Changes in height, weight, BMI and in the prevalence of obesity among 9- to 11-year-old affluent Portuguese schoolboys, between 1960 and 2000.
There is a lack of detailed series of growth data that can be used to analyse secular trends in growth and obesity of Portuguese children. The purpose of this study was to examine the secular trend in height, weight, BMI and in the prevalence of obesity (including overweight), during the last four decades, in a sample of high socio-economic status Portuguese boys. All candidates (9-11 years) to a military boarding school (Colegio Militar) in Lisbon, Portugal, examined between 1962 and 2006 were the subjects of this study. Records of height and weight measured during medical examination were obtained (n=3176). Body mass index (kg m(-2)) (BMI) was calculated and the International Obesity Taskforce (IOTF) cut-offs were used to define overweight and obesity. The data obtained provide evidence for accelerating rates of overweight and obesity in affluent Portuguese boys, concomitant with a greater secular increase in mean weight, compared to that of height. Obesity (including overweight) more than doubled in the group of 9-year-olds (highest prevalence of 47.3% in 2000) and tripled in the group of 10- and 11-year-olds with greatest changes occurring between 1990 and 2000. The results suggest that a high family income does not necessarily translate into more informed choices about healthy foods and lifestyles, with a strong influence in the prevalence of obesity. This pattern of association between socio-economic status and obesity may reflect a late socio-economic transition of Portugal, compared to that of other high-income countries.


Bladder dysfunction after bilateral ectopic ureterocele repair.
We examined postoperative outcome, with emphasis on bladder function, in pediatric patients who underwent bilateral ectopic ureterocele repair. We reviewed the records of 117 patients with orthotopic and ectopic ureteroceles treated between 1977 and 2000. Twelve of these patients had bilateral ectopic ureteroceles. All patients with bilateral ureteroceles were females 1 day to 2 years old at referral. Initial treatment was transureteral puncture in 6 cases, transurethral unroofing in 2 and extravesical bilateral reimplantation in 1. Of the remaining 3 patients the initial treatment was unilateral heminephroureterectomy in 1 and bilateral heminephroureterectomy in 2. Definitive treatment included bilateral upper to lower ureteroureterostomy, ureterocelectomy with trigonal and bladder neck reconstruction, and bilateral ureteroneocystotomy with or without tapering of the recipient ureter. In patients who underwent upper pole partial nephrectomy the distal upper pole ureter was removed in conjunction with trigonal surgery and ureteroneocystotomy. There was significant morbidity in this group of patients, including voiding dysfunction and poor bladder emptying with residual urine greater than 20% of bladder capacity in 7 of 10 patients studied by serial bladder ultrasonography. Urodynamic evaluation in 3 patients revealed increased bladder compliance and large volume residual urine. Of these 3 patients 2 perform clean intermittent catheterization. Recurrent symptomatic bacteruria was noted in 7 of the 12 patients. Patients undergoing bilateral ectopic ureterocele repair are at increased risk for postoperative voiding dysfunction. Whether this risk is present preoperatively or is a result of trigonal surgery is unclear.


In-Situ XPS Monitoring and Characterization of Electrochemically Prepared Au Nanoparticles in an Ionic Liquid.
Gold nanoparticles (Au NPs) have been electrochemically prepared in situ and in vacuo using two different electrochemical device configurations, containing an ionic liquid (IL), N-N-diethyl-N-methyl-N-(2-methoxyethyl)ammonium bis(trifluoromethanesulfonyl)imide, that serves both as reaction and as stabilizing media for the NPs. It was observed in both devices that Au NPs were created using an anodically triggered route. The created Au NPs are relatively small (3-7 nm) and reside within the IL medium. X-ray photoelectron spectroscopy is utilized to follow not only the formation of the NPs but also their charging/discharging properties, by monitoring the charging shifts of the Au4f peak representing the electrodes and also the Au NPs as well as the F1s peak of the IL after polarizing one of the electrodes. Accordingly, DC polarization across the electrodes leads to a uniform binding energy shift of F1s of the IL along with that of Au4f of the NPs within. Moreover, this shift corresponds to only half of the applied potential. AC polarization brings out another dimension for demonstrating further the harmony between the charging/discharging property of the IL medium and the Au NPs in temporally and laterally resolved fashions. Polarization of the electrodes result in perfect spectral separation of the Au4f peaks of the NPs from those of the metal in both static (DC) and in time- and position-dependent (AC) modes.


Dicationic ionic liquid thermal decomposition pathways.
The rapid expansion in the study and use of ionic liquids (ILs) is a result of their unique properties including negligible volatility, high thermal stability, and ability to dissolve disparate compounds. However, because ILs have infinitely variable structures (often referred to as "tunability"), these properties can differ considerably. Herein, we focus on the thermal stability of 15 bis-/dicationic ionic liquids. Specifically, their thermal breakdown products are examined to determine the structural linkages, bonds, or atoms most susceptible to thermally induced changes and whether such changes occur before possible volatilization. In most cases, the heteroatom-carbon single bonds were susceptible to thermolytic decomposition. Graphical abstract Capture of dicationic ionic liquid thermal decomposition products for subsequent identification.


[Clinical significance of secondary cytoreductive surgery for recurrent advanced ovarian cancer].
To study the role of secondary cytoreductive surgery (SCR) in patients with recurrent advanced epithelial ovarian cancer. From Jan. 1986 to Dec. 1997, 60 women with recurrent advanced epithelial ovarian cancer treated with SCR were retrospectively reviewed. Survival curves were computed using the Kaplan-Meier method with differences in survival estimated by log-rank test. Independent prognostic factors were identified by Cox's stepwise regression, and the affecting factors of SCR evaluated by Logistic stepwise regression. Of the 60 patients, 23 (38.3%) were cytoreduced to small macroscopic residual (</= 1 cm) and 37 retained larger residual, with an estimated median survival of 19 months and 8 months respectively. Multivariate analysis revealed that residual disease (P = 0.0041) after SCR, as well as refractory ascites (P = 0.0191) and progression-free interval (P = 0.0116), were independent factors of survival. Refractory ascites (relative risk = 20.36, P = 0.0072) and residual disease after primary surgery (relative risk = 5.16, P = 0.0096) were factors affecting SCR. Secondary cytoreductive surgery is definitely effective in the treatment of recurrent advanced epithelial ovarian carcinoma, particularly in those who have received primary optimal cytoreduction with a progression-free interval > 12 months and without refractory ascites.


Deoxyribonucleic acid bacteriophage of methanomonas methylovora.
A new bacteriophage of low guanine plus cytosine (GC) content for Methanomonas methylovora has been isolated. Phage deoxyribonucleic acid contained 32 to 35% GC.


Exploring the platelet proteome via combinatorial, hexapeptide ligand libraries.
A combinatorial ligand library, composed of millions of diverse hexapeptide baits, able to capture and concentrate the "low-abundance" proteome while drastically cutting the concentration of the most abundant species, has been applied to the exploration of the soluble platelet proteome. Mass spectrometry analysis of untreated and library-treated platelets has resulted in the identification of 435 unique gene products. Of those, 147 entries (35% of the total) have not been described among the list of >1100 proteins in proteomic platelet investigations reported before. In addition, the analysis of excised spots from two-dimensional electrophoresis analysis allowed 57 other proteins to be added that were not found in LC-MS analysis, 33 of them not described before in proteomics studies, bringing the total number of new gene products to 180. Thus, the present data add a non-negligible number of species for continuing the "cartography" of the proteomic asset of platelets, in view of completing the mapping procedure for a deeper understanding of the physiology and pathology of this blood cell. Because the capturing process is performed under physiological conditions, by exploiting, for binding to the combinatorial library, the native protein configuration, the described technique is not adapted to capture highly hydrophobic proteins, which need strong denaturing and solubilizing conditions that are incompatible with our working procedure. Thus, our list reports essentially hydrophilic proteins, with negative GRAVY indexes.


[Ileocecal intussusceptions].
To present treatment of patients with ileocecal intussusception. There were 3 patients with ileocecal intussusception for the period from June 2016 to August 2017. Abdominal sonography is main diagnostic method for intestinal intussusception. X-ray examination including contrast-enhanced irrigography gives more complete information about suspected intussusception. It is necessary to differentiate intestinal intussusception from other diseases accompanied by abdominal pain, vomiting, bloody discharge from rectum, abdominal neoplasm. Minimally invasive laparoscopic approach is advisable for diagnosis and treatment of intestinal intussusception.


Antenatal glucocorticoid treatment and polymorphisms of the glucocorticoid and mineralocorticoid receptors are associated with IQ and behavior in young adults born very preterm.
Preterm survivors exhibit neurodevelopmental impairments. Whether this association is influenced by antenatal glucocorticoid treatment and glucocorticoid sensitivity is unknown. This study aimed to study the effects of antenatal glucocorticoid treatment and glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) polymorphisms on behavior and intelligence quotient (IQ). This study was part of the 19-year follow-up of the Project On Preterm and Small-for-gestational-age birth cohort. Multicenter study. Three hundred forty-four 19-year-olds born very preterm (gestational age < 32 wk), of whom 71 had received betamethasone antenatally. Single antenatal treatment course of betamethasone. Behavior (Young Adult Self Report and Young Adult Behavior Checklist for parents) and IQ (digital Multicultural Capacity Test-intermediate level). Data were analyzed by linear regression and presented as regression coefficient (95% confidence interval [CI]). Sex ratio, GR (R23K; N363S) and MR (-2G/C; I180V) genotypes were equally distributed between treated and nontreated subjects. Independent of treatment, R23K carriers had improved IQ scores (β 9.3; 95% CI, 3.4 to 15.1) and a tendency toward more favorable total problem behavior scores (β -8.5; 95% CI, -17.3 to 0.2) ; -2G/C CC carriers had poorer IQ scores (β -6.2; 95% CI, -10.5 to -1.9); I180V carriers had more favorable internalizing behavior scores (β -2.0; 95% CI, -3.9 to -0.1). Antenatal glucocorticoid treatment was associated with more unfavorable behavior scores, especially internalizing behavior (β 2.4; 95% CI, 0.3 to 4.5). Interaction between GR and MR polymorphisms and antenatal glucocorticoid treatment was observed, with poorer IQ scores for exposed N363S carriers; poorer intellectual subdomain scores for exposed I180V-carriers; more favorable total problem behavior scores for exposed R23K carriers. Genetic variations in glucocorticoid sensitivity and antenatal glucocorticoid treatment are associated with IQ and behavior in young adult preterm survivors.


The triplet channel in the photodissociation of ozone in the Hartley band: classical trajectory surface hopping analysis.
The triplet channel in the photodissociation of ozone in the Hartley band, O3 + hv-->O(3P) + O2(3sigma), is investigated by means of a classical trajectory surface hopping method using ab initio diabatic potential energy surfaces for the B and the R states. Because of the strong recoil in the R state along the breaking O-O bond, O2(3sigma) is produced with a high rotational energy. The nonadiabatic transition probability depends markedly on the coordinate along the crossing seam. As a consequence a unique correlation is found between the internuclear geometry at the crossing and the final vibrational state of O2(3sigma). The calculated distribution of the translational energy is in good accord with the measured distribution.


LncRNA Gm43843 Promotes Cardiac Hypertrophy via miR-153-3p/Cacna1c Axis.
Long noncoding RNAs (lncRNAs) have been reported to engage in many human diseases, including cardiac hypertrophy. Cardiac hypertrophy was mainly caused by excessive pressure load, which can eventually lead to a decline in myocardial contractility. Gm43843, a novel lncRNA, has not been well explored in cardiac hypertrophy so far. Herein, we are going to search the function and the underlying molecular mechanism of Gm43843 in cardiac hypertrophy. Gm43843 levels were measured via qRT-PCR in mouse myocardial cells when they are treated with angiogenin II (Ang II) or transfected with different plasmids. Western blot assay was implemented to detect the cardiac hypertrophy-related protein markers, while the cell was analyzed via immunofluorescence (IF) assay to evaluate the hypertrophy. Meanwhile, the binding of Gm43843 and the putative targets was examined based on mechanistic assay results. We found that Gm43843 expression was increased with the elevated concentration of Ang II. Inhibited Gm43843 was detected to reduce the hypertrophy of mouse myocardial cells. Meanwhile, Gm43843/miR-153-3p/Cacna1c axis was found to modulate cardiac hypertrophy. In short, Gm43843 promotes cardiac hypertrophy via miR-153-3p/Cacna1c axis.


Consequences of lethal-whole-body gamma radiation and possible ameliorative role of melatonin.
Gamma radiation induces the generation of free radicals, leading to serious cellular damages in biological systems. Radioprotectors act as prophylactic agents that are administered to shield normal cells and tissues from the deleterious effects of radiation. Melatonin synergistically acts as an immune-stimulator and antioxidant. We investigated the possible radioprotective role of melatonin (100 mg/kg i.p.) against lethal-whole-body radiation- (10 Gy) induced sickness, body weight loss, and mortality in rats. Results of the present study suggest that exposure to lethal-whole-body radiation incurred mortality, body weight loss, and apoptosis and it also depleted the immunity and the antioxidant status of the rats. Our results show that melatonin pretreatment provides protection against radiation induced mortality, oxidative stress, and immune-suppression. The melatonin pretreated irradiated rats showed less change in body weight as compared to radiation only group. On the other hand, melatonin appeared to have another radioprotective role, suggesting that melatonin may reduce apoptosis through a caspase-3-mediated pathway by blocking caspase-3 activity.


Effects of prazosin HCl on the urethral pressure profile in patients with benign prostatic hyperplasia.
The effects of prazosin HCl on the urethral pressure profile (UPP) were studied in 14 patients with benign prostatic hyperplasia. Urethral pressure profilometry was performed 1 h after oral administration of 1 or 2 mg prazosin HCl. Functional profile and continence zone lengths were significantly reduced following administration of 1 or 2 mg prazosin HCl, as compared with the pretreatment lengths. The administration of 2 mg prazosin HCl resulted in a significant decrease in prostatic peak pressure, whereas the maximum urethral closure pressure exhibited an insignificant decrease. The results suggest that the effects of prazosin HCl on UPP were dose dependent within the range from 1 to 2 mg.


High Ia (HLA-DR) and low CD11b (Mo1) expression may predict early conversion to leukemia in myelodysplastic syndromes.
The FAB classification of myelodysplastic syndromes (MDS) has been useful in predicting prognosis; however, additional methods are required to detect patients at high risk for early conversion to acute nonlymphoblastic leukemia (ANLL). Using a panel of monoclonal antibodies to myelomonocytic surface antigens (MMSA) and flow cytometry, we studied bone marrow cells from 26 patients with MDS of all five FAB subtypes. The MMSA studied included Ia (HLA-DR), CD11b (Mo1), CD14 (Mo2, My4), CD13 (My7), and CD33 (My9). Marrows were considered "positive" for a given MMSA if the percentage of reactive cells exceeded the upper limit of the normal range. Twenty-four of twenty-six patients (92.3%) were CD13 (My7)+, suggesting that CD13 may serve as a diagnostic marker for MDS. Ten of twelve patients who developed ANLL during a median follow-up of 44 weeks were Ia(HLA-DR)+. The Kaplan-Meier estimated median time to leukemia (TTL) was 16 weeks for Ia+ patients and 88 weeks for Ia- patients (P = 0.004). All six patients who developed ANLL before 16 weeks from diagnosis were Ia+, while none of the Ia- patients converted to ANLL before 24 weeks. Nine of thirteen patients with low CD11b (Mo1) expression (< 53% reactive cells) developed ANLL, compared with only two of 11 patients with high CD11b expression (> 53% reactive cells). Kaplan-Meier estimated TTL was 29 weeks for patients with low CD11b, compared to 160 weeks for patients with high CD11b (P < 0.05). Patients who met both criteria, Ia+ and low CD11b, represented the poorest prognostic subgroup, with median TTL of 13 weeks compared with 88 weeks for the others (P = 0.017). Ia and CD11b patterns were not specific for MDS subtype, and their expression did not correlate with blast count. These data suggest that MDS patients whose bone marrow cells demonstrate high Ia (HLA-DR) and low CD11b (Mo1) expression represent a poor prognostic subgroup with short TTL. These patients may be candidates for early aggressive or investigational treatment.


Increased fatty acid synthesis inhibits nitrogen starvation-induced autophagy in lipid droplet-deficient yeast.
Macroautophagy is a degradative pathway whereby cells encapsulate and degrade cytoplasmic material within endogenously-built membranes. Previous studies have suggested that autophagosome membranes originate from lipid droplets. However, it was recently shown that rapamycin could induce autophagy in cells lacking these organelles. Here we show that lipid droplet-deprived cells are unable to perform autophagy in response to nitrogen-starvation because of an accelerated lipid synthesis that is not observed with rapamycin. Using cerulenin, a potent inhibitor of fatty acid synthase, and exogenous addition of palmitic acid we could restore nitrogen-starvation induced autophagy in the absence of lipid droplets.


Parallel histories of horizontal gene transfer facilitated extreme reduction of endosymbiont genomes in sap-feeding insects.
Bacteria confined to intracellular environments experience extensive genome reduction. In extreme cases, insect endosymbionts have evolved genomes that are so gene-poor that they blur the distinction between bacteria and endosymbiotically derived organelles such as mitochondria and plastids. To understand the host's role in this extreme gene loss, we analyzed gene content and expression in the nuclear genome of the psyllid Pachypsylla venusta, a sap-feeding insect that harbors an ancient endosymbiont (Carsonella) with one of the most reduced bacterial genomes ever identified. Carsonella retains many genes required for synthesis of essential amino acids that are scarce in plant sap, but most of these biosynthetic pathways have been disrupted by gene loss. Host genes that are upregulated in psyllid cells housing Carsonella appear to compensate for endosymbiont gene losses, resulting in highly integrated metabolic pathways that mirror those observed in other sap-feeding insects. The host contribution to these pathways is mediated by a combination of native eukaryotic genes and bacterial genes that were horizontally transferred from multiple donor lineages early in the evolution of psyllids, including one gene that appears to have been directly acquired from Carsonella. By comparing the psyllid genome to a recent analysis of mealybugs, we found that a remarkably similar set of functional pathways have been shaped by independent transfers of bacterial genes to the two hosts. These results show that horizontal gene transfer is an important and recurring mechanism driving coevolution between insects and their bacterial endosymbionts and highlight interesting similarities and contrasts with the evolutionary history of mitochondria and plastids.


Does abdominal massage improve gastrointestinal functions of intensive care patients with an endotracheal tube?: A randomized clinical trial.
Gastrointestinal dysfunction is one of the most common problems among patients hospitalized in intensive care units. Currently, medicinal and non-medicinal methods are being used to prevent gastrointestinal problems. Among non-medicinal methods, abdominal massage is considered as a relatively acceptable method. The present study aims to examine the effect of abdominal massage on gastrointestinal functions of the intensive care patients with an endotracheal tube. In this clinical trial, 70 intensive care patients with an endotracheal tube were chosen by convenience sampling and allocated to an intervention or a control group randomly. In the intervention group, a 15-min abdominal massage was conducted twice a day for three days, while the control group received only routine cares. The abdominal circumference, gastric residual volume, times of defecation, and frequency of constipation were measured. Gastric residual volume decreased significantly in the intervention group and increased significantly in the control group; however, there was no significant difference between two groups (P = .15). There was a significant difference between two groups regarding abdominal circumference and it was decreased in the intervention group (P < .001). The defecation times significantly increased in the intervention group (P = .002). After the intervention, the prevalence of constipation was significantly decreased in the intervention group (P = .008). The results revealed that abdominal massage could improve gastrointestinal functions in enterally fed patients with an endotracheal tube. It is suggested to use abdominal massage as an adjunct therapy for improving gastrointestinal functions in intensive care patients.


Skin regeneration for children with burn scar contracture using autologous cultured dermal substitutes and superthin auto-skin grafts: preliminary clinical study.
We have evaluated a novel treatment of burn scar contracture in children. This method involves the application of an autologous cultured dermal substitute (CDS), followed by a graft of superthin split-thickness skin. In the first operation, the autologous CDS was applied to the skin defect that had occurred after releasing the scar contracture. In the second operation, a superthin thickness skin graft (4 approximately 6/1000 inches) was applied 5 approximately 12 days after the first operation. The autologous CDS was applied to 10 sites of 5 children. On 8 sites, the skin grafts were contracted to some extent at an early stage. However, these skin grafts were stretched gradually to a range from 60% to 100% of an original size. At 2 sites, the skin grafts had stretched from 110% to 130% of the original size. This strategy may be useful for the treatment of burn scar contracture in children.


Osteoporosis Prevention and Management.
Osteoporosis, defined by BMD at the hip or lumbar spine that is less than or equal to 2.5 standard deviations below the mean BMD of a young-adult reference population, is the most common bone disease in humans affecting both sexes and all races. It's a silent killer affecting the quality of life due to fractures and postural changes. In osteoporosis there is an imbalance between bone formation and bone resorption in favor of latter. Preventive measures and treatments are available to combat this evil. Counseling is the integral part of prevention as well as treatment of osteoporosis. Preventive strategy includes life style changes, exercise, intake of calcium and vitamin D, avoiding alcohol, smoking and excessive intake of salt. Estrogen therapy/estrogen+progesterone therapy (ET/EPT) is no longer recommended as a first-line therapy for the prevention of osteoporosis. They may be used in the therapy for osteoporosis in women under 60. Diagnosis and classification are made by assessment of BMD using DEXA or ultrasound and laboratory investigations. Management includes estimation of 10-year fracture risk using FRAX, life style and diet modification and pharmacological therapy. The drugs used in osteoporosis may be those that inhibit bone resorption-bisphosphonates, denosumab, calcitonin, SERMs, estrogen and progesterone-or that stimulate bone formation-PTH, Teriparatide. Combination therapies are not recommended as they do not have proven additional BMD/fracture benefits. No therapy should be indefinite in duration. There are no uniform recommendations to all patients. Duration decisions need to be individualized. While on treatment monitoring should be done with BMD assessment by DEXA/ultrasound and bone turnover markers.


Coagulation activation in extracorporeal hemodialysis.
The authors evaluated the behavior of protein C activity, factor X and factor VII coagulant activity and serum lipoprotein(a) before and after dialytic treatment in patients on maintenance hemodialysis. They observed depressed protein C activity that significantly (p < 0.005) increased and became normal immediately after hemodialysis while factor X and factor VII increased (p < 0.01; p < 0.05) despite heparinization together with amount of serum lipoprotein(a). In vitro incubation (30' at 37 degrees C) of uremic and healthy blood showed a decrease in serum lipoprotein(a) concentration. After heparin addition (final concentration 0.5 U/ml) lipoprotein(a) increased in the uremic blood only. The clinical and physiopathological implications of these results are discussed.


Evolutionarily emerged G tracts between the polypyrimidine tract and 3' AG are splicing silencers enriched in genes involved in cancer.
The 3' splice site (SS) at the end of pre-mRNA introns has a consensus sequence (Y)nNYAG for constitutive splicing of mammalian genes. Deviation from this consensus could change or interrupt the usage of the splice site leading to alternative or aberrant splicing, which could affect normal cell function or even the development of diseases. We have shown that the position "N" can be replaced by a CA-rich RNA element called CaRRE1 to regulate the alternative splicing of a group of genes. Taking it a step further, we searched the human genome for purine-rich elements between the -3 and -10 positions of the 3' splice sites of annotated introns. This identified several thousand such 3'SS; more than a thousand of them contain at least one copy of G tract. These sites deviate significantly from the consensus of constitutive splice sites and are highly associated with alterative splicing events, particularly alternative 3' splice and intron retention. We show by mutagenesis analysis and RNA interference that the G tracts are splicing silencers and a group of the associated exons are controlled by the G tract binding proteins hnRNP H/F. Species comparison of a group of the 3'SS among vertebrates suggests that most (~87%) of the G tracts emerged in ancestors of mammals during evolution. Moreover, the host genes are most significantly associated with cancer. We call these elements together with CaRRE1 regulatory RNA elements between the Py and 3'AG (REPA). The emergence of REPA in this highly constrained region indicates that this location has been remarkably permissive for the emergence of de novo regulatory RNA elements, even purine-rich motifs, in a large group of mammalian genes during evolution. This evolutionary change controls alternative splicing, likely to diversify proteomes for particular cellular functions.


Tackling exclusion: A pilot mixed method quasi-experimental identity capital intervention for young people exiting homelessness.
Longitudinal studies examining the life trajectories of young people after they have exited homelessness have identified concerns with persistent social and economic exclusion, struggles to shake off identities of homelessness, and housing instability. This pilot study sought to explore the feasibility of improving socioeconomic inclusion outcomes by bolstering identity capital (sense of purpose and control, self-efficacy and self-esteem) among young people who had experienced homelessness. Nineteen individuals (aged 18-26) who had transitioned out of homelessness within the past three years participated in a six-week, six-session program focused on building identity capital. The study employed a mixed method prospective cohort hybrid design with an intervention group (Group One) and a delayed intervention comparison group (Group Two). Participants were interviewed every three months until nine months post-intervention. None of the youth who began the intervention dropped out of the program, with the exception of one participant who moved across the country and was unable to continue. Immediately after participating in the intervention, Group One had statistically significant improvements (p < .05) and large to very large effect sizes in self-esteem (d = 1.16) and physical community integration (d = 1.79) compared to changes in Group Two over the same period, which had not yet begun the intervention. In the pooled analysis, small to moderate effect sizes in hopelessness, physical community integration, and self-esteem were observed at all post-intervention time points. Notably, at six- and nine-months post-intervention, statistically significant improvements (p < .05) and moderate effect sizes in hopelessness (d = -0.73 and d = -0.60 respectively) and self-esteem (d = 0.71 and d = 0.53 respectively) were observed. Youth shared they appreciated the normalizing (vs. pathologizing) of strategies they needed to learn and spoke of the importance of framing new skills as something one needs "to have a better life" vs. "to get better." These early findings signal that targeting identity capital is feasible and may be a promising approach to incorporate into a more complex intervention that includes housing, education, and employment supports to help youth transition out of homelessness. Future research could build on these findings through a sufficiently powered randomized controlled trial.


The secret identities of TMPRSS2: Fertility factor, virus trafficker, inflammation moderator, prostate protector and tumor suppressor.
The human TMPRSS2 gene is pathogenetically implicated in both coronaviral lung infection and prostate cancer, suggesting its potential as a drug target in both contexts. SARS-COV-2 spike polypeptides are primed by the host transmembrane TMPRSS2 protease, triggering virus fusion with epithelial cell membranes followed by an endocytotic internalisation process that bypasses normal endosomal activation of cathepsin-mediated innate immunity; viral co-opting of TMPRSS2 thus favors microbial survivability by attenuating host inflammatory responses. In contrast, most early hormone-dependent prostate cancers express TMPRSS2:ERG fusion genes arising from deletions that eliminate the TMPRSS2 coding region while juxtaposing its androgen-inducible promoter and the open reading frame of ERG, upregulating pro-inflammatory ERG while functionally disabling TMPRSS2. Moreover, inflammatory oxidative DNA damage selects for TMPRSS2:ERG-fused cancers, whereas patients treated with antiinflammatory drugs develop fewer of these fusion-dependent tumors. These findings imply that TMPRSS2 protects the prostate by enabling endosomal bypass of pathogens which could otherwise trigger inflammation-induced DNA damage that predisposes to TMPRSS2:ERG fusions. Hence, the high oncogenic selectability of TMPRSS2:ERG fusions may reflect a unique pro-inflammatory synergy between androgenic ERG gain-of-function and fusogenic TMPRSS2 loss-of-function, cautioning against the use of TMPRSS2-inhibitory drugs to prevent or treat early prostate cancer.


Suppression of hyaluronan synthesis alleviates inflammatory responses in murine arthritis and in human rheumatoid synovial fibroblasts.
To clarify the roles of hyaluronan (HA) in joint inflammation and the process of joint destruction, using 4-methylumbelliferone (4-MU), an inhibitor of HA synthesis, in a mouse model of collagen-induced arthritis (CIA) and in a monolayer culture of fibroblast-like synoviocytes (FLS) derived from patients with rheumatoid arthritis. DAB/1J mice were immunized with type II collagen. The effects of 4-MU were evaluated by the physiologic arthritis score, paw swelling, the histologic arthritis score, and expression of matrix metalloproteinase 3 (MMP-3) and MMP-13 in chondrocytes and synovial tissue. In vitro, the effect of 4-MU on messenger RNA and protein expression of MMP-1 and MMP-3 was determined. The effects of 4-MU on HA deposition and on serum/medium concentrations of HA were analyzed using biotinylated HA binding protein staining and an HA binding assay, respectively. Treatment with 4-MU in mice with CIA dramatically decreased the severity of arthritis (based on the arthritis score), paw thickness, and histopathologic changes. MMP-3 and MMP-13 expression in chondrocytes and synovial cells was significantly inhibited by 4-MU in vivo. Treatment with 4-MU also inhibited MMP-1 and MMP-3 expression in tumor necrosis factor α-stimulated FLS, in a dose-dependent manner. The 4-MU-induced decreases in the serum HA concentration in mice with CIA and in "medium" and "pericellular" HA concentrations in cultured FLS support the contention that the inhibitory mechanism of 4-MU is mediated by HA suppression. Reduced disease activity induced by 4-MU in mice with CIA revealed HA to be a crucial regulator in the course of arthritis. Therefore, 4-MU is a potential therapeutic agent in arthritis, and its inhibitory mechanism is possibly mediated by suppression of HA synthesis.


In vitro assessment of mutagenic and genotoxic effects of coumarin derivatives 6,7-dihydroxycoumarin and 4-methylesculetin.
Coumarins are naturally occurring compounds, widely distributed throughout the plant kingdom (Plantae), and possess important pharmacological properties, including inhibition of oxidative stress. In this context, newly synthesized coumarin compounds are being produced due to their potent antioxidant activities. Therefore, the aim of the present study was to determine the in vitro cytotoxic, mutagenic, and genotoxic effects of 6,7-dihydroxycoumarin (6,7-HC) and 4-methylesculetin (4-ME) using the Salmonella/microsome test and in cultured human lymphocytes the comet assay and micronucleus test. The three coumarin derivatives concentrations evaluated in comet and MN assays were 2, 8, and 32 μg/mL, selected through a preliminary trypan blue-staining assay. In the Ames test, the 5 concentrations tested were 62.5, 125, 250, 500, and 750 μg/plate. Positive (methyl methane-sulfonate, MMS) and negative (dimethyl sulfoxide, DMSO) control groups were also included in the analysis. Our results showed that 4-ME induced greater cytotoxicity at high concentrations than 6,7-HC. In addition, both compounds were not mutagenic in the Ames test and not genotoxic or clastogenic/aneugenic in cultured human lymphocytes.


Developing and improving after-school programs to enhance youth's personal growth and adjustment: a special issue of AJCP.
Participating in after-school programs (ASPs) has become a common experience for children. This special issue provides a perspective on the current status of research on ASPs. This introductory article overviews the historical and current context of ASPs and then describes a developmental ecological model to guide research in this area. The model offers a framework from which to organize and synthesize the research presented in this issue. Key principles include a holistic view of development that recognizes interrelations between multiple domains of youth adjustment, attention to multiple, relevant factors within and outside of youth that affect development, examining the dynamic interplay between persons, program features, and other contexts over time, and understanding the active role of youth in affecting their own development. These principles are examined in relation to five main areas: youth characteristics, social ecologies, program features, participation, and short- and long-term outcomes. Recommendations for future research are discussed.


Linking diatom sensitivity to herbicides to phylogeny: a step forward for biomonitoring?
Phylogeny has not yet been fully accepted in the field of ecotoxicology, despite studies demonstrating its potential for developing environmental biomonitoring tools, as it can provide an a priori assessment of the sensitivity of several indicator organisms. We therefore investigated the relationship between phylogeny and sensitivity to herbicides in freshwater diatom species. This study was performed on four photosystem II inhibitor herbicides (atrazine, terbutryn, diuron, and isoproturon) and 14 diatom species representative of Lake Geneva biofilm diversity. Using recent statistical tools provided by phylogenetics, we observed a strong phylogenetic signal for diatom sensitivity to herbicides. There was a major division in sensitivity to herbicides within the phylogenetic tree. The most sensitive species were mainly centrics and araphid diatoms (in this study, Thalassiosirales and Fragilariales), whereas the most resistant species were mainly pennates (in this study, Cymbellales, Naviculales, and Bacillariales). However, there was considerable variability in diatom sensitivity within the raphid clade, which could be explained by differences in trophic preferences (autotrophy or heterotrophy). These traits appeared to be complementary in explaining the differences in sensitivity observed at a refined phylogenetic level. Using phylogeny together with complementary traits, as trophic preferences, may help to predict the sensitivity of communities with a view to protecting their ecosystem.


Research on Heterogeneous Traveler Travel Mode Choices with Differences under a Mixed Traffic Environment.
Autonomous vehicles (AVs) have been made possible by advances in sensing and computing technologies. However, the high cost of AVs makes privatization take longer. Therefore, companies with autonomous vehicles can develop shared autonomous vehicle (SAV) projects. AVs with a high level of automation require high upgrade and use costs. In order to meet the needs of more customers and reduce the investment cost of the company, SAVs with different levels of automation may coexist for a long time. Faced with multiple travel modes (autonomous cars with different levels of automation, private cars, and buses), travelers' travel mode choices are worth studying. To further differentiate the types of travelers, this paper defines high-income travelers and low-income travelers. The difference between these two types of travelers is whether they have a private car. The differences in time value and willingness to pay of the two types of travelers are considered. Based on the above considerations, this paper establishes a multi-modal selection model with the goal of maximizing the total utility of all travelers and uses the imperial competition algorithm to solve it. The results show that low-income travelers are more likely to choose buses and autonomous vehicles with lower levels of automation, while high-income travelers tend to choose higher levels of automation due to their high value of travel time.


A comparison of foot/ground interaction during stair negotiation and level walking in young and older women.
Stair design and environmental conditions may play a role in slip accidents on stairs in the workplace, but little is known about the slip resistance requirements on stairs compared to level walking. Older adults have an increased risk of falling compared to younger adults and may be at greater risk during stair negotiation. The purpose of this study was to determine whether the ground reaction force profiles and peak required coefficient of friction (RCOF) differed between young and elderly women or between stair ascent, stair descent and overground walking. While there was a trend towards less risky stair descent behaviour in the older women in terms of their peak RCOF values during stair descent, the increased vertical loading rate in the older women may imply reduced dynamic balance control. The largest mean RCOF peaks occurred during stair ascent in both young and older women, but there were several overground walking trials in both groups and a few stair descent trials of the young women, which resulted in RCOF peaks greater than 0.5. These results should be considered when choosing stair surface materials, particularly in occupational and outdoor settings where the tread surfaces may become wet or contaminated.


Gender Disparity in Industry Relationships With Academic Interventional Radiology Physicians.
OBJECTIVE. Industry relationships drive technologic innovation in interventional radiology and offer opportunities for professional growth. Women are underrepresented in interventional radiology despite the growing recognition of the importance of diversity. This study characterized gender disparities in financial relationships between industry and academic interventional radiologists. MATERIALS AND METHODS. In this retrospective cross-sectional study, U.S. academic interventional radiology physicians and their academic ranks were identified by searching websites of practices with accredited interventional radiology fellowship programs. Publicly available databases were queried to collect each physician's gender, years since medical school graduation, h-index, academic rank, and industry payments in 2018. Wilcoxon and chi-square tests compared payments between genders. A general linear model assessed the impact of academic rank, years since graduation, gender, and h-index on payments. RESULTS. Of 842 academic interventional radiology physicians, 108 (13%) were women. A total $14,206,599.41 was received by 686 doctors (81%); only $147,975.28 (1%) was received by women. A lower percentage of women (74%) than men (83%) received payments (p = 0.04); median total payments were lower for women ($535) than men ($792) (p = 0.01). Academic rank, h-index, years since graduation, and male gender were independent predictors of higher payments. Industry payments supporting technologic advancement were made exclusively to men. CONCLUSION. Female interventional radiology physicians received fewer and lower industry payments, earning 1% of total payments despite constituting 13% of physicians. Gender independently predicted industry payments, regardless of h-index, academic rank, or years since graduation. Gender disparity in interventional radiology physician-industry relationships warrants further investigation and correction.


Clindamycin resistance in the Bacteroides fragilis group: association with hospital-acquired infections.
A retrospective study was conducted to assess the relationships between clindamycin resistance in members of the Bacteroides fragilis group, previous antimicrobial therapy, and the context for the development of infection, whether in the community or during hospitalization. Eighty-five clindamycin-resistant clinical strains (one isolate per patient) isolated from January 1988 to October 1994 were matched (one to one) with clindamycin-susceptible isolates recovered during the same period, and the charts of the patients from whom the isolates were recovered were reviewed retrospectively. Of the clindamycin-resistant strains, 65% were recovered from patients with hospital-acquired infections compared with 40% of the clindamycin-susceptible strains (odds ratio [OR], 2.75; 95% confidence interval [CI], 1.41-5.38; P = .002). Prior antimicrobial therapy for > or = 48 hours was also associated with clindamycin resistance (OR, 2.33; 95% CI, 1.16-4.70; P = .02). However, clindamycin resistance remained associated with hospital-acquired infections independent of prior antimicrobial therapy (Mantel-Haenszel weighted average OR, 2.22; 95% CI, 1.03-4.89; P = .04). Clinicians should consider the risks for clindamycin resistance when treating hospital-acquired infections caused by members of the B. fragilis group.


[Endocrinological and metabolic disorders in the patients with massive bowel resection in the newborn period].
Massive (70%) resection of the small bowel was performed in seven newborn infants. Follow-up study was undertaken in four of these patients and the growth and endocrinological status were evaluated. Body weight and height of three patients were below 50th percentile. On glucose tolerance test, peak IRI was low and insulinogenic indices were below normal range. These findings suggest that there are some mechanisms which suppress the secretion of insulin. Pituitary and thyroid function were within normal limits but secondary sexual manifestation was not seen in a fifteen year old boy. Hyperoxaluria was seen in three children, and one had kidney stone with some impairment of renal function.


Potentiation of 2'-deoxyguanosine cytotoxicity by a novel inhibitor of purine nucleoside phosphorylase, 8-amino-9-benzylguanine.
We have synthesized and evaluated a series of 9-substituted analogues of 8-aminoguanine, a known inhibitor of human purine nucleoside phosphorylase (PNP) activity. The ability of these agents to inhibit PNP has been investigated. All compounds were found to act as competitive (with inosine) inhibitors of PNP, with Ki values ranging from 0.2 to 290 microM. The most potent of these analogues, 8-amino-9-benzylguanine; exhibited a Ki value that was 4-fold lower than that determined for the parent base, 8-aminoguanine. As a metabolically stable compound in human blood, 8-amino-9-benzylguanine was more effective than 8-aminoguanine at potentiating the toxicity of 2'-deoxyguanosine to MOLT-4 T-lymphoblasts in culture. 8-Amino-9-benzylguanine is the most potent base or nucleoside inhibitor of human PNP reported to date, and it is a promising lead compound in the development of more effective PNP inhibitors.


Local electrostatics algorithm for classical molecular dynamics simulations.
An implementation of a local, linear scaling algorithm for computing electrostatic interactions in molecular dynamics simulations that was recently proposed [J. Rottler and A. C. Maggs, Phys. Rev. Lett. 93, 170201 (2004)] is presented. Coulombic forces are mediated by a propagating electric field that obeys Gauss's law. A detailed description of the numerical implementation is presented, and the accuracy is calibrated by comparing the electrostatic force to that obtained from a standard Ewald summation. A parallelized implementation exhibits excellent scaling behavior on a contemporary low latency compute cluster, and therefore becomes an interesting alternative to existing algorithms for computing electrostatics in large-scale molecular dynamics. The approach opens new possibilities for the study of physical situations that are difficult or impossible to treat with standard reciprocal space methods, in particular nonperiodic boundary conditions and spatially heterogeneous dielectric environments in implicit solvent models.


The effect of stabilizer on the mechanical response of double-emulsion-templated polymersomes.
Recent studies have shown that polymersomes templated by microfluidic double-emulsion possess several advantages such as high monodispersity and encapsulation efficiency compared with those generated based on thin-film rehydration and electroformation. Stabilizers, including bovine serum albumin (BSA) and polyvinyl alcohol (PVA), have been used to enhance the formation and stability of double emulsions that are used as templates for the generation of polymersomes. In this work, the effect of stabilizers on the mechanical response of double-emulsion-templated polymersomes using micropipette aspiration is investigated. It is demonstrated that the existence of stabilizers results in the inelastic response in poly-mersomes in the early stage of solvent removal. However, aged polymersomes that have little residual solvent show elastic behavior. Polymersomes prepared from PVA-stabilized double emulsions have noticeably lower area expansion moduli than polymersomes prepared from stabilizer-free and BSA-stabilized double emulsions, suggesting that PVA is incorporated in the bilayer membrane of polymersomes.


My Team of Care Study: A Pilot Randomized Controlled Trial of a Web-Based Communication Tool for Collaborative Care in Patients With Advanced Cancer.
The management of patients with complex care needs requires the expertise of health care providers from multiple settings and specialties. As such, there is a need for cross-setting, cross-disciplinary solutions that address deficits in communication and continuity of care. We have developed a Web-based tool for clinical collaboration, called Loop, which assembles the patient and care team in a virtual space for the purpose of facilitating communication around care management. The objectives of this pilot study were to evaluate the feasibility of integrating a tool like Loop into current care practices and to capture preliminary measures of the effect of Loop on continuity of care, quality of care, symptom distress, and health care utilization. We conducted an open-label pilot cluster randomized controlled trial allocating patients with advanced cancer (defined as stage III or IV disease) with ≥3 months prognosis, their participating health care team and caregivers to receive either the Loop intervention or usual care. Outcome data were collected from patients on a monthly basis for 3 months. Trial feasibility was measured with rate of uptake, as well as recruitment and system usage. The Picker Continuity of Care subscale, Palliative care Outcomes Scale, Edmonton Symptom Assessment Scale, and Ambulatory and Home Care Record were patient self-reported measures of continuity of care, quality of care, symptom distress, and health services utilization, respectively. We conducted a content analysis of messages posted on Loop to understand how the system was used. Nineteen physicians (oncologists or palliative care physicians) were randomized to the intervention or control arms. One hundred twenty-seven of their patients with advanced cancer were approached and 48 patients enrolled. Of 24 patients in the intervention arm, 20 (83.3%) registered onto Loop. In the intervention and control arms, 12 and 11 patients completed three months of follow-up, respectively. A mean of 1.2 (range: 0 to 4) additional healthcare providers with an average total of 3 healthcare providers participated per team. An unadjusted between-arm increase of +11.4 was observed on the Picker scale in favor of the intervention arm. Other measures showed negligible changes. Loop was primarily used for medical care management, symptom reporting, and appointment coordination. The results of this study show that implementation of Loop was feasible. It provides useful information for planning future studies further examining effectiveness and team collaboration. Numerically higher scores were observed for the Loop arm relative to the control arm with respect to continuity of care. Future work is required to understand the incentives and barriers to participation so that the implementation of tools like Loop can be optimized. ClinicalTrials.gov NCT02372994; https://clinicaltrials.gov/ct2/show/NCT02372994 (Archived by WebCite at http://www.webcitation.org/6r00L4Skb).


Structural, biochemical and non-traditional cardiovascular risk markers in PCOS.
Polycystic ovary syndrome (PCOS) is a heterogeneous syndrome of reproductive and metabolic derangements. The combination of anovulation and hyperandrogenism signifies the classic form of PCOS which displays the adverse metabolic phenotype of the syndrome. This phenotype includes visceral obesity and insulin resistance as well as a constellation of other traditional cardiovascular risk factors, mainly low grade inflammation, disturbances of glucose metabolism and dyslipidemia. The resultant increased risk for cardiovascular disease may affect not only obese but also lean women with classic PCOS. The mechanisms underlying the increased cardiovascular risk in the context of PCOS may include not only metabolic aberrations, but also hormonal factors, in particular hyperandrogenemia. However, the consequences in terms of CV morbidity remain questionable due to the difficulties in conducting long-term, prospective studies aimed at identifying potential late-arriving clinical outcomes.


Recovery and characterization of the metal polymeric organic fraction (polymerin) from olive oil mill wastewaters.
A dark and complex metal polymeric organic mixture, named polymerin, was recovered from olive oil mill wastewaters (OMWW) and characterized by chemical analysis, diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS), and atomic absorption spectrometry (AAS). Polymerin proved to be composed of carbohydrates (52.40 mg 100(-1), w/w), melanin (26.14 mg 100(-1)), and proteins (10.40 mg 100(-1)), and the respective composition of monosaccharides, phenols, and amino acids was determined. It also contained metals (11.06 mg 100(-1)), mainly K(+) and, to a lesser extent, Na(+), Ca(2+), Mg(2+), Zn(2+), Fe(3+), and Cu(2+), which were naturally bound and chelated through carboxylate anions and other characteristic nucleophilic functional groups naturally occurring in polymerin. The distribution of polymerin relative molecular size was assessed to be approximately between 500.0 and 2.0 kDa by calibrated molecular weight gel filtration chromatography, indicating also that a fraction consisted of protein, melanin, and polysaccharide, strongly aggregated to each other in a supramolecular status by a combination of covalent and hydrogen bonds and CH/Pi interactions, and another fraction of only free polysaccharide. Polymerin was transformed into a potassium salt deglycosylated derivative, named KSDpolymerin, which was also characterized by chemical analysis, DRIFTS, and AAS. KSDpolymerin consisted of carbohydrates (6.00 mg 100(-1)), melanin (52.49 mg 100(-1)), and proteins (35.40 mg 100(-1)), and the composition of monosaccharides, phenols, and amino acids was determined. It also contained metals (6.11 mg 100(-1)), mainly K(+) and to a lesser extent Na(+), Ca(2+), Mg(2+), Zn(2+) and Fe(3+), bound as in polymerin. All the organic components were strongly linked in a supramolecular aggregate status and the relative average molecular size proved to be 6.3 kDa. Finally, we briefly discuss the possible use of such polymerins in agriculture as bioamendments and macro- and microelement biointegrators and as a biofilter for toxic metal removal, in light of their similarity with humic acids.


The role of effectors and host immunity in plant-necrotrophic fungal interactions.
Fungal diseases pose constant threats to the global economy and food safety. As the largest group of plant fungal pathogens, necrotrophic fungi cause heavy crop losses worldwide. The molecular mechanisms of the interaction between necrotrophic fungi and plants are complex and involve sophisticated recognition and signaling networks. Here, we review recent findings on the roles of phytotoxin and proteinaceous effectors, pathogen-associated molecular patterns (PAMPs), and small RNAs from necrotrophic fungi. We also consider the functions of damage-associated molecular patterns (DAMPs), the receptor-like protein kinase BIK1, and epigenetic regulation in plant immunity to necrotrophic fungi.


Phagotrophic protists preserve antibiotic-resistant opportunistic human pathogens in the vegetable phyllosphere.
Food safety of leafy greens is an emerging public health issue as they can harbor opportunistic human pathogens (OHPs) and expose OHPs to consumers. Protists are an integral part of phyllosphere microbial ecosystems. However, our understanding of protist-pathogen associations in the phyllosphere and their consequences on public health remains poor. Here, we examined phyllosphere protists, human pathogen marker genes (HPMGs), and protist endosymbionts from four species of leafy greens from major supermarkets in Xiamen, China. Our results showed that Staphylococcus aureus and Klebsiella pneumoniae were the dominant human pathogens in the vegetable phyllosphere. The distribution of HPMGs and protistan communities differed between vegetable species, of which Chinese chive possessed the most diverse protists and highest abundance of HPMGs. HPMGs abundance positively correlated with the diversity and relative abundance of phagotrophic protists. Whole genome sequencing further uncovered that most isolated phyllosphere protists harbored multiple OHPs which carried antibiotic resistance genes, virulence factors, and metal resistance genes and had the potential to HGT. Colpoda were identified as key phagotrophic protists which positively linked to OHPs and carried diverse resistance and virulence potential endosymbiont OHPs including Pseudomonas nitroreducens, Achromobacter xylosoxidans, and Stenotrophomonas maltophilia. We highlight that phyllosphere protists contribute to the transmission of resistant OHPs through internalization and thus pose risks to the food safety of leafy greens and human health. Our study provides insights into the protist-OHP interactions in the phyllosphere, which will help in food safety surveillance and human health.


Multibreed genomic prediction using multitrait genomic residual maximum likelihood and multitask Bayesian variable selection.
Genomic prediction is applicable to individuals of different breeds. Empirical results to date, however, show limited benefits in using information on multiple breeds in the context of genomic prediction. We investigated a multitask Bayesian model, presented previously by others, implemented in a Bayesian stochastic search variable selection (BSSVS) model. This model allowed for evidence of quantitative trait loci (QTL) to be accumulated across breeds or for both QTL that segregate across breeds and breed-specific QTL. In both cases, single nucleotide polymorphism effects were estimated with information from a single breed. Other models considered were a single-trait and multitrait genomic residual maximum likelihood (GREML) model, with breeds considered as different traits, and a single-trait BSSVS model. All single-trait models were applied to each of the 2 breeds separately and to the pooled data of both breeds. The data used included a training data set of 6,278 Holstein and 722 Jersey bulls, as well as 374 Jersey validation bulls. All animals had genotypes for 474,773 single nucleotide polymorphisms after editing and phenotypes for milk, fat, and protein yields. Using the same training data, BSSVS consistently outperformed GREML. The multitask BSSVS, however, did not outperform single-trait BSSVS, which used pooled Holstein and Jersey data for training. Thus, the rigorous assumption that the traits are the same in both breeds yielded a slightly better prediction than a model that had to estimate the correlation between the breeds from the data. Adding the Holstein data significantly increased the accuracy of the single-trait GREML and BSSVS in predicting the Jerseys for milk and protein, in line with estimated correlations between the breeds of 0.66 and 0.47 for milk and protein yields, whereas only the BSSVS model significantly improved the accuracy for fat yield with an estimated correlation between breeds of only 0.05. The relatively high genetic correlations for milk and protein yields, and the superiority of the pooling strategy, is likely the result of the observed admixture between both breeds in our data. The Bayesian model was able to detect several QTL in Holsteins, which likely enabled it to outperform GREML. The inability of the multitask Bayesian models to outperform a simple pooling strategy may be explained by the fact that the pooling strategy assumes equal effects in both breeds; furthermore, this assumption may be valid for moderate- to large-sized QTL, which are important for multibreed genomic prediction.


Dietary nucleotides and human immune cells. II. Modulation of PBMC growth and cytokine secretion.
The immune system is dependent on purines and pyrimidines as building blocks for DNA and RNA synthesis to enable rapid cell proliferation and protein synthesis. Emerging evidence suggests that dietary nucleotides optimize immune function. We investigated whether growth and function of human immune cells were affected by an exogenous source of nucleotides during specific antigen challenge. Peripheral blood mononuclear cells from healthy individuals (n = 10) were stimulated with influenza virus antigen and DNA-Na+ from fish soft roe, RNA from bakers yeast (Saccharomyces cerevisiae), 2'deoxyadenosine 5'-monophosphate sodium, 2'deoxycytidine 5'-monophosphate sodium, 2'deoxyguanosine 5'-monophosphate sodium, or 2'deoxyuridine 5'-monophosphate disodium. Growth effects were ascertained by measuring the amount of tritium-labeled Thymidine 5'-monophosphate sodium incorporated into cell DNA. Cell function was measured by detection of interferon-gamma (IFN-gamma), tumor necrosis factor-alpha, and interleukin-10 production. Specific nucleotide derivatives alone did not affect the growth of healthy peripheral blood mononuclear cells. However, the nucleotide derivatives influenced immune cell growth and cytokine secretion when cocultured with specific antigen. DNA, RNA, deoxyadenosine monophosphate, deoxycytidine monophosphate, and deoxyuridine monophosphate increased influenza virus antigen-induced immune cell proliferation. In contrast, deoxyadenosine monophosphate and thymosine monophosphate inhibited the antigen-induced growth response. RNA and deoxyadenosine monophosphate cocultured with virus antigen significantly increased peripheral blood mononuclear cell secretion of IFN-gamma, interleukin-10, and tumor necrosis factor-alpha. DNA increased virus antigen-induced immune cell secretion of IFN-gamma only, whereas deoxyuridine monophosphate significantly increased secretion of interleukin-10 only. Deoxyguanosine monophosphate completely inhibited virus-triggered IFN-gamma secretion, whereas thymosine monophosphate did not change the secretion pattern of measured cytokines. Nucleotide derivatives affect growth and function of specific virus antigen-stimulated human immune cells in vitro.


Psychological stress in adoptive parents of special-needs children.
This article focuses on the nature and extent of parental stress among adoptive parents of special-needs children. In-depth face-to-face interviews of adoptive parents of 35 children were conducted, on average, four months postplacement (but before adoption). One-year follow-up interviews were conducted with parents of 15 (43%) of these children. Qualitative and quantitative data were collected, including parenting stress scores. Results indicated higher than average levels of stress, particularly on subscales related to parent-child dysfunctional interactions and to raising a difficult child. Increased stress levels were associated with poorer family adjustment and with higher levels of child behavior problems. Stress levels remained mostly unchanged over the year. Responses to open-ended questions identified five stress categories: child characteristics, parent-child interactions, family cohesion, parental adjustment, and adoptions service issues. Practice and research implications are discussed.


[The cytological status of the nasal mucosa and the buccal epithelium in coal miners].
Sixty-four persons were examined. The examination was undertaken to study the cytomophological parameters of the cells of the nasal mucosa and the buccal epithelium in coal miners. Group 1 consisted of 18 donors without contact with industrial dust; Group 2 comprised 24 apparently healthy miners; Group 3 included 22 workers (drift miners) with Stage 1 anthracosilicosis, grade 1 respiratory failure. The patients with Stage 1 anthracosilicosis had noticeably worse morphofunctional characteristics of the epithelium that displayed extensive fields with pronounced structural changes, such as destruction and desquamation of the integumentary epithelium of the nasal mucosa. Nasal mucosal atrophic changes were observed in 50% of the examined miners. Examination of the buccal epithelium in apparently healthy miners (code 0) and in workers with Stage I anthracosilicosis revealed the increased proportion of microfloral (Streptococcus) contamination by 79% and 3.7 times, respectively.


Episodic twice-daily treatment for recurrent genital herpes.
A new dosage regimen of orally administered acyclovir, 800 mg twice daily for five days, for the treatment of recurrent genital herpes was compared with the standard dosage of 200 mg given five times per day. A double-blind study of 157 patients was used to evaluate the safety and efficacy of both regimens. The new regimen was well tolerated, more convenient, and as effective as the standard dosage. In male patients, the new regimen may be more effective than the standard regimen of 200 mg given five times per day to treat lesions that are already present.


Implications of dominance hierarchy on hummingbird-plant interactions in a temperate forest in Northwestern Mexico.
The structuring of plant-hummingbird networks can be explained by multiple factors, including species abundance (i.e., the neutrality hypothesis), matching of bill and flower morphology, phenological overlap, phylogenetic constraints, and feeding behavior. The importance of complementary morphology and phenological overlap on the hummingbird-plant network has been extensively studied, while the importance of hummingbird behavior has received less attention. In this work, we evaluated the relative importance of species abundance, morphological matching, and floral energy content in predicting the frequency of hummingbird-plant interactions. Then, we determined whether the hummingbird species' dominance hierarchy is associated with modules within the network. Moreover, we evaluated whether hummingbird specialization (d') is related to bill morphology (bill length and curvature) and dominance hierarchy. Finally, we determined whether generalist core hummingbird species are lees dominant in the community. We recorded plant-hummingbird interactions and behavioral dominance of hummingbird species in a temperate forest in Northwestern Mexico (El Palmito, Mexico). We measured flowers' corolla length and nectar traits and hummingbirds' weight and bill traits. We recorded 2,272 interactions among 13 hummingbird and 10 plant species. The main driver of plant-hummingbird interactions was species abundance, consistent with the neutrality interaction theory. Hummingbird specialization was related to dominance and bill length, but not to bill curvature of hummingbird species. However, generalist core hummingbird species (species that interact with many plant species) were less dominant. The frequency of interactions between hummingbirds and plants was determined by the abundance of hummingbirds and their flowers, and the dominance of hummingbird species determined the separation of the different modules and specialization. Our study suggests that abundance and feeding behavior may play an important role in North America's hummingbird-plant networks.


[An innovative laser for the minimally invasive treatment of benign prostatic hyperplasia].
In an aging population, the number of patients suffering from benign prostatic hyperplasia is increasing. Furthermore, this older part of the population often bears multiple co-morbidities requiring permanent anticoagulation or antiaggregration medication. This has led to encourage the development of new surgical techniques. Photovaporization of the prostate (PVP) in particular provides improved hemostasis, and allow to operate patients without interrupting anticoagulation therapy. Functional results of PVP with a medium-term followup are similar to the current standards of transurethral resection of the prostate (TURP). Finally, PVP allows a significantly shorter hospital stay than TURP.


Pseudolipasin A is a specific inhibitor for phospholipase A2 activity of Pseudomonas aeruginosa cytotoxin ExoU.
A number of bacterial pathogens utilize the type III secretion pathway to deliver effector proteins directly into the host cell cytoplasm. Certain strains of Pseudomonas aeruginosa associated with acute infections express a potent cytotoxin, exoenzyme U (ExoU), that is delivered via the type III secretion pathway directly into contacting host cells. Once inside the mammalian cell, ExoU rapidly lyses the intoxicated cells via its phospholipase A(2) (PLA(2)) activity. A high-throughput cell-based assay was developed to screen libraries of compounds for those capable of protecting cells against the cytotoxic effects of ExoU. A number of compounds were identified in this screen, including one group that blocks the intracellular activity of ExoU. In addition, these compounds specifically inhibited the PLA(2) activity of ExoU in vitro, whereas eukaryotic secreted PLA(2) and cytosolic PLA(2) were not inhibited. This novel inhibitor of ExoU-specific PLA(2) activity, named pseudolipasin A, may provide a new lead for virulence factor-based therapeutic design.


Physiologically-based modelling in mice suggests an aggravated loss of clearance capacity after toxic liver damage.
Diseases and toxins may lead to death of active liver tissue, resulting in a loss of total clearance capacity at the whole-body level. However, it remains difficult to study, whether the loss of metabolizing tissue is sufficient to explain loss of metabolic capacity of the liver or whether the surviving tissue undergoes an adaptive response to compensate the loss. To understand the cellular impact of toxic liver damage in an in vivo situation, we here used physiologically-based pharmacokinetic modelling to investigate pharmacokinetics of a specifically designed drug cocktail at three different sampling sites of the body in healthy mice and mice treated with carbon tetrachloride (CCl4). Liver zonation was explicitly quantified in the models through immunostaining of cytochrome P450s enzymes. Comparative analyses between the simulated decrease in clearance capacity and the experimentally measured loss in tissue volume indicated that CCl4-induced impairment of metabolic functions goes beyond the mere loss of metabolically active tissue. The here established integrative modelling strategy hence provides mechanistic insights into functional consequences of toxic liver damage in an in vivo situation, which would not have been accessible by conventional methods.


Molecular Mechanisms of Cardiomyocyte Death in Drug-Induced Cardiotoxicity.
Homeostatic regulation of cardiomyocytes plays a crucial role in maintaining the normal physiological activity of cardiac tissue. Severe cardiotoxicity results in cardiac diseases including but not limited to arrhythmia, myocardial infarction and myocardial hypertrophy. Drug-induced cardiotoxicity limits or forbids further use of the implicated drugs. Such drugs that are currently available in the clinic include anti-tumor drugs (doxorubicin, cisplatin, trastuzumab, etc.), antidiabetic drugs (rosiglitazone and pioglitazone), and an antiviral drug (zidovudine). This review focused on cardiomyocyte death forms and related mechanisms underlying clinical drug-induced cardiotoxicity, including apoptosis, autophagy, necrosis, necroptosis, pryoptosis, and ferroptosis. The key proteins involved in cardiomyocyte death signaling were discussed and evaluated, aiming to provide a theoretical basis and target for the prevention and treatment of drug-induced cardiotoxicity in the clinical practice.


A molecular dynamics and computational study of ligand docking and electron transfer in ferritins.
The mechanism of the reductive release of iron from the cavity of the iron storage protein, ferritin, has been difficult to confirm on the molecular level using experimental studies. In this paper, we use a variety of computational tools to study the binding of flavin redox agents to the protein surface, and the subsequent electron transfer (ET) through the protein coat. Flavin binding sites are identified that represent efficient routes to reduction of Fe(III) across the protein coat in human and bacterial ferritins. Using the pathways model and Dutton's packing density model, we show that ET across the protein coat to nucleation sites is feasible. Different protein configurations for human heavy and light chain ferritin were obtained along classical molecular dynamics trajectories and used for flavin binding and ET studies. We find that protein configuration affects both the binding and ET rate constants significantly. We show that the maximum possible ET rate constants to the nucleation site GLU-61 in human heavy chain ferritin for protein configurations along a MD simulation trajectory can differ by about 8 orders of magnitude compared to the crystal structure and in human light-chain ferritin rate constants vary by about 4 orders of magnitude.


Detection of antibodies to 35 kD determinant of M. leprae in urine and serum of leprosy patients.
Urine and serum samples from 67 subjects comprising 55 active cases of different types of leprosy and 12 normal controls were subjected to monoclonal antibody based urine antibody competition test (UACT) and serum antibody competition test (SACT) respectively. It was possible to demonstrate M. leprae specific antibodies in the urine of 50% of the seropositive subjects. Urine antibody positivity was observed to the extent of 52% in BL/LL subjects, 50% in BB and 43% in TT/BT types of leprosy.


Extraordinary N atom tunneling in formation of InN shell layer on GaN nanorod m-plane sidewall.
We report the extraordinary tunneling process that finds the lower cohesive energy route for stablizing InN shell layer on m-plane sidewall of GaN nanorod. The [0001] orientated GaN nanorod array is grown on sapphire substrate patterned with Ga nanoparticle by metal-organic vapor deposition method, based on which the simulation structures of c-plane top surface and m-plane sidewall surface is constructed for the first-principles calculations. The results show that the introduction of In wetting monolayer could effectively lower the cohesive energy of adalayers on non-polar GaN surfaces. Most importantly, it is revealed that there exists an extraordinary tunneling process in which the N atoms will drag out the In wetting atoms and tunnel through to form stable InN shell layer on the nanorod sidewall.


Strain-blood pressure index for evaluation of early changes in elasticity of anterior tibial artery in patients with type 2 diabetes mellitus.
The aim of this study was to investigate the feasibility and value of strain-blood pressure index (SBPI) to assess early changes in elasticity of anterior tibial artery in patients with type 2 diabetes mellitus (T2DM). Eighty-one randomly selected in-patients with T2DM were divided into 2 groups--a vascular complication negative group (n=42) and a vascular complication positive group (n=39). Forty healthy volunteers were enrolled in a control group. Ultrasonographic scans using Xstrain™ technique were conducted for every patient to obtain the maximum circumferential strain (CSmax) of anterior tibial artery; patient blood pressure was also measured for calculating strain-blood pressure index (SBPI=CSmax/[(local pulse pressure)/local diastolic blood pressure] ×100%. Afterwards, SBPIs of various groups were comparatively analyzed. Differences in SBPIs among the 3 groups were statistically significant (control group > negative group > positive group, P<0.05). SBPI could be used as a new indicator for the evaluation on the anterior tibial arterial elasticity of T2DM patients and it was able to reflect the early elasticity changes in anterior tibial arteries in T2DM patients with atherosclerosis.


Divergence of estimated fetal weight and birth weight in singleton fetuses.
To evaluate differences in distribution of estimated fetal weight (EFW) and birth weight (BW) of ongoing fetuses and neonates of the same gestational age. Reference curves for EFW (Hadlock BPD-HC-AC-FL formula, N = 1191) and BW (N = 1036) in singleton pregnancies from 24+0 to 40+6 gestational weeks were calculated. Multiple pregnancies, fetuses with major or multiple abnormalities or syndromes and iatrogenic preterm deliveries due to preeclampsia or abnormal fetal Doppler were excluded. The standardized residuals for EFW and BW were calculated and compared. EFW and BW can be accurately described by quadratic equations (R2 = 0.944 and 0.807, respectively). The distribution of standardized residuals for BW using the EFW formula was negative from 28+0 to 35+6 weeks. The 50th and 5th centiles of BW were lower than those of EFW throughout prematurity, and they converged at approximately 38 gestational weeks. The 5th centile for BW was 30% lower than the 5th centile for EFW at 27 weeks, 27.5% lower at 30 weeks and 19.4% at 34 weeks. Preterm infants have lower BW distribution compared to the expected EFW of ongoing pregnancies of the same gestational age, supporting the concept of hidden intrauterine morbidity for a proportion of these infants.


Bond strength of self-etch adhesives after saliva contamination at different application steps.
This study evaluated and compared the effect of saliva contamination and possible decontamination methods on bond strengths of two self-etching adhesive systems (Clearfil SE Bond [CSE], Optibond Solo Plus SE [OSE]). Flat occlusal dentin surfaces were created on 180 extracted human molar teeth. The two bonding systems and corresponding composite resins (Clearfil AP-X, Kerr Point 4) were bonded to the dentin under six surface conditions (n=15/group): group 1 (control): primer/bonding/composite; group 2: saliva/drying/primer/bonding/composite; group 3: primer/saliva/rinsing/drying/primer/bonding/composite; group 4: primer/saliva/rinsing/drying/bonding/composite; group 5: primer/bonding (cured)/saliva/rinsing/drying/primer/bonding/composite; group 6: primer/bonding (cured)/saliva/removing contaminated layer with a bur/rinsing/drying/primer/bonding/composite. Shear bond strength was tested after specimens were stored in distilled water at 37°C for 24 hours. One-way analysis of variance and Tukey post hoc tests were used for statistical analyses. For CSE, groups 2, 3, and 4 and for OSE, groups 6, 2, and 4 showed significantly lower bond strengths than the control group (p<0.05). CSE groups 5 and 6 and OSE groups 3 and 5 revealed bond strengths similar to the control. When saliva contamination occurred after light polymerization of the bonding agent, repeating the bonding procedure recovered the bonding capacity of both self-etch adhesives. However, saliva contamination before or after primer application negatively affected their bond strength.


[Clinical feature and genetic analysis of a family affected by congenital bile acid synthesis defect type 2: identification of 2 novel mutations in AKR1D1 gene].
Congenital bile acid synthesis defect type 2 (CBAS2) is an autosomal recessive disorder caused by biallelic mutations of AKR1D1 gene, which encodes the Δ4-3-oxo-steroid 5β-reductase. Cholestatic jaundice is the main clinical manifestation, accompanied by malabsorption of fat and fat-soluble vitamins. This paper reported the clinical and genetic features of a CBAS2 patient definitely diagnosed by AKR1D1 genetic analysis. An 8-month-old male infant was referred to the hospital with the complaint of jaundiced skin and sclera over 7 months. On physical examination, growth retardation and malnutrition were discovered besides mild jaundice of the skin and sclera. The liver was palpable 8 cm below the right subcostal margin with medium texture, and the spleen was not enlarged. On liver function test, elevated levels of bilirubin (predominantly conjugated bilirubin) and transaminases were detected, but serum total bile acids and γ-glutamyl transpeptidase levels were within the normal ranges. Liver histopathologic analysis showed disorganized bile ducts, obvious multinucleated giant cells, significant cholestasis in hepatocytes, together with portal and interstitial fibrosis and lymphocytic infiltration. Via next generation sequencing analysis and Sanger sequencing confirmation, the infant proved to be a compound heterozygote of the AKR1D1 variants c.579+2delT and c.853C>T(p.Q285X), two novel mutations originated from his mother and father, respectively. CBAS2 was thus definitely diagnosed, and chenodeoxycholic acid was given orally. As a result, the abnormal liver function and hepatomegaly were improved gradually. On a follow-up 3 months later, a soft liver was palpable 2.5 cm below the right subcostal margin, and all liver function indices recovered to normal ranges.


[Where there's a Will, there's a Way? A nationwide Online-Survey of Psychiatrists about the Use of Alternatives to Coercive Measures].
A series of legal regulations on the use of coercive measures in psychiatry initiated a vivid medico-ethical debate during the last year. The changed legal bases now require the use of alternatives before applying coercion as a "last resort". In this study we investigated whether and which alternatives are applied by psychiatrists in order to prevent coercive measures in general psychiatric hospitals and which factors are associated with their application. A sample of 343 psychiatrists was recruited by contacting psychiatric hospitals throughout Germany. In an online-survey attitudes to coercive measures and the use of alternatives to coercion were assessed by self-report. Before initiating their most recent coercive measures almost half (46%) of the participants employed only 2 or less alternatives. Patient related, individual and structural factors were reported as reasons for the failure of such measures. The use of alternatives was associated with a more positive assessment of their effectiveness as well as a more negative attitude towards coercive measures. Alternative measures are applied by many psychiatrists, but are not standard practice. Thus, there is a considerable room for improved practice.


Polyreactive IgM initiates complement activation by PF4/heparin complexes through the classical pathway.
The mechanisms by which exposure to heparin initiates antibody responses in many, if not most, recipients are poorly understood. We recently demonstrated that antigenic platelet factor 4 (PF4)/heparin complexes activate complement in plasma and bind to B cells. Here, we describe how this process is initiated. We observed wide stable variation in complement activation when PF4/heparin was added to plasma of healthy donors, indicating a responder "phenotype" (high, intermediate, or low). Proteomic analysis of plasma from these healthy donors showed a strong correlation between complement activation and plasma immunoglobulin M (IgM) levels (r = 0.898; P < .005), but not other Ig isotypes. Complement activation response to PF4/heparin in plasma displaying the low donor phenotype was enhanced by adding pooled IgM from healthy donors, but not monoclonal IgM. Depletion of IgM from plasma abrogated C3c generation by PF4/heparin. The complement-activating features of IgM are likely mediated by nonimmune, or natural, IgM, as cord blood and a monoclonal polyreactive IgM generate C3c in the presence of PF4/heparin. IgM facilitates complement and antigen deposition on B cells in vitro and in patients receiving heparin. Anti-C1q antibody prevents IgM-mediated complement activation by PF4/heparin complexes, indicating classical pathway involvement. These studies demonstrate that variability in plasma IgM levels correlates with functional complement responses to PF4/heparin. Polyreactive IgM binds PF4/heparin, triggers activation of the classical complement pathway, and promotes antigen and complement deposition on B cells. These studies provide new insights into the evolution of the heparin-induced thrombocytopenia immune response and may provide a biomarker of risk.


Optometric manpower in the Commonwealth of Puerto Rico: estimates and projections, 1982-2025.
The 1982 study investigated the potential impact of the IAUPR School of Optometry on the adequacy of supply of optometrists in Puerto Rico for the years of 1980-2000. This article is designed to: (1) update the 1982 study; (2) appraise the accuracy of the 1982 projections; (3) re-evaluate the status of optometric manpower in Puerto Rico through the year 2025; and (4) provide the School of Optometry with information necessary to make informed judgments about future enrollments. Estimates of supply are based on data from the Colegio de Optometras de Puerto Rico, the Sección de Oftalmología de la Asociación Médica de Puerto Rico, and the enrollment and graduation registries from the School of Optometry. Requirements are based on estimates of annual effective demand, provider-to-population ratios, per capita demand, and optometric productivity. Optometrists comprised 52.2% of Puerto Rico's actively practicing vision care manpower in 1995, with a mean optometrist-to-population ratio of 8.2 per 100,000. The number ranged from 28 in Mayagüez to 107 in San Juan. Under different assumptions regarding supply, productivity, and demand, surpluses and deficits are estimated and projected for the years 1995 to 2025. Depending on the assumptions used, an undersupply or an oversupply of optometrists may be found in Puerto Rico, currently and in the future. Projections of supply and demand predict a considerable range--from a surplus of 961 optometrists to a deficit of 2,085 optometrists in the year 2025.


Aspirin compared with acetaminophen in the treatment of fever and other symptoms of upper respiratory tract infection in adults: a multicenter, randomized, double-blind, double-dummy, placebo-controlled, parallel-group, single-dose, 6-hour dose-ranging study.
Aspirin (acetylsalicylic acid) and acetaminophen (paracetamol) are frequently used to treat fever and other symptoms of upper respiratory tract infection (URTI). Both are available over the counter for use at the standard recommended doses of 500 and 1000 mg per single use. This study investigated the efficacy, safety profiles, and tolerability of aspirin 500 and 1000 mg and acetaminophen 500 and 1000 mg compared with placebo in adult patients with acute febrile URTI of suspected viral origin. This was a multicenter, randomized, double-blind, double-dummy, placebo-controlled, parallel-group trial conducted in Ukraine and Russia. Patients with URTI and acute fever of > or =38.5 degrees C received a single dose of aspirin 500 or 1000 mg, acetaminophen 500 or 1000 mg, or matching placebo. Oral body temperature was measured in the clinic at specified time points up to 6 hours after dosing. The intensity of other symptoms of URTI was rated by patients at baseline and at 2, 4, and 6 hours after dosing (scale from 0 = none to 10 = severe). The primary efficacy measure was the AUC for the change in orally measured body temperature from the time of treatment (baseline) to 4 hours after dosing. Secondary outcome measures included the change in body temperature from baseline to specified time points between 0.5 and 6 hours after dosing, the difference between baseline and the lowest measured body temperature, the time to the lowest measured body temperature, and the intensity of other symptoms of URTI (ie, headache, sinus sensitivity to percussion, sore throat, achiness, and feverish discomfort). Tolerability was monitored by recording of adverse events. Three hundred ninety-two patients were enrolled (78 in both aspirin groups, 79 in both acetaminophen groups, 78 in the placebo group). Demographic and baseline characteristics were comparable in the 5 groups; 51% of patients were male, with a mean age of 37.4 years and a mean body weight of 74.3 kg. The AUC values for the change in body temperature 0 to 4 hours after dosing were 3.18 (95% CI, 2.78-3.57) for aspirin 500 mg, 4.26 (95% CI, 3.84-4.68) for aspirin 1000 mg, 3.13 (95% CI, 2.77-3.49) for acetaminophen 500 mg, 4.11 (95% CI, 3.73-4.49) for acetaminophen 1000 mg, and 0.76 (95% CI, 0.38-1.13) for placebo. In terms of the primary efficacy variable, all active treatments were significantly superior to placebo (P < 0.001, 1-sided t test), with no significant differences between them. Reductions in body temperature were significantly greater with the 1000-mg doses of both active treatments compared with the 500-mg doses (P< 0.001, 1-sided t test). The mean maximum temperature reductions were 1.32 degrees C, 1.25 degrees C, 1.67 degrees C,1.71 degrees C, and 0.63 degrees C in the respective treatment groups. Significant reductions were seen in the mean intensity of headache, achiness, and feverish discomfort with all active treatments at most time points (P < 0.001), but not in sinus sensitivity to percussion or sore throat. All treatments were equally well tolerated, and no clinically significant adverse events occurred. In this single-dose study, aspirin 500 and 1000 mg and acetaminophen 500 and 1000 mg were more effective against fever and other symptoms of URTI than placebo. Both active treatments showed dose-related efficacy, and there was no significant difference between equal doses of the 2 agents. Safety profiles and tolerability were also comparable between treatments.


A comparative study of nutrient intakes of migrant and Australian children in Western Australia.
Little is known about the dietary patterns and nutrient intakes of preschool children in Australia. A study was undertaken in Perth on Australian and migrant children to obtain information on preschool diets. It was found that, although the mean nutrient intakes in both groups were adequate, some individual migrant national groups showed deficiencies of one or more nutrients. Many children were obtaining excessive calories and protein. The consumption of "empty calorie" foods was also high. In order to find different ways to teach good principles and practice of nutrition, the types of media which might influence parents were studied. It was considered that television and, to a lesser degree, radio were media which might exert a considerable effect if they were used to the best advantage. These forms of communication particularly were of potential value, as some migrant parents could not read English and some were illiterate. A positive nutrition education programme to combat commerical food advertising of "empty calorie" foods is recommended.


Bacterial leakage in root canals filled with resin-based and mineral trioxide aggregate-based sealers.
Sealing ability is one of the most important features of endodontic sealers. The purpose of this in vitro study was to compare the sealing ability of a resin-based sealer with a mineral trioxide aggregate-based sealer. A total of 60 single-rooted extracted human teeth were randomly divided into two experimental groups (n = 25) and two control groups (n = 5). After canal preparation and smear layer removal, both groups were obturated with gutta-percha and sealer. Resin-based AH26 sealer was used in the first group and Fillapex(®) sealer in the second group. Two layers of nail varnish were applied on tooth surfaces except for the apical 2 mm. In the negative control group, nail varnish was applied on the entire surface. The teeth were mounted according to Lima et al. study and then sterilized by ethylene oxide gas. The samples were evaluated for bacterial microleakage using Enterococcus faecalis (ATCC 29212) for 90 days. Data were analyzed by survival test (P < 0.05). Control groups had either immediate leakage or no leakage. The Fillapex(®) showed significantly higher amounts of microleakage compared with AH26 sealer (P < 0.05) and both groups exhibited significant differences in comparison with control groups. Both sealers had bacterial leakage. Sealing ability of AH26 was significantly higher than that of Fillapex(®).


Intraisolate mitochondrial genetic polymorphism and gene variants coexpression in arbuscular mycorrhizal fungi.
Arbuscular mycorrhizal fungi (AMF) are multinucleated and coenocytic organisms, in which the extent of the intraisolate nuclear genetic variation has been a source of debate. Conversely, their mitochondrial genomes (mtDNAs) have appeared to be homogeneous within isolates in all next generation sequencing (NGS)-based studies. Although several lines of evidence have challenged mtDNA homogeneity in AMF, extensive survey to investigate intraisolate allelic diversity has not previously been undertaken. In this study, we used a conventional polymerase chain reaction -based approach on selected mitochondrial regions with a high-fidelity DNA polymerase, followed by cloning and Sanger sequencing. Two isolates of Rhizophagus irregularis were used, one cultivated in vitro for several generations (DAOM-197198) and the other recently isolated from the field (DAOM-242422). At different loci in both isolates, we found intraisolate allelic variation within the mtDNA and in a single copy nuclear marker, which highlighted the presence of several nonsynonymous mutations in protein coding genes. We confirmed that some of this variation persisted in the transcriptome, giving rise to at least four distinct nad4 transcripts in DAOM-197198. We also detected the presence of numerous mitochondrial DNA copies within nuclear genomes (numts), providing insights to understand this important evolutionary process in AMF. Our study reveals that genetic variation in Glomeromycota is higher than what had been previously assumed and also suggests that it could have been grossly underestimated in most NGS-based AMF studies, both in mitochondrial and nuclear genomes, due to the presence of low-level mutations.


Differential processing of autoantigens in lysosomes from human monocyte-derived and peripheral blood dendritic cells.
Dendritic cells (DC) initiate immunity and maintain tolerance. Although in vitro-generated DC, usually derived from peripheral blood monocytes (MO-DC), serve as prototype DC to analyze the biology and biochemistry of DC, phenotypically distinct primary types of DC, including CD1c-DC, are present in peripheral blood (PB-DC). The composition of lysosomal proteases in PB-DC and the way their MHC class II-associated Ag-processing machinery handles a clinically relevant Ag are unknown. We show that CD1c-DC lack significant amounts of active cathepsins (Cat) S, L, and B as well as the asparagine-specific endopeptidase, the major enzymes believed to mediate MHC class II-associated Ag processing. However, at a functional level, lysosomal extracts from CD1c-DC processed the multiple sclerosis-associated autoantigens myelin basic protein and myelin oligodendrocyte glycoprotein in vitro more effectively than MO-DC. Although processing was dominated by CatS, CatD, and asparagine-specific endopeptidase in MO-DC, it was dominated by CatG in CD1c-DC. Thus, human MO-DC and PB-DC significantly differ with respect to their repertoire of active endocytic proteases, so that both proteolytic machineries process a given autoantigen via different proteolytic pathways.


Is employer coverage of elective egg freezing coercive?: a survey of medical students' knowledge, intentions, and attitudes towards elective egg freezing and employer coverage.
The purpose of this study was to understand medical students' knowledge, intentions, and attitudes towards oocyte cryopreservation and employer coverage of such treatment. This cross-sectional study was performed via an online cross-sectional survey distributed to 280 female medical students from March through August 2016. Demographics, attitudes towards employer coverage, and factors influencing decision-making were assessed via a self-reported multiple-choice questionnaire. The relationship between respondents' attitudes towards employer coverage and other parameters was analyzed. A total of 99 responses were obtained out of 280 female medical students. Most respondents (71%) would consider oocyte cryopreservation (potential freezers), although 8% would not consider the procedure and 21% were unsure. Seventy-six percent of respondents felt pressure to delay childbearing. Potential freezers were more likely to be single (p = 0.001), to report feeling pressure to delay childbearing (p = 0.016), and to consider egg freezing if offered by an employer (p < 0.001). Importantly, 71% percent did not view employer coverage as coercive and 77% of respondents would not delay childbearing due to employer coverage. Factors influencing decision-making in potential freezers were absence of a suitable partner (83%), likelihood of success (95%), and health of offspring (94%), among others. Knowledge about the low chance of pregnancy per oocyte (6-10%) would influence decision-making in 42% of potential freezers. Oocyte freezing is an acceptable strategy for the majority of young women surveyed. Pressure to delay childbearing was related to openness to freeze eggs. The majority of respondents did not find employer coverage for egg freezing coercive although further research is needed with larger, representative samples to ascertain the relationship between pressure to delay childbearing due to work demands and employer coverage for egg freezing.