PROX1 promotes hepatocellular carcinoma metastasis by way of up-regulating hypoxia-inducible factor 1α expression and protein stability.
Hepatocellular carcinoma (HCC) is one of the most common cancers and the third leading cause of death from cancer worldwide. HCC has a very poor prognosis because of tumor invasiveness, frequent intrahepatic spread, and extrahepatic metastasis. The molecular mechanism of HCC invasiveness and metastasis is poorly understood. The homeobox protein PROX1 is required for hepatocyte migration during mouse embryonic liver development. In this study, we show that high PROX1 protein expression in primary HCC tissues is associated with significantly worse survival and early tumor recurrence in postoperative HCC patients. Knockdown of PROX1 expression in HCC cells inhibited cell migration and invasiveness in vitro and HCC metastasis in nude mice while overexpression of PROX1 in HCC cells promoted these processes. PROX1's pro-metastasis activity is most likely attributed to its up-regulation of hypoxia-inducible factor 1α (HIF-1α) transcription and stabilization of HIF-1α protein by recruiting histone deacetylase 1 (HDAC1) to prevent the acetylation of HIF-1α, which subsequently induces an epithelial-mesenchymal transition response in HCC cells. We further demonstrated the prognostic value of using the combination of PROX1 and HDAC1 levels to predict postoperative survival and early recurrence of HCC. PROX1 is a critical factor that promotes HCC metastasis.


Dynamics of a model for the variability of the interspike intervals in a retinal neuron.
Recently, a model has been proposed to explain the statistics of the variability of interspike intervals of ganglion cells in the retina of goldfish under steady-state stimulation. In this note, it is shown that the dynamical behaviour of the model, both under steady-state and dynamical stimuli, is characterized by input-invariance of the output random process after a time transformation. This allows to study the signal-processing properties of the model, and to test its applicability by a more complete experimental analysis.


Sympathetic nervous system modulates macrophage function.
We have reported previously that sympathectomy augments immune responses in mice and rats. In the present study, we show that ablation of the sympathetic nervous system augments macrophage function as measured by increased TNF secretion. We also show that a factor present in the sympathetic ganglia of newborn rats, suppresses secretion of TNF by LPS-stimulated macrophages as does the beta-adrenergic agonist isoproterenol.


Relation between the size of motor units and the spectral characteristics of their action potentials. email@example.com.
The purpose of this study was to clarify the influence of the size of an individual motor unit on the spectral characteristics of its motor unit action potentials (MUAPs). In 4 human subjects, we first averaged the isometric force and the surface EMG signals triggered by the intramuscularly recorded action potentials of each motor unit during voluntary isometric contraction. Then, we obtained averaged twitch contraction curves, averaged MUAPs derived from surface EMG signals (S-MUAPs), and the power spectrum of the S-MUAPs. Finally, we tested for correlations among these results in each subject. There was a positive correlation among the mean power frequency of the S-MUAPs, the maximal amplitude of the S-MUAPs, and the maximal twitch tension of their motor unit in each subject (r = 0.58-0.85; P < 0.05). Since the twitch tension and the amplitude of the S-MUAPs are well-known predictors of the size of motor units, we conclude that the spectral characteristics of the S-MUAPs reflect the size of the motor unit from which they originate.


Efficacy of Fentanyl Transdermal Patch in Impacted Mandibular Third Molar Surgery-A Comparative Study.
Removal of mandibular third molars surgically is one of the most frequently performed oral surgical procedures which are often accompanied with post-operative pain, swelling and trismus. Despite general progress in pain management, moderate to severe acute post-operative pain after removal of lower third molars remains a problem. Fentanyl is an extremely effective drug in the treatment of severe chronic pain such as cancer pain and post-operative pains which acts by increasing patient's tolerance to pain. Fentanyl Transdermal System (FTS) is a rectangular transdermal patch which contains high concentration of fentanyl, a potent short-acting Schedule II opiate. In this study the efficacy of transdermal fentanyl for management of post-operative pain after impacted mandibular 3rd molar surgery is evaluated. 20 patients within the age group of 18-40 years with asymptomatic impacted mandibular third molars were equally divided into 2 groups as group A & group B which underwent surgery in Local Anaesthesia. In every patient one side belonged to group A and other side belonged to group B. 50 μg FTS was applied in group A while placebo patch was applied in group B. Patients in group A performed significantly better than group B in terms of mean pain intensity scores assessed by VAS and VRS along with minimum need of post-operative rescue analgesics. It was found that FTS resulted in significantly better pain relief, longer pain-free intervals, and lesser post-operative analgesic consumption.


Seeking an optimal dose of preoperative corticosteroids in chronic rhinosinusitis with nasal polyposis: A randomized controlled trial.
Preoperative corticosteroids have been shown to improve surgical visibility and intraoperative blood loss for chronic rhinosinusitis with nasal polyposis (CRSwNP) patients undergoing endoscopic sinus surgery (ESS). However, there is no consensus on the optimal dosing regimen. A randomized, controlled trial was conducted to compare low, medium, and high dose corticosteroids prior to ESS. Patients with CRSwNP refractory to medical management were randomized to low (N = 8), medium (N = 10), or high (N = 5) dosing regimens of corticosteroids prior to ESS. Baseline disease severity was measured with the 22-item Sino-nasal Outcome Test and Lund-Mackay scores. Modified Lund-Kennedy endoscopic scores (MLKES) were measured at baseline and after corticosteroid treatment. Intraoperative parameters were measured including Boezaart surgical visibility score, intraoperative blood loss, and operative time. Medium dose corticosteroids demonstrated a superior surgical visibility score to low dose and comparable results to high dose, but these results were not significant (p = 0.33). No significant difference was observed between groups for total blood loss (p = 0.15), operative time (p = 0.87), or change in MLKES (p = 0.27). Current recommendations include the use of preoperative corticosteroids in patients with CRSwNP undergoing ESS, but there is no consensus on dose or duration. We did not find a statistically significant difference in surgical field visibility, intraoperative blood loss, or operative time between different dosing regimens. Further studies are needed to evaluate the efficacy of a low-dose preoperative regimen with the goal of reducing cumulative patient exposure to systemic corticosteroids.


Patients with pretreatment leukoencephalopathy and older patients have more cognitive decline after whole brain radiotherapy.
To investigate predictors of cognitive decline after whole brain radiotherapy (WBRT) for brain metastases. A secondary analysis of a phase 2 clinical trial was conducted in patients who received stereotactic radiosurgery for 1-10 brain metastases and WBRT (NCT01046123). The Montreal Cognitive Assessment (MoCA) was performed at baseline and every 3 months after WBRT. Baseline T2-weighted fluid attenuation inversion recovery magnetic resonance imaging was independently assessed by two neuroradiologists for the presence of white matter hyperintensities (WMH) using the Fazekas visual rating scale. WMH were also manually segmented for volumetric analysis. Univariable and multivariable logistic regression were used to test the association between baseline variables and MoCA score decline. Forty-six patients survived ≥ 3 months after treatment. Age (OR 1.12 (1.04-1.21), p < 0.01), baseline WMH volume (OR 1.20, 95% CI 1.06-1.52, p = 0.02) and baseline Fazekas score ≥ 3/6 (OR 6.4, 95% CI 1.7-24.7, p < 0.01) were predictive of MoCA score decline. In multivariable analysis, age was the only significant predictor of MoCA decline. However, all three patients with pre-treatment leukoencephalopathy (Fazekas score = 6/6) had notable adverse outcomes due to cognitive impairment: one required full-time home nursing support and two were institutionalized. A greater decline in cognition after WBRT was observed in older patients and patients with a higher baseline WMH burden. Although this study is small and hypothesis-generating, we propose that radiation oncologists should exercise caution in prescribing WBRT if leukoencephalopathy is present on pre-treatment imaging. clinicaltrials.gov identifier NCT01046123. First posted January 11, 2010. https://clinicaltrials.gov/ct2/show/NCT01046123.


Sexual behaviors at home and abroad: an online survey of Canadian young adult travelers.
For young adults, travel- an accessible and aspirational experience- may be accompanied by high-risk lifestyle behaviors abroad, which in turn, increases the risk of sexually transmitted and blood-borne infections (STBBI). This study aimed to examine sexual and risk behaviors of young Canadian adults both at-home and during international travel. Sexually-active Canadians, aged 18-25 years (N = 646) who travelled abroad in 2016, completed an online, cross-sectional survey analyzed by descriptive statistics. Outcome measures included young Canadian adults' lifestyle risk and sexual behaviors at-home and abroad. Sexual behaviors, both penetrative and non-penetrative activities, decreased significantly (p < 0.001; McNemar test) abroad compared to at-home. International travel elicited a statistically significant increase in alcohol consumption compared to at-home (Wilcoxon, z = - 11.341, p < 0.001). Partner type (new trip-acquired partner) abroad was associated with a greater number of travel-acquired sexual partners (Mann-Whitney, U = 4901, p < 0.001), inconsistent condom use during penetrative sex (U = 7215, p = 0.009), and sex under the influence of alcohol (Test of Two Proportions, p < 0.001). Although many young Canadian respondents practiced abstinence in their 2016 travel, for sexually-active travelers, new partner-type was related to high risk sexual behaviors. Young Canadians exhibited sexual risk behaviors both at-home and while travelling; suggesting the need for both domestic and pre-travel sexual health interventions.


MarineMetagenomeDB: a public repository for curated and standardized metadata for marine metagenomes.
Metagenomics is an expanding field within microbial ecology, microbiology, and related disciplines. The number of metagenomes deposited in major public repositories such as Sequence Read Archive (SRA) and Metagenomic Rapid Annotations using Subsystems Technology (MG-RAST) is rising exponentially. However, data mining and interpretation can be challenging due to mis-annotated and misleading metadata entries. In this study, we describe the Marine Metagenome Metadata Database (MarineMetagenomeDB) to help researchers identify marine metagenomes of interest for re-analysis and meta-analysis. To this end, we have manually curated the associated metadata of several thousands of microbial metagenomes currently deposited at SRA and MG-RAST. In total, 125 terms were curated according to 17 different classes (e.g., biome, material, oceanic zone, geographic feature and oceanographic phenomena). Other standardized features include sample attributes (e.g., salinity, depth), sample location (e.g., latitude, longitude), and sequencing features (e.g., sequencing platform, sequence count). MarineMetagenomeDB version 1.0 contains 11,449 marine metagenomes from SRA and MG-RAST distributed across all oceans and several seas. Most samples were sequenced using Illumina sequencing technology (84.33%). More than 55% of the samples were collected from the Pacific and the Atlantic Oceans. About 40% of the samples had their biomes assigned as 'ocean'. The 'Quick Search' and 'Advanced Search' tabs allow users to use different filters to select samples of interest dynamically in the web app. The interactive map allows the visualization of samples based on their location on the world map. The web app is also equipped with a novel download tool (on both Windows and Linux operating systems), that allows easy download of raw sequence data of selected samples from their respective repositories. As a use case, we demonstrated how to use the MarineMetagenomeDB web app to select estuarine metagenomes for potential large-scale microbial biogeography studies. The MarineMetagenomeDB is a powerful resource for non-bioinformaticians to find marine metagenome samples with curated metadata and stimulate meta-studies involving marine microbiomes. Our user-friendly web app is publicly available at https://webapp.ufz.de/marmdb/ .


