 2 h. The Men X HF-hydrolyzed polysaccharide to glucosamine along with the reference standard was identified using collision-induced dissociation (CID) electrospray mass spectroscopy and the MS/MS fragments of m/z 162, m/z 144 and m/z 84. Meningococcal polysaccharide concentration was determined with a correlation coefficient r2 >0.99 using polysaccharide reference standard. The serogroups A, W, and Y were converted to their monosaccharides units and quantified using this method however, milder acid hydrolysis 0.1 M HCl 80 °C 2 h for release of sialic acid for Men C polysaccharide was found to be more suitable. These methods will provide necessary tools and prove to be beneficial to laboratories developing new saccharide-based vaccine combinations.


Angiogenesis, cell proliferation and apoptosis in gastric ulcer healing. Effect of a selective cox-2 inhibitor.
To elucidate the role of cyclooxygenase-2, we compared the effects of rofecoxib, a selective cyclooxygenase-2 inhibitor, and ibuprofen, a nonselective cyclooxygenase inhibitor, on the evolution of acetic-acid-induced gastric ulcers in rats, evaluating growth factor expression, the angiogenic process, cell proliferation and cell apoptosis. Levels of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF), angiogenesis and cell proliferation were analysed by immunohistochemical methods, and apoptosis was evaluated by an enzyme immunoassay. Both growth factors and microvessels appeared to be abundant in the granulation tissue of the ulcer bed. Rofecoxib (2.5 mg/kg/day) and ibuprofen (100 mg/kg/day) delayed ulcer healing, but only rofecoxib treatment provoked a reduction of bFGF expression and inhibition of the development of new microvessels. No changes in VEGF expression were detected. Results also showed that proliferation and apoptosis were increased in control ulcerated animals. Rofecoxib reduced significantly both processes. These findings demonstrate that a reduction of bFGF expression and an antiangiogenic action, as well as proliferation/apoptosis inhibition, are some of the mechanisms possibly implicated in the delay in ulcer healing seen after the administration of the highly selective COX-2 inhibitor rofecoxib.


Interferon induced IFIT family genes in host antiviral defense.
Secretion of interferons (IFNs) from virus-infected cells is a hallmark of host antiviral immunity and in fact, IFNs exert their antiviral activities through the induction of antiviral proteins. The IFN-induced protein with tetratricopeptide repeats (IFITs) family is among hundreds of IFN-stimulated genes. This family contains a cluster of duplicated loci. Most mammals have IFIT1, IFIT2, IFIT3 and IFIT5; however, bird, marsupial, frog and fish have only IFIT5. Regardless of species, IFIT5 is always adjacent to SLC16A12. IFIT family genes are predominantly induced by type I and type III interferons and are regulated by the pattern recognition and the JAK-STAT signaling pathway. IFIT family proteins are involved in many processes in response to viral infection. However, some viruses can escape the antiviral functions of the IFIT family by suppressing IFIT family genes expression or methylation of 5' cap of viral molecules. In addition, the variants of IFIT family genes could significantly influence the outcome of hepatitis C virus (HCV) therapy. We believe that our current review provides a comprehensive picture for the community to understand the structure and function of IFIT family genes in response to pathogens in human, as well as in animals.


Estimating intervention effects on infectious disease control: The effect of community mobility reduction on Coronavirus spread.
Understanding the effects of interventions, such as restrictions on community and large group gatherings, is critical to controlling the spread of COVID-19. Susceptible-Infectious-Recovered (SIR) models are traditionally used to forecast the infection rates but do not provide insights into the causal effects of interventions. We propose a spatiotemporal model that estimates the causal effect of changes in community mobility (intervention) on infection rates. Using an approximation to the SIR model and incorporating spatiotemporal dependence, the proposed model estimates a direct and indirect (spillover) effect of intervention. Under an interference and treatment ignorability assumption, this model is able to estimate causal intervention effects, and additionally allows for spatial interference between locations. Reductions in community mobility were measured by cell phone movement data. The results suggest that the reductions in mobility decrease Coronavirus cases 4 to 7 weeks after the intervention.


Guidance for National Tuberculosis Programmes on the management of tuberculosis in children - an update.
About one million children develop tuberculosis (TB) annually worldwide. Childhood TB is common in Malawi accounting for about 12% of all TB cases. Childhood TB differs from TB in adults in ways that have important implications for the prevention, diagnosis and treatment of TB in children. Young children living in close contact with a case of smear-positive pulmonary TB are at particular risk of infection and TB disease. Screening of the household contacts of an infectious source case is therefore recommended to identify children with TB and enable their prompt treatment, and to provide children who do not have TB with isoniazid preventive treatment. It is recognised that there is a need to improve the diagnosis and management of children with TB, the prevention of TB in children and to ensure their inclusion under the implementation of the Stop TB strategy by National TB Programmes. A subgroup of the WHO DOTS Expansion Working Group called the Stop TB Partnership Childhood TB Subgroup published guidelines for the management of child TB in 2006. The guidelines are designed to complement current national and international guidelines on the implementation of the Stop TB Strategy and existing guidelines, but also to fill existing gaps to ensure that children with M. tuberculosis infection and TB disease are identified early and managed effectively. This paper summarises some of the most important information and recommendations put forward in those guidelines.


Nonstandard Maternal Work Schedules: Implications for African American Children's Early Language Outcomes.
In this study, observed maternal positive engagement and perception of work-family spillover were examined as mediators of the association between maternal nonstandard work schedules and children's expressive language outcomes in 231 African American families living in rural households. Mothers reported their work schedules when their child was 24 months of age and children's expressive language development was assessed during a picture book task at 24 months and with a standardized assessment at 36 months. After controlling for family demographics, child, and maternal characteristics, maternal employment in nonstandard schedules at the 24 month timepoint was associated with lower expressive language ability among African American children concurrently and at 36 months of age. Importantly, the negative association between nonstandard schedules and children's expressive language ability at 24 months of age was mediated by maternal positive engagement and negative work-family spillover, while at 36 months of age, the association was mediated only by negative work-family spillover. These findings suggest complex links between mothers' work environments and African American children's developmental outcomes.


Matrix metalloproteinase-9: a deleterious link between hepatic ischemia-reperfusion and colorectal cancer.
Despite the advent of improved surgical techniques and the development of cytotoxic chemotherapeutic agents useful for the treatment of colorectal cancer, the primary clinical challenge remains that of preventing and combating metastatic spread. Surgical resection is the best treatment for colorectal metastases isolated to the liver. However, in rodent models, the hepatic ischemia-reperfusion (I/R) applied during the surgery accelerates the outgrowth of implanted tumors. Among the adverse effects of I/R on cellular function, several studies have demonstrated an over expression of the matrix metalloproteinase-9 (MMP-9) in the ischemic liver. Since several studies showed high local levels of expression and activity of this proteolytic enzyme in the primary colorectal adenocarcinoma, the role of MMP-9 might be considered as a potential common mediator, favoring both growth of local tumor and the dissemination of colorectal carcinoma metastases.


