Impacts of national surveillance for uncommon conditions in childhood.
The Australian Paediatric Surveillance Unit (APSU) facilitates the conduct of national collaborative research that is consistent with national health priorities, has potential to impact on public health, and addresses gaps in knowledge. Since 1993 paediatricians and other child health specialists have contributed monthly data on rare childhood conditions to the APSU. Over 40 conditions, including infectious diseases, injuries, vaccine-preventable diseases and genetic disorders have been studied. Information on epidemiology, frequency, diagnosis, management and short-term outcomes of these conditions is collected and provides evidence to support changes to clinical practice, prevention policy and allocation of health resources. In this review we give examples of the value of information gathered through the APSU surveillance system in the last 14 years.


Pattern recognition receptors involved in the inflammatory attenuating effects of soybean isoflavone in β-amyloid peptides 1-42 treated rats.
Pattern recognition receptors (PRRs) play important roles in the inflammatory responses to Alzheimer's disease (AD). Our previous study indicated that soybean isoflavone (SIF) exhibited anti-inflammatory effect in rats treated by β-amyloid peptides1-42 (Aβ1-42). In present study, we further detected the effects of SIF against inflammation caused by Aβ1-42 treatment in rats. Serum inflammatory mediators and neurotrophic factors including transforming growth factor-β (TGF-β), inducible nitric oxide synthase (iNOS), brain-derived neurotrophic factor (BDNF) and S100β were detected by enzyme-like immunosorbent assay (ELISA). Reverse transcription-polymerase chain reaction (RT-PCR) and western blot methods were applied for detecting mRNA and protein expression of interleukin-1β (IL-1β), iNOS, tumor necrosis factor-α (TNF-α), TGF-β, BDNF, S100β, myeloid differentiation factor88 (Myd88), Toll-like receptor2 (TLR2), formyl peptide receptors (FPRs), inhibitor κB kinase (IKK) and inhibitor κB-α (IκB-α) in rat's brain tissue. Our results indicated that SIF could reduce the production of IL-1β, TNF-α and iNOS induced by Aβ1-42 in serum and brain of rats. SIF also significantly reversed Aβ1-42-induced up-regulation of TLR2, FPR, Myd88, IKK and decreased IκB-α mRNA and protein expressions in rats. These results suggested that TLR2 and FPR might involve in the inflammatory process induced by Aβ1-42 treatment, and SIF was an efficiency compound in reversing the inflammation caused by Aβ1-42 treatment.


[In vitro susceptibility of Trichomonas vaginalis to metronidazole, ornidazole and proton pump inhibitors pantoprazole and esomeprazole].
The current treatment of trichomoniasis is based on the use of 5-nitroimidazole derivatives. Although metronidazole is reliable, inexpensive and highly effective against anaerobic microorganisms and protozoa, the development of metronidazole-resistant T.vaginalis strains pose to an increasing problem. Nitroimidazoles are compounds having azomycin (2-nitroimidazole) chemical structure and are obtained from Streptomyces strains. Benzimidazole, which is found in the structure of proton pump inhibitors, is also present in the other components that have antiprotozoal activity. In this study, the in vitro susceptibility of T.vaginalis against metronidazole, ornidazole, and the proton pump inhibitors which are tested recently as antiprotozoal agents; pantoprazole and esomeprazole was investigated. For this purpose a clinical T.vaginalis strain which was formerly isolated and stored after cryopreservation process in our laboratory was used. Minimum inhibitory concentration (MIC) and minimum lethal concentration (MLC) values of those agents against to this strain were determined in vitro by dilution method in 24-well cell culture plates. Trypticase yeast extract maltose medium, horse serum and antibiotic (penicillin + streptomycin) were distributed to each well of cell culture plates and after metronidazole, ornidazole, pantoprazole and esomeprazole solutions were added to two wells for each as 800, 400, 200, 100, 50 and 25 µg/ml, followed by the addition of 1 ml 5x10(3) T.vaginalis trophozoites into each well. Plates were incubated at 37°C, and viability and motility of the trophozoites were evaluated under light microscope at 24, 48 and 72 hours after incubation. MIC and MLC values of metronidazole/ornidazole in the 72(th) hour were found as 50 µg/ml and 100 µg/ml, respectively. MIC and MLC values for pantoprazole in the 72th hour were 200 µg/ml and 400 µg/ml, while the values for esomeprazole were 400 µg/ml ve 800 µg/ml, respectively. As a result, T.vaginalis strain used in the study was susceptible to metronidazole and ornidazole, besides, it was considered that pantoprazole and esomeprazole were also effective to the parasite and could be used as alternative drugs. However, further in vitro and clinical studies are clearly needed on the antiprotozoal effects of proton pump inhibitors. To our knowledge, this study was the first in literature, which esomeprazole's susceptibility on T.vaginalis was investigated in vitro.


One percent alendronate and aloe vera gel local host modulating agents in chronic periodontitis patients with class II furcation defects: A randomized, controlled clinical trial.
Alendronate (ALN) has antiresorptive and osteostimulative properties. The major component of aloe vera (AV) gel is acemannan, which has been found to have osteogenic properties. The aim of the present study is to explore the effectiveness of 1% ALN and AV gel as an adjunct to scaling and root planing (SRP) in chronic periodontitis patients with class II furcation defects. Ninety volunteers were randomly assigned to three treatment groups: (a) SRP plus placebo gel; (b) SRP plus 1% ALN gel; and (c) SRP plus AV gel. Clinical and radiographic parameters were recorded at baseline and at 6 and 12 months. The mean probing depth reduction and relative horizontal clinical attachment level (CAL) and relative vertical CAL gains were greater in the ALN group than in the AV and placebo groups at 6 and 12 months. Furthermore, a significantly greater mean percentage of defect depth reduction (DDR) was found in the ALN group (38.09 ± 9.53, 44.86 ± 6.29) than the AV groups (11.94 ± 15.10, 14.59 ± 25.49) at 6 and 12 months, respectively. ALN showed significant improvement in all clinical parameters, along with greater DDR, compared to AV in the treatment of class II furcation defects as an adjunct to SRP.


[Study of the penicillinase of the plague microbe, the synthesis of which is determined by the R-episome].
Penicillinase produced by a culture of the plague microbe with episomic resistance to benzylpenicillin was isolated and purified. Comparative investigation of the substrate spectrum, Michaelis constant and antigenic properties of the enzymes from the plague and dysentery microbes (R-factor donor) showed that transfer of the R-episome to the new host did not affect the investigated properties of penicillinase the synthesis of which was controlled by this episome.


Static and dynamic pressure-volume curves reflect different aspects of respiratory system mechanics in experimental acute respiratory distress syndrome.
A lower inflection point, an upper inflection (or deflection) point, and respiratory system compliance can be estimated from an inspiratory static pressure-volume (SPV) curve of the respiratory system. Such data are often used to guide selection of positive end-expiratory pressure (PEEP)/tidal volume combinations. Dynamic pressure-volume (DPV) curves obtained during tidal ventilation are effortlessly displayed on modern mechanical ventilator monitors and bear a theoretical but unproven relationship to the more labor-intensive SPV curves. Attempting to relate the SPV and DPV curves, we assessed both curves under a range of conditions in a canine oleic acid lung injury model. Five mongrel dogs were anesthetized, paralyzed, and monitored to assure a stable preparation. Acute lung injury was induced by infusing oleic acid. SPV curves were constructed by the super-syringe method. DPV curves were constructed for a range of PEEP and inspiratory constant flow settings while ventilating at a frequency of 15 breaths/min and tidal volume of 350 mL. Functional residual capacity at PEEP = 0 cm H2O was measured by helium dilution. The change in lung volume by PEEP at 8, 16, and 24 cm H2O was measured by respiratory inductance plethysmography. The slope of the second portion of the DPV curve did not parallel the corresponding slope of the SPV curve. The mean lower inflection point of the SPV curve was 13.2 cm H2O, whereas the lower inflection point of the DPV curve was related to the prevailing flow and PEEP settings. The absolute lung volume during the DPV recordings exceeded (p < 0.05) that anticipated from the SPV curves by (values are mean +/- SEM) 267 +/- 86 mL, 425 +/- 129 mL, and 494 +/- 129 mL at end expiration for PEEP = 8, 16, and 24 cm H2O, respectively. The contours of the SPV curve are not reflected by those of the DPV curve in this model of acute lung injury. Therefore, this study indicates that DPV curve should not be used to guide the selection of PEEP/tidal volume combinations. Furthermore, an increase in end-expiratory lung volume occurs during tidal ventilation that is not reflected by the classical SPV curve, suggesting a stable component of lung volume recruitment attributable to tidal ventilation, independent of PEEP.


Paradoxical insulin-induced increase in gluconeogenesis in response to prolonged hypoglycemia in conscious dogs.
The aim of this study was to determine the effects of differing insulin concentrations on the gluconeogenic response to equivalent prolonged hypoglycemia. Insulin was infused intraportally, for 3 h, into normal 18-h fasted conscious dogs at 2 (lower, n = 6) or 8 mU.kg-1.min-1 (high, n = 7) on separate occasions. This resulted in steady-state arterial insulin levels of 80 +/- 8 and 610 +/- 55 microU/ml, respectively. Glucose was infused during high dose to maintain the hypoglycemic plateau (50 +/- 1 mg/dl) equivalent to lower. Epinephrine (806 +/- 180 vs. 2,589 +/- 260 pg/ml), norepinephrine (303 +/- 55 vs. 535 +/- 60 pg/ml), cortisol (5.8 +/- 1.2 vs. 12.1 +/- 1.5 micrograms/dl), and pancreatic polypeptide (598 +/- 250 vs. 1,198 +/- 150 pg/ml) were all increased (P < 0.05) in the presence of high-dose insulin. Net hepatic glucose production increased significantly from 2.2 +/- 0.3 to 3.8 +/- 0.5 mg.kg-1.min-1 (P < 0.05) during high-dose infusion but remained at basal levels (2.3 +/- 0.4 mg.kg-1.min-1) during lower-dose insulin. During the 3rd h of hypoglycemia, gluconeogenesis accounted for between 42 and 100% of glucose production during high-dose infusion but only 22-52% during lower-dose insulin. Intrahepatic gluconeogenic efficiency, however, increased similarly during both protocols. Lipolysis, as indicated by arterial blood glycerol levels, increased by a greater amount during high- compared with lower-dose insulin infusion. Six hyperinsulinemic euglycemic control experiments (2 or 8 mU.kg-1.min-1, n = 3 in each) provided baseline data. Gluconeogenesis remained similar to basal levels, but lipolysis was significantly suppressed during both series of hyperinsulinemic euglycemic studies. In summary, these data suggest that 1) the important counterregulatory processes of gluconeogenesis and lipolysis can be significantly increased during prolonged hypoglycemia despite an eightfold increase in circulating insulin levels and 2) the amplified gluconeogenic rate present during the hypoglycemic high-dose insulin infusions was caused by enhanced substrate delivery to the liver rather than an increase in intrahepatic gluconeogenic efficiency.


MicroRNA-16 and microRNA-424 regulate cell-autonomous angiogenic functions in endothelial cells via targeting vascular endothelial growth factor receptor-2 and fibroblast growth factor receptor-1.
MicroRNAs play key roles in modulating a variety of cellular processes by posttranscriptional regulation of their target genes. Vascular endothelial growth factor (VEGF), VEGF receptor-2 (VEGFR2), and fibroblast growth factor receptor-1 (FGFR1) were identified by bioinformatic approaches and subsequently validated as targets of microRNA (miR)-16 and miR-424 in endothelial cells (ECs). Mimetics of these microRNAs reduced VEGF, VEGFR2, and FGFR1 expression, whereas specific antagonists enhanced their expression. Expression of mature miR-16 and miR-424 was upregulated on VEGF or basic fibroblast growth factor (bFGF) treatment. This upregulation was accompanied by a parallel increase in primary transcript (pri-miR)-16-1 and pri-miR-16-2 but not in pri-miR-424 levels, indicating a VEGF/bFGF-dependent transcriptional and posttranscriptional regulation of miR-16 and miR-424, respectively. Reduced expression of VEGFR2 and FGFR1 by miR-16 or miR-424 overexpression regulated VEGF and bFGF signaling through these receptors, thereby affecting the activity of downstream components of the pathways. Functionally, miR-16 or miR-424 overexpression reduced proliferation, migration, and cord formation of ECs in vitro, and lentiviral overexpression of miR-16 reduced the ability of ECs to form blood vessels in vivo. We conclude that these miRNAs fine-tune the expression of selected endothelial angiogenic mediators in response to these growth factors. Altogether, these findings suggest that miR-16 and miR-424 play important roles in regulating cell-intrinsic angiogenic activity of ECs.


New intronic Fibroblast Growth Factor Receptor 1 (FGFR1) mutation leading to disrupted splicing and Kallmann syndrome.
Congenital hypogonadotropic hypogonadism (CHH), which can present with a defective sense of smell (Kallmann syndrome, KS), is a clinically and genetically heterogeneous disorder. Over 31 genes have been associated with CHH, but most of the patients still lack a molecular genetic diagnosis. Some cases may be explained by mutations that disrupt the splicing of already established CHH genes but that are unrecognized either because they are located deep in introns or are not predicted to disrupt splicing. Here we identified a patient with a previously unreported Fibroblast Growth Factor Receptor 1 (FGFR1) mutation, c.1664-9T>G, that leads to the skipping of exon 13 of FGFR1. Notably, the mutation was not predicted to cause a significant alteration in the splicing motif but in vitro analysis confirmed the pathogenicity of the mutation. Our results thus reveal a new splicing-affecting mutation in FGFR1 and suggest that all new sequence variants located close to exon/intron boundaries should be experimentally investigated for pathogenicity, rather than relying solely on computer prediction programs.


Hope and coping in HIV-infected African-American women of reproductive age.
African-American women of reproductive age, particularly those living in the southern United States, represent a disproportionate number of women with HIV/AIDS. Often women who become infected with HIV in the South must cope not only with the disease, but with economic stresses and racial stigma, as well. Faced with these changes, these women experience increased distress and loss of hope. The purpose of this study was to examine levels of hope in a group of HIV-infected African-American women and to identify coping strategies that were associated with women maintaining a sense of hope for the future. A descriptive design was used to test the relationships between hope and coping strategies used by HIV-infected African-American women. Reported levels of hope were significantly lower for study participants than for women with breast cancer or for hospitalized adults with cancer who were receiving chemotherapy. Statistically significant positive relationships were observed between hope and the total coping score (r = .37, p = .009) hope and managing the illness (r = .47, p = .001) and between hope and spiritual activities (r = .40, p = .004). A statistically significant negative relationship was observed between hope and avoidance coping (r = -.35, p = .009).


The ephemeral nature of wording effects.
This article explores the analysis and interpretation of wording effects associated with using direct and reverse items in psychological assessment. Previous research using bifactor models has suggested a substantive nature of this effect. The present study uses mixture modeling to systematically examine an alternative hypothesis and surpass recognized limitations in the bifactor modeling approach. In preliminary supplemental Studies S1 and S2, we examined the presence of participants who exhibited wording effects and evaluated their impact on the dimensionality of Rosenberg's Self-Esteem and the Revised Life Orientation Test, confirming the ubiquity of wording effects in scales containing direct and reverse items. Then, after analyzing the data for both scales (n = 5,953), we found that, despite a significant association between wording factors (Study 1), a low proportion of participants simultaneously exhibited asymmetric responses in both scales (Study 2). Similarly, despite finding both longitudinal invariance and temporal stability of this effect in three waves (n = 3,712, Study 3), a small proportion of participants was identified with asymmetric responses over time (Study 4), reflected in lower transition parameters compared to the other patterns of profiles examined. In both cases, we illustrate how bifactor models capitalize on the responses of individuals who do not even exhibit wording effects, yielding spurious correlations suggesting a substantive nature of the wording effect. These findings support the notion of an ephemeral nature underlying wording effects. The discussion focuses on alternative hypotheses to understand these findings and emphasizes the utility of including reverse items in psychological assessment. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Similar clinical characteristics of familial and sporadic inflammatory bowel disease in South Korea.
To investigate differences of clinical characteristics and disease courses between familial and sporadic inflammatory bowel disease (IBD) patients. We obtained clinical data on Crohn's disease (CD) (n = 691) and ulcerative colitis (n = 1113) from a tertiary referral medical center between 2005 and 2012. Seventeen patients (2.5%) with CD and 27 patients (2.4%) with ulcerative colitis (UC) were identified as having a familial history of IBD, including the first and second degree relatives. For each control case, three times the number of age-, sex-, and diagnosis year-matched CD and UC patients, without a family history of IBD, were randomly selected in this case control study. There were no significant differences in age or main symptom at diagnosis, extraintestinal manifestation, location/extent, behavior of disease activity, number of hospitalizations, number of operations, operation type, number of relapses, or oral medical treatment between familial and sporadic CD and UC patients. Median (min-max) follow-up periods after diagnosis of familial CD and sporadic CD patients were 84 (24-312) and 36 (8-240) mo, respectively (P = 0.008). Familial CD patients more frequently used anti-tumor necrosis factor (TNF) antibodies compared to sporadic CD patients (17.6% vs 0%, P = 0.014). In conclusion, a family history of IBD does not seem to be an important predictive factor affecting clinical characteristics or disease course even if there is a more frequent use of anti-TNF antibodies in familial CD patients compared to sporadic CD patients.


Novel pressure-to-cornea index in glaucoma.
Several conversion tables and formulas have been suggested to correct applanation intraocular pressure (IOP) for central corneal thickness (CCT). CCT is also thought to represent an independent glaucoma risk factor. In an attempt to integrate IOP and CCT into a unified risk factor and avoid uncertain correction for tonometric inaccuracy, a new pressure-to-cornea index (PCI) is proposed. PCI (IOP/CCT(3)) was defined as the ratio between untreated IOP and CCT(3) in mm (ultrasound pachymetry). PCI distribution in 220 normal controls, 53 patients with normal-tension glaucoma (NTG), 76 with ocular hypertension (OHT), and 89 with primary open-angle glaucoma (POAG) was investigated. PCI's ability to discriminate between glaucoma (NTG+POAG) and non-glaucoma (controls+OHT) was compared with that of three published formulae for correcting IOP for CCT. Receiver operating characteristic (ROC) curves were built. Mean PCI values were: Controls 92.0 (SD 24.8), NTG 129.1 (SD 25.8), OHT 134.0 (SD 26.5), POAG 173.6 (SD 40.9). To minimise IOP bias, eyes within the same 2 mm Hg range between 16 and 29 mm Hg (16-17, 18-19, etc) were separately compared: control and NTG eyes as well as OHT and POAG eyes differed significantly. PCI demonstrated a larger area under the ROC curve (AUC) and significantly higher sensitivity at fixed 80% and 90% specificities compared with each of the correction formulas; optimum PCI cut-off value 133.8. A PCI range of 120-140 is proposed as the upper limit of "normality", 120 being the cut-off value for eyes with untreated pressures <or=21 mm Hg, 140 when untreated pressure >or=22 mm Hg. PCI may reflect individual susceptibility to a given IOP level, and thus represent a glaucoma risk factor. Longitudinal studies are needed to prove its prognostic value.


Development of a prognostic prediction model for patients with cutaneous malignant melanoma: a study based on the SEER database.
To investigate the prognostic factors of cutaneous malignant melanoma (CMM) and establish an effective nomogram survival prediction model. The clinical data of patients diagnosed with stage M0 CMM from 2000 to 2019 in the Surveillance, Epidemiology, and End Results (SEER) database were collected and retrospectively analyzed. The variables that may be related to prognosis were analyzed by Lasso-Cox regression analysis using R software. Independent prognostic factors were screened. A nomogram model for predicting the prognosis of CMMC was drawn, and its accuracy was verified by c-index, NR, IDI and calibration curve. A total of 2,679 patients with CMM were included. Lasso-Cox analysis showed that male sex, multiple tumors, higher T stage, SEER stage, widowed, divorced, and separated often indicated poor prognosis. The nomogram model calibration curve was in good agreement with the ideal curve, and the C-index was 0.734 in the training group and 0.761 in the validation group, respectively. In the training group, the AUC of 1-, 3-, 5- and 8-year survival were 0.80, 0.75, 0.74 and 0.72, respectively. In the validation group, the AUC of 1-, 3-, 5- and 8-year survival were 0.75, 0.79, 0.78 and 0.79, respectively. NRI and IDI were superior to the prediction ability of TNM stage and SEER stage (p < 0.05). The established prognostic score can divide patients into high and low score groups with significant prognostic difference (p < 0.05). Sex, SEER stage, T stage, total number of tumors and marital status are independent prognostic factors for CMM patients, and the nomogram model presented a better performance than TNM stage and SEER stage in predicting the prognosis of CMM patients.


Hemispheric language asymmetry in first episode psychosis and schizotypy: the role of cannabis consumption and cognitive disorganization.
Cannabis use has been related to an elevated psychosis risk and attenuated cognitive functioning. Cannabis-related cognitive impairments are also observed in populations along the psychosis dimension. We here investigated whether a potential behavioral marker of the psychosis dimension (attenuated functional hemispheric asymmetry) is even further attenuated in individuals using cannabis (CU) vs those not using cannabis (nCU). We tested 29 patients with first-episode psychosis (FEP; 11 CU) and 90 healthy controls (38 CU) on lateralized lexical decisions assessing left-hemisphere language dominance. In patients, psychotic symptoms were assessed by Positive & Negative Symptom Scale (PANSS). In controls, self-reported schizotypy was assessed (The Oxford-Liverpool Inventory of Feelings and Experiences: O-LIFE). Results indicated that nCU FEP patients had a relative reduced hemispheric asymmetry, as did controls with increasing cognitive disorganization (CogDis) scores, in particular when belonging to the group of nCU controls. Positive, disorganized and negative PANSS scores in patients and negative and positive schizotypy in controls were unrelated to hemispheric asymmetry. These findings suggest that cannabis use potentially balances rather than exacerbates uncommon hemispheric laterality patterns. Moreover, in healthy populations, the potential stabilization of typical hemispheric asymmetry in CU might be most relevant to individuals with elevated CogDis. We discuss the potential beneficial and harmful effects of cannabis use along the psychosis dimension together with propositions for future studies that should account for the mediating role of additional substances (eg nicotine), cannabis composition (eg cannabidiol content), and individual differences (eg physical health, or absence of significant polysubstance use).


Sclerosing polidocanol injections of small vessels to treat the chronic painful tendon.
The chronic painful tendon (tendinopathy, tendinosis) is generally considered difficult to treat, not seldom causing long-term disability and sometimes ending the sports or work carreér. Most common sites for tendinopathy are the Achilles-, patellar-, extensor carpi radialis brevis (ERCB)-, and supraspinatus tendons. The origin of pain has for many years been unknown, but recently, by using ultrasound (US) + colour Doppler (CD), immunohistochemical analyses of tendon biopsies, and diagnostic injections of local anaestesia, we found a close relationship between areas with vasculo-neural ingrowth and tendon pain. Sensory nerves (Substance-P-SP and Calcitonin Gene Related Peptide-CGRP) were found inside and outside the vascular wall. In following clinical studies we have demonstrated good short-and mid-term clinical results using treatment with US+CD-guided sclerosing polidocanol injections, targeting the area with neovessels outside the tendon. Two-year follow ups have showed remaining good clinical results, and sonographically signs of remodelling with a significantly thinner tendon with a more normal structure. Whether the effects of polidocanol are mediated through destruction of neovessels, activity on nerves or a combination, is under evaluation.


Predictable information in neural signals during resting state is reduced in autism spectrum disorder.
The neurophysiological underpinnings of the nonsocial symptoms of autism spectrum disorder (ASD) which include sensory and perceptual atypicalities remain poorly understood. Well-known accounts of less dominant top-down influences and more dominant bottom-up processes compete to explain these characteristics. These accounts have been recently embedded in the popular framework of predictive coding theory. To differentiate between competing accounts, we studied altered information dynamics in ASD by quantifying predictable information in neural signals. Predictable information in neural signals measures the amount of stored information that is used for the next time step of a neural process. Thus, predictable information limits the (prior) information which might be available for other brain areas, for example, to build predictions for upcoming sensory information. We studied predictable information in neural signals based on resting-state magnetoencephalography (MEG) recordings of 19 ASD patients and 19 neurotypical controls aged between 14 and 27 years. Using whole-brain beamformer source analysis, we found reduced predictable information in ASD patients across the whole brain, but in particular in posterior regions of the default mode network. In these regions, epoch-by-epoch predictable information was positively correlated with source power in the alpha and beta frequency range as well as autocorrelation decay time. Predictable information in precuneus and cerebellum was negatively associated with nonsocial symptom severity, indicating a relevance of the analysis of predictable information for clinical research in ASD. Our findings are compatible with the assumption that use or precision of prior knowledge is reduced in ASD patients.


Time From HIV Diagnosis to Viral Suppression: Survival Analysis of Statewide Surveillance Data in Alabama, 2012 to 2014.
Evaluation of the time from HIV diagnosis to viral suppression (VS) captures the collective effectiveness of HIV prevention and treatment activities in a given locale and provides a more global estimate of how effectively the larger HIV care system is working in a given geographic area or jurisdiction. This study aimed to evaluate temporal and geographic variability in VS among persons with newly diagnosed HIV infection in Alabama between 2012 and 2014. With data from the National HIV Surveillance System, we evaluated median time from HIV diagnosis to VS (<200 c/mL) overall and stratified by Alabama public health area (PHA) among persons with HIV diagnosed during 2012 to 2014 using the Kaplan-Meier approach. Among 1979 newly diagnosed persons, 1181 (59.67%) achieved VS within 12 months of diagnosis; 52.6% (353/671) in 2012, 59.5% (377/634) in 2013, and 66.9% (451/674) in 2014. Median time from HIV diagnosis to VS was 8 months: 10 months in 2012, 8 months in 2013, and 6 months in 2014. Across 11 PHAs in Alabama, 12-month VS ranged from 45.8% (130/284) to 84% (26/31), and median time from diagnosis to VS ranged from 5 to 13 months. Temporal improvement in persons achieving VS following HIV diagnosis statewide in Alabama is encouraging. However, considerable geographic variability warrants further evaluation to inform public health action. Time from HIV diagnosis to VS represents a meaningful indicator that can be incorporated into public health surveillance and programming.


Predictors of restenosis after treatment of bifurcational lesions with paclitaxel eluting stents: a multicenter prospective registry of 150 consecutive patients.
The aim of the study was the assessment of the clinical, angiographic and procedural characteristics correlated with freedom from adverse events at 1 year in a real life setting of consecutive bifurcation lesions. Even if stent implantation has shown to be superior to conventional balloon angioplasty in most coronary lesions, bifurcation treatment with stent implantation both in main and in side branch (SB) still raises controversy. We reviewed the results obtained in a prospective multicenter registry of 150 patients with 158 bifurcation lesions involving a SB of sufficient diameter to be treated, if necessary, with a polymer based paclitaxel eluting stent (PES, TAXUS). Two stents were used in 118 lesions (74.7%). Final kissing balloon inflation was performed in 87/118 lesions (73.7%) and in 30/40 lesions (75.0%) of the 2 and 1 stent group respectively. At 1-year clinical follow-up we observed 4 stent thromboses, all involving the SBs of the 2 stents group (2.7%). Unlike previous reports, revascularization involved the main vessel in the majority of patients (21/150, 14.0%). After an exploratory multivariable analysis the only parameter predictive of target lesion revascularization (TLR) (HR 0.52; CI 95% 0.11-0.86; p = 0.02) and target vessel revascularization (TVR) (HR 0.47; CI 95% 0.14-0.90; p = 0.03) was postprocedural main branch minimal lumen diameter (MB-MLD). In a real life setting of consecutive bifurcation lesions, thrombosis rate, concentrated in the SB and the 2-stents group, and need for target lesion revascularization remain higher than in less complex lesion subgroups treated with PES. No differences in immediate success and TLR were observed between 2 stents and 1 stent groups. The frequently observed suboptimal stent expansion and final MB-MLD predict 1 year revascularization.


Mesolimbic Neurobehavioral Mechanisms of Reward Motivation in Anorexia Nervosa: A Multimodal Imaging Study.
Diminished motivation to pursue and obtain primary and secondary rewards has been demonstrated in anorexia nervosa (AN). However, the neurobehavioral mechanisms underlying the behavioral activation component of aberrant reward motivation remains incompletely understood. This work aims to explore this underexplored facet of reward motivation in AN. We recruited female adolescents with AN, restricting type (n = 32) and a healthy control group (n = 28). All participants underwent functional magnetic resonance imaging (fMRI) while performing a monetary reward task. Diffusion MRI data was also collected to examine the reward motivation circuit's structural connectivity. Behavioral results demonstrated slower speed of reward-seeking behavior in those with AN compared with controls. Accompanying this was lower functional connectivity and reduced white matter structural integrity of the connection between the ventral tegmental area/substantia nigra pars compacta and the nucleus accumbens within the mesolimbic circuit. Further, there was evidence of neurobehavioral decoupling in AN between reward-seeking behavior and mesolimbic regional activation and functional connectivity. Aberrant activity of the bed nucleus of the stria terminalis (BNST) and its connectivity with the mesolimbic system was also evident in AN during the reward motivation period. Our findings suggest functional and structural dysconnectivity within a mesolimbic reward circuit, neurofunctional decoupling from reward-seeking behavior, and abnormal BNST function and circuit interaction with the mesolimbic system. These results show behavioral indicators of aberrant reward motivation in AN, particularly in its activational component. This is mediated neuronally by mesolimbic reward circuit functional and structural dysconnectivity as well as neurobehavioral decoupling. Based on these findings, we suggest a novel circuit-based mechanism of impaired reward processing in AN, with the potential for translation to developing more targeted and effective treatments in this difficult-to-treat psychiatric condition.


Intensive Care Nurses' Experiences Related to Dying Patients: A Qualitative Study.
To describe intensive care nurses' experiences of caring for dying patients. This study was carried out between July 15, 2019, and September 15, 2019, in a university hospital's intensive care unit. We conducted in-depth semi-structured interviews with a purposive sample of 14 intensive care nurses to describe their experiences related to patient deaths. Qualitative thematic analysis was used to identify, analyse and report the identified themes. Four themes were identified: (I) Emotions experienced the first time their patient passed away; (II) feelings and thoughts on impact of death; (III) difficulties encountered when providing care and (IV) coping methods with this situation. Despite the passage of time, nurses are unable to forget their death experiences when they first encountered. They oftentimes use ineffective methods of coping and were negatively affected physically and emotionally.


Insulinlike growth factor I receptors in rabbit gastrointestinal tract. Characterization and autoradiographic localization.
Insulinlike growth factor I is a potent mitogen with insulinlike metabolic effects. Insulinlike growth factor I is synthesized in the liver, intestine, and other organs. Insulinlike growth factor I receptors are widely distributed and structurally similar to insulin receptors. Frozen sections of rabbit gastrointestinal tract were incubated in buffer containing 40 pmol/L [125I]insulinlike growth factor I. Binding was saturable, temperature- and time-dependent, and reversible. Saturation binding experiments showed a single class of high-affinity receptors (Kd = 0.9 nmol/L, Bmax = 0.36 pmol/mg protein). The IC50s for insulinlike growth factor I and insulinlike growth factor II were 3 nmol/L and 90 nmol/L, respectively; whereas insulin at 1-3 mumol/L displaced 50% of specific binding. Autoradiography of insulinlike growth factor I binding demonstrated significant differences in receptor density in gastrointestinal smooth muscle, epithelium of the esophagus, stomach, small intestine, and colon. These results indicate that a single class of specific, high-affinity insulinlike growth factor I receptors were distributed in muscular and mucosal layers of the entire rabbit gastrointestinal tract. Insulinlike growth factor I is likely to be an important local mediator of intestinal growth and metabolism.


[Intravital and electron microscopic analysis of the arterioles by immersion and perfusion technics of fixation of the rat mesentery].
The technique of the intravital microscopic control, videotaping, cinemoregistration and per single-frame analysis made it possible to demonstrate for the first time that a double fixation in glutaraldehyde and osmium has no effect on the arteriolar lumen. Comparing the data on the intravital and a detailed electron microscopic study, it was possible to reveal certain peculiarities and advantages of the fixative perfusion and immersion techniques applied. The investigation establishes a basis for extended morphological studies of small blood vessels and morpho-physiological comparisons.


An exploration of student nurses' experiences of formative assessment.
The idea that formative assessment has the potential to prepare students, not only to succeed in summative assessments during the course, but also in the world beyond the classroom [Melland, H., Volden, C., 1998. Classroom assessment: linking teaching and learning. Journal of Nursing Education 37(6), 275-277] fuelled the desire to explore student nurses experiences of being assessed formatively. Focus group discussion, within a UK Higher Education setting, captured the holistic, dynamic and individual experiences student nurses (n=14) have of formative assessment. Ethical approval was obtained. Findings from three separate focus group discussions indicate that lecturers do not use the term "formative assessment" in their communication with the student nurses; student preparation and effort is greater when assessment is for summative purposes; oral feedback is preferable to written feedback which can, at times, be illegible and utilise unfamiliar vocabulary; lecturer comments are regarded as being more valuable than grades; student nurses are not being prepared for the critical feedback associated with peer review and they may, therefore, be vulnerable to the process and outcome of peer review. Thus, the UK centric focus of this small qualitative research study need not detract from its ability to add to the global knowledge base on formative assessment in nursing.


Release of Different Cell Mediators During Retinal Pigment Epithelium Regeneration Following Selective Retina Therapy.
To investigate the effect of selective retina therapy (SRT) on the release of AMD-relevant cell mediators, such as matrix metalloproteinases (MMPs), VEGF, and pigment epithelium derived factor (PEDF) using different laser spot sizes and densities. Porcine RPE-choroid explants were treated with a pulsed 532 nm Nd:YAG laser using (1) large spot sizes, (2) small spot sizes with a high-density (hd) treatment, and (3) small spot sizes with a low-density (ld) treatment. Explants were cultivated in modified Ussing chambers. RPE regeneration and RPE cell death were investigated by calcein-AM staining and immunofluorescence. The MMP release was examined via zymography and immunofluorescence. VEGF and PEDF secretion was analyzed by ELISA. During pigment epithelium regeneration (PER), mitosis and RPE cell migration were observed. Four days after SRT (large spot size) the content of active MMP2 increased significantly (P < 0.01). Hd treatment with small spot sizes resulted also in an increase of active MMP2 (P < 0.05). In immunofluorescence explants showed a localized expression of MMP2 within the healing lesions after irradiation. The PEDF level increased significantly (P = 0.01) after SRT with large spot sizes. VEGF secretion decreased significantly (P < 0.05) following SRT with large spot sizes and with hd treatment of small spot sizes. SRT induces a cytokine profile, which may improve the flux across Bruch's membrane, slows down progression of early AMD by RPE regeneration, and inhibits the formation of choroidal neovascularization. The cytokine release depends on the size and density of applied laser spots.


Implementing the Bounce Back trauma intervention in urban elementary schools: A real-world replication trial.
The current study provides the first replication trial of Bounce Back, a school-based intervention for elementary students exposed to trauma, in a different school district and geographical area. Participants in this study were 52 1st through 4th graders (Mage = 7.76 years; 65% male) who were predominately Latino (82%). Schools were randomly assigned to immediate treatment or waitlist control. Differential treatment effects (Time × Group Interaction) were found for child-reported posttraumatic stress disorder (PTSD) and parent-reported child coping, indicating that the immediate treatment group showed greater reductions in PTSD and improvements in coping compared with the delayed group. Differential treatment effects were not significant for depression or anxiety. Significant maintenance effects were found for both child-reported PTSD and depression as well as parent-reported PTSD and coping for the immediate treatment group at follow-up. Significant treatment effects were also found in the delayed treatment group, showing reductions in child-reported PTSD, depression, and anxiety as well as parent-reported depression and coping upon receiving treatment. In conclusion, the current study suggests that Bounce Back is an effective intervention for reducing PTSD symptoms and improving coping skills, even among a sample experiencing high levels of trauma and other ongoing stressors. (PsycINFO Database Record


A neural signature of metabolic syndrome.
That metabolic syndrome (MetS) is associated with age-related cognitive decline is well established. The neurobiological changes underlying these cognitive deficits, however, are not well understood. The goal of this study was to determine whether MetS is associated with regional differences in gray-matter volume (GMV) using a cross-sectional, between-group contrast design in a large, ethnically homogenous sample. T1-weighted MRIs were sampled from the genetics of brain structure (GOBS) data archive for 208 Mexican-American participants: 104 participants met or exceeded standard criteria for MetS and 104 participants were age- and sex-matched metabolically healthy controls. Participants ranged in age from 18 to 74 years (37.3 ± 13.2 years, 56.7% female). Images were analyzed in a whole-brain, voxel-wise manner using voxel-based morphometry (VBM). Three contrast analyses were performed, a whole sample analysis of all 208 participants, and two post hoc half-sample analyses split by age along the median (35.5 years). Significant associations between MetS and decreased GMV were observed in multiple, spatially discrete brain regions including the posterior cerebellum, brainstem, orbitofrontal cortex, bilateral caudate nuclei, right parahippocampus, right amygdala, right insula, lingual gyrus, and right superior temporal gyrus. Age, as shown in the post hoc analyses, was demonstrated to be a significant covariate. A further functional interpretation of the structures exhibiting lower GMV in MetS reflected a significant involvement in reward perception, emotional valence, and reasoning. Additional studies are needed to characterize the influence of MetS's individual clinical components on brain structure and to explore the bidirectional association between GMV and MetS.


Ischemic colitis: A forgotten entity. Results of a retrospective study in 118 patients.
The aim of our study was to document our 6-year experiences in identifying the clinical characteristics, laboratory findings, risk factors and the outcomes of patients with ischemic colitis (IC) in a community hospital setting. The medical records of patients who were diagnosed with IC from 2007 to 2013 in two community hospitals were retrospectively reviewed. Their clinical characteristics, laboratory results, radiological, endoscopic and histological evidence, anatomic location of the lesion, comorbidities, concomitant use of drugs, and so on, were collected. A total of 118 patients with IC was identified, most were elderly individuals with a female predominance. The most common symptoms were abdominal pain, rectal bleeding and diarrhea. Hypertension, hyperlipidemia, coronary artery disease and diabetes mellitus were the most common comorbidities. Erythema, edema and erosions/ulcerations were the most common endoscopic findings. Left colon was the most affected location of lesion (84.8%), and there was one case of pancolitis. The descending colon was the most common affected segment, while rectum was the least affected segment. Severe IC occurred in 12.7% of the patients. Death within 30 days from the diagnosis of the disease occurred in 4.2%. IC is majorly occurred in elderly with a female predominance. Cardiovascular disease and its associated risk factors are the most common comorbidities. Left colon is the most affected location of the disease and the overall mortality rate was 4.2%. Physicians should make every effort to identify these patients, especially those with high risks.


FTIR spectroscopy and thermodynamics of hydrogen adsorbed in a cross-linked polymer.
The adsorption of H(2) in a cross-linked poly(styrene-co-divinylbenzene) (St-DVB) microporous polymer (BET surface area 920 m(2) g(-1)) is studied by volumetric and gravimetric methods, FTIR spectroscopy at variable temperature (300-14 K) and ab initio calculations. At 77 K the polymer reversibly stores up to 1.3 mass% H(2) at a pressure of 1 bar and 1.8 mass% at 10 bar. The adsorption process involves the specific interaction of H(2) with the structural phenyl rings through weak dispersive forces. The interacting molecules become IR active and give rise to vibrational and rotational-vibrational manifestations which are affected by the temperature, the contact time and the H(2) equilibrium pressure. The spectra of the H(2)/St-DVB system reported here represent the first IR evidence of the adsorption of hydrogen on unsaturated molecules. The adsorption enthalpy is evaluated by the VTIR (variable temperature IR spectroscopy) method (C. Otero Areán et al., Phys. Chem. Chem. Phys., 2007, DOI: 10.1039/b615535a) and compared with the results of ab initio calculations for the H(2)/benzene interaction and with literature data.


RANZCP experiences in establishing and progressing an externally focussed mental health policy and partnership agenda.
This paper traces the background of involvement and increasing external activity of the Royal Australian and New Zealand College of Psychiatrists (RANZCP) in the policy and project area. Throughout 2008, representatives of the RANZCP paused to review progress and celebrate successes in the implementation of the College's stated aim to develop an externally focussed policy agenda. A summary of key activities across the past 4-5 years is outlined, including the key leadership role undertaken by the RANZCP in the recent formation of the Mental Health Professionals Association's partnership. Tracing the history of the establishment of the RANZCP externally focussed policy functions, the paper provides details of the extensive range of projects and activities undertaken to date. Also highlighted is the broad range of resources that have been developed and are now available for College members including trainees. The progress achieved to date is reflective of RANZCP's deliberate strategic actions and intent to work more closely with others and take an increasingly active role in the development of mental health policy and service delivery standards across the Australian and New Zealand landscape. The functions are now embedded with the College's newly revised Strategic Plan.


Energy-based devices in thyroid surgery-an overview.
In the mid-20th century Theodor Kocher standardized the conventional clamp-and-tie thyroidectomy, and a procedure that was banned or prohibited for so long was labeled as "extremely safe and efficient". Ever since, innovations and refinements in the field of thyroid surgery have focused on improving patient clinical outcome profiles, and offering patients procedures that are tailored to their concerns and desires without compromising the concepts of safety and efficacy. This led to a paradigm shift in thyroid surgery and the introduction of minimal access thyroid procedures. Unsurprisingly, this paralleled the constant technological evolution in surgical devices. Advanced energy-based devices were introduced into thyroid surgery more than a decade ago. Initially, their introduction was surrounded by sckepticism, and was considered a double-edged sword equally giving accolade and criticism. Ultimately, they have proved to be very useful in thyroid surgery, and pivotal to its evolution. In experienced hands, thyroid surgery performed using an advanced energy-based device is considered 'at least' as safe and effective as its conventional clamp-and-tie counterpart. Furthermore, it offers additional advantages that meet the best interest of the patient, surgeon, health care facility, and the society. This article provides an overview on the introduction of innovative technology into thyroid surgery.


Symposium on Nonpulmonary Aspects in Chest Radiology. The pulmonary ligament.
The pulmonary ligament forms an important attachment of the lower lobe to the mediastinum and therefore influences the ultimate configuration of pneumothorax, lower-lobe atelectasis, and mediastinal pleural effusions. Since the ligament consists of a double pleural sheath, under certain circumstances fluid, air, and so on can collect within it, producing a lesion of triangular configuration. The latter must be differentiated from an air cyst or atelectasis.


Asymmetric distribution of gap junctions amongst identified photoreceptor axons of Lucilia cuprina (Diptera).
The relative number of gap junctions within the ring of axon terminals of identified adult photoreceptors has been counted, in the lamina cartridges of Lucilia cuprina. Terminals are similar in size, but some pairs of terminals make up to four times as many junctions with each other as do other pairs; the frequency of connection varies markedly along the length of the cartridge. Junctions across the cartridge occasionally occur out of the normal sequence, frequently in the upper cartridge between one pair of axons. The distributions suggest that mechanical factors transmitted down from the upper cartridge are responsible for the non-uniformities. There may be indiscriminate competition between terminals at some stage of development for a fixed quota of junctions, the groupings of which have to reach a minimum size to remain viable. Amongst the neurones of the cartridge, great specificity is shown in which cells form gap junctions: only receptors R1-6 are involved, making junctions only with each other. Within this class R1-6, however, there is no evidence from the distribution of gap junctions for unique cell labelling, that distinguishes one photoreceptor from another. Connections appear to form indiscriminately, on the basis of proximity. This same generalization holds true for a particular class of chemical feedback synapse. The identity of tight-junction-like structures on the photoreceptor axon membrane is also discussed.


Palladium-catalyzed arylic/allylic aminations: permutable domino sequences for the synthesis of dihydroquinolines from Morita-Baylis-Hillman adducts.
An efficient palladium-catalyzed synthesis of 1,2-dihydroquinolines has been developed via the reaction between anilines and Morita-Baylis-Hillman adducts derived from o-bromobenzaldehyde. This new Pd(0)-catalyzed pseudo-domino type I sequence involves a Buchwald-Hartwig arylic amination and an allylic amination. When starting from an o-bromo allylic alcohol, the chronology is arylic amination/allylic arylation. However, the sequence reverses when the reaction is performed on the corresponding o-bromo allylic acetate.


[Analysis of handgrip strength from elderly women: a comparative study among age groups].
The senior population has increasing recently and demanding greater attention due to of falling related to the reduction of muscle strength. The early falling risk identification has been prized by many countries and allows the implementation of preventive actions, such as the participation of physical activities, which have been considered a promising way to prevent the loss of muscle mass and strength. By this way, the present application intended to identify the handgrip profile, known as an important predictor of physical function, of Brazilian women of different ages. Eight-four women were divided into four age groups (20-27, 50-64, 65-74, and 75-86 years old) being made the comparison among the peak of handgrip strength. It was observed smaller values of handgrip strength (p >0.05) for age groups 50-64,65-74 and 75-86 years old when compared to age group 20-27 years old. It has been identified a negative correlation among age and the peak of handgrip strength (Spearman's Rho = -0,78, p > 0.05) which was associated to much smaller values of peak of handgrip strength between age group 75-86 years old compared to age groups 50-64, and 65-74 years old (p > 0.05). The results demonstrate a functional decline beginning at the fifth decade, which could guide preventive actions such as the incentive to a physical engagement in activity programs. It was suggested the development of other studies with a bigger sample which encloses other age groups and males.


An intensive assessment of alcohol use and emergency department utilization in homeless alcohol-dependent adults.
Excessive alcohol use among the homeless may contribute to their high rates of emergency department use. Survey-based studies have provided some information on the relation between alcohol and emergency department use among the homeless. This study used an intensive schedule of random breath collections and self-report assessments to examine the relation between emergency department utilization and alcohol use in homeless alcohol-dependent adults. Data were from homeless alcohol-dependent adults (N=116) who were participating in a therapeutic workplace that provided job-skills training every weekday for 26 weeks. Breath-sample collections and assessments of self-reported alcohol use were scheduled each week, an average of twice per week per participant, at random times between 9:00 A.M. and 5:00 P.M. Participants received $35 for each breath sample collected. Self-reports of emergency department use were assessed throughout the study. Thirty-four percent of participants reported attending an emergency department and reported an average of 2.2 emergency department visits (range 1-10 visits). Alcohol intoxication was the most common reason for emergency department use. Participants who used the emergency department had significantly more alcohol-positive breath samples and more self-reported heavy alcohol use than participants who did not use the emergency department. This study provided a rare intensive assessment of alcohol and emergency department use in homeless alcohol-dependent adults over an extended period. Emergency department use was high and was significantly related to indices of alcohol use.


Eco-friendly TEMPO/laccase/O2 biocatalytic system for degradation of Indigo Carmine: operative conditions and laccase inactivation.
The biocatalytic system laccase/TEMPO/O2 has attracted the attention of researchers over the past two decades. A variety of applications for the system include organic synthesis, modification of cellulose, and oxidative degradation of environmental contaminants. A rigorous and predictable quantitative assessment of the change in enzymatic activity under the influence of a mediator is important for such a system. In this study, the operative conditions for carrying out a model reaction for the degradation of the synthetic dye Indigo Carmine in the presence of Trametes versicolor laccase/TEMPO were determined and the enzyme inactivation under the action of a mediator and substrate was studied. The long-term stability of Trametes versicolor laccase was assessed and the regression model of the response surface of laccase activity under the influence of TEMPO was created. It has been shown that laccase is inactivated in the presence of TEMPO, but the addition of the dye, CuSO4 or CuCl2 reduces this effect. The system under study can be used repeatedly for the Indigo Carmine decolorization, however, a gradual falling rate during the process is observed from cycle to cycle. This is due to two reasons - firstly, a decrease in the enzyme activity with each batch and secondly, the consumption of the mediator (22% within 5 days). Relatively high enzyme activity (>40%) is maintained after 73 cycles (1 portion of IC contained 25 μM) using 500 μM TEMPO and 0.12 U mL-1 laccase. The laccase/TEMPO system has shown its effectiveness in the treatment of artificial wastewater containing high concentrations of Indigo carmine (0.5 g L-1). In this case, the dye solution becomes 100% colorless within 5 hours in the presence of dye bath components and within 7.5 hours in a buffer solution.


Inbreeding, Native American ancestry and child mortality: linking human selection and paediatric medicine.
The children of related parents show increased risk of early mortality. The Native American genome typically exhibits long stretches of homozygosity, and Latin Americans are highly heterogeneous regarding the individual burden of homozygosity, the proportion and the type of Native American ancestry. We analysed nationwide mortality and genome-wide genotype data from admixed Chileans to investigate the relationship between common causes of child mortality, homozygosity and Native American ancestry. Results from two-stage linear-Poisson regression revealed a strong association between the sum length of runs of homozygosity (SROH) above 1.5 Megabases (Mb) in each genome and mortality due to intracranial non-traumatic haemorrhage of foetus and newborn (5% increased risk of death per Mb in SROH, P = 1 × 10-3) and disorders related to short gestation and low birth weight (P = 3 × 10-4). The major indigenous populations in Chile are Aymara-Quechua in the north of the country and the Mapuche-Huilliche in the south. The individual proportion of Aymara-Quechua ancestry was associated with an increased risk of death due to anencephaly and similar malformations (P = 4 × 10-5), and the risk of death due to Edwards and Patau trisomy syndromes decreased 4% per 1% Aymara-Quechua ancestry proportion (P = 4 × 10-4) and 5% per 1% Mapuche-Huilliche ancestry proportion (P = 2 × 10-3). The present results suggest that short gestation, low birth weight and intracranial non-traumatic haemorrhage mediate the negative effect of inbreeding on human selection. Independent validation of the identified associations between common causes of child death, homozygosity and fine-scale ancestry proportions may inform paediatric medicine.


Biogeography, host specificity, and molecular phylogeny of the basidiomycetous yeast Phaffia rhodozyma and its sexual form, Xanthophyllomyces dendrorhous.
Phaffia rhodozyma (sexual form, Xanthophyllomyces dendrorhous) is a basidiomycetous yeast that has been found in tree exudates in the Northern Hemisphere at high altitudes and latitudes. This yeast produces astaxanthin, a carotenoid pigment with biotechnological importance because it is used in aquaculture for fish pigmentation. We isolated X. dendrorhous from the Southern Hemisphere (Patagonia, Argentina), where it was associated with fruiting bodies of Cyttaria hariotii, an ascomycetous parasite of Nothofagus trees. We compared internal transcribed spacer (ITS)-based phylogenies of P. rhodozyma and its tree host (Betulaceae, Corneaceae, Fagaceae, and Nothofagaceae) and found them to be generally concordant, suggesting that different yeast lineages colonize different trees and providing an explanation for the phylogenetic distance observed between the type strains of P. rhodozyma and X. dendrorhous. We hypothesize that the association of Xanthophyllomyces with Cyttaria derives from a previous association of the yeast with Nothofagus, and the sister relationship between Nothofagaceae and Betulaceae plus Fagaceae correlates with the phylogeny of X. dendrorhous strains originating from these three plant families. The two most basal strains of X. dendrorhous are those isolated from Cornus, an ancestral genus in the phylogenetic analysis of the host trees. Thus, we question previous conclusions that P. rhodozyma and X. dendrorhous represent different species since the polymorphisms detected in the ITS and intergenic spacer sequences can be attributed to intraspecific variation associated with host specificity. Our study provides a deeper understanding of Phaffia biogeography, ecology, and molecular phylogeny. Such knowledge is essential for the comprehension of many aspects of the biology of this organism and will facilitate the study of astaxanthin production within an evolutionary and ecological framework.


Immune tolerance and immunosuppression in solid organ transplantation.
Organ transplantation is the treatment of choice for patients with end-stage organ failure. Most of them will require lifelong immunosuppression to prevent both acute and chronic rejection. T-cell recognition of the allograft major histocompatibility complex antigens is the central event initiating cellular rejection of the allograft, and subsequent full T-cell activation requires three signals.Immunosuppressive regimens currently used in clinical practice are nonspecific and target T-cell activation, clonal expansion or differentiation into effector T cells. While these therapeutic regimens have advanced considerably and one-year graft survival figures for most solid organ transplants (SOTs) are >90%, the long-term graft survival remains fair owing to graft loss from chronic rejection. The 'holy grail' of SOT is therefore the development of a permanent specific immune tolerance against donor allogeneic antigens without the long-term use of immunosuppression.


The oral hygiene status of institution dwelling orphans in Benin City, Nigeria.
Orphans like other vulnerable children face a number of challenges including limited or no access to basic health care including oral health care, which is one of their unmet health care needs. Neglected oral health care is associated with the development and progression of periodontal diseases among others. To determine the oral hygiene status of institution dwelling orphans. Thirty eight orphans from four orphanages in Benin City, Edo State of Nigeria were clinically examined and their oral hygiene status determined using the simplified oral hygiene index of Greene and Vermillion (OHI-S). Seventy-three percent of the orphans were found to have fair oral hygiene comprising mostly of those aged 6-13 years. More females were in this category while more males presented with poor oral hygiene status. More orphans presented with fair oral hygiene that indicated inadequate oral care. There was poor oral health education and limited access to services. There is need for these to be improved as a solution to poor oral health status of these vulnerable children.


Construction of a genetic linkage map and QTL analysis in bambara groundnut.
Bambara groundnut (Vigna subterranea (L.) Verdc.) is an indigenous underutilized legume that has the potential to improve food security in semi-arid Africa. So far, there are a lack of reports of controlled breeding populations that could be used for variety development and genetic studies. We report here the construction of the first genetic linkage map of bambara groundnut using a F3 population derived from a "narrow" cross between two domesticated landraces (Tiga Nicuru and DipC) with marked divergence in phenotypic traits. The map consists of 238 DArT array and SSR based markers in 21 linkage groups with a total genetic distance of 608.3 cM. In addition, phenotypic traits were evaluated for a quantitative trait loci (QTL) analysis over two generations. A total of 36 significant QTLs were detected for 19 traits. The phenotypic effect explained by a single QTL ranged from 11.6% to 49.9%. Two stable QTLs were mapped for internode length and growth habit. The identified QTLs could be useful for marker-assisted selection in bambara groundnut breeding programmes.


Thrombocytopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: A meta-analysis.
Coronavirus disease 2019 (COVID-19) is a novel infectious disease with lack of established laboratory markers available to evaluate illness severity. In this study, we investigate whether platelet count could differentiate between COVID-19 patients with or without severe disease. Additionally, we evaluate if thrombocytopenia is associated with severe COVID-19. An electronic search in Medline, Scopus and Web of Science was performed to identify studies reporting data on platelet count in COVID-19 patients. A meta-analysis was performed, with calculation of weighted mean difference (WMD) of platelet number in COVID-19 patients with or without severe disease and odds ratio (OR) of thrombocytopenia for severe form of COVID-19. Nine studies with 1779 COVID-19 patients, 399 (22.4%) with severe disease, were included in the meta-analysis. The pooled analysis revealed that platelet count was significantly lower in patients with more severe COVID-19 (WMD -31 × 109/L; 95% CI, from -35 to -29 × 109/L). A subgroup analysis comparing patients by survival, found an even lower platelet count was observed with mortality (WMD, -48 × 109/L; 95% CI, -57 to -39 × 109/L. In the four studies (n = 1427) which reported data on rate of thrombocytopenia, a low platelet count was associated with over fivefold enhanced risk of severe COVID-19 (OR, 5.1; 95% CI, 1.8-14.6). Low platelet count is associated with increased risk of severe disease and mortality in patients with COVID-19, and thus should serve as clinical indicator of worsening illness during hospitalization.


The mosaic oat genome gives insights into a uniquely healthy cereal crop.
Cultivated oat (Avena sativa L.) is an allohexaploid (AACCDD, 2n = 6x = 42) thought to have been domesticated more than 3,000 years ago while growing as a weed in wheat, emmer and barley fields in Anatolia1,2. Oat has a low carbon footprint, substantial health benefits and the potential to replace animal-based food products. However, the lack of a fully annotated reference genome has hampered efforts to deconvolute its complex evolutionary history and functional gene dynamics. Here we present a high-quality reference genome of A. sativa and close relatives of its diploid (Avena longiglumis, AA, 2n = 14) and tetraploid (Avena insularis, CCDD, 2n = 4x = 28) progenitors. We reveal the mosaic structure of the oat genome, trace large-scale genomic reorganizations in the polyploidization history of oat and illustrate a breeding barrier associated with the genome architecture of oat. We showcase detailed analyses of gene families implicated in human health and nutrition, which adds to the evidence supporting oat safety in gluten-free diets, and we perform mapping-by-sequencing of an agronomic trait related to water-use efficiency. This resource for the Avena genus will help to leverage knowledge from other cereal genomes, improve understanding of basic oat biology and accelerate genomics-assisted breeding and reanalysis of quantitative trait studies.


Infection and interferon production in systemic juvenile chronic arthritis: a prospective study.
Twenty-four episodes of disease exacerbation in 19 children suffering from systemic juvenile chronic arthritis were studied. Sixteen of these were preceded by an infection (chi 2 = 20.14, p less than 0.001), mostly of the upper respiratory tract. In the 10 cases seen during an infection causative agents were identified in 5 (herpes simplex, rhinovirus, and on 3 occasions streptococcus). The total number of infections was not increased when compared with infection rates predicted by several reported studies. In the absence of clinical infection, specific antibody titres to a panel of microbial antigens were similar to those of a control group but with a trend toward higher titres in patients with hypergammaglobulinaemia. Interferon (IFN) responses were not defective, though sequential in-vitro IFN production from peripheral blood mononuclear cells (PBM) fluctuated considerably in the same patients, occasionally being absent with no obvious clinical correlate. IFN-alpha was induced by stimulation with Newcastle disease virus (NDV), and the mean responses of the patients were significantly greater than those of controls. IFN-gamma production on phytohaemagglutinin (PHA) stimulation was similar in patients and control groups. IFN was not detected in any of the sera from patients or controls.


Skeletal imaging and management of bone disease.
Up to 90% of patients with multiple myeloma develop bone lesions. The lesions are purely osteolytic because of increased osteoclast activity and markedly suppressed or absent osteoblast activity. The "gold standard" for imaging myeloma bone lesions is the metastatic bone survey. However, plain radiographs are relatively insensitive and can only demonstrate lytic disease when 30% of trabecular bone loss has occurred. Technicium-99m bone scanning is not appropriate for evaluating myeloma patients since bone scans underestimate the extent of bone involvement in patients with myeloma. The limited reproducibility of bone surveys have led to the use of computerized tomography (CT) scanning, magnetic resonance imaging (MRI) and positron emission tomography (PET) scans to evaluate the extent of bone disease. CT scans are more sensitive than plain radiographs for detecting small lytic lesions, and MRI scans detect marrow involvement by the tumor. PET scans have been used to detect bone lesions in patients with myeloma, are more sensitive than plain radiographs, and have the same sensitivity as MRIs for detecting bone disease in the spine and pelvis. Treatment of myeloma bone disease involves treatment of the underlying malignancy and its manifestations. Current treatments that will be discussed include bisphosphonate therapy, kyphoplasty, vertebroplasty, radiation therapy, and novel agents to suppress osteoclastic bone resorption. In addition, complications with bisphosphonate therapy will be reviewed, in particular, osteonecrosis of the jaw associated with bisphosphonate therapy. As survival of myeloma patients increases, therapies to prevent the complications of aggressive myeloma bone disease become more important.


A human claudin-1-derived peptide inhibits hepatitis C virus entry.
Hepatitis C virus (HCV) entry is a complicated process that requires multiple host factors, such as CD81, scavenger receptor BI, claudin-1 (CLDN1), and occludin. The interaction of virus and cellular entry factors represents a promising target for novel anti-HCV drug development. In this study, we sought to identify peptide inhibitors for HCV entry by screening a library of overlapping peptides covering the four above-mentioned entry factors. An 18-amino acid peptide (designated as CL58) that was derived from the CLDN1 intracellular and first transmembrane region inhibited both de novo and established HCV infection in vitro. Unlike previously reported peptides corresponding to CLDN1 extracellular loops, CL58 did not alter the normal distribution of CLDN1 and was not cytotoxic in vitro at concentrations nearly 100-fold higher than the effective antiviral dose. The inhibitory effect of CL58 appeared to occur at a late step during viral entry, presumably after initial binding. Finally, overexpressed CL58 was able to interact with HCV envelope proteins. We identified a novel CLDN1-derived peptide that inhibits HCV entry at a postbinding step. The findings expand our knowledge of the roles that CLDN1 play in HCV entry and highlight the potential for developing a new class of inhibitors targeting the viral entry process.


Current status and burning issues in immunotoxicity testing of drugs.
Besides pathology endpoints, additional immune function endpoints have been included in the Note for Guidance on Repeated Dose Toxicity by the European Union (July 2001), which concern the analysis of antibody responses to a T-cell-dependent antigen. Guidance papers of other regulatory authorities are published as well. The main issue is the need for functional immunotoxicity testing to detect unintended immunosuppression. The International Conference on Harmonization (ICH) has surveyed studies from the files of the pharmaceutical industry to find the proportion of compounds that can be detected by additional immunotoxicity testing. Preliminary analysis shows that 10-15% of the compounds in the survey only react positively to the additional tests. More data are requested from the pharmaceutical industry. The Expert Working Group of the ICH has decided to choose a cause-for-concern approach to immunotoxicity rather than a routine-screening approach. The causes for concern are to be defined during ICH negotiations.


[Yersinia enterocolitica. A seroprevalence study and report of 3 clinical cases].
Yersinia enterocolitica is a gram negative bacillus that emerged in the past two decades as an important enteric pathogen associated with a wide spectrum of clinical manifestations. The authors present a seroepidemiological survey, in 200 hospitalized patients, and describe three curious case reports of this infection, including a serious case of endocarditis.


Base excision repair initiated rolling circle amplification-based fluorescent assay for screening uracil-DNA glycosylase activity using Endo IV-assisted cleavage of AP probes.
Uracil-DNA glycosylase (UDG) is a crucial damage repair enzyme that initiates the cellular base excision repair pathway that maintains the integrity of the genome. Abnormal UDG activity may induce the malfunction of uracil excision repair that is directly related to a range of diseases including cancers, genotypic diseases, and human immunodeficiencies. In this work, a simple, robust and cost effective biosensing platform for the ultrasensitive detection of UDG activity is established based on the combination of base excision repair-initiated primer generation for rolling circular amplification (RCA) with Endo IV-assisted signal amplification. In the presence of target UDG, UDG can catalyze the removal of uracil on a hairpin probe (HP) leaving an apurinic/apyrimidinic (AP site) which can be cleaved by Endo IV to generate a primer for triggering the RCA reaction. Subsequently, numerous AP site-embedded signal probes, acting as fluorescence-quenched probes, combine with the RCA products to perform signal transduction and quadradic signal amplification through an Endo IV-catalyzed cleavage reaction, thus significantly enhancing the fluorescence signal, which can be used for UDG activity screening. Under optimum conditions, this biosensor exhibits improved sensitivity toward target UDG with a detection limit of as low as 9.3 × 10-5 U mL-1 and a wide detection range across 5 orders of magnitude. Additionally, our biosensor demonstrates high selectivity toward UDG for simple, rapid, and low-cost detection. Furthermore, by redesigning the modification of HP and using of suitable endonuclease enzymes, this RCA coupled with Endo IV-assisted signal amplification strategy might be applied for the detection of various other targets, such as thymine DNA glycosylase, 8-oxoguanine DNA glycosylase, DNA methyltransferase, and so on. Hence, the proposed strategy provides a useful and versatile biosensing platform for the ultrasensitive detection of UDG activity and related fundamental biomedicine research and clinical diagnosis.


Mantle flow distribution beneath the California margin.
Although the surface deformation of tectonic plate boundaries is well determined by geological and geodetic measurements, the pattern of flow below the lithosphere remains poorly constrained. We use the crustal velocity field of the Plate Boundary Observatory to illuminate the distribution of horizontal flow beneath the California margin. At lower-crustal and upper-mantle depths, the boundary between the Pacific and North American plates is off-centered from the San Andreas fault, concentrated in a region that encompasses the trace of nearby active faults. A major step is associated with return flow below the Eastern California Shear Zone, leading to the extrusion of the Mojave block and a re-distribution of fault activity since the Pleistocene. Major earthquakes in California have occurred above the regions of current plastic strain accumulation. Deformation is mechanically coupled from the crust to the asthenosphere, with mantle flow overlaid by a kinematically consistent network of faults in the brittle crust.


Impact of temporalis muscle thickness in elderly patients with newly diagnosed glioblastoma treated with radio or radio-chemotherapy.
There is an unmet need for new biomarkers able to predict both the outcomes of up-front therapy and the compliance of elderly patients diagnosed with glioblastoma. For this purpose, temporal muscle thickness is a promising tool to be investigated. Data from 52 glioblastoma patients older than 65 years, treated with post-operative radio or radio-chemotherapy and referred to Pisa University Hospital, were retrieved. The thickness of temporal muscle (TMT) was divided into quartiles and correlated with overall survival (Our primary endpoint). Survival curves were calculated using Kaplan-Meier method, and log-rank test was used to evaluate the differences between curves. Patients in the lower quartile of TMT, with TMT thinner than 7 mm, have survived longer; both univariate and multivariate analyses showed a statistically significant correlation between TMT and overall survival (P = 0.012 and P = 0.003, respectively). Future prospective and more extensive studies focused on elderly glioblastoma patients are needed to confirm the role of TMT as prognostic value on OS and to help explaining this association.


Stimulation of IL-2 production in murine lymphocytes by substance P and related tachykinins.
Substance P (SP), a tachykinin neuropeptide, has been previously reported to stimulate IL-2 production in murine T cell lines activated with phorbol esters. Here we extend these observations by establishing the stimulatory effect of SP and related tachykinins on IL-2 production by normal murine lymphocytes and on purified CD4+ T cells. SP proved to be the most efficient IL-2 inducer, exerting its maximal effect at concentrations that were 4 to 5 orders of magnitude lower than the optimal stimulatory concentrations of physalaemin, NKA, or NKB. SP stimulated IL-2 production in a dose-dependent manner, with an optimal concentration range of 10(-10) to 10(-14) M, comparable with physiologic concentrations of SP found in blood and other organs. The effect of SP was carried by the carboxyl-terminal part of the molecule (SP4-11). The specificity of SP activity was confirmed by the inhibitory effect of spantide, a tachykinin antagonist, and of CP-96,345, a nonpeptide antagonist specific for NK-1-type receptors. In unfractionated spleen cell cultures SP induced de novo IL-2 protein synthesis. SP could induce IL-2 production either directly, or in combination with Con A or anti-CD3 antibody treatments. The effect of SP in conjunction with Con A was synergistic, whereas the effect in conjunction with anti-CD3 antibodies was additive, suggesting different molecular mechanisms for these stimulatory factors. In the absence of additional costimuli the effect of SP in unfractionated spleen cell cultures was partially mediated through the induction of IL-1, and both SP and IL-1 were required for IL-2 induction in purified CD4+ T cells. In contrast to its stimulatory effect on the generation of IL-2, SP did not induce IFN-gamma production in murine spleen cells. The stimulatory effect of SP on IL-2 production suggests that some of the already described immunostimulatory activities of SP could be mediated through the up-regulation of IL-2 production in normal lymphocytes.


Randomised Controlled Trials of Alcohol-Based Surgical Site Skin Preparation for the Prevention of Surgical Site Infections: Systematic Review and Meta-Analysis.
(1) Background: Surgical site skin preparation is an important approach to prevent postoperative wound infections. International guidelines recommend that alcohol-based combinations be used, however, the optimal combination remains uncertain. This study compares the effectiveness of alcohol-based chlorhexidine and alcohol-based iodophor for surgical site skin preparation for prevention of surgical site infections (SSIs). (2) Methods: Randomised controlled trials comparing alcohol-based interventions for surgical site skin preparation were included. The proportion of SSIs was compared using risk ratios (RR) with 95% confidence intervals (95% CI). The meta-analysis was performed with a fixed effect model using Mantel-Haenszel methods. As an a priori subgroup analysis SSI risk was examined according to different surgical procedural groups. (3) Results: Thirteen studies were included (n = 6023 participants). The use of chlorhexidine-alcohol was associated with a reduction in risk of SSIs compared with iodophor-alcohol (RR 0.790; 95% CI 0.669, 0.932). On sub-group analysis, chlorhexidine-alcohol was associated with a reduction in SSIs in caesarean surgery (RR 0.614; 95% CI 0.453, 0.831) however, chlorhexidine-alcohol was associated with an increased risk of SSI in bone and joint surgery (RR 2.667; 95% CI 1.051, 6.765). When excluding studies at high risk of bias on sensitivity analysis, this difference in alcohol-based combinations for bone and joint surgery was no longer observed (RR 2.636; 95% CI 0.995, 6.983). (4) Conclusions: The use of chlorhexidine-alcohol skin preparations was associated with a reduced risk of SSI compared to iodophor-alcohol agents. However, the efficacy of alcohol-based preparation agents may differ according to the surgical procedure group. This difference must be interpreted with caution given the low number of studies and potential for bias, however, it warrants further investigation into the potential biological and clinical validity of these findings.


Coordinate production of three exoenzymes of Staphylococcus staphylolyticus.
Staphylococcus staphylolyticus produced three exoenzymes (a staphylolytic endopeptidase, a hexosaminidase and a protease) coordinately under a range of conditions of induction and repression by various peptides and carbohydrates. Mutants of S. staphylolyticus were isolated and shown to have pleiotropic variations in the production of the three enzymes. Hypo- or hyperproducing mutants of one enzyme were invariably hypo- or hyperproducers for the other two enzymes. Mutants that had lost the ability to produce one of the exoenzymes invariably failed to produce the other two enzymes. Revertants isolated from non-producers that regained the ability to produce one of the exoenzymes always regained the ability to produce the other two as well. These results suggest that the three exoenzymes share a common regulatory or processing mechanism.


[Helicobacter pylori diagnosis in children with recurrent abdominal pain].
We studied 40 children with recurrent abdominal pain during a period of six months (january to june 1993) entered at the gastroenterology service of the Instituto Nacional de Pediatria in México City. In all of then we performed in all of them an upper gastrointestinal endoscopy with 3 biopsies from gastric mucosa (antrum) for histological examination and urease tests. We also did an ELISA test looking for an H. Pylori specific serum IgG response. Our control group were 40 healthy children in whom we did only the ELISA test. We did not find any statistics differences between the histologic findings (gold standard) and the urease and ELISA tests. With IgG antibodies prevalence for H. Pylori in children with recurrent abdominal pain were 57% in contrast with our control group in whom the prevalence was 5%.


Two forms of Staphylococcus aureus in blood of patients with staphylococcal sepsis.
Two distinctly different and stable forms of Staphylococcus aureus were isolated from the blood of each of two patients with staphylococcal sepsis. In each case, one form was hemolytic and the other nonhemolytic, although both had the same biochemical reactions, phage types, and antibiotic susceptibilities, and both were virulent for mice. Variant forms of S. aureus may be selected in vivo by host factors and may be responsible for causing and/or perpetuating infection.


Pumping the shunt revisited. A longitudinal study.
Most cerebrospinal fluid (CSF) shunts employed in the treatment of hydrocephalus include in their designs a pump mechanism that has been used in office practice as an indicator of whether the shunt is functioning properly; however, the pumping characteristics of shunts have been shown to correlate poorly with clinical status at a single point in time. A longitudinal study was performed to determine whether interval changes in the pumping characteristics of shunts correlate with changes in clinical status. 115 patients were examined on at least two occasions by a single pediatric neurosurgeon. At the time of the second examination, 10 patients were experiencing symptomatic shunt malfunction confirmed by neuroimaging investigations and operative findings; the remaining 105 patients were unchanged clinically at the time of the second examination. Considered as a test for CSF shunt malfunction, the interval shunt pumping test had a sensitivity of 0.50, a specificity of 0.64, and a likelihood ratio of 1.39. In the sample of patients studied, the negative predictive value was 0.93, and the positive predictive value was only 0.12. The interval shunt pumping test is not sensitive enough to rule out the possibility of shunt malfunction, nor can a positive interval shunt pumping test be considered an indication for an expensive diagnostic investigation in the asymptomatic patient.


Processing in the hepatitis C virus E2-NS2 region: identification of p7 and two distinct E2-specific products with different C termini.
The hepatitis C virus (HCV) H strain polyprotein is cleaved to produce at least nine distinct products: NH2-C-E1-E2-NS2-NS3-NS4A-NS4B-NS5A-NS5B-CO OH. In this report, a series of C-terminal truncations and fusion with a human c-myc epitope tag allowed identification of a tenth HCV-encoded cleavage product, p7, which is located between the E2 and NS2 proteins. As determined by N-terminal sequence analysis, p7 begins with position 747 of the HCV H strain polyprotein. p7 is preceded by a hydrophobic sequence at the C terminus of E2 which may direct its translocation into the endoplasmic reticulum, allowing cleavage at the E2/p7 site by host signal peptidase. This hypothesis is supported by the observation that cleavage at the E2/p7 and p7/NS2 sites in cell-free translation studies was dependent upon the addition of microsomal membranes. However, unlike typical cotranslational signal peptidase cleavages, pulse-chase experiments indicate that cleavage at the E2/p7 site is incomplete, leading to the production of two E2-specific species, E2 and E2-p7. Possible roles of p7 and E2-p7 in the HCV life cycle are discussed.


A 64-channel ASIC for in-vitro simultaneous recording and stimulation of neurons using microelectrode arrays.
A 64 channels CMOS chip dedicated to in-vitro simultaneous recording and stimulation of neurons using microelectrode arrays has been developed. It includes, for each channel, a low noise, variable gain (10, 75 or 750), 0.08 Hz-3 kHz bandwidth measurement path with unity-gain for lower frequencies to allow measurement of the electrochemical potential. A snapshot style Sample & Hold circuitry allows to have "images" of the 64 channels at a maximum sampling frequency of 50 kHz. Input-referred noise of the measurement path is 4.3 microV RMS integrated from 0.08 Hz to 3 kHz. To get rid of the random, slowly varying, DC offset potential that exists at the electrode-electrolyte interface, the ASIC can be supplied with floating VSS, VDD. Circuit size is 2.4 mm per 11.2 mm (0.35 microm CMOS process) and its power consumption is about 125 mW.


Deformability measurements on individual sickle cells using a new system with pO2 and temperature control.
Although the rheologic behavior of sickle erythrocytes (SS cells) is highly dependent on oxygen tension (pO2) and temperature, very little data exist regarding the effects of deoxygenation and reoxygenation on the rheology of "individual" SS cells at body temperature. We have devised and assessed a new experiment system, in which micropipette aspiration can be performed on individual cells in a constant-temperature chamber that has ports for changing media with different pO2 (effected in 30 to 120 seconds) and sensing probes for monitoring pO2 and temperature. This system enabled us to simultaneously alter and monitor pO2 at 37 +/- 0.5 degrees C, and to monitor and study a single cell under microscopic observation. The static rigidity (E) and dynamic rigidity (eta) of individual SS cells were determined by repeated aspirations of the same cell under various pO2. With stepwise reductions in pO2, E and eta showed no significant changes before sickling, but once sickled, their values markedly increased by 10(2)- to 10(3)-fold concomitantly with morphologic alteration of the cell. Thus, the deformability of a single SS cell behaves in an "all or none" manner at a critical pO2, and earlier studies on the effect of deoxygenation on the rheology of SS cell suspensions probably reflect the overall behavior of SS cells with widely distributed critical pO2.


Open access data sharing in genomic research.
The current emphasis on broad sharing of human genomic data generated in research in order to maximize utility and public benefit is a significant legacy of the Human Genome Project. Concerns about privacy and discrimination have led to policy responses that restrict access to genomic data as the means for protecting research participants. Our research and experience show, however, that a considerable number of research participants agree to open access sharing of their genomic data when given the choice. General policies that limit access to all genomic data fail to respect the autonomy of these participants and, at the same time, unnecessarily limit the utility of the data. We advocate instead a more balanced approach that allows for individual choice and encourages informed decision making, while protecting against the misuse of genomic data through enhanced legislation.


Breakdown of phosphatidylinositol 4,5-bisphosphate in a T-cell leukaemia line stimulated by phytohaemagglutinin is not dependent on Ca2+ mobilization.
Addition of phytohaemagglutinin (PHA) to the [32P]Pi-prelabelled JURKAT cells, a human T-cell leukaemia line, resulted in a decrease of [32P]phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] to about 35% of the control value. The decrease was almost complete within 30s after the PHA addition. This decrease was followed by an increase in the 32P-labelling of phosphatidic acid (maximally 2.8-fold at 2 min). The stimulation of myo-[2-3H]inositol-prelabelled JURKAT cells by PHA induced an accumulation of [2-3H]inositol trisphosphate in the presence of 5 mM-LiCl. The result indicates hydrolysis of PtdIns (4,5)P2 by a phospholipase C. The PHA stimulation of JURKAT cells induced about 6-fold increase in the cytosolic free Ca2+ concentration, [Ca2+]i, which was reported by Quin-2, a fluorescent Ca2+ indicator. Studies with partially Ca2+-depleted JURKAT cells, with the Ca2+ ionophore A23187, and with 8-(diethylamino)-octyl-3,4,5-trimethoxybenzoate indicate that the breakdown of PtdIns(4,5)P2 is not mediated through changes of [Ca2+]i. These results therefore indicate that the PHA-induced breakdown of PtdIns(4,5)P2 in JURKAT cells is not dependent on the Ca2+ mobilization.


Trace element absorption in infants as a foundation to setting upper limits for trace elements in infant formulas.
The bioavailability of the trace elements iron, zinc, copper and manganese from human milk is high compared to cow's milk and infant formulas. This high bioavailability may be explained by the presence of lactoferrin in human milk, which may facilitate iron and manganese uptake via an intestinal receptor for this protein. High concentrations of ascorbate and citrate may also facilitate uptake of trace elements from human milk and milk formulas, while a high concentration of casein in cow's milk and cow's milk formulas may limit trace element absorption from these diets. Trace element absorption from soy formula is low, mostly due to the presence of phytate but possibly also due to some protein fraction. Trace elements sharing absorptive pathways compete for uptake, and imbalances in the ratios between trace elements (Fe/Zn, Zn/Cu, Fe/Mn) in formulas may impair trace element absorption. These factors need to be taken into consideration when setting upper limits for trace elements in formulas. With our present knowledge, an upper limit for iron of 14 mg/l, for zinc, 12 mg/l, copper, 1.2 mg/l, and manganese, 0.6 mg/l are suggested. The capacity of infants to homeostatically adapt to varying intakes of trace elements needs to be further evaluated.


Bolstering diagnostic reasoning skills with adaptive learning.
Adaptive learning emerges when precise assessment informs delivery of educational materials. This study will demonstrate how data from Human Dx, a case-based e-learning platform, can characterize an individual's diagnostic reasoning skills, and deliver tailored content to improve accuracy. Pearson Chi-square analysis was used to assess variability in accuracy across three groups of participants (attendings, residents, and medical students) and three categories of cases (core medical, surgical, and other). Logistic regression analyses were conducted to explore the relationship between solve duration and accuracy. Mean accuracy and duration were calculated for 370 individuals. Repeated measures analysis of variance (ANOVA) were used to assess variability for an individual solver across the three categories. There were significant differences in accuracy across the three groups and the three categories (p < 0.001). Individual solvers have significant variance in accuracy across the three categories. Shorter solve duration predicted higher accuracy. Patterns of performance were identified; four profiles are highlighted to demonstrate potential adaptive learning interventions. Human Dx can assess diagnostic reasoning skills. When weaknesses are identified, adaptive learning strategies can push content to promote skill development. This has implications for customizing curricular elements to improve the diagnostic skills of healthcare professionals.


The effects on Trypanosoma cruzi of novel synthetic naphthoquinones are mediated by mitochondrial dysfunction.
Despite ongoing efforts, the current treatment for Chagas disease is still unsatisfactory, mainly because of the severe side effects and variable efficacy of the available nitroheterocycles. Our group has been assaying natural quinones isolated from Brazilian flora, and their derivatives, as alternative chemotherapeutic agents against Trypanosoma cruzi. From C-allyl lawsone three naphthofuranquinones were synthesized, which were active against trypomastigotes and epimastigotes. Here, we further investigated the activity and the mechanisms of action of these quinones. They exhibited powerful effects on intracellular amastigotes, presenting low toxicity to the host cells. Ultrastructural analyses of treated epimastigotes and trypomastigotes indicated a potent effect of the three naphthofuranquinones on the parasite mitochondrion, which appeared drastically swollen and with a washed-out matrix profile. Fluorescence-activated cell sorting analysis of rhodamine 123-stained T. cruzi showed that the three naphthofuranquinones caused a potent dose-dependent collapse of the mitochondrial membrane potential, especially in the epimastigote form. Naphthofuranquinones also decreased specifically mitochondrial complex I-III activity in both epimastigotes and trypomastigotes, parallel to a reduction in succinate-induced oxygen consumption. Mitochondrial hydrogen peroxide formation was also increased in epimastigotes after treatment with the naphthofuranquinones. Our results indicate that the trypanocidal action of the naphthofuranquinones is associated with mitochondrial dysfunction, leading to increased reactive oxygen species generation and parasite death.


Diaphragm motion affects flow patterns in an artificial heart.
In the sac-driven artificial heart, the flow characteristics are coupled to the dynamics of the sac motion. The opening dynamics of the sac wall can, for example, strongly affect the chamber flow characteristics during diastole by directing or impeding the inflow. Poor sac motion can reduce the volume output of the pump and may increase the potential for thrombus formation within the ventricular chamber. It is particularly important for laboratory studies of the flow fields in artificial hearts that the diaphragm motion properly simulates the sac motion observed in vivo. In the present study, flow visualization was performed to investigate the relationship between the chamber flow characteristics of a Penn State artificial heart and the motion of the diaphragm during the filling phase during in vitro experimentation. The chamber flow pattern and diaphragm motion were recorded as a function of time, using high-speed videography. Experiments were conducted to determine the influence of diaphragm motion on the flow characteristics by altering the filling pressure, diaphragm thickness, and fluid density. Diaphragm motion was quantified by tracking the position of three surface points over the cardiac cycle. The alignment of these three surface trajectories can be used to quantify the uniformity of diaphragm motion. As a result, diaphragm motion was determined to be nonuniform under most operating conditions with the diaphragm opening in a wave-like pattern starting at the bottom of the chamber and propagating toward the inflow/outflow ports. This opening pattern simulates the opening pattern observed in an in vitro study of the clinical blood sac used in the Lionheart LVAD.