Pericarditis.
Pericarditis is a common but frequently subclinical entity. There are a number of causes, including infection, systemic illness, cardiac disease, trauma, and neoplasm. Iatrogenic causes include surgery, cardiac instrumentation, irradiation, and medications. The clinical presentation varies, depending on the cause. Chest pain and dyspnea are characteristic complaints. A typical progression of ECG changes occurs during the course of acute pericarditis. These changes occasionally require differentiation from those of acute myocardial infarction or normal variant ST segment elevation. Echocardiography is the most sensitive technique for detecting the presence of pericardial effusion. In addition, a number of echocardiographic findings are characteristic of larger effusions and cardiac tamponade. Any form of pericarditis may lead to the development of cardiac tamponade. Malignant effusion is probably the most common single cause.


Angiotensin II and guanine nucleotides stimulate formation of inositol 1,4,5-trisphosphate and its metabolites in permeabilized adrenal glomerulosa cells.
Angiotensin II (AII) interacts with specific receptors in the adrenal glomerulosa cell and stimulates the hydrolysis of plasma membrane phosphoinositides by phospholipase C, with production of inositol 1,4,5-trisphosphate (Ins-1,4,5-P3) and subsequent mobilization of intracellular Ca2+. In electrically permeabilized, [3H]inositol-labeled glomerulosa cells, AII stimulated Ins-1,4,5-P3 production within 15 s with half-maximal potency of 10(-9) M. The nonhydrolyzable GTP analog, guanosine 5'-O-thiotriphosphate (GTP gamma S), stimulated Ins-1,4,5-P3 formation in a dose-dependent manner with half-maximal effect at 10(-7) M. AII-activated Ins-1,4,5-P3 production was further increased by guanine nucleotides. The rate at which GTP gamma S-stimulated inositol polyphosphate production was consistently slower than that of AII. In adrenal membrane preparations, GTP gamma S-stimulated polyphosphoinositide hydrolysis was enhanced by Ca2+, with half-maximal activity at 300 nM free Ca2+. Ins-1,4,5-P3 formation was also increased by NaF, further indicating the involvement of a guanine nucleotide regulatory protein. In addition to Ins-1,4,5-P3 and its metabolites formed during degradation via the 4-monophosphate pathway, AII and GTP gamma S stimulated the formation of the phosphorylated metabolite inositol 1,3,4,5-tetrakisphosphate and inositol 1,3,4-trisphosphate in permeabilized cells. The absence of a significant rise in inositol 1-monophosphate indicated that phosphatidylinositol hydrolysis was not stimulated by AII or GTP gamma S. Pretreatment of glomerulosa cells with pertussis toxin for 12 h before permeabilization did not inhibit AII- or GTP gamma S-stimulated inositol polyphosphate formation. However, treatment with cholera toxin, forskolin, or 8-Br-cAMP for 12 h enhanced both basal and ligand-stimulated Ins-1,4,5-P3 production. These observations suggest that agonist binding to the AII receptor activates a polyphosphoinositide-specific phospholipase C in the adrenal glomerulosa cell, and that a distinctive guanine regulatory protein is involved in this mechanism.


Epitope recognized by anti-glomerular basement membrane (GBM) antibody in a patient with repeated relapse of anti-GBM disease.
The major epitopes recognized by autoantibodies in anti-glomerular basement membrane (GBM) disease are found in the α3-subunit non-collagenous domain of type IV collagen [α3(IV)NC1], which is present in the glomerular and alveolar basement membranes. These epitopes are structurally cryptic, owing to the hexamer formation of the non-collagenous domain of α3, α4, and α5 subunits and are expressed by the dissociation of the hexamer. Anti-GBM disease usually manifests as a single attack (SA), and we rarely see patients who repeatedly relapse. We recently treated a patient with anti-GBM disease who exhibited repeated relapse (RR). Here, we conducted immunohistochemistry of formalin-fixed paraffin-embedded normal kidney sections and immunoblotting using recombinant human α3(IV)NC1 to compare the epitopes recognized by anti-GBM antibodies in the RR patient and SA patients. Although a clear staining of GBM especially in the connecting basement membrane of Bowman's capsule was observed when IgGs of SA patients were used as primary antibodies, such staining was not obtained when IgG of the RR patient was employed. In immunoblotting of α3(IV)NC1 using the IgG of the RR patient as a primary antibody, an 18-kDa band was detected besides the 56.8-kDa band corresponding to the whole-size α3(IV)NC1. Whereas the 56.8-kDa band disappeared after digestion of the recombinant α3(IV)NC1 by protease, the 18-kDa band remained. Furthermore, the 18-kDa band was not detected by a commercially available anti-α3(IV)NC1 monoclonal antibody. These findings suggest that the IgG of the RR patient recognizes the epitope distinct from that recognized by the anti-α3(IV)NC1 monoclonal antibody.


Selected as the best paper in JAGS in the 1970s mission of the National Institute on Aging.
The National Institute on Aging (NIA), the newest of the 11 National Institutes of Health, is dedicated to improving the quality of life of the old in America through biomedical, social, and behavioral research. Aging is viewed as more than just decline and deterioration; it is also a process of continued development and accumulated knowledge. The NIA will encourage innovative research but will not support the delivery of health services, as that is the domain of the other agencies. In areas of overlap, such as diseases common to the old, the NIA will collaborate with other Institutes. A good target area for collaboration is senile dementia. Other areas of interest to the NIA are: encouraging the incorporation of geriatric medicine as a subspecialty, developing retirement test patterns, and investigating drug-drug and drug-age interactions, personality and social processes, and immunocompetence.


C. elegans Glia Are Bona Fide Odorant Receptor Cells.
There is increasing evidence that supporting/glial cells in sensory systems function in sensory transduction. Duan et al. demonstrate that the glial cells of the C. elegans amphid apparatus serve as odorant receptor cells and regulate neuronal output and behavior.


Smoking during pregnancy and risk of abnormal glucose tolerance: a prospective cohort study.
Disturbances in glucose metabolism during pregnancy are associated with negative sequalae for both mother and infant. The association between smoking and abnormal glucose tolerance (AGT) remains controversial. Therefore, the aim of this study was to examine the relationship between smoking prior to and during pregnancy and risk of AGT. We utilized data from a prospective cohort of 1,006 Hispanic (predominantly Puerto Rican) prenatal care patients in Western Massachusetts. Women reported pre- and early pregnancy smoking at recruitment (mean = 15 weeks) and mid pregnancy smoking at a second interview (mean = 28 weeks). AGT was defined as > 135 mg/dL on the routine 1-hour glucose tolerance test (1-hr OGTT). We used multivariable regression to assess the effect of pre, early, and mid-pregnancy smoking on risk of AGT and screening plasma glucose value from the 1-hr OGTT. In age-adjusted models, women who smoked > 0-9 cigarettes/day in pre-pregnancy had an increased risk of AGT (OR = 1.90; 95% CI 1.02-3.55) compared to non-smokers; this was attenuated in multivariable models. Smoking in early (OR = 0.48; 95% CI 0.21-1.10) and mid pregnancy (OR = 0.38; 95% CI 0.13-1.11) were not associated with AGT in multivariable models. Smoking during early and mid pregnancy were independently associated with lower glucose screening values, while smoking in pre-pregnancy was not. In this prospective cohort of Hispanic women, we did not observe an association between smoking prior to or during pregnancy and risk of AGT. Findings from this study, although based on small numbers of cases, extend prior research to the Hispanic population.


Revisiting published genomes with fresh eyes and new data: Revising old sequencing data can yield unexpected insights and identify errors.
Old data are like yesterday's leftovers: sapped of novelty and excitement. But revisiting old sequence data with a fresh mind and new techniques can yield new and unexpected results.


Exposure to microorganisms associated with allergic alveolitis and febrile reactions to mold dust in farmers.
To compare exposure to microorganisms associated with allergic alveolitis (AA) and with febrile reactions to inhaled mold dust (organic dust toxic syndrome [ODTS]) in farmers and in normal subjects. A prospective study in which exposure was evaluated within two weeks of medical consultation for AA or ODTS. Samples were collected during normal farming (background) and during the handling of materials associated with disease or causing maximal exposure in reference farms (worst case). Swedish farms Eleven farmers with a confirmed diagnosis of AA from ten farms, 16 subjects with symptoms of ODTS from 12 farms, and 17 reference farmers. Worst-case samples representative of the exposure preceding disease were obtained on four farms where five farmers had had AA; the samples contained on average 2.6 +/- 1.8 x 10(9) (SD) spores/m3 of air. On six farms where nine farmers had had ODTS, representative samples averaged 13 +/- 13 x 10(9) spores/m3, and on reference farms this figure was 0.12 +/- 0.20 x 10(9) spores/m3. The daily spore dose associated with allergic alveolitis was 2 x 10(9) spores/d, which was ten times higher than on reference farms. The average dose associated with ODTS was 2 x 10(10) spores. Worst-case samples, collected during 10 to 30 min, contributed to more than 90 percent of the day exposure on farms where AA or ODTS had occurred. Allergic alveolitis was associated with high exposure levels on most weekdays for weeks, and ODTS was associated with extreme exposure occurring on a single day. There was no correlation with individual spore types and disease and the present results are compatible with a hypothesis that common cell wall components of microorganisms may cause "toxic" symptoms and stimulate immune reactions.


Syringomyelia of the thoracic spinal cord associated with spinal meningiomas.
Syringomyelia is known to occur secondary to compression of the spinal cord. We report the case of a female patient who underwent removal of a spinal meningioma. She re-presented 30 years later with multiple meningiomas causing cord compression. After a 4 year interval she was found to have developed a syrinx proximal to the site of compression. Comparison with previous case reports suggest that the causation of syringomyelia is multi-factorial.


The role of access to electricity, female education, and public health expenditure on female health outcomes: evidence from SAARC-ASEAN countries.
The importance of the status of female health should have research priority due to the unique medical needs of women. Hence this paper attempts to explore the nexus of access to electricity, female education, and public health expenditure with female health outcomes in the SAARC-ASEAN countries. Using the data of 2002-2018, and applying the cross-sectional dependence test, Modified Wald test, Wooldridge test, the Panel corrected standard error (PCSE) model, the Feasible generalized least square (FGLS) model, and the pair-wise Granger causality test, the robust outcomes on female health are found. Access to electricity, female education rate, public health expenditure, economic growth, and immunization rate, all have a positive effect on female life expectancy at birth, and a negative effect on the female adult mortality rate. The urbanization rate has a significantly positive impact on female life expectancy at birth but an insignificant impact on female adult mortality rate. The one-way causal relationship between the variables are also revealed. All the results are rational and have important milestone for the health sector. The health status of females should be improved and protected by formulating effective policies on access to electricity, female education, public health expenditure, immunization, economic growth, and urbanization.


Chronic optogenetic activation augments aβ pathology in a mouse model of Alzheimer disease.
In vivo experimental evidence indicates that acute neuronal activation increases Aβ release from presynaptic terminals, whereas long-term effects of chronic synaptic activation on Aβ pathology remain unclear. To address this issue, we adopted optogenetics and transduced stabilized step-function opsin, a channelrhodopsin engineered to elicit a long-lasting neuronal hyperexcitability, into the hippocampal perforant pathway of APP transgenic mice. In vivo microdialysis revealed a ∼24% increase in the hippocampal interstitial fluid Aβ42 levels immediately after acute light activation. Five months of chronic optogenetic stimulation increased Aβ burden specifically in the projection area of the perforant pathway (i.e., outer molecular layer of the dentate gyrus) of the stimulated side by ∼2.5-fold compared with that in the contralateral side. Epileptic seizures were observed during the course of chronic stimulation, which might have partly contributed to the Aβ pathology. These findings implicate functional abnormalities of specific neuronal circuitry in Aβ pathology and Alzheimer disease.


A secreted receptor related to M1 protein of Streptococcus pyogenes binds to fibrinogen, IgG, and albumin.
An extracellular protein (eMP) of Streptococcus pyogenes M type 1 was isolated by affinity chromatography on albumin- and IgG-Sepharose. The protein was found to bind to the human plasma proteins, fibrinogen, IgG, and albumin. Analysis of eMP by Western blotting demonstrated a major band with a molecular weight of 49 kD which was responsible for binding of the three plasma proteins. The purified protein was found to bind selectively to human and primate polyclonal IgG, human and mouse albumin, as well as human fibrinogen which has been the only fibrinogen tested. Serological investigations revealed a close relation of eMP to streptococcal M1 protein. It showed a reaction of identity with cell-extracted M1 protein in immunodiffusion. Moreover, the 49 kD peptide responsible for binding, was recognized with an antiserum directed against the 20 amino acids comprising synthetic peptide (42VAL-61GLU) of the N-terminal part of the M1 protein sequence. The affinity of M protein to plasma proteins other than fibrinogen opens new approaches to its purification by affinity chromatography.


Hereditary cancer syndrome: Part 1.--Clinical and educational issues.
To review current information on the biology and characteristics of hereditary cancer syndromes (HCS), and to identify families with HCS, various methods to communicate the diagnosis to families, and associated considerations for clinical practice and education. Published articles and book chapters. HCS, which accounts for approximately 5%-10% of all malignancies, is characterized by diagnosis of the same malignancy in multiple family members, an earlier age of onset than expected, an increased frequency of bilateral cancers in paired organs, and the presence of premalignant syndromes. Identifying families with HCS and referring them to screening programs are necessary to reduce morbidity and mortality in these families. Many clinical, educational, and research issues are emerging. Nurses need to be aware of HCS in order to identify families with HCS and refer them to screening programs. Information about HCS needs to be incorporated into basic, graduate, and continuing education nursing programs to increase awareness of HCS. Further nursing research is needed to better understand the best way to communicate the diagnosis to families, identify the psychosocial needs of individuals from these families, and facilitate cancer prevention and detection measures in these families.


Commentary: Why treatment is the best choice for childhood mental disorders - a commentary on Roest et al. (2022).
An important question in mental healthcare for children is whether treatments are effective and safe in the long run. Here, we comment on a recent editorial perspective by Roest et al. (2022), who argue, based on an overview of systematic reviews, 'that there is no convincing evidence that interventions for the most common childhood disorders are beneficial in the long term'. We believe that the available evidence does not justify this conclusion and express our concern regarding the harmful effects of their message. We show that there is evidence to suggest beneficial longer term treatment effects for each of the disorders and explain why evidence-based treatment should be offered to children with mental disorders.


Infantile cataract: comparison of two surgical approaches.
To compare the results of 2 cataract extraction techniques with primary intraocular lens (IOL) implantation in children. Retrospective comparative case series study. This study included children with congenital or developmental cataract. In all cases, anterior capsulorhexis, lens aspiration, posterior continuous curvilinear capsulorhexis, and primary IOL implantation were performed. We compared 2 surgical approaches. In the first approach, after IOL implantation in the bag, posterior optic capture (OC) was performed without anterior vitrectomy (OC technique); in the second approach, anterior vitrectomy was performed without OC of the IOL (AV technique). Patient demographic data as well as ethnic origin, child's age at cataract diagnosis, child's age at surgery, axial length, IOL power in diopters, visual acuity, visual axis opacification, and complications were assessed. One hundred twenty-three eyes were included for surgical approach outcomes comparison; 21 eyes underwent the OC surgical approach and 102 the AV surgical approach. The mean patient age at surgery was 57.3 ± 47.1 months. The mean follow-up was 63.13 months (range 12-202 months). Epithelial lens reproliferation was the major adverse event in our series, affecting 21.1% of patients' eyes; the mean time to epithelial lens reproliferation development was 90 ± 9.70 months. There was no statistically significant difference between the two groups in best spectacle-corrected visual acuity or epithelial lens reproliferation incidence. In our case series we did not find any difference between surgical techniques.


Quantitative effects of methylzoxymethanol acetate on Purkinje cell dendritic growth.
A quantitative analysis was made of alterations in the dendritic organisation of Purkinje cells in the cerebellum of the rat following the administration of the degranulating agent, methylazoxymethanol acetate (MAM). This drug depleted the granule cell population of the cerebellar cortex and disturbed Purkinje cell alignment such that a number of Purkinje cells became inverted and grew in the white matter. The quantitative changes that occurred in the dendritic trees of these cells (increase in segment length, decrease in segment numbers, trichotomy and branching probability) were similar to those seen following other degranulation procedures. The size of the Purkinje cell dendritic tree was found to be related to the number of parallel fibres present in the molecular layer. These results were discussed in relation to current theories of neuronal development and were shown to lend further support to the filopodial attachment hypothesis of dendritic growth.


Protective effect of FGF21 on type 1 diabetes-induced testicular apoptotic cell death probably via both mitochondrial- and endoplasmic reticulum stress-dependent pathways in the mouse model.
Fibroblast growth factor 21 (FGF21) is a novel member identified and was reported to express predominantly in pancreas, liver and adipose tissue, and relatively less in other organs, such as the testis. However, the role of FGF21 in the testis has never been addressed. The present study examined FGF21 expression at mRNA level by real-time RT-PCR assay in the testis of fasting and non-fasting mice or mice with type 1 diabetes that was induced with streptozotocin. We also examined the effect of Fgf21 gene deletion or supplementation of the exogenous FGF21 on the testicular apoptotic cell death spontaneously or induced by type 1 diabetes in FGF21 knockout (FGF21-KO) mice. Deletion of Fgf21 gene does not affect testicular cell proliferation, but significantly increases the spontaneous incidence of testicular TUNEL positive cells with increases in the Bax/Bcl2 expression ratio and apoptosis-inducing factor (AIF) expression. Diabetes induced significant increases in testicular TUNEL positive cells, Bax/Bcl2 expression ratio, AIF expression, CHOP and cleaved caspase-12 expression, and oxidative damage, but did not change the expression of cleaved caspase-3 and caspase-8. Deletion of Fgf21 gene also significantly enhances diabetes-induced TUNEL positive cells along with the increased expression of Bax/Bcl2 ratio, AIF, CHOP, cleaved caspase-12, and oxidative damage, which was significantly prevented by the supplementation of exogenous FGF21. These results suggest that Fgf21 gene may involve in maintaining normal spermatogenesis and also protect the germ cells from diabetes-induced apoptotic cell death probably via the prevention of diabetes-induced oxidative damage.


Fractionation of mouse skin carcinogens in cagarette smoke condensate.
The results of a series of mouse-skin paintings are given for fractions prepared by two schemes designed to concentrate the polycyclic aromatic hydrocarbons (PAH) and their heterocyclic analogues (HETC) present in cigarette smoke condensate into single fractions. It is demonstrated that, for each group, a single index of tumour response, the "Weibull risk parameter" (WRP), can be calculated which, considered in conjunction with two other parameters common to all the groups, adequately describes the pattern of tumour incidence in that group. These indices can be used to calculate for each fraction a further statistic, the "tumorigenic ratio" (TR), which conveniently measures the activity of the fraction relative to whole-smoke condensate on a weight-for-weight basis. From the analyses it is shown that the separation processes can successfully concentrate all types of mouse-skin carcinogenic material, irrespective of the type of condensate used, and that a combination of processes prepares an active concentrate representing 2% by weight of the original condensate.


Cutaneous T-cell lymphoma in a patient with neurofibromatosis type 1.
A variety of neoplasms may occur in association with neurofibromatosis type 1 (NF1). We describe a patient with NF1 and mycosis fungoides. Recommendations for the initial and long-term evaluations of patients with neurofibromatosis are presented.


Current knowledge of idiopathic scoliosis among practising physiotherapists in South Africa.
Idiopathic scoliosis (IS) is a common musculoskeletal condition with a multi-factorial aetiology characterised by a three-dimensional torsional deformity of the spine. To ascertain the current level of knowledge on IS among registered practising physiotherapists who expressed an interest in orthopaedic, muscular, manual and manipulative therapy in South Africa (SA). An online survey was used to collect the data. The questions were based on an existing questionnaire, validated by a South African panel of experts in the field of musculoskeletal physiotherapy and updated based on the 2016 Society of Scoliosis Orthopaedic Rehabilitation Treatment (SOSORT) guidelines for the assessment and management of IS. Two hundred and twenty-three physiotherapists spread across the nine provinces of SA met the inclusion criteria and were included in our study. Our findings showed that about one-third (33.6%) of the physiotherapists could answer more than 50% of these questions correctly, and 16.5% could answer 70% of the questions correctly in relation to the widely accepted guidelines on IS management. The participants had a poor understanding of the diagnosis and treatment involved in managing patients with IS and a lack of knowledge regarding the methods of conservative treatment for scoliosis. Future studies should be aimed at assessing intervention strategies to improve the knowledge of IS in physiotherapists in SA, especially regarding diagnosis and identifying appropriate management strategies. Physiotherapists are often the first contact practitioners for patients presenting with scoliosis and therefore need to have the necessary clinical knowledge on the assessment and management of IS. Our study can improve the awareness among the South African physiotherapists regarding IS and its complex presentation and management.


Prone Positioning With Deep Inspiration Breath Hold for Left Breast Radiotherapy.
With advances in treatment, outcomes for early-stage breast cancer are improving. We investigated the combination of prone position and deep inspiration breath hold to decrease cardiac doses for left-sided breast radiotherapy. Fifteen patients with left-sided breast cancer were enrolled on a single-institution prospective study. Each patient underwent 2 prone positioned computed tomography simulation scans utilizing free breathing and breath-hold. Separate treatment plans for each computed tomography simulation scan were created using tangential fields, and heart and left lung doses were compared between free breathing and breath-hold plans. The technique with the lower mean dose for the heart was used for treatment. All patients were treated with a hypofractionated regimen of 40 to 42 Gy in 15 to 16 fractions, followed by a lumpectomy cavity boost of 10 Gy in 5 fractions when indicated. Wilcoxon paired signed rank tests and paired t tests were performed for statistical analysis of dosimetric endpoints. The median age of our patients was 58 years (range, 40-72 years). One patient was not able to tolerate prone positioning at simulation, leaving 14 patients with evaluable paired scans. The average mean heart dose with free breathing and with breath-hold was 0.93 Gy and 0.72 Gy, respectively (P = .0063). The average max heart dose with free breathing and with breath-hold was 15.70 Gy and 7.19 Gy, respectively (P = .001). The average mean left lung dose with free breathing and with breath-hold was 0.65 Gy and 0.88 Gy, respectively (P = .011). Our results indicate that breath-hold using the real-time position management system may provide additional cardiac dose reduction in patients receiving prone left-breast radiotherapy treated with tangential fields.


Human gaze behaviour during action execution and observation.
Gaze shifts and fixations appear to be proactive in both action execution and observation. We investigated a dependency of anticipatory gaze behaviour by using a block stacking task. Blocks were rectangles depicted on a computer screen and the stacking movements were controlled via computer mouse. Subjects either had to execute the task or had to observe it made by the experimenter, or by the computer. The dependency of gaze behaviour on the visibility of a virtual effector, the visibility of the actor, and the nature of the actor was tested by measuring eye movements. Anticipatory eye movements were predominant when the subjects themselves executed the task. During action observation, gaze behaviour did neither depend on the visibility nor depend on the nature of the actor. However, big variability was found between the subjects suggesting the use of two different strategies in action observation: some subjects were mainly tracking the blocks during stacking movements; others were strongly anticipating. We suggest that gaze behaviour during action observation is not predetermined by rigid neural circuitry, but strongly depends on the context. The possibility to explain the causal mechanism, as well as the ownership of the action may be crucial preconditions for anticipatory gaze behaviour.


Comparison of fixed dose reduced-intensity conditioning with fludarabine and busulfan to PK-guided busulfan AUC (FluBu4K) in hematopoietic stem cell transplant for AML/MDS.
A retrospective cohort study was conducted to assess differences in efficacy and tolerability between a busulfan AUC target of 16.4 mg × Hr/L per day (FluBu4K) and a conventional RIC regimen (FluBu2). Adult patients with a diagnosis of AML or MDS who received fludarabine + busulfan conditioning with or without antithymocyte globulin between 2015 and 2018 were included. The primary outcome was relapse free survival. Overall, 74 patients received conditioning with either FluBu4K or FluBu2. At 18 months, relapse-free survival was not significantly different, at 63.9% with FluBu4k compared to 57.5% with FluBu2 (p = 0.49). There was a statistically significant difference in the cumulative incidence of relapse at 18 months in favor of the FluBu4K regimen, at 12.0% vs 32.5% (p = 0.047). The results of this study indicate that for select patients, there may be benefit in choosing targeted FluBu4K over FluBu2. Adverse effects other than mucositis were not significantly different.


Radiology report "disclaimers" increase the use of abdominal CT in the work-up of pediatric abdominal pain.
Pediatric abdominal pain is commonly evaluated in the emergency department (ED) initially by ultrasonography (U/S). Radiology reports often include commentary about U/S limitations and possible need for additional testing or evaluation independent of study interpretation. We sought to determine if presence of a "disclaimer" is associated with additional imaging. Design: Retrospective cohort. Community ED with volume of 85,000 annual visits. Consecutive ED patients <21-years-old with appendix U/S over 12-months. Radiologist reports were assessed for disclaimers and if definitive diagnoses of appendicitis were made. The incidence of subsequent CT imaging was determined and group differences between categories were calculated. 441 eligible patients were identified with average age 11.7years. Of all U/S studies, 26% were definitive for appendicitis and 74% were non-definitive. Disclaimers were included on 60% of all studies, including 13% of definitive studies and 76% of non-definitive studies. 25% of all studies including a disclaimer had follow-up CT versus 10% of studies without a disclaimer (15% difference; 95% CI: 9-21). For patients with definitive interpretations, 6% had follow-up CT with no significant difference between groups with or without a disclaimer. For patients with non-definitive studies, 26% with a disclaimer had follow-up CT scans versus 13% without a disclaimer (13% difference; 95% CI: 4-22). Appendix ultrasound interpretations often include a disclaimer, which leads to a 150% increase in follow-up CT imaging. We suggest that radiologists consider the impact of including such a disclaimer, knowing that this may contribute to possible unnecessary imaging.


Neuronal network activity in the hippocampus of tau transgenic (Tg4510) mice.
Development of neurofibrillary tangles in Alzheimer's disease correlates with neuronal loss and dementia. Transgenic Tg4510 mice model the tauopathy of the disease, with these mice exhibiting progressive, region-specific neuronal loss, and behavioral deficits. In the present study, neuronal network activity in the hippocampus of 7-month-old Tg4510 mice was investigated and compared with age-matched wild-type (WT) mice. Multisite field potentials were recorded using 16-site silicon probes, inserted across the hippocampus in urethane anesthetized mice. The hippocampal network theta oscillation was evaluated in these mice by stimulating the brainstem nucleus pontis oralis. Subsequently, population spikes in the dentate gyrus were identified in response to perforant path stimulation, and long-term potentiation was elicited by theta burst stimulation. Tg4510 mice showed dramatically reduced dentate gyrus population spike amplitude; however, the magnitude of theta burst stimulation-induced long-term potentiation was identical in WT and transgenic mice. WT and Tg4510 mice showed identical increase in frequency to nucleus pontis oralis stimulation, whereas absolute theta power was severely reduced in the Tg4510 animals. Because total signal power over the entire frequency band range was reduced, there was no difference in relative theta power between WT and Tg4510 mice. These presently described electrophysiological findings can be directly attributed to the drastic reduction of pyramidal/granule neurons in Tg4510 mice, which could be the main contributing factor to their impaired behavior and cognitive function. However, the remaining synapses and neuronal circuitry seem to function properly in these assays.


Accumulation of chromium (VI) from aqueous solutions using water lilies (Nymphaea spontanea).
This study describes an investigation using tropical water lilies (Nymphaea spontanea) to remove hexavalent chromium from aqueous solutions and electroplating waste. The results show that water lilies are capable of accumulating substantial amount of Cr(VI), up to 2.119 mg g(-1) from a 10 mg l(-1) solution. The roots of the plant accumulated the highest amount of Cr(VI) followed by leaves and petioles, indicating that roots play an important role in the bioremediation process. The maturity of the plant exerts a great effect on the removal and accumulation of Cr(VI). Plants of 9 weeks old accumulated the most Cr(VI) followed by those of 6 and 3 weeks old. The results also show that removal of Cr(VI) by water lilies is more efficient when the metal is present singly than in the presence of Cu(II) or in waste solution. This may be largely associated with more pronounced phytotoxicity effect on the biochemical changes in the plants and saturation of binding sites. Significant toxicity effect on the plant was evident as shown in the reduction of chlorophyll, protein and sugar contents in plants exposed to Cr(VI) in this investigation.


Osseointegration of osteoporotic bone implants: Role of stem cells, Silica and Strontium - A concise review.
Osteoporotic fracture treatment has become a skeletal reconstructive challenge due to accelerated bone turnover and impaired bone regeneration potential. Poor osseointegration ability of the osteoporotic bone usually results in implant pull out and failure. Adoption of conventional bone fracture treatment strategies like autografts and allografts have limited applications in such pathological conditions. Hence biomaterials functionalised with therapeutic ions or drugs may be adopted to aid the delivery of therapeutic factors at the defect site to promote bone healing and implant integration, towards functional restoration of the fractured bone. This concise review narrates on improving the osseointegration ability of biomaterials using functional ions like Silica and Strontium. Silica based bone substitutes are known to promote bone healing in non pathological conditions. Further, Strontium based drugs show significant effects in the prevention and treatment of osteoporotic bones. In addition, stem cell therapy has become the focus of orthopaedic research attributed to its ability to restore and accelerate the bone healing process, but the clinical application of stem cells in osteoporotic condition is scarce. Present review suggests a novel strategy of combining the therapeutic potential of functional ions like Silica, Strontium and stem cells within a single implant unit to facilitate osseointegration and osteogenesis, so as to reduce the chances of implant rejection/pull out and encourage osteoporotic bone re-union.


Campylobacter enteritis in South Australia.
Campylobacter jejuni was isolated on coproculture from 13 of 224 patients with suspected infectious diarrhoea whose faecal specimens were examined during a three-month period. These organisms were not isolated from 530 specimens received from asymptomatic and healthy individuals. Diarrhoea and cramping abdominal pain generally lasting two to three days were the major symptoms, though occasional patients had a more prolonged illness. Ingestion of campylobacter resulted in enteric infection with increasing numbers of campylobacter in the stool. Clinical laboratories should attempt to isolate these organisms from patients with diarrhoea.


Prophylactic cerclage in the management of triplet pregnancies.
The purpose of this study was to determine if prophylactic cerclage improves pregnancy outcome in women with triplet pregnancies without a history of cervical insufficiency. Triplet pregnancies with > or = 1 day of outpatient surveillance beginning before 32 weeks' gestation were identified from a database of women in the US who received outpatient preterm labor surveillance services between January 1990 and May 2004. Triplet pregnancies managed with prophylactic cerclage were compared with triplet pregnancies in which cerclage was not placed. Patients with a diagnosis of cervical insufficiency in a previous or in the index pregnancy were excluded from analysis. The primary outcome was incidence of preterm birth before 32 weeks. Groups were compared using Fisher exact test, and Student t test with 2-sided P values < .05 considered statistically significant. Three thousand two hundred seventy-eight triplet pregnancies met criteria for inclusion, of which 248 women (7.6%) received prophylactic cerclage. No significant differences were seen in mean gestational age at delivery, incidence of preterm birth before 32 weeks, birth weight, or neonatal days in the hospital. This study had 80% power to detect a 30% reduction in the primary outcome. Prophylactic cerclage did not result in improved pregnancy or neonatal outcomes in triplet pregnancies without a history of cervical insufficiency.


Heterologous desensitization of bradykinin-induced phosphatidylinositol response and Ca2+ mobilization by neurotensin in NG108-15 cells.
The heterologous desensitization of the bradykinin (BK)-induced increase in intracellular Ca2+ concentration ([Ca2+]i) by neurotensin was studied in neuroblastoma x glioma hybrid NG108-15 cells. The addition of neurotensin to the cells resulted in an increase in [Ca2+]i and an increase in the formation of inositol phosphates in Ca2+-free medium. Pretreatment of the cells with neurotensin resulted in 43% decrease in the BK-induced increase of [Ca2+]i. The increase in [Ca2+]i induced by ionomycin, which causes Ca2+ release from the intracellular pool, was not decreased by pretreatment with neurotensin. This indicates that the inhibitory effect of neurotensin on the BK-induced increase of [Ca2+]i was not due to depletion of the intracellular Ca2+ pool. Pretreatment with neurotensin also caused a 47% decrease in the BK-induced formation of inositol trisphosphates (IP3). This decrease was not due to depletion of phosphatidylinositol bisphosphates. Neurotensin did not inhibit [3H]BK binding to cell membranes. These results show that neurotensin desensitizes the BK responses of NG108-15 cells, heterologously, perhaps by changes in phospholipase C and/or guanine nucleotide-binding protein (G-protein).


Differential detergent treatment allows immunofluorescent localization of the Newcastle disease virus matrix protein within the nucleus of infected cells.
Paramyxoviruses are cytoplasmic viruses and presumably do not require any nuclear function for their replication. However, recent studies using monoclonal antibodies directed against the Newcastle disease virus matrix (M) protein have found a large portion of the M protein apparently associated with the nucleus of infected cells. Whether the M protein is associated with the cytoplasmic surface of the nucleus or whether the M protein is actually located within the nucleus has not been clearly determined. To examine this question, conditions for selectively permeabilizing the cytoplasmic membrane were sought. After treating fixed cells with a low concentration (0.02%) of the nonionic detergent Triton X-100, the cytoplasmic antigen vimentin was stained with a monoclonal antibody, but nuclear antigens were not. Apparently, 0.02% Triton permeabilizes the plasma membrane while leaving the nuclear membrane intact. Under these conditions, monoclonal antibodies directed against the NDV phosphoprotein and hemagglutinin/neuraminidase glycoprotein stained infected cells, but a monoclonal antibody to the M protein did not. The inability of the anti-M monoclonal antibody to stain the nucleus, even though the outer nuclear membrane is accessible under these conditions, indicates that the M protein is not associated with the outer membrane of the nucleus. The nuclei of infected cells treated with a higher concentration (0.05%) of Triton X-100 were stained both with antibodies to nuclear antigens and with the anti-M monoclonal antibody.


Clinicopathological and Molecular Insights into Gallbladder Cancer.
Although gallbladder cancer (GBC) is rare, it is one of the few cancers with a higher mortality rate than incidence, accounting for 1 [...].


The development and preliminary psychometric properties of two positive psychology outcome measures for people with dementia: the PPOM and the EID-Q.
Positive psychology research in dementia care has largely been confined to the qualitative literature because of the lack of robust outcome measures. The aim of this study was to develop positive psychology outcome measures for people with dementia. Two measures were each developed in four stages. Firstly, literature reviews were conducted to identify and operationalise salient positive psychology themes in the qualitative literature and to examine existing measures of positive psychology. Secondly, themes were discussed within a qualitative study to add content validity for identified concepts (n = 17). Thirdly, draft measures were submitted to a panel of experts for feedback (n = 6). Finally, measures were used in a small-scale pilot study (n = 33) to establish psychometric properties. Salient positive psychology themes were identified as hope, resilience, a sense of independence and social engagement. Existing measures of hope and resilience were adapted to form the Positive Psychology Outcome Measure (PPOM). Due to the inter-relatedness of independence and engagement for people with dementia, 28 items were developed for a new scale of Engagement and Independence in Dementia Questionnaire (EID-Q) following extensive qualitative work. Both measures demonstrated acceptable internal consistency (α = .849 and α = .907 respectively) and convergent validity. Two new positive psychology outcome measures were developed using a robust four-stage procedure. Preliminary psychometric data was adequate and the measures were easy to use, and acceptable for people with dementia.


Evidence for a transcortin-like component in human breast cyst fluid.
The occurrence of a specific glucocorticoid binding activity was investigated in breast cyst fluid (BCF) samples aspirated from 481 women under treatment for breast cystic disease. [3H]cortisol was incubated with BCF at 4 degrees C with and without 100-fold molar excess of non-radioactive steroid in order to account for non-specific binding. Corticosterone, progesterone and dexamethasone-binding activities were also investigated in about 50% of the specimens. Consistent amounts of a specific cortisol-, corticosterone- and progesterone-binding component were observed in about 30% of samples. Apparent binding values ranged from 4.31 to 80.78 nmol/l for cortisol, from 3.94 to 75.72 nmol/l for corticosterone, and from 1.18 to 16.45 nmol/l for progesterone. No specific binding for dexamethasone was detected. Scatchard analyses for [3H]cortisol and [3H]progesterone were made in pools of 'positive' BCF, human serum and whey of human milk, respectively. The mean values of the apparent equilibrium association constant (Ka) were compatible with the existence of high affinity protein-hormone interactions in each considered medium. Data obtained in ligand competition experiments for different steroid molecules suggest the similarity of the glucocorticoid- and progesterone-binding component found in 30% of BCF samples examined with the plasma corticosteroid-binding globulin (CBG, transcortin) and especially with the transcortin-like component detected in the whey of the human milk. It is suggested that the transcortin-like component may play an important role in controlling kinetics of transport and in regulating the effective levels of cortisol and progesterone in numerous breast cyst fluids.


The Cellient automated cell block system is useful in the differential diagnosis of atypical glandular cells in Papanicolaou tests.
Atypical glandular cells (AGC) is a very important diagnosis in gynecological cytology. In the current study, the authors investigated the usefulness of Cellient cell blocks (CB) for characterizing AGC on Papanicolaou (Pap) tests. A total of 148 patients with an AGC diagnosis based on Pap tests by cytotechnologists and referred to cytopathologists were studied. Among these patients, there were 68 patients with CB preparations and 80 patients with Pap tests only (TP-AGC group). Follow-up results by Pap tests or biopsies were obtained in 117 of 148 patients. The median follow-up was 13 months (range, 1 month-36 months). Of the 68 patients with CBs, 31 (46%) were reclassified as negative for dysplasia or low-grade intraepithelial lesion; 30 patients (44%) retained a diagnosis of AGC (CB-AGC group); and 7 patients (10%) were given specific diagnoses of high-grade intraepithelial lesion (3 patients), endocervical adenocarcinoma in situ (1 patient), and invasive adenocarcinoma (3 patients). On follow-up, the CB-AGC group was found to have a significantly lower rate of negative/low-grade squamous intraepithelial lesion diagnoses compared with the TP-AGC group (55% vs 85%; P= .006). The CB-AGC group had a significantly higher rate of endocervical or endometrial adenocarcinoma compared with the TP-AGC group (36% vs 8%; P= .003) at the time of follow-up. The rates of high-grade squamous intraepithelial lesion were not found to be statistically different between these 2 groups (9% vs 7%; P= .66). The Cellient CB is a useful technique to further categorize a diagnosis of AGC on Pap tests. Using the Cellient CB system, the pathologist has the ability to improve the diagnostic accuracy of AGC so that unnecessary colposcopic evaluation or biopsies can be avoided.


In situ and tomographic observations of defect free channel formation in ion irradiated stainless steels.
The effects of heavy-ion irradiation on dislocation processes in stainless steels were investigated using in situ irradiation and deformation in the transmission electron microscope as well as post mortem electron tomography to retrieve information on the three-dimensional dislocation state. Irradiation-induced defects were found to pose a strong collective barrier to dislocation motion, leading to dislocation pileups forming in grain interiors and at grain boundaries. The passage of multiple dislocations along the same slip plane removes the irradiation defects and leads to the eventual formation of a defect-free channel. These channels are composed of densely tangled dislocation networks which line the channel-matrix walls as well as residual dislocation debris in the channel interiors. The structures of the dislocation tangles were found to be similar to those encountered in later stages of deformation in unirradiated materials, with the exception that they developed earlier in the deformation process and were confined to the defect free channels. Also, defect free channels were found to widen through both source widening as well as complex cross-slip mechanisms.


Activities of daily living in Parkinson's disease: Time/gender perspective.
The objectives of this study were to explore the changes in the activities of daily living (ADL) in persons with Parkinson's disease (pwPD) over time and to investigate possible differences in ADL performance between men and women with PD. One hundred twenty-nine persons (76 men) with a clinically established PD self-assessed their ADL performance from the time of diagnosis up to 8 years follow-up using the ADL taxonomy. Other demographic and clinical data (motor state, cognition, depression) were also collected and subjected to further analysis. Nine of 12 domains in the ADL taxonomy showed a change over time (Eating and Drinking [P = .009], Mobility [P < .001], Toilet activities [P = .031], Dressing [P < .001], Personal hygiene [P < .001], Communication [P < .001], Cooking [P = .001], Shopping [P < .001] and Cleaning [P < .001]). In addition to time, two domains, (Shopping [P = .007] and Cleaning [P = .027]) also showed an effect of gender with worse scores in women. The nine ADL domains showing effect of time, showed temporary improvement at 12 months follow-up, most probably due to dopaminergic medication. All nine domains deteriorated at later follow-up. As expected, there was deterioration in self-assessed performance in the majority od ADL domains over time. Women assessed their ADLs worse in two domains (Shopping and Cleaning) probably reflecting a general gender-related activity pattern rather than being a PD-specific finding.


Bioactive seco-abietane rearranged diterpenoids from the aerial parts of Salvia prionitis.
Five previously undescribed 4,5-seco-abietane rearrange diterpenoids (1-5, Prionidipene A-E) were isolated from the aerial parts of Salvia prionitis, along with thirteen known seco-abietane diterpenoids (6-18). The structures of 1-5 were elucidated mainly based on analysis of NMR and MS data. The absolute configurations of 1-3 were determined by evaluation of experimental and calculated electronic circular dichroism (ECD) spectra. Putative biosynthetic pathways toward the formation of 1 and 2 are proposed. The nitric oxide (NO) production inhibitory effects of all isolates in lipopolysaccharide (LPS)-induced in RAW 264.7 cells were evaluated. Interestingly, compounds 4 and 9 with a furan-ring showed potent inhibitory activity with IC50 values of 14.56 and 15.11 μM, respectively.


Behavioral treatment options for urinary incontinence.
Behavioral treatments improve bladder control by changing the incontinent patient's behavior, especially his or her voiding habits, and by teaching skills for preventing urine loss. These treatments are effective for most outpatient men and women with stress, urge, or mixed incontinence. The average reduction in the frequency of incontinence ranges from 57% to 86%. In long-term care settings, treatment is generally more challenging and yields more modest results. The advantages of behavioral interventions include the absence of side-effects, patient comfort, and high levels of patient satisfaction. Although most patients who receive behavioral treatment achieve significant improvement, most are not completely dry. Thus, there is a need for research to explore ways to enhance the effectiveness of these conservative therapies. Combining behavioral treatment with other treatments may have additive effects. Research is also needed to understand better the mechanisms of therapeutic change, the best methods for teaching pelvic floor muscle control, the optimal exercise regimens, the predictors of outcome, and the efficacy of behavioral treatments in men. Although behavioral interventions are more accepted today than 20 years ago, they are still not widely available or integrated into most clinical practices, and we know little of how effective they will be in these settings. Thus, it will be important to develop and evaluate creative modes of delivery, such as group intervention (especially by nonphysician providers), in a variety of clinical settings.


Low plasma renin activity in diabetes. Relation to urine prostaglandin excretion.
Renal functional abnormalities, occurring before overt renal disease and possibly due to abnormal vascular control mechanisms, have been described in diabetes mellitus. We used intravenous (i.v.) furosemide, which stimulates renal prostaglandin (PG) synthesis and renin release, to compare these vasoactive systems in 14 diabetic and 23 normal control subjects. Using urine thromboxane B2 (TXB2) as an index of renal synthesis of the vasoconstrictor prostanoid TXA2, and urine 6keto-PGF1 alpha for the vasodilator PGI2, we found evidence of increased renal TXA2 synthesis in diabetic subjects in response to furosemide. The increased TXA2 synthesis did not occur at the expense of PGI2 synthesis, as urine 6keto-PGF1 alpha was not reduced. Increased TXB2 excretion in diabetic subjects was particularly marked in the first 10 min after i.v. furosemide. During this time, diabetic males excreted 31 +/- 6 ng of TXB2 compared with 10 +/- 1 ng for normal males (P less than 0.05), while diabetic females excreted 15 +/- 3 ng compared with 7 +/- 1 ng for normal females (P less than 0.05). Also, 6keto-PGF1 alpha excretion at 10 min was increased in diabetic subjects: males, 29 +/- 3 ng versus 19 +/- 3 (P less than 0.05); females, 33 +/- 8 versus 16 +/- 3 (P less than 0.05). The ratio of TXB2 to 6keto-PGF1 alpha tended to be higher in diabetic males.(ABSTRACT TRUNCATED AT 250 WORDS)


Few but severe viral infections in children with cancer: a prospective RT-PCR and PCR-based 12-month study.
Treatment of low-risk febrile episodes with oral administered antibiotics at home is a new approach in pediatric oncology and protective isolation is loosened in more centers. The impact of viral respiratory infections in febrile diseases in this population is still unclear in terms of occurrence and morbidity. A prospective follow-up study of all febrile episodes during 12 months in a pediatric oncology department with a high level of protective isolation was set-up with expanded molecular viral examinations. Reverse transcriptase polymerase chain reaction (RT-PCR) and PCR diagnostics of ten viruses, two atypical bacteria, and one fungus were performed and clinical information on all infections was registered. A total of 250 febrile episodes in 66 patients were registered. In all, 198 respiratory secretions, predominantly oral washes, and 165 anal swabs were analyzed. Twenty-two infections were diagnosed: 7 rhinovirus infections, 4 respiratory syncytial virus (RSV) infections, 2 herpes simplex virus (HSV) infections, 2 varicella-zoster-virus (VZV) infections, 1 influenza B virus infection, 1 parainfluenza virus type 3 infection (PIV3), 1 human metapneumovirus (HMPV) infection, 1 enterovirus infection, 0 adenovirus infections, 0 influenza A virus infections, and 3 non-viral pneumonias: 1 M. Pneumonia, 1 C. Pneumonia, and 1 P. Carinii. The detected pathogens correlated well to the clinical disease. Patients with viral infections were as affected as patients with bacteria in the blood. One of 19 viral infections was lethal, a RSV pneumonia. C-reactive protein concentrations were not able to distinguish viral infections from bacteremias. The applied sampling method was acceptable and molecular diagnosis of viruses, atypical bacteria and P. Carinii increased the microbiological verification of infections by 35%. Viral infections were few in our protected population but caused severe infectious complications in these patients.


The effect of postconditioning CS experience on recovery from radiation-induced taste aversion.
Seventy-two hours after saccharin (CS) was paired with either a 100R or sham radiation exposure, rats received a 0-, 3-, 6-, 12-, 24-, or 46-hour saccharin-alone presentation followed by a 23-hour two-bottle preference test. Generally, faster recovery from the aversion was observed in animals receiving longer CS-alone presentations. The present procedure differs from previous work done with other toxins in that animals were not fluid-deprived during the postconditioning period. This enabled animals to constantly control the volume, duration, and inter-bout interval of the saccharin drinking episodes independent of any experimentally imposed drinking schedule. In addition, the two-bottle test provided a sensitive measure of the status of the saccharin aversion following the saccharin-alone presentation.


Ginseng gintonin, aging societies, and geriatric brain diseases.
A dramatic increase in aging populations and low birth rates rapidly drive aging societies and increase aging-associated neurodegenerative diseases. However, functional food or medicinal formulations to prevent geriatric brain disorders are not readily available. Panax ginseng is a candidate, since ginseng has long-been consumed as a rejuvenating agent. However, the underlying molecular mechanisms and the components of ginseng that are responsible for brain rejuvenation and human longevity are unknown. Accumulating evidence shows that gintonin is a candidate for the anti-aging ingredient of ginseng, especially in brain senescence. Gintonin, a glycolipoprotein complex, contains three lipid-derived G protein-coupled receptor ligands: lysophosphatidic acids (LPAs), lysophosphatidylinositols (LPIs), and linoleic acid (LA). LPA, LPI, and LA act on six LPA receptor subtypes, GPR55, and GPR40, respectively. These G protein-coupled receptors are distributed within the nervous and non-nervous systems of the human body. Gintonin-enriched fraction (GEF) exhibits anti-brain senescence and effects against disorders such as Alzheimer's disease (AD), Huntington's disease (HD), and Parkinson's disease (PD). Oral administration of gintonin in animal models of d-galactose-induced brain aging, AD, HD, and PD restored cognitive and motor functions. The underlying molecular mechanisms of gintonin-mediated anti-brain aging and anti-neurodegenerative diseases include neurogenesis, autophagy stimulation, anti-apoptosis, anti-oxidative stress, and anti-inflammatory activities. This review describes the characteristics of gintonin and GEF, and how gintonin exerts its effects on brain aging and brain associated-neurodegenerative diseases. Finally, we describe how GEF can be applied to improve the quality of life of senior citizens in aging societies.


Polyethylenimine-functionalized polyacrylonitrile anion exchange fiber as a novel adsorbent for rapid removal of nitrate from wastewater.
The development of an adsorbent with high adsorption ability and favorable cyclic regeneration performance for the removal of nitrate residues from wastewater is a task of vital importance. To this end, polyacrylonitrile fiber (PANF) was modified with polyethyleneimine (PEI), and alkyl groups were then introduced around the active amine groups to prepare three polymer-based anion exchange fibers (PAN-PEI-3C, PAN-PEI-5C, and PAN-PEI-8C). The novel fibers were characterized using techniques such as scanning electron microscopy (SEM), energy-dispersive spectroscopy (EDS), Fourier-transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), and thermogravimetric analysis (TGA). The adsorption isotherms of the fibers were best fitted by the Langmuir model, and PAN-PEI-5C exhibited a higher adsorption amount of nitrate (31.32 mg/g) than the other adsorbents. The equilibrium was reached expeditiously (within 10 min), and both pseudo-first-order and pseudo-second-order models could well describe the adsorption kinetics. More attractively, the saturated PAN-PEI-5C could be eluted using a low-concentration (0.3 M) NaCl solution, without any sharp loss of adsorption amount for five consecutive cycles in the presence of dissolved organic matter (DOM). Furthermore, PAN-PEI-5C could effectively adsorb low-concentration nitrate from real secondary effluents in a fixed-bed column experiment. Our work provides a promising and low-cost material for the removal of nitrate residues in practical applications.


Transfrontal perforation of the lamina terminalis.
Perforation of the lamina terminalis through a frontal burrhole in occlusive hydrocephalus is discussed, with details of technique, indications, and results. The follow-up of some patients who were treated between 1945 and 1955 is described in case reports.


Electron microscopy changes of cochlear implant electrodes with permanently high impedances.
Impedance measurements by means of telemetry have provided us with an objective test of cochlear implant function. Unmeasurable impedance suggests a possible defect on the corresponding channel of the electrode. However, increasing impedances could suggest inflammatory and/or proliferating processes along the electrode. In this report we examined correlations between high impedance, measured in vivo and in vitro findings on the electrode surfaces. We describe recurrent increases in cochlear implant electrode impedance in the same channels, which could initially be reversed by reprogramming the implant, and with anti-inflammatory treatment using cortisone and antibiotics. Subsequently, however, the impedances remained consistently high, indicating a cochlear implant defect. After the removal of the cochlear implant, the electrodes were examined using light and scanning electron microscopy. Examination of the electrodes with normal impedance values revealed, in the great majority of the electrodes, silver shining surfaces. On the other hand, electrodes with high impedances were found coated with tissue. Further analysis of these electrodes using scanning electron microscopy also demonstrated surface changes. Persistently high impedances were related to changes on the electrodes' surface and to coating with tissue in this case. These changes can result in adhesive processes and technical malfunction, leading to explantation and difficult re-implantation. Therefore, close and professional supervision of cochlear implant patients is needed.


Possible role of free radicals in theophylline-induced seizures in mice.
Theophylline is a methylxanthine bronchodilator with a narrow therapeutic index and is prone to induce seizures, the mechanisms for which are not clearly defined. Free radicals have considerable neurotoxic potential and the present study evaluated the possible involvement of these bioactive moieties in aminophylline-induced seizures in mice. Aminophylline (50-250 mg/kg) induced convulsions and mortality in mice in a dose-dependent manner. The anti-oxidants, melatonin (25-100 mg/kg) and N-actylcysteine (100 and 200 mg/kg) attenuated aminophylline seizures and mortality. Similar antagonism of aminophylline seizures was also observed after pretreatments with nitric oxide (NO) synthase inhibitors, L-NAME (3 and 10 mg/kg) and 7-nitroindazole (10 and 30 mg/kg). Further, combined treatment with otherwise sub-effective doses of melatonin and L-NAME or 7-nitroindazole produced marked protective effects against these seizures. Aminophylline-induced seizures enhanced malondialdehyde (MDA) concentrations and NO metabolite (NOx) levels in the brain homogenates of mice, and these were attenuated by melatonin and L-NAME pretreatments. The results are suggestive of the possible involvement of free radicals (reactive oxygen and reactive nitrogen species) in the convulsiogenic effects of aminophylline.


Current approaches to measuring human islet-antigen specific T cell function in type 1 diabetes.
Type 1 diabetes (T1D) is an autoimmune disease caused by the T cell-mediated destruction of the pancreatic insulin-producing beta cells. Currently there are no widely accepted and standardized assays available to analyse the function of autoreactive T cells involved in T1D. The development of such an assay would greatly aid efforts to understand the pathogenesis of T1D and is also urgently required to guide the development of antigen-based therapies intended to prevent, or cure, T1D. Here we describe some of the assays used currently to detect autoreactive T cells in human blood and review critically their strengths and weaknesses. The challenges and future prospects for the T cell assays are discussed.


High gene flow and outcrossing within populations of two cryptic fungal pathogens on a native and non-native host in Cameroon.
In this study, we determined the genetic diversity of 126 isolates representing both Lasiodiplodia theobromae and Lasiodiplodia pseudotheobromae, collected from Theobroma cacao and Terminalia spp. in Cameroon, using simple sequence repeat (SSR) markers. SSR alleles showed clear genetic distinction between L. theobromae and L. pseudotheobromae, supporting their earlier separation as sister species. Both L. theobromae and L. pseudotheobromae populations from Cameroon had high levels of gene diversity, moderate degrees of genotypic diversity, and high levels of gene flow between isolates from T. cacao and Terminalia spp. There was no evidence for geographic substructure in these populations across the region studied, and the SSR alleles were randomly associated in both species, suggesting outcrossing. The significant levels of aggressiveness, evolutionary potential represented by high levels of diversity, outcrossing and gene flow between geographically and host defined populations, identify these fungi as high-risk pathogens for their native and non-native hosts in Cameroon.


Donor anti-Jk(a) causing hemolysis in a liver transplant recipient.
Hemolytic transfusion reactions have been observed in recipients of ABO- and/or D-mismatched marrow, peripheral blood, and solid organs. Passenger lymphocyte syndrome occurs when immunocompetent donor lymphocytes transferred during transplantation produce alloantibodies against host antigens. The first case of a delayed, anti-Jk(a)-mediated hemolytic reaction in a liver transplant recipient, caused by passenger donor lymphocytes, is reported here. A 43-year-old man underwent liver transplantation. Six weeks later, the patient underwent a second liver transplant. On Day 10 of the second transplant, clinical hemolysis ensued; anti-Jk(a) was detected. The patient's DAT became positive, and anti-Jk(a) was eluted from his RBCs. On Day 35 of the patient's second transplant, 3 weeks after the last blood transfusion, the patients' DAT was still weakly positive with anti-Jk(a) in the eluate. Six months later, serum antibody screening was negative, but the DAT was still weakly positive. The patient's RBCs tested Jk(a+), whereas the second donor's RBCs were Jk(a-). This is the first documentation of clinically significant hemolysis caused by anti-Jk(a), produced by passenger lymphocytes transferred from the donor's liver to the transplant recipient.


Color Doppler sonography and scintigraphy of the testis: a prospective, comparative analysis in children with acute scrotal pain.
To compare testicular color Doppler sonography with testicular scintigraphy in differentiating between surgical and nonsurgical conditions of the pediatric testis, and to evaluate the role of testicular color Doppler sonography in the pediatric population. Forty-six children (age range, 1 day to 18 years; median age, 11 years) with acute scrotal pain were evaluated with both scintigraphy and color Doppler sonography by two separate groups of radiologists who had no knowledge of the results of the other modality. The final radiologic diagnosis was classified as a surgical condition, nonsurgical condition, or indeterminate and was compared with the patient's surgical diagnosis or clinical diagnosis, which was established by response to treatment and follow-up. Sonography correctly diagnosed 11 of 14 surgical conditions and 31 of 32 nonsurgical conditions. There was one indeterminate sonogram. There were no false-positive examinations, and there were three false-negative examinations (sensitivity = 78.6% [95% CI, 66.7-90.5%], specificity = 96.9% [95% CI, 94.3-99.5%], accuracy = 91.3%). Color flow was demonstrated in the asymptomatic testis in 34 of 44 boys. Scintigraphy correctly diagnosed 11 of 14 surgical conditions and 29 of 32 nonsurgical conditions. There were two indeterminate scintigrams. There were two false-positive examinations and two false-negative examinations (sensitivity = 78.6% [95% CI, 66.7%-90.5%], specificity = 90.6% [95%CI, 82.2%-99.0%], accuracy = 87.0%). Color Doppler sonography and scintigraphy show similar sensitivity for the diagnosis of testicular torsion. A small number of false-negative cases can occur with either modality. The two studies may provide complementary information in indeterminate cases.


Forecasting Maternal Complications Based on the Impact of Gross National Income Using Various Models for Rwanda.
Preferably maternal mortalities are predominant in low- and middle-income countries (LMICs). In some African countries, including Rwanda, programs related to health-care delivery to reduce significantly severe complications including mortalities are established. Unfortunately, historical and forecasted maternal mortality reduction and the influence of gross national income (GNI) were not accessed. This study is aimed to forecast the three years of maternal mortalities (MMs) based on the influence of gross national income (GNI) in Rwanda. The period involved is from January 2009 to April 2018. Data analyzed were obtained from the Central Hospital of the University of Kigali (CHUK) and mined data from the WHO database. Time series approach (Box-Jenkins and exponential smoothing) and linear regression models were applied. Besides, IBM-SPSS and Eviews were used in the analysis. The results revealed that MMs were not statistically different in several years, and there was a significant correlation between MMs and GNI (-0.610, P value 0.012 < 0.05). A double exponential smoothing model (DESM) was fitted for the best forecast and ARIMA (0,1,0) and linear regression models for a quick forecast. There was a slight effect of GNI in maternal mortality reduction, which leads to the steady decrease of the forecasted maternal mortality up to May 2021. The Government of Rwanda should intensively strengthen the health-care system, save the children programs, and support pregnant women by using GNI for reducing MMs at an advanced level.


Transcriptional, hormonal and histological alterations in the ovaries of BALB/c mice exposed to TCDD in connection with multigenerational female infertility.
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the most toxic congener of dioxins, has a proven reproductive toxicity. Due to the lack of evidence on the multigenerational female reproductive toxicity of TCDD through the maternal exposure, the current study aims to evaluate, on the one hand, the acute reproductive toxicity of TCDD on adult female pre-gestational exposed to a critical single dose of TCDD (25 μg/kg) for a week (group referred to as AFnG; adult female/non-gestation). On the other hand, the transcription, hormonal and histological effects of TCDD on the females of two generations F1 and F2, were also investigated after the exposure of pregnant females to TCDD on gestational day 13 (GD13) (group referred to as AFG; adult female/gestation). First, our data showed alternations in the ovarian expressional pattern of certain key genes involved in the detoxification of TCDD as well as in the biosynthesis of steroidal hormones. The expression of Cyp1a1 was highly induced in TCDD-AFnG group, but reduced in both F1 and F2. While the transcripts levels of Cyp11a1 and 3βhsd2 were decreased, Cyp19a1 transcripts were increased as a function of TCDD exposure. This was synchronized with a dramatic increase in the level of estradiol hormone in the females of both experimental groups. Beside a significant reduce in their size and weight, ovaries of TCDD-exposed females showed serious histological alterations marked by atrophy of the ovary, congestion in the blood vessels, necrosis in the layer of granular cells, dissolution of the oocyte and nucleus of ovarian follicles. Finally, the female fertility was dramatically affected across generations with a reduced male\female ratio. Our data indicate that the exposure of pregnant female to TCDD has serious negative effects in the female productive system across generations and suggest the use of hormonal alternation as biomarker to monitor and assess the indirect exposure of these generations to TCDD.


Use of tubular retractors to access deep brain lesions: A case series.
Deep-seated intracranial lesions can be accessed using blade retractors that may disrupt white matter tracts, exert pressure on adjacent tissue, and lead to post-operative venous injury. Tubular retractors may minimize disruption to white matter tracts by radially dispersing pressure onto surrounding tissue. This study characterizes perioperative outcomes in patients undergoing biopsy or resection of intracranial pathologies using tubular retractors. Adult patients (≥18 years) undergoing neurosurgical intervention using tubular retractors at a single health system (January 2016-February 2022) were identified through chart review. Demographics, disease characteristics, management data, and clinical outcomes were collected. A total of 49 patients were included; 23 (47%) had primary brain tumors, 8 (16%) metastases, 6 (12%) intracranial hemorrhage (ICH), 5 (10%) cavernomas, and 7 (14%) other pathologies. Lesions were located subcortically (n = 19, 39%), intraventricularly (n = 15, 31%), and in deep gray matter (n = 11, 22%). Gross total resection (GTR) or near GTR was achieved in 21 of 26 (80.8%) patients with intracranial lesions where GTR was the goal of surgery; 10 of 11 (90.9%) biopsies in patients with masses were diagnostic. Five of six (83.3%) ICHs were totally or near totally evacuated. Seventeen patients (35%) had major complications post-operatively. The most common complications were DVT/PE (n = 7, 14%) and seizures (n = 6, 12%). For patients who experienced post-operative seizures, 3 had seizures preoperatively and 1 had seizures in the context of electrolyte derangements. No patients died of post-operative complications. This operative approach may facilitate safe and efficacious biopsy or resection of deep-seated intracranial pathologies.


Improved PCR for identification of Pseudomonas aeruginosa.
The aim of the present study was to develop a noble and specific marker for a quantitative polymerase chain reaction (PCR) assay for the species-specific detection of Pseudomonas aeruginosa based on the O-antigen acetylase gene. It is an important challenge to characterize populations of the bacterium P. aeruginosa, an opportunist by virtue of its physiological and genetic adaptability. However, molecular and serological methods currently available for sensitive and specific detection of P. aeruginosa are by no means satisfactory because there have been critical defects in the diagnosis and identification of P. aeruginosa strains in that these assays also detect other Pseudomonas species, or do not obtain amplified products from P. aeruginosa strains. Therefore, a primer set was designed based on the O-antigen acetylase gene of P. aeruginosa PA01 because it has been known that this gene is structurally diverse among species. The specificity of the primer set was evaluated using genomic DNA from six isolates of P. aeruginosa, 18 different species of Pseudomonas, and 23 other reference pathogenic bacteria. The primer set used in the PCR assay amplified a 232-bp amplicon for only six P. aeruginosa strains. The assay was also able to detect at least 1.41 × 10(3) copies/μl of cloned amplified target DNA using purified DNA, or 2.7 × 10(2) colony-forming unit per reaction when using calibrated cell suspension. In conclusion, this assay can be applied as a practical diagnostic method for epidemiological research and the sanitary management of water with a low level or latent infection of P. aeruginosa.


Effects of limited aeration and of the ArcAB system on intermediary pyruvate catabolism in Escherichia coli.
The capacity of Escherichia coli to adapt its catabolism to prevailing redox conditions resides mainly in three catabolic branch points involving (i) pyruvate formate-lyase (PFL) and the pyruvate dehydrogenase complex (PDHc), (ii) the exclusively fermentative enzymes and those of the Krebs cycle, and (iii) the alternative terminal cytochrome bd and cytochrome bo oxidases. A quantitative analysis of the relative catabolic fluxes through these pathways is presented for steady-state glucose-limited chemostat cultures with controlled oxygen availability ranging from full aerobiosis to complete anaerobiosis. Remarkably, PFL contributed significantly to the catabolic flux under microaerobic conditions and was found to be active simultaneously with PDHc and cytochrome bd oxidase-dependent respiration. The synthesis of PFL and cytochrome bd oxidase was found to be maximal in the lower microaerobic range but not in a delta ArcA mutant, and we conclude that the Arc system is more active with respect to regulation of these two positively regulated operons during microaerobiosis than during anaerobiosis.


Metal biosorption in lignocellulosic biofuel biorefinery effluent: an initial step towards sustainability of water resources.
Biosorption of metals by microorganisms is a promising technology to remove accumulated non-process elements in highly recycled biorefinery process water. Removal of these elements would enable greater water reuse and reduce the environmental impact of effluent discharge. A model lignocellulosic ethanol biorefinery wastewater was created based on pulp mill effluent. This generated a wastewater with an environmentally realistic high loading of dissolved natural organic matter (900 mg/l), a potentially important factor influencing metal biosorption. Analysis of feedstock and pulp mill effluent indicated that Mn and Zn are likely to be problematic in highly recycled lignocellulosic ethanol biorefinery process water. Therefore, the growth of several bacteria and fungi from existing collections, and some isolated from pulp mill effluent were tested in the model wastewater spiked with Mn and Zn (0.2 mM). Wastewater isolates grew the best in the wastewater. Metal uptake varied by species and was much greater for Zn than Mn. A bacterium, Novosphingobium nitrogenifigens Y88(T), removed the most metal per unit biomass, 35 and 17 mg Mn/g. No other organism tested decreased the Mn concentration. A yeast, Candida tropicalis, produced the most biomass and removed the most total metal (38 % of Zn), while uptake per unit biomass was 24 mg Zn/g. These results indicate that microorganisms can remove significant amounts of metals in wastewater with high concentrations of dissolved natural organic matter. Metal sorption by autochthonous microorganisms in an anaerobic bioreactor may be able to extend water reuse and therefore lower the water consumption of future biorefineries.


Untranslated regions (UTRs) orchestrate translation reprogramming in cellular stress responses.
Stress is the result of an organism's interaction with environmental challenges. Regulations of gene expression including translation modulations are critical for adaptation and survival under stress. Untranslated regions (UTRs) of the transcripts play significant roles in translation regulation and continue to raise many intriguing questions in our understanding of cellular stress physiology. IRES (Internal ribosome entry site) and uORF (upstream open reading frame) mediated alternative translation initiations are emerging as unique mechanisms. Recent studies have revealed novel means of mRNAs stabilization in stress granules and their reversible modifications. Differential regulation of select transcripts is possible by the interplay between the adenine/uridine-rich elements (AREs) in 3'UTR with their binding proteins (AUBP) and by microRNA-mediated effects. Coordination of these various mechanisms control translation and thereby enables appropriate responses to environmental stress. In this review, we focus on the role of sequence signatures both at 5' and 3'UTRs in translation reprogramming during cellular stress responses.


[Conditions for the standardization of the process of cephalosporin biosynthesis].
Dependence of the final results of cephalosporin biosynthesis on the parameters of the operating conditions and the design of fermentors was shown. The value of the specific power input for agitation had a significant effect on the biosynthetic process. An equation for estimating the final results of the biosynthetic process by the values of the operating conditions and the fermentor design parameters is presented.


Modelling flow rate gradient elution in reversed-phase liquid chromatography.
The fundamental equation of flow programming elution was tested in several different types of flow-rate gradients (step, linear, multilinear, parabolic and more combined gradients) implemented in the separation of two multicomponent mixtures of solutes. The retention prediction obtained for all solutes under all flow-programmed conditions was excellent. In addition, although flow programming appears quite limited in its ability to provide improved performance in liquid chromatography, there are specific flow-rate profiles which provide significant improvement in the rearrangement of the peaks within a chromatogram.


Using Cross-Classified Structural Equation Models to Examine the Accuracy of Personality Judgments.
Whether, when, and why perceivers are able to accurately infer the personality traits of other individuals is a key topic in psychological science. Studies examining this question typically ask a number of perceivers to judge a number of targets with regard to a specific trait. The resulting data are then analyzed by averaging the judgments across perceivers or by computing the respective statistic for each single perceiver. Here, we discuss the limitations of the average-perceiver and single-perceiver approaches. Furthermore, we argue that and illustrate how cross-classified structural equation models can be used for the flexible analysis of accuracy data.


Spoilage relating to the storage and transport of cereals and oil seeds.
Cereal grains are liable to damage during shipment as a result of mould growth that generates both heat and moisture. Such heating, like that for insect infestation, results in moisture migration that can cause damage to other parts of the stow. Increasing storage temperature may also increase equilibrium relative humidity (ERH) above the threshold for mould growth. To avoid damage, the initial water content and the loading temperature have to be considered together to prevent any part of the stow exceeding this threshold. Temperature differences between the centre of the grain and its periphery, whether due to mould or insect heating, shipboard sources of heat or decreasing ambient temperatures, must be minimised and the period of time from loading to discharge kept as short as possible.


Comparison of technetium uptake in small joints with other indices of inflammation in rheumatoid arthritis.
The uptake of 99mTc in the small joints of the hand has been compared to various other mesures of inflammation in 22 patients with rheumatoid arthritis. The 99mTc uptake in the finger joints can reflect both disease activity at a given time and change in activity over a period of time. The place of Tc uptake amongst other measures of inflammation, from the point of view of the 'relative efficiency' of the assessment method, is rather inferior. In evaluating the effect of antiphlogistic drugs on local inflammation, techneticum uptake may, however, prove more discriminating than grip-strength or the number of painful joints, since the latter measures depend largely on the degree of destruction.


Long-term follow-up of Jewish women with a BRCA1 and BRCA2 mutation who underwent population genetic screening.
There are two mutations in BRCA1 and one in BRCA2, which are present in up to 2.5% of Jewish women. Population genetic testing for Jewish women has been proposed; however, it is unclear how this would impact the uptake of cancer prevention options and psychosocial functioning in women with a positive result. Two thousand and eighty unselected Jewish women were tested for the Jewish BRCA mutations, and 1.1% were positive. Cancer-related distress was measured before testing, and at 1 and 2 years post-testing. Information on uptake of cancer risk reduction options was collected at 2 years. Breast and ovarian cancer risks were estimated using BRCAPRO. Within 2 years of receiving a positive result, 11.1% of women had prophylactic mastectomy, and 89.5% had a prophylactic oophorectomy. The mean breast cancer risk was estimated to be 37.2% at time of testing, compared to 20.9% at 2 years post-testing. The mean ovarian cancer risk was estimated to be 24.5% at time of testing, compared to 7.5% at 2 years following testing. Distress decreased between 1 and 2 years for women with prophylactic mastectomy and oophorectomy (P = 0.02), and for women with prophylactic oophorectomy only (P = 0.04) but not for those with neither surgery. The majority of Jewish women with a BRCA mutation identified through a population screening elected prophylactic oophorectomy, but a few had a prophylactic mastectomy. Uptake of either surgery resulted in decreased distress. Provision of population BRCA testing resulted in reduced risks of breast and ovarian cancers in women with a mutation.