Capillary electrophoresis as a technique to analyze sequence-induced anomalously migrating DNA fragments.
Sequence-induced anomalous migration of double-stranded (ds) DNA in native gel electrophoresis is a well known phenomenon. The retardation of migration is more obvious in polyacrylamide compared with agarose gels, and is greatly affected by the concentration of the gel and the temperature. This anomalous migration results in a difference between calculated and actual sizes of the affected DNA fragments. A low viscosity polymer solution (DNA Fragment Analysis Reagent) under investigation for use in dsDNA analysis by capillary electrophoresis is shown to be useful for the visualization of anomalies in migration of dsDNA fragments. Comparable with traditional slab gel systems, the retardation effect, indicative of bent or curved DNA, is strongly dependent on polymer concentration and separation temperature. These dependencies have implications on the accurate sizing of dsDNA fragments with unknown sequences and secondary structures.


IFIT3 and IFIT2/3 promote IFIT1-mediated translation inhibition by enhancing binding to non-self RNA.
Interferon-induced proteins with tetratricopeptide repeats (IFITs) are highly expressed during the cell-intrinsic immune response to viral infection. IFIT1 inhibits translation by binding directly to the 5' end of foreign RNAs, particularly those with non-self cap structures, precluding the recruitment of the cap-binding eukaryotic translation initiation factor 4F and ribosome recruitment. The presence of IFIT1 imposes a requirement on viruses that replicate in the cytoplasm to maintain mechanisms to avoid its restrictive effects. Interaction of different IFIT family members is well described, but little is known of the molecular basis of IFIT association or its impact on function. Here, we reconstituted different complexes of IFIT1, IFIT2 and IFIT3 in vitro, which enabled us to reveal critical aspects of IFIT complex assembly. IFIT1 and IFIT3 interact via a YxxxL motif present in the C-terminus of each protein. IFIT2 and IFIT3 homodimers dissociate to form a more stable heterodimer that also associates with IFIT1. We show for the first time that IFIT3 stabilizes IFIT1 protein expression, promotes IFIT1 binding to a cap0 Zika virus reporter mRNA and enhances IFIT1 translation inhibition. This work reveals molecular aspects of IFIT interaction and provides an important missing link between IFIT assembly and function.


Transforming growth factor alpha protects against Fas-mediated liver apoptosis in mice.
The Fas/Fas ligand interaction plays a crucial role in various liver diseases, and administration of agonistic anti-Fas antibody to mice causes massive hepatic apoptosis and fulminant hepatic failure. Several growth factors have recently been found to function in preventing apoptosis. In this study, we demonstrated that overexpression of transforming growth factor alpha (TGFalpha) has a dramatic protective effect on Fas-mediated hepatic apoptosis at the biochemical and histological levels. Moreover, 85.7% (six out of seven) of TGFalpha transgenic mice survived the lethal liver damage, whereas all wild-type mice died. Expression of Bcl-xL, an anti-apoptotic protein, was greatly increased in the transgenic mice. Taken together, our findings suggest that TGFalpha protects against Fas-mediated liver apoptosis in vivo and up-regulation of Bcl-xL may participate in protective effect of TGFalpha.


Lactic Dehydrogenase in the In Vitro Evaluation of Hemolytic Properties of Ventricular Assist Device.
Ventricular assist devices (VADs) can effectively improve the survival rate of patients with end-stage heart failure, but the hemolytic complications induced by long-time VAD support have received wide attention recently. The conventional evaluation method of the hemolytic properties of VADs by the indicator of plasma free hemoglobin (PFH) concentration is used but not sensitive enough to meet the needs of the actual examinations. In this study, an experimental method was applied for the evaluation of the injuries and damages caused by VADs to erythrocytes by both indicators of PFH and lactic dehydrogenase (LDH) in the in vitro hemolysis assay of VADs. The changes of LDH and PFH concentrations in plasma with the shear stress and the exposure time under a fixed shear stress were measured and analyzed to investigate the sensitivity and accuracy of the evaluation of erythrocyte damage by LDH. Furthermore, through 24 h in vitro hemolysis tests, the changes of LDH and PFH concentrations in blood samples were measured in combination with the microscopic histological changes and ultrastructural changes of erythrocytes, to assess the possibility of LDH evaluating the hemolysis of VADs. The changes of the concentration of LDH were more sensitive than those of PFH to different shear stress and exposure times, especially lower stress. Meanwhile, in the 24 h in vitro hemolysis assay, the PFH concentration in the blood samples showed no significant changes in the first 8 h, while the LDH concentration increased significantly in the first 3 h, which was consistent with the morphological changes of erythrocytes. Compared with the changes of the PFH concentration, the LDH concentration is sensitive to the damage of erythrocytes caused by VADs. It was considered that LDH could be applied as an additional indicator in the evaluation of erythrocyte damage and hemolytic properties of VADs in combination with the normalized index of hemolysis, for the more accurate assessment of the blood compatibility of VADs.


Cranio-caudal movements of the liver, pancreas and kidneys in respiration.
The range of movement of the liver, pancreas and kidneys in maximum and normal respiration, and the ability to suspend respiration repeatedly leaving the organs in exactly the same position with the aid of given instructions or a combination of instructions and a simple tool were investigated. The range of movement of the most mobile organ (liver) was 5.5 cm during maximum, 2.5 cm during normal, 0.9 cm during suspended respiration, and 0.2 cm during suspended respiration with a bar placed above the abdomen.


Altered ion transporter expression in bronchial epithelium in mountaineers with high-altitude pulmonary edema.
Hypoxia inhibits activity and expression of transport proteins of cultured lung alveolar epithelial cells. Here we tested whether hypoxia at high altitude affected the expression of ion transport proteins in tissues obtained from controls and mountaineers with high-altitude pulmonary edema (HAPE) at the Capanna Margherita (4,559 m). Expression was determined by RT-PCR and Western blots from brush biopsies of bronchial epithelium and from leukocytes obtained before and during the stay at high altitude. At low altitude, amounts of mRNAs were not different between control and HAPE-susceptible subjects. At high altitude, the amount of mRNA of Na-K-ATPase, CFTR, and beta-actin of brush biopsies did not change in controls but decreased significantly (-60%) in HAPE-susceptible subjects. There was no change in Na channel mRNAs at high altitude in controls and HAPE. No statistically significant correlation was found between the expression of Na transporters and PO2 and O2 saturation. In leukocytes, 28S-rRNA and Na-K-ATPase decreased at altitude in control and HAPE-susceptible subjects, but no significant change in Na-K-ATPase protein was found. Hypoxia-inducible factor-1alpha mRNA and GAPDH mRNA tended to increase in leukocytes obtained from HAPE-susceptible subjects at high altitude but did not change in controls. These results show that hypoxia induces differences in mRNA expression of ion transport-related proteins between HAPE-susceptible and control subjects but that these changes may not necessarily predict differences in protein concentration or activity. It is therefore unclear whether these differences are related to the pathophysiology of HAPE.


RNA transcripts of the human immunodeficiency virus transactivation response element can inhibit action of the viral transactivator.
Tandem repeats of the transactivation response element (TAR) of the human immunodeficiency virus 1 (HIV-1) were generated using a specially constructed "tandemizing" plasmid, pGem-Tan. This plasmid exploits the rotational nonequivalence of Ava I restriction sites to generate multiple copies of an inserted sequence. Twelve tandem repeats of the TAR were then placed in sense and antisense orientations behind a strong human beta-actin gene promoter. The TAR constructs were transfected with an appropriate HIV-1-driven reporter and tat gene expression plasmids into NT2/D1 cells, a pluripotential human embryonic teratocarcinoma cell line. Twelve tandem TAR repeats in the sense orientation suppressed 85-90% of the transactivating function of the virus-encoded tat protein, whereas the antisense construct or constructs containing single copies of TAR in either sense or antisense orientations were relatively ineffective. The suppression was specific for reporter gene constructs containing an intact HIV-1 long terminal repeat: Reporter genes driven by other promoters or by an HIV-1 long terminal repeat lacking the TAR were not suppressed. Suppression of activation by tat required transcription into RNA: Similar constructs containing the TAR repeats but lacking a eukaryotic promoter failed to suppress tat activation. In the absence of tat, the TAR DNA stimulated 2- to 5-fold the expression of gene constructs driven not only by the HIV-1 long terminal repeat but also by the human beta-actin gene and the simian virus 40 promoters.


Cyclic AMP-dependent memory mutants are defective in the food choice behavior of Drosophila.
Acute choice behavior in ingesting two different concentrations of sucrose in Drosophila is presumed to include learning and memory. Effects on this behavior were examined for four mutations that block associative learning (dunce, rutabaga, amnesiac, and radish). Three of these mutations cause cyclic AMP signaling defects and significantly reduced taste discrimination. The exception was radish, which affects neither. Electrophysiological recordings confirmed that the sensitivity of taste receptors is almost indistinguishable in all flies, whether wild type or mutant. These results suggest that food choice behavior in Drosophila involves central nervous learning and memory operating via cyclic AMP signaling pathways.


Predictive Model for the Design of Zwitterionic Polymer Brushes: A Statistical Design of Experiments Approach.
The performance of polymer interfaces in biology is governed by a wide spectrum of interfacial properties. With the ultimate goal of identifying design parameters for stem cell culture coatings, we developed a statistical model that describes the dependence of brush properties on surface-initiated polymerization (SIP) parameters. Employing a design of experiments (DOE) approach, we identified operating boundaries within which four gel architecture regimes can be realized, including a new regime of associated brushes in thin films. Our statistical model can accurately predict the brush thickness and the degree of intermolecular association of poly[{2-(methacryloyloxy) ethyl} dimethyl-(3-sulfopropyl) ammonium hydroxide] (PMEDSAH), a previously reported synthetic substrate for feeder-free and xeno-free culture of human embryonic stem cells. DOE-based multifunctional predictions offer a powerful quantitative framework for designing polymer interfaces. For example, model predictions can be used to decrease the critical thickness at which the wettability transition occurs by simply increasing the catalyst quantity from 1 to 3 mol %.


Protective effect of liraglutide on the myocardium of type 2 diabetic rats by inhibiting polyadenosine diphosphate-ribose polymerase-1.
In recent years, studies have found that the occurrence and development of diabetic cardiomyopathy (DCM) is closely related to an increase in polyadenosine diphosphate-ribose polymerase-1 (PARP-1) activity. PARP-1 activation could be involved in the pathophysiological process of DCM by promoting oxidative stress, the inflammatory response, apoptosis and myocardial fibrosis. To investigate the mechanism of liraglutide in improving myocardial injury in type 2 diabetic rats, further clarified the protective effect of liraglutide on the heart, and provided a new option for the treatment of DCM. Forty healthy male SD rats aged 6 wk were randomly divided into two groups, a normal control group (n = 10) and a model group (n = 30), which were fed an ordinary diet and a high-sugar and high-fat diet, respectively. After successful modeling, the rats in the model group were fed a high-glucose and high-fat diet for 4 wk and randomly divided into a model group and an intervention group (further divided into a high-dose group and a low-dose group). The rats were fed a high-glucose and high-fat diet for 8 wk and then started drug intervention. Blood samples were collected from the abdominal aorta to detect fasting blood glucose and lipid profiles. Intact heart tissue was dissected, and its weight was used to calculate the heart weight index. Haematoxylin and eosin staining was used to observe the pathological changes in the myocardium and the expression of PARP-1 in the heart by immunohistochemistry. The body weight and heart weight index of rats in the model group were significantly increased compared with those in the normal control group, and those in the intervention group were decreased compared with those in the model group, with a more obvious decrease observed in the high-dose group (P < 0.05). In the model group, myocardial fibers were disordered, and inflammatory cells and interstitial fibrosis were observed. The cardiomyopathy of rats in the intervention group was improved to different degrees, the myocardial fibers were arranged neatly, and the myocardial cells were clearly striated; the improvement was more obvious in the high-dose group. Compared with the normal control group, the expression of PARP-1 in myocardial tissue of the model group was increased, and the difference was statistically significant (P < 0.05). After liraglutide intervention, compared with the model group, the expression of PARP-1 in myocardial tissue was decreased, and the reduction was more obvious in the high-dose group (P < 0.05) but still higher than that in the normal control group. Liraglutide may improve myocardial injury in type 2 diabetic rats by inhibiting the expression of myocardial PARP-1 in a dose-dependent manner.


Coexistence of anticipated and layered chaotic synchronization in time-delay systems.
We study the dynamic stabilities of unidirectionally coupled linear arrays of chaotic oscillators with time-delay feedbacks in star configuration, and find that if all oscillators in the network are identical, then the oscillators in the linear arrays can anticipate the driving oscillators, and simultaneously the oscillators in the linear arrays with the same position with respect to the central one are in synchronous chaotic state. Compared with the anticipated synchronization, the layered synchronization is first generated and last destroyed as the coupling constant is increased. This coexistence of anticipated and layered chaotic synchronization is destroyed by long time feedback. If the driving and driven oscillators are different, then only layered chaotic synchronization is possible.


Two new disposable bioreactors for plant cell culture: The wave and undertow bioreactor and the slug bubble bioreactor.
The present article describes two novel flexible plastic-based disposable bioreactors. The first one, the WU bioreactor, is based on the principle of a wave and undertow mechanism that provides agitation while offering convenient mixing and aeration to the plant cell culture contained within the bioreactor. The second one is a high aspect ratio bubble column bioreactor, where agitation and aeration are achieved through the intermittent generation of large diameter bubbles, "Taylor-like" or "slug bubbles" (SB bioreactor). It allows an easy volume increase from a few liters to larger volumes up to several hundred liters with the use of multiple units. The cultivation of tobacco and soya cells producing isoflavones is described up to 70 and 100 L working volume for the SB bioreactor and WU bioreactor, respectively. The bioreactors being disposable and pre-sterilized before use, cleaning, sterilization, and maintenance operations are strongly reduced or eliminated. Both bioreactors represent efficient and low cost cell culture systems, applicable to various cell cultures at small and medium scale, complementary to traditional stainless-steel bioreactors.


Conjunctival melanoma copy number alterations and correlation with mutation status, tumor features, and clinical outcome.
Relatively little is known about the genetic aberrations of conjunctival melanomas (CoM) and their correlation with clinical and histomorphological features as well as prognosis. The aim of this large collaborative multicenter study was to determine potential key biomarkers for metastatic risk and any druggable targets for high metastatic risk CoM. Using Affymetrix single nucleotide polymorphism genotyping arrays on 59 CoM, we detected frequent amplifications on chromosome (chr) 6p and deletions on 7q, and characterized mutation-specific copy number alterations. Deletions on chr 10q11.21-26.2, a region harboring the tumor suppressor genes, PDCD4, SUFU, NEURL1, PTEN, RASSF4, DMBT1, and C10orf90 and C10orf99, significantly correlated with metastasis (Fisher's exact, p ≤ 0.04), lymphatic invasion (Fisher's exact, p ≤ 0.02), increasing tumor thickness (Mann-Whitney, p ≤ 0.02), and BRAF mutation (Fisher's exact, p ≤ 0.05). This enhanced insight into CoM biology is a step toward identifying patients at risk of metastasis and potential therapeutic targets for systemic disease.


[Polymer fume fever[].
Polymer fume fever is a self-limiting condition with influenza-like symptoms (fever, headache, dry cough, dyspnoea and myalgia). It is caused by inhalation of toxic products released by combustion of fluoro-carbon polymers. There is no causal treatment, and the symptoms usually clear up spontaneously within 24 hours. This article describes an accident where 13 soldiers became ill when exposed to fumes released from a tent oven painted with a coating containing fluoro-carbons.


Electrophilic Aromatic Substitution: New Insights into an Old Class of Reactions.
The classic SEAr mechanism of electrophilic aromatic substitution (EAS) reactions described in textbooks, monographs, and reviews comprises the obligatory formation of arenium ion intermediates (σ complexes) in a two-stage process. Our findings from several studies of EAS reactions challenge the generality of this mechanistic paradigm. This Account focuses on recent computational and experimental results for three types of EAS reactions: halogenation with molecular chlorine and bromine, nitration by mixed acid (mixture of nitric and sulfuric acids), and sulfonation with SO3. Our combined computational and experimental investigation of the chlorination of anisole with molecular chlorine in CCl4 found that addition-elimination pathways compete with the direct substitution processes. Detailed NMR investigation of the course of experimental anisole chlorination at varying temperatures revealed the formation of addition byproducts. Moreover, in the absence of Lewis acid catalysis, the direct halogenation processes do not involve arenium ion intermediates but instead proceed via concerted single transition states. We also obtained analogous results for the chlorination and bromination of several arenes in nonpolar solvents. We explored by theoretical computations and experimental spectroscopic studies the classic reaction of benzene nitration by mixed acid. The structure of the first intermediate in this process has been a subject of contradicting views. We have reported clear experimental UV/vis spectroscopic evidence for the formation of the first intermediate in this reaction. Our broader theoretical modeling of the process considers the effects of the medium as a bulk solvent but also the specific interactions of a H2SO4 solvent molecule with intermediates and transition states along the reaction path. In harmony with the obtained spectroscopic data, our computational results reveal that the structure of the initial π complex precludes the possibility of electronic charge transfer from the benzene π system to the nitronium unit. In contrast to usual interpretations, our computational results provide compelling evidence that in nonpolar, noncomplexing media and in the absence of catalysts, the mechanism of aromatic sulfonation with sulfur trioxide is concerted and does not involve the conventional σ-complex (Wheland) intermediates. Stable under such conditions, (SO3)2 dimers react with benzene much more readily than monomeric sulfur trioxide. In polar (complexing) media, the reaction follows the classic two-stage SEAr mechanism. Still, the rate-controlling transition state involves two SO3 molecules. The reactivity and regioselectivity in EAS reactions that follow the classic mechanistic scheme are quantified using a theoretically evaluated quantity, the electrophile affinity (Eα), which measures the stabilization energy associated with the formation of arenium ions. Examples of applications are provided.


Study of microvascular polyester prosthesis in rat carotid arteries.
The implantation of a microvascular polyester prosthesis (MPP) (internal diameter 1 mm, length 10 mm) in the carotid arteries was studied in 48 Sprague-Dawley rats. The left carotid artery was resected to 7 mm in length and replaced with MPP by means of sleeve anastomoses. Postoperatively the patency was monitored with Doppler ultrasound at 24 and 72 hr, and at 1, 2, 3, 4, 8, and 12 weeks and was confirmed either by direct inspection intraoperatively or by angiography at the time of removal. At each monitoring time, all the thrombosed and some selected patent grafts were removed and prepared for scanning electron microscopy (SEM) study. The early patency rate was 100% within 24 hr, and the cumulative long-term patency rate was 77.1% at 12 weeks. Rapid and complete endothelial lining (EL) restoration was demonstrated 3 weeks after operation, which provided a smooth and nonthrombogenic surface, and contributed to the long-term patency. Ten of the 11 failed grafts occurred within 3 weeks, that is, before EL, due to thrombosis. These observations indicate that MPP can be successfully used as arterial conduits in rats, and an enhanced patency rate may be expected with the use of anticoagulants or endothelial cell seeding for prevention of early thrombosis.


Unified model for the ultrafast decay of pyrimidine nucleobases.
Ultrafast decay processes detected after absorption of UV radiation in gas-phase pyrimidine nucleobases uracil, thymine, and cytosine are ascribed to the barrierless character of the pathway along the low-lying 1(pipi*) hypersurface connecting the Franck-Condon region with an out-of-plane distorted ethene-like conical intersection with the ground state. Longer lifetime decays and low quantum yield emission are on the other hand related to the presence of a 1(pipi*) state planar minimum on the S1 surface and the barriers to access other conical intersections. A unified model for the three systems is established on the basis of accurate multiconfigurational CASPT2 calculations, whereas the effect of the different levels of theory on the results is carefully analyzed.


The synthetic melanocortin (CKPV)2 exerts anti-fungal and anti-inflammatory effects against Candida albicans vaginitis via inducing macrophage M2 polarization.
In this study, we examined anti-fungal and anti-inflammatory effects of the synthetic melanocortin peptide (Ac-Cys-Lys-Pro-Val-NH2)2 or (CKPV)2 against Candida albicans vaginitis. Our in vitro results showed that (CKPV)2 dose-dependently inhibited Candida albicans colonies formation. In a rat Candida albicans vaginitis model, (CKPV)2 significantly inhibited vaginal Candida albicans survival and macrophages sub-epithelial mucosa infiltration. For mechanisms study, we observed that (CKPV)2 inhibited macrophages phagocytosis of Candida albicans. Meanwhile, (CKPV)2 administration inhibited macrophage pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) release, while increasing the arginase activity and anti-inflammatory cytokine IL-10 production, suggesting macrophages M1 to M2 polarization. Cyclic AMP (cAMP) production was also induced by (CKPV)2 administration in macrophages. These above effects on macrophages by (CKPV)2 were almost reversed by melanocortin receptor-1(MC1R) siRNA knockdown, indicating the requirement of MC1R in the process. Altogether, our results suggest that (CKPV)2 exerted anti-fungal and anti-inflammatory activities against Candida albicans vaginitis probably through inducing macrophages M1 to M2 polarization and MC1R activation.


Severity and burden of hand, foot and mouth disease in Asia: a modelling study.
Hand, foot and mouth disease (HFMD) affects millions of children across Asia annually, leading to an increase in implemented control policies such as surveillance, isolation and social distancing in affected jurisdictions. However, limited knowledge of disease burden and severity causes difficulty in policy optimisation as the associated economic cost cannot be easily estimated. We use a data synthesis approach to provide a comprehensive picture of HFMD disease burden, estimating infection risk, symptomatic rates, the risk of complications and death, and overall disability-adjusted life-year (DALY) losses, along with associated uncertainties. Complementary data from a variety of sources were synthesised with mathematical models to obtain estimates of severity of HFMD. This includes serological and other data extracted through a systematic review of HFMD epidemiology previously published by the authors, and laboratory investigations and sentinel reports from Singapore's surveillance system. HFMD is estimated to cause 96 900 (95% CI 40 600 to 259 000) age-weighted DALYs per annum in eight high-burden countries in East and Southeast Asia, with the majority of DALYs attributed to years of life lost. The symptomatic case hospitalisation rate of HFMD is 6% (2.8%-14.9%), of which 18.7% (6.7%-31.5%) are expected to develop complications. 5% (2.9%-7.4%) of such cases are fatal, bringing the overall case fatality ratio to be 52.3 (24.4-92.7) per 100 000 symptomatic infections. In contrast, the EV-A71 case fatality ratio is estimated to be at least 229.7 (75.4-672.1) per 100 000 symptomatic cases. Asymptomatic rate for EV-A71 is 71.4% (68.3%-74.3%) for ages 1-4, the years of greatest incidence. Despite the high incidence rate of HFMD, total DALY due to HFMD is limited in comparison to other endemic diseases in the region, such as dengue and upper respiratory tract infection. With the majority of DALY caused by years of life lost, it is possible to mitigate most with increased EV-A71 vaccine coverage.


Homeostasis, thymic hormones and aging.
The thymic-pituitary axis constitutes a bidirectional circuit where the ascending feedback loop is effected by thymic factors of epithelial origin. The aim of the present article is, first, to introduce the idea of an immune-neuroendocrine homeostatic network in higher animals. Next, the relevance of the thymus in this network and the possible role of this gland in the neuroendocrine imbalances associated with aging are discussed. A number of studies are next reviewed which show that the endocrine thymus produces several bioactive molecules, generally called thymic hormones, which in addition to possessing immunoregulatory properties are also active on nervous and endocrine circuits. In particular, the reported activities of thymosin fraction five, thymosin alpha 1 and thymosin beta 4 on beta-endorphin, adrenocorticotropic hormone, glucocorticoids, luteinizing hormone-releasing hormone and luteinizing hormone secretion in different animal and cell models are reviewed. The known hypophysiotropic actions of other thymic hormones like thymulin, homeostatic thymus hormone and thymus factor are also summarized, and the impact of aging on pituitary responsiveness to thymic hormones is discussed. As a conclusion, it is proposed that in addition to its central role in the regulation of the immune function, the thymus gland may extend its influence to nonimmunologic components of the body, including the neuroendocrine system. The early onset of thymus involution might, therefore, act as a triggering event which would initiate the gradual decline in homeostatic potential that characterizes the aging process.


A Fast Channel Assignment Scheme for Emergency Handling in Wireless Body Area Networks.
Ubiquitous healthcare is a promising technology that has attracted significant attention in recent years; this has led to the realization of wireless body area networks (WBANs). For designing a robust WBAN system, the WBAN has to solve the drawbacks of wireless technology. Also, a WBAN has to support immediate, reliable data transmission for medical services during emergencies. Hence, this study proposes a new MAC superframe structure that can handle emergencies by delivering strongly correlated regular data to a caretaker, within a certain time threshold. Simulation results demonstrate that the proposed MAC protocol achieves low latency and high throughput.


Immunomodulatory effect of vitamin D on immune response to dengue virus infection.
Dengue, an acute febrile illness which in some cases requires hospitalization and occasionally a fatal disease, caused by dengue virus is a potential threat to the public health systems throughout the world. Approved antivirals are not available for treating dengue. Immunomodulators, that can reduce inflammation which if not treated properly results in vascular leakage, are being attempted as therapeutics against severe dengue. Vitamin D, an immunomodulatory hormone, with both antiviral and immunomodulatory effects, is an appropriate choice for investigation as a potential drug against dengue. Investigations of vitamin D levels by many studies have suggested vitamin D levels as a potential marker for predicting severe dengue. In-vitro studies have shown that 1, 25 dihydroxy vitamin D3 (1,25(OH)2D3), active form of vitamin D, can reduce the expression of dengue virus entry receptors, restrict the viral replication and can modulate the expression of inflammatory cytokines in dengue virus infected cells. The results from in-vitro studies also have cautioned that insufficient levels of vitamin D supplementation might increase the virus replication. Available evidence suggests vitamin D based therapeutics against dengue and provides ray of light for treating dengue patients but, the available evidence needs to be supported by beneficial outcomes in clinical trials.


Longitudinal Integrated Ambulatory, Didactic, and Evidenced-Based Medicine Curriculum in Internal Medicine.
The Accreditation Council for Graduate Medical Education (ACGME) endorses evolving scholarly education regarding evidence-based medicine (EBM) and its clinical application in Internal Medicine (IM). The IM residents at Navy Medical Readiness and Training Center San Diego (NMRTC-SD) communicated the need for both increased ambulatory didactic sessions as well as a formal EBM curriculum. Prior to the academic year of 2021-2022, no formal ambulatory or EBM curriculum existed. In July 2021, an integrated EBM-ambulatory curriculum was implemented. A pre-curriculum needs assessment was performed and thereafter an eight-session integrated ambulatory-EBM curriculum was implemented in the 2021-2022 academic year. Faculty members facilitated small group discussions focused on a particular didactic topic and EBM principle and integrated the learning of both into one session. After each session, residents completed a feedback form. At the end of the year, a post-curriculum needs assessment was collected. Thirty-four residents of all post-graduate years (PGY) levels participated from July 2021 to June 2022. Primary outcomes were satisfaction with the didactic portion of the curriculum, perception of receipt of adequate training in EBM principles, and perception of level of competency in practicing EBM principles. Overall, participants reported a substantial increase in satisfaction with didactic teaching and a large increase in the perceived competency in practicing EBM principles. This integrated didactic-EBM curriculum represents an effective method of incorporating didactic topics in IM with the teaching and application of EBM principles, which improved resident satisfaction with the curricula and self-perception of competency in critically appraising medical literature.


Sex difference in urine concentration across differing ages, sodium intake, and level of kidney disease.
Men are known to be at greater risk of urolithiasis and cardiovascular and renal diseases than women. Previous studies suggest that greater urine concentration is associated with acceleration of progression of chronic kidney disease (CKD), increased urinary albumin excretion, and delayed renal sodium excretion. The present review addresses possible sex-related differences in urine volume and osmolality (U(osm)) that could participate in this male risk predominance. Because of the scarcity of information, we reanalyzed 24-h urine data collected previously by different investigators for other purposes. In nine studies concerning healthy subjects (6 studies) or patients with CKD or diabetes mellitus, U(osm) (or another index of urine concentration based on the urine/plasma creatinine concentration ratio) was 21-39% higher (i.e., about a 150 mosm/kgH2O difference) in men than in women. Urine volume was not statistically different. Thus, the larger osmolar load of men (related to their higher food intake) is excreted in a more concentrated urine with no difference in urine volume. This sex difference was not influenced by the level of sodium excretion and was still present in CKD patients. Sex differences in thirst threshold, AVP level, and other regulatory mediators may all contribute to the higher male U(osm). Because of the previously demonstrated adverse effects of vasopressin and/or high urine concentrating activity, the greater tendency of men to concentrate urine could participate in their greater susceptibility to urolithiasis and hypertension and to the faster progression towards end-stage renal failure.


Phase I evaluation of an anti-breast carcinoma monoclonal antibody 260F9-recombinant ricin A chain immunoconjugate.
Four women with metastatic breast cancer were treated with monoclonal antibody 260F9-recombinant ricin A chain, a ricin A chain immunoconjugate (IC) which targets a Mr 55,000 antigen expressed by human mammary carcinomas. Patients were treated by daily, 1-h i.v. injections for 6 to 8 consecutive days. Two patients were treated with 10 micrograms/kg daily and the two others were treated with 50 micrograms/kg daily. The trial was suspended after four patients had been treated because patients treated with a continuous infusion schedule with this IC had developed significant neurological toxicity at doses similar to those used in this study. The half-life of the IC showed a t 1/2 alpha of approximately 1.8 h, a t 1/2 beta of approximately 8.3 h, and a peak concentration of about 200 ng/ml, at the lower dose level, and showed a t 1/2 alpha of approximately 2.5 h, t 1/2 beta of about 10.4 h, and a peak concentration of 500 and 850 ng/ml for the two patients at the higher dose level. All four patients developed evidence of a human anticonjugate antibody response within 16 days of the onset of therapy. The treatment was associated with significant toxicity, manifested by a syndrome consisting of weight gain, edema, hypoalbuminemia, and dyspnea. Similar symptoms were observed in patients treated by continuous infusions of the IC. This clinical syndrome, seen at doses of IC which were insufficient to saturate antigen-expressing malignant tumor deposits in this trial, has been seen in other IC therapy trials and in clinical trials using the cytokine interleukin 2. To investigate a possible mechanism responsible for this toxicity, human monocytes were incubated with varying concentrations of IC. There was detectable binding of IC to human monocytes at IC concentrations which were achieved clinically in this trial. Furthermore, the binding appeared to be abrogated by preincubation of the monocytes with pooled human immunoglobulin, thus suggesting that binding occurs via Fc gamma receptor-mediated mechanisms. Binding was not affected if different linkers between recombinant ricin A chain and the antibody were used or if a different antibody moiety was used in the IC preparation. Chemically linked dimers of MOPC-21 bound to human monocytes at least as well as the ICs; this binding was not abrogated by preincubation with pooled human immunoglobulin. Since the IC preparations used in this clinical trial contained small percentages of dimers and/or multimers, the clinical toxicity syndromes which we observed may be related to this series of observations.(ABSTRACT TRUNCATED AT 400 WORDS)


Detection of heterozygous C8 beta deficiency by PCR in a healthy Italian population.
In Italy a rather high number of homozygotes with late complement component defects has been found among patients with meningococcal disease. It seems that clinical manifestations of meningococcal disease are less severe in patients with complement deficiency than in normal individuals. This situation could even be more evident in the heterozygous carriers for whom a selective advantage is discussed. In this study we have screened a cohort of 527 Italian blood donors from western Sicily for the presence of C8B mutated allele. Heterozygotes for C8 beta deficiency were identified using a specific PCR assay to detect a C-->T transition in exon 9 of the C8B gene. This mutation represents the most frequent genetic mechanism for C8 beta deficiency in Caucasians. A rapid PCR screening test was performed on DNA extracted from pooled blood samples of up to 8 individuals. A single male individual with heterozygous C8 beta deficiency was detected. In the family studies it was shown that his two brothers and the mother were heterozygous carriers too. Functional activity of the classical and alternative complement pathways were normal. No neisserial infections or inflammatory diseases were found in the family history. It was shown that the allele-specific PCR is a sensitive and rapid method to examine large numbers of DNA samples. It permitted to assess the real prevalence of the C8B mutated null allele in the general population free of ascertainment bias.


New Member of the V1V2-Directed CAP256-VRC26 Lineage That Shows Increased Breadth and Exceptional Potency.
The epitopes defined by HIV-1 broadly neutralizing antibodies (bNAbs) are valuable templates for vaccine design, and studies of the immunological development of these antibodies are providing insights for vaccination strategies. In addition, the most potent and broadly reactive of these bNAbs have potential for clinical use. We previously described a family of 12 V1V2-directed neutralizing antibodies, CAP256-VRC26, isolated from an HIV-1 clade C-infected donor at years 1, 2, and 4 of infection (N. A. Doria-Rose et al., Nature 509:55-62, 2014, http://dx.doi.org/10.1038/nature13036). Here, we report on the isolation and characterization of new members of the family mostly obtained at time points of peak serum neutralization breadth and potency. Thirteen antibodies were isolated from B cell culture, and eight were isolated using trimeric envelope probes for differential single B cell sorting. One of the new antibodies displayed a 10-fold greater neutralization potency than previously published lineage members. This antibody, CAP256-VRC26.25, neutralized 57% of diverse clade viral isolates and 70% of clade C isolates with remarkable potency. Among the viruses neutralized, the median 50% inhibitory concentration was 0.001 μg/ml. All 33 lineage members targeted a quaternary epitope focused on V2. While all known bNAbs targeting the V1V2 region interact with the N160 glycan, the CAP256-VRC26 antibodies showed an inverse correlation of neutralization potency with dependence on this glycan. Overall, our results highlight the ongoing evolution within a single antibody lineage and describe more potent and broadly neutralizing members with potential clinical utility, particularly in areas where clade C is prevalent. Studies of HIV-1 broadly neutralizing antibodies (bNAbs) provide valuable information for vaccine design, and the most potent and broadly reactive of these bNAbs have potential for clinical use. We previously described a family of V1V2-directed neutralizing antibodies from an HIV-1 clade C-infected donor. Here, we report on the isolation and characterization of new members of the family mostly obtained at time points of peak serum neutralization breadth and potency. One of the new antibodies, CAP256-VRC26.25, displayed a 10-fold greater neutralization potency than previously described lineage members. It neutralized 57% of diverse clade viral isolates and 70% of clade C isolates with remarkable potency: the median 50% inhibitory concentration was 0.001 μg/ml. Our results highlight the ongoing evolution within a single antibody lineage and describe more potent and broadly neutralizing members with potential clinical utility, particularly in areas where clade C is prevalent.


Iodine deficiency up-regulates monocarboxylate transporter 8 expression of mouse thyroid gland.
Iodine deficiency is a major factor affecting thyroid auto-regulation, the quantity of iodine may greatly influence the synthesis of thyroid hormones (THs). It has long been believed that TH enters the cell through passive diffusion. Recent studies have suggested that several transporters could facilitate transportation of TH. The monocarboxylate transporter 8 (MCT8) was identified as a very active and specific TH transporter. The purpose of this study was to investigate whether iodine insufficient affected the expression of MCT8 in the thyroid gland. Sixty BALB/c mice were randomly divided into two groups: control group was fed with standard feed (iodine concentration of 300 µg/kg); while low-iodine (LI) group received iodine-insufficient feed (iodine concentration of 20-40 µg/kg). After 3 months, 10 mice of each group were sacrificed. The remaining 20 mice of each group were kept till 6 months. From the LI group, we randomly selected 15 mice and injected triiodothyronine (T3, 100 µg/kg body weight per day) intraperitoneally for 24, 48 or 72 hours (5 mice for each time-point). Then, all the mice were sacrificed. Mouse serum thyroxine (T4), T3, and thyroid-stimulating hormone (TSH) levels were determined by chemiluminescence immunoassay (CIA). The protein content or messenger RNA (mRNA) level of thyroid MCT8 was measured by Western blotting analysis or real time RT-PCR respectively. MCT8 subcellular location in thyroid tissues was probed with immunohistochemistry (IHC) assay. We found that mouse serum T3 and T4 levels decreased and TSH level increased by the end of the third month. Consistent with these findings, there was significant goiter and hypothyroidism in the LI group. Meanwhile, the MCT8 mRNA increased to 1.36-fold of the level in the control group at the 3(rd) month. At 6(th) month, the serum T4 level in LI mice remained at a lower level, and MCT8 mRNA expression continued rising to nearly 1.60-fold compared with the control group. The protein content was also about 3 times higher than that in the control group. IHC results also revealed MCT8 was of higher expression and localized in the cytoplasm of thyroid follicular cells. After providing exogenous T3 to iodine deficient mice, the serum T3 and T4 gradually increased, whereas MCT8 mRNA and protein both started to decrease and returned to the same level as the control group. There is a compensatory increase in thyroid MCT8 expression to enhance its capability to transport TH from thyroid to the blood circulation in iodine deficient mice.


Iron toxicity resistance strategies in tropical grasses: The role of apoplastic radicular barriers.
The revegetation of mined areas poses a great challenge to the iron ore mining industry. The initial recovery process in degraded areas might rely on the use of Fe-resistant grasses. Tropical grasses, such as Paspalum densum and Echinochloa crus-galli, show different resistance strategies to iron toxicity; however, these mechanisms are poorly understood. The Fe-resistance mechanisms and direct iron toxicity as a function of root apex removal were investigated. To achieve this purpose, both grass species were grown for up to 480 hr in a nutrient solution containing 0.019 or 7 mmol/L Fe-EDTA after the root apices had been removed or maintained. Cultivation in the presence of excess iron-induced leaf bronzing and the formation of iron plaque on the root surfaces of both grass species, but was more significant on those plants whose root apex had been removed. Iron accumulation was higher in the roots, but reached phytotoxic levels in the aerial parts as well. It did not hinder the biosynthesis of chloroplastidic pigments. No significant changes in gas exchange and chlorophyll a fluorescence occurred in either grass when their roots were kept intact; the contrary was true for plants with excised root apices. In both studied grasses, the root apoplastic barriers had an important function in the restriction of iron translocation from the root to the aerial plant parts, especially in E. crus-galli. Root apex removal negatively influenced the iron toxicity resistance mechanisms (tolerance in P. densum and avoidance in E. crus-galli).


Comparison of Risk Factors, Safety, and Efficacy Outcomes of Mechanical Thrombectomy in Posterior vs. Anterior Circulation Large Vessel Occlusion.
Background and Purpose: It is believed that stroke occurring due to posterior circulation large vessel occlusion (PCLVO) and that occurring due to anterior circulation large vessel occlusion (ACLVO) differ in terms of their pathophysiology and the outcome of their acute management in relation to endovascular mechanical thrombectomy (MT). Limited sample size and few randomized controlled trials (RCTs) with respect to PCLVO make the safety and efficacy of MT, which has been confirmed in ACLVO, difficult to assess in the posterior circulation. We therefore conducted a meta-analysis to study to which extent MT in PCLVO differs from ACLVO. Materials and Methods: We searched the databases PubMed, Cochrane, and EMBASE for studies published between 2010 and January 2021, with information on risk factors, safety, and efficacy outcomes of MT in PCLVO vs. ACLVO and conducted a systematic review and meta-analysis; we compared baseline characteristics, reperfusion treatment profiles [including rates of intravenous thrombolysis (IVT) and onset-to-IVT and onset-to-groin puncture times], recanalization success [Thrombolysis In Cerebral Infarction scale (TICI) 2b/3], symptomatic intracranial hemorrhage (sICH), and favorable functional outcome [modified Rankin Score (mRS) 0-2] and mortality at 90 days. Results: Sixteen studies with MT PCLVO (1,172 patients) and ACLVO (7,726 patients) were obtained from the search. The pooled estimates showed higher baseline National Institutes of Health Stroke Scale (NIHSS) score (SMD 0.32, 95% CI 0.15-0.48) in the PCLVO group. PCLVO patients received less often IVT (OR 0.65, 95% CI 0.53-0.79). Onset-to-IVT time (SMD 0.86, 95% CI 0.45-1.26) and onset-to-groin puncture time (SMD 0.59, 95% CI 0.33-0.85) were longer in the PCLVO group. The likelihood of obtaining successful recanalization and favorable functional outcome at 90 days was comparable between the two groups. PCLVO was, however, associated with less sICH (OR 0.56, 95% CI 0.37-0.85) but higher mortality (OR 1.92, 95% CI 1.46-2.53). Conclusions: This meta-analysis indicates that MT in PCLVO may be comparably efficient in obtaining successful recanalization and 90 day favorable functional outcome just as in ACLVO. Less sICH in MT-treated PCLVO patients might be the result of the lower IVT rate in this group. Higher baseline NIHSS and longer onset-to-IVT and onset-to-groin puncture times may have contributed to a higher 90 day mortality in PCLVO patients.


Terminal deletion 2q37.3 in a patient with Klippel-Trenaunay-Weber syndrome.
Klippel-Trenaunay-Weber syndrome (KTWS) is a rare congenital disorder, characterized by capillary, venous and lymphatic vascular malformations in association with bone and soft tissue hypertrophy. We report a KTWS patient with extensive hemangiomatosis of the right lower limb, trunk and upper limbs; bone and soft tissue hypertrophy of upper limbs, scapular girdle and right lower limb; and muscle atrophy on left lower limb with marked body asymmetry, scoliosis and toe malformations. These pathological features are associated with moderate mental retardation, mild renal and hepatic abnormalities. We identified by array CGH (Comparative Genomic Hybridization) a submicroscopic deletion 2q37.3 that could be related to impaired cognitive function. To our knowledge this is the first reported 2q37.3 microdeletion in a patient with KTWS.


Characterization of the cation and temperature dependence of DNA quadruplex hydrogen bond properties using high-resolution NMR.
Variations in the hydrogen bond network of the Oxy-1.5 DNA guanine quadruplex have been monitored by trans-H-bond scalar couplings, (h2)J(N2N7), for Na(+)-, K(+)-, and NH(4)(+)-bound forms over a temperature range from 5 to 55 degrees C. The variations in (h2)J(N2N7) couplings exhibit an overall trend of Na(+) > K(+) > NH(4)(+) and correlate with the different cation positions and N2-H2...N7 H-bond lengths in the respective structures. A global weakening of the (h2)J(N2N7) couplings with increasing temperature for the three DNA quadruplex species is accompanied by a global increase of the acceptor (15)N7 chemical shifts. Above 35 degrees C, spectral heterogeneity indicates thermal denaturation for the Na(+)-bound form, whereas spectral homogeneity persists up to 55 degrees C for the K(+)- and NH(4)(+)-coordinated forms. The average relative change of the (h2)J(N2N7) couplings amounts to approximately 0.8 x 10(-3)/K and is thus considerably smaller than respective values reported for nucleic acid duplexes. The significantly higher thermal stability of H-bond geometries in the DNA quadruplexes can be rationalized by their cation coordination of the G-quartets and the extensive H-bond network between the four strands. A detailed analysis of individual (h2)J(N2N7) couplings reveals that the 5' strand end, comprising base pairs G1-G9* and G4*-G1, is the most thermolabile region of the DNA quadruplex in all three cation-bound forms.


Intensity-Modified Recreational Volleyball Training Improves Health Markers and Physical Fitness in 25-55-Year-Old Men.
The present study is aimed at determining the effects of intensity-modified recreational volleyball training on health markers and physical fitness in healthy middle-aged men. Thirty-four healthy untrained men aged 25-55 years were randomized to either a modified recreational volleyball group (MRV, n = 17) or a recreational volleyball group (RV, n = 17). Both groups performed volleyball training twice a week over 12 weeks, with participants in MRV playing a modified game with higher intensity due to shorter breaks between rallies. The small to moderate improvements of both groups were observed in SBP (MRV g av = -0.50 [-0.67, -0.33] vs. RV g av = -0.37 [-0.55, -0.20]) to a similar extent (p = 0.12). However, only the MRV significantly improved (p < 0.001) the mean body weight (g av = -0.35 [-0.52, -0.18]) and BMI (g av = -0.39 [-0.56, -0.22]) to a moderate extent and the YYIR1 performance (g av = 2.45 [2.22, 2.69]) to a large extent. Even though both groups significantly improved the rest HR, the mean change of rest HR was significantly greater in MRV as compared to the RV (p < 0.001, ŋ p 2 = 0.47). The study revealed that an intensity-modified type of recreational volleyball, involving shorter breaks between rallies, improves cardiorespiratory fitness and health markers for men aged 25-55 years.


Lofexidine in opiate withdrawal: a safety and usage survey.
A retrospective, observational survey, conducted under the remit of the Safety Assessment of Marketed Medicines guidelines, collected data on nearly 1100 patients who had attempted an opiate detoxification with lofexidine, to identify current treatment protocols and safety. This approach offered a number of advantages over a prospective, randomized, clinical trial. It captured data on 'real-life' patients with a variety of co-existing illnesses and taking a wide range of concurrent medications. Data on exposure to lofexidine by three pregnant patients were documented and different dosage regimens have been described. The retrospective approach was not, however, without some limitations. The patients' medical notes were found to be incomplete and causality had not been assigned for many of the adverse events. However, providing the limitations of the retrospective approach are acknowledged, useful information has been collected on the current usage and safety of lofexidine, which has enabled the manufacturer to make a number of recommendations. Copyright (c) 2000 John Wiley & Sons, Ltd.


How do older adults experience and perceive socially assistive robots in aged care: a systematic review of qualitative evidence.
The aim of this review was to gain a better understanding of how older adults experience, perceive, think, and feel about the use of socially assistive robots (SARs) in aged care settings. We conducted a literature search for studies that used a qualitative or a mixed-method approach having a significant qualitative element. Pubmed, Cinahl, Embase, Scopus, and Web of Science electronic databases were queried. Candidate articles published in journals and conference proceedings were considered for review. Two independent reviewers assessed the included studies for methodological quality using the Critical Appraisal Skills Program, after which data on subjects' self-reported opinions and perceptions were extracted and synthesized using thematic analyses. Seventeen studies producing 23 publications were included. Based on the opinions of older adults, four themes emerged in relation to the use of SARS: (1) roles of a SAR; (2) interaction between the older adult and the SAR, which could be further subdivided into (a) the technical aspect of the interaction and (b) the human aspect of the interaction; (3) appearance of the SAR; and (4) normative/ethical issues regarding the use of SARs in aged care. Older adults have clear positive and negative opinions about different aspects of SARs in aged care. Nonetheless, some opinions can be ambiguous and need more attention if SARs are to be considered for use in aged care. Understanding older adults' lived experiences with SARs creates the possibility of using an approach that embeds technological innovation into the care practice itself.


Interaction of Cocos nucifera cream casein with humic acid suspensions.
Two caseins labelled as CaSMG (casein without fats) and CaMG (casein with fats) were extracted from coconut cream. Both caseins were used as coagulants for the aggregation of humic acid (HA) particles in synthetic water at pH = 6 during the jar-test essays. The optimum dosage of CaMG or CaSMG and the residual turbidities of treated water obtained depend on the type of used casein (CaMG or CaSMG) and the concentration of particles in solution. The optimal doses of CaMG and CaSMG are respectively 280 and 180 mg/L for solution S(1) (HA aqueous solution at 15 mg/L), and then 340 and 240 mg/L for solution S(2) (HA aqueous solution at 25 mg/L). The residual turbidities of treated water are respectively 6.88 and 3.85 NTU for solution S(1) and 4.52 and 2.53 NTU for solution S(2). The collected sediment volumes are respectively 1.2 and 1.5 mL for solutions S(1) and S(2). The electrophoretic mobility measurement and transmission electron microscopy images of flocs formed during the flocculation essays suggest that both caseins operate through both mechanisms (charge neutralisation and bridging process mechanism), this last one seems to be predominant. The aggregates formed are the large clusters and result from adsorption of HA particles by the casein molecules.


[Simultaneous determination of pesticides in agricultural products by LC/MS/MS using clean-up with ultrafiltration].
A method for simultaneous determination of multiple pesticide residues in agricultural products was developed by using a pretreatment with ultrafiltration, followed by liquid chromatography-tandem mass spectrometry (LC/MS/MS). The pretreatment process (extraction of pesticides from agricultural products with methanol, dilution of the extract with water, and ultrafiltration) gave recoveries in the range of 50-150% for 63 of 83 pesticides spiked at 0.25 microg/ g into 6 agricultural products. The detection limits of pesticides by LC/MS/MS were below 0.0005-0.05 micro/g. This method is useful for screening purposes and for multiresidue analysis of pesticides in agricultural products. Pesticide residues in 50 domestic crops were investigated by this method, and residues of 14 pesticides were detected in 30 crops.


Peripheral deletional tolerance of alloreactive CD8 but not CD4 T cells is dependent on the PD-1/PD-L1 pathway.
Although interaction between programmed death-1 (PD-1) and the ligand PD-L1 has been shown to mediate CD8 cell exhaustion in the setting of chronic infection or the absence of CD4 help, a role for this pathway in attenuating early alloreactive CD8 cell responses has not been identified. We demonstrate that the PD-1/PD-L1 pathway is needed to rapidly tolerize alloreactive CD8 cells in a model that requires CD4 cells and culminates in CD8 cell deletion. This protocol involves allogeneic bone marrow transplantation (BMT) following conditioning with low-dose total body irradiation and anti-CD154 antibody. Tolerized donor-reactive T-cell receptor transgenic CD8 cells are shown to be in an abortive activation state prior to their deletion, showing early and prolonged expression of activation markers (compared with rejecting CD8 cells) while being functionally silenced by day 4 after transplantation. Although both tolerized and rejecting alloreactive CD8 cells up-regulate PD-1, CD8 cell tolerance is dependent on the PD-1/PD-L1 pathway. In contrast, CD4 cells are tolerized independently of this pathway following BMT with anti-CD154. These studies demonstrate a dichotomy between the requirements for CD4 and CD8 tolerance and identify a role for PD-1 in the rapid tolerization of an alloreactive T-cell population via a deletional mechanism.


Evaluation of a pilot-scaled paddle dryer for the production of ethanol from lignocellulose including inhibitor removal and high-solids enzymatic hydrolysis.
The advantage of using paddle dryers (PD) in the production of sugars and 2nd generation ethanol from pretreated wheat straw was investigated. This machinery was employed in order to detoxify steam-exploded substrates and to mix different slurries in the hydrolysis step. The obtained hydrolysate was fermented by the yeast Saccharomyces cerevisiae. Acetic acid and furfural were reduced up to 11 and 26 fold respectively in the detoxified substrate. When fermentation was carried out at low solid suspension, the use of PD was as effective as water extraction in detoxifying exploded biomass, giving ethanol yields of 90% at 0.05 solid/liquid ratio (S/L) and 80% at 0.10 S/L. Moreover, by using PD the cellulose conversion yield was significantly improved in the hydrolysis step: when operating at higher S/L (0.4), the hydrolysis efficiency was twice the one achieved by using a bioreactor with a Rushton stirrer.