Response of Propsilocerus akamusi (Diptera: Chironomidae) to the leachates from AMD-contaminated sediments: Implications for metal bioremediation of AMD-polluted areas.
Acid mine water (AMD) is a global environmental problem caused by coal mining with the characteristics of low pH and high concentrations of metals and sulfates. It is a pertinent topic to seek both economical and environmentally friendly approaches to minimize the harmful effects of AMD on the environment. Insect larvae are considered a promising solution for pollution treatment. Chironomidae is the most tolerant family to contaminants in pools and its larvae have a strong capacity for metal accumulation from sediment. This paper aimed to evaluate the larvae of Propsilocerus akamusi, a dominant species in the chironomid community, as a new species for entomoremediation in AMD-polluted areas. We detected the toxic effects of AMD on P. akamusi larvae based on their survival and the trace metals bioaccumulation capabilities of P. akamusi larvae. Moreover, we analyzed the expression patterns of four stress-response genes, HSP70, Eno1, HbV, and Hb VII in P. akamusi larvae. Our results revealed that AMD exposure did not significantly affect the survival of the P. akamusi larvae and individuals exposed to some AMD gradients even exhibited higher survival. We also observed the significantly accumulated concentrations of Fe, Ni, and Zn as well as higher bioaccumulation factors (BAFs) for Ni and Zn in the P. akamusi larvae exposure to AMD. Induced expression of Eno1 and Hb VII may play important roles in the AMD tolerance of P. akamusi larvae. This study indicated the potential application of P. akamusi larvae in the metal bioremediation of AMD-polluted areas. STATEMENT OF ENVIRONMENTAL IMPLICATION: Acid mine drainage (AMD) is a global environmental problem related to coal mining activities. AMD pollution has become a long-term, worldwide issue for its interactive and complex stress factors. Bioremediation is an effective method to remove the metals of AMD from wastewater to prevent downstream pollution. However, the disadvantages of the slow growth rate, susceptibility to seasonal changes, difficult post-harvest management, and small biomass of hyperaccumulating plants greatly limit the usefulness of phytoremediation. Insect larvae may be useful candidate organisms to overcome these shortcomings and have been considered a promising pollution solution. Propsilocerus akamusi is a dominant species in the chironomid community and is distributed widely in many lakes of eastern Asia. This species has extraordinary abilities to resist various stresses. This research is the first time to our knowledge to evaluate the application of P. akamusi as a new species in entomoremediation in AMD-contaminated areas.


Incomplete follow-up of positive HPV tests: overview of randomised controlled trials on primary cervical screening.
It has been suggested that adjustment for incomplete compliance with follow-up in women with positive human papillomavirus (HPV) tests would be appropriate for estimating the true sensitivity of cervical screening with HPV testing. We assessed the compliance and its impact on > or =CIN3 detection in all eight randomised controlled trials (RCT) with published baseline-round data. We extracted data on recommended follow-up procedures, follow-up compliance, and > or =CIN3 detection for both arms of each RCT, and assessed their correlation. Compliance with a direct referral for colposcopy was around 90% in all RCTs, whereas compliance with repeated testing among HPV-positive/cytology-negative women was around 60% in three RCTs and 73% in one RCT. Detection of > or =CIN3 was significantly increased in two out of six RCTs with reported data. The correlation between compliance with follow-up in HPV-positive women and relative > or =CIN3 detection was 0.48 (P=0.33). There is at present scant evidence to support the view that the measured sensitivity of HPV screening is a simple reflection of compliance with follow-up. Adjustment of measured cervical intraepithelial neoplasia detection on the basis of compliance data may not always be justifiable, and if adjustment is made, it should be used very judiciously.


Software-based screening for efficient sgRNAs in Lactococcus lactis.
The two essential editing elements in the clustered regularly interspaced short palindromic repeats (CRISPR) editing system are promoter and single-guide RNA (sgRNA), the latter of which determines whether Cas protein can precisely target a specific location to edit the targeted gene. Therefore, the selection of sgRNA is crucial to the efficiency of the CRISPR editing system. Various online prediction tools for sgRNA are currently available. These tools can predict all possible sgRNAs of the targeted gene and rank sgRNAs according to certain scoring criteria according to the demands of the user. We designed sgRNAs for Lactococcus lactis NZ9000 LLNZ_RS02020 (ldh) and LLNZ_RS10925 (upp) individually using online prediction software - CRISPOR - and successfully constructed a series of knockout strains to allow comparison of the knockout efficiency of each sgRNA and analyze the differences between software predictions and actual experimental results. Our experimental results showed that the actual editing efficiency of the screened sgRNAs did not match the predicted results - a phenomenon that suggests that established findings from eukaryotic studies are not universally applicable to prokaryotes. Software prediction can still be used as a tool for the initial screening of sgRNAs before further selection of suitable sgRNAs through experimental experience. © 2023 Society of Chemical Industry.


Quality assurance of nurse triage: consistency of results over three years.
The study objective was to evaluate the capability and the consistency of the triage nurse to categorize correctly emergency patients and its impact on the waiting time for physician examination over a period of 3 years. The study was performed at the emergency department of the Barzilai Medical Center, Ashkelon, Israel. A retrospective review of the medical records was performed. All patients who were examined by a triage nurse during 2 randomly chosen consecutive weeks during the years 1995 and 1998 participated. All the medical records were reviewed by the authors and the following information was extracted from the medical records: nurse triage category, time of initial evaluation by a triage nurse, duration of employment of the nurse in the ED, and her experience as a triage nurse, time of initial examination by a physician, the total length of stay in the ED, the history taken by the triage nurse and the physician, and the physician's urgency category. Patient in urgency category 1 is a patient whose condition may deteriorate if not examined within 1 hour; patient in category 2 is a patient whose condition may deteriorate if not examined within 2 hours; category 3 is all the rest. Any deterioration and or delay of treatment of the patients were also recorded. Data concerning patients with an initial complaint of chest pain were extracted separately. The data were analyzed using the SPSS software and the results were tested by the student t test and chi square test. Interobserver agreement was measured using the kappa value. A total of 2,886 completely full medical records were reviewed by the authors: 1,310 records from period I (1995) and 1576 from period II (1998). Of the patients 92% and 88.2% were classified by the triage nurse as category 3 in periods I and II respectively, 7% and 9.8% as category 2, and 1% and 2% as category 1 respectively. Full agreement of triage category between nurse and physician was found in 90.5% of the cases in period I and 93% in period II (kappa = 0.90 and kappa = 0.93 respectively). In period I, 70% of the patients in category 1 were examined by a physician in 1 hour versus 100% in period II. Almost all the patients in category 2 were examined within 2 hours (98%, 97%), and 98% of those in category 3 were examined within 3 hours. The average waiting time for physician examination in category 1 patients dropped from 43.1 minutes in period I to 18.2 minutes in period II. The average waiting time for the triage nurse was 9 minutes in period I, and 7.42 minutes in period II. The average length of stay in the ED in period I was 1 hour and 24 minutes and 1 hour and 30 minutes in period II. Of the anamneses taken by the triage nurse 91.8% were fully identical with the physicians' anamneses, but in period II this percentage jumped to 98%. Patients with chest pain were categorized correctly by the triage nurse in 76.8% of the cases in period I and 72.4% in period II, with an overtriage of 18.6% and 20.7% respectively (kappa = 0.75, kappa = 0.70 respectively). In our study, nurse triage was safe and effective in classifying patients to urgency categories. The results are consistent and even improved over a 3-year period. The rates of incorrect classification, deterioration, and delay of treatment of patients because of incorrect triage are very low. Most of the patients were examined by the physician within the expected time. Triage nurse predicted correctly the urgency category of patients with chest in most of the cases and the rate of missing acute coronary events was very low.


Bees' honey attenuation of metanil-yellow-induced hepatotoxicity in rats.
The present study aims to investigate the protective effect of bees' honey against metanil-yellow-induced hepatotoxicity in rats. Rats were divided into 7 groups: control group; three groups treated with 50, 100, and 200 mg/kg metanil yellow, and three groups treated with metanil yellow plus 2.5 mg · kg(-1) · day(-1) bees' honey for 8 weeks. The obtained data showed that the antioxidant/anti-inflammatory activity of bees' honey reduced the oxidative stress in the liver tissue and downregulated the inflammatory markers. In addition, the elevated levels of AGE and the activated NF- κ B in the metanil-yellow-treated animals were significantly attenuated. Moreover, the levels of TNF- α and IL-1 β were significantly attenuated as a result of bees' honey administration. Furthermore, the histopathological examination of the liver showed that bees' honey reduced fatty degeneration, cytoplasmic vacuolization, and necrosis in metanil-yellow-treated rats. In conclusion, the obtained data suggest that bees' honey has hepatoprotective effect on acute liver injuries induced by metanil-yellow in vivo, and the results suggested that the effect of bees' honey against metanil yellow-induced liver damage is related to its antioxidant/anti-inflammatory properties which attenuate the activation of NF- κ B and its controlled genes like TNF- α and IL-1 β .


Programing of an Intravascular Immune Firewall by the Gut Microbiota Protects against Pathogen Dissemination during Infection.
Eradication of pathogens from the bloodstream is critical to prevent disseminated infections and sepsis. Kupffer cells in the liver form an intravascular firewall that captures and clears pathogens from the blood. Here, we show that the catching and killing of circulating pathogens by Kupffer cells in vivo are promoted by the gut microbiota through commensal-derived D-lactate that reaches the liver via the portal vein. The integrity of this Kupffer cell-mediated intravascular firewall requires continuous crosstalk with gut commensals, as microbiota depletion with antibiotics leads to a failure of pathogen clearance and overwhelming disseminated infection. Furthermore, administration of purified D-lactate to germ-free mice, or gnotobiotic colonization with D-lactate-producing commensals, restores Kupffer cell-mediated pathogen clearance by the liver firewall. Thus, the gut microbiota programs an intravascular immune firewall that protects against the spread of bacterial infections via the bloodstream.


Locally invasive, castrate-resistant prostate cancer in a Pten/Trp53 double knockout mouse model of prostate cancer monitored with non-invasive bioluminescent imaging.
Here we have improved an existing mouse model of prostate cancer based on prostate-specific deletion of Pten and Trp53 by incorporating a Cre-activatable luciferase reporter. By coupling the deletion of those genes to the activation of a luciferase reporter, we were able to monitor tumor burden non-invasively over time. We show that, consistent with previous reports, deletion of both Pten and Trp53 on a C57BL/6 background accelerates tumor growth and results in both the loss of androgen receptor expression and castrate resistant tumors as compared with loss of Pten alone. Loss of Trp53 results in the development of sarcomatoid histology and the expression of markers of epithelial-to-mesenchymal transition Zeb1 and vimentin, with kinetics and penetrance dependent on whether one or both alleles of Trp53 were deleted. Homozygous deletion of Trp53 and Pten resulted in uniformly lethal disease by 25 weeks. While we were able to detect locally invasive disease in the peritoneal cavity in aggressive tumors from the double knockout mice, we were unable to detect lymphatic or hematogenous metastatic disease in lymph nodes or at distant sites.


A realistic appraisal of methods to enhance desiccation tolerance of entomopathogenic nematodes.
Understanding the desiccation survival attributes of infective juveniles of entomopathogenic nematodes (EPN) of the genera Steinernema and Heterorhabditis, is central to evaluating the reality of enhancing the shelf-life and field persistence of commercial formulations. Early work on the structural and physiological aspects of desiccation survival focused on the role of the molted cuticle in controlling the rate of water loss and the importance of energy reserves, particularly neutral lipids. The accumulation of trehalose was also found to enhance desiccation survival. Isolation of natural populations that can survive harsh environments, such as deserts, indicated that some populations have enhanced abilities to survive desiccation. However, survival abilities of EPN are limited compared with those of some species of plant-parasitic nematodes inhabiting aerial parts of plants. Research on EPN stress tolerance has expanded on two main lines: i) to select strains of species, currently in use commercially, which have increased tolerance to environmental extremes; and ii) to utilize molecular information, including expressed sequence tags and genome sequence data, to determine the underlying genetic factors that control longevity and stress tolerance of EPN. However, given the inherent limitations of EPN survival ability, it is likely that improved formulation will be the major factor to enhance EPN longevity and, perhaps, increase the range of applications.


Influence of recent vegetation on labile and recalcitrant carbon soil pools in central Queensland, Australia: evidence from thermal analysis-quadrupole mass spectrometry-isotope ratio mass spectrometry.
The effect of a recent vegetation change (<100 years) from C(4) grassland to C(3) woodland in central Queensland, Australia, on soil organic matter (SOM) composition and SOM dynamics has been investigated using a novel coupled thermogravimetry-differential scanning calorimetry-quadrupole.mass spectrometry-isotope ratio mass spectrometry (TG-DSC-QMS-IRMS) system. TG-DSC-QMS-IRMS distinguishes the C isotope composition of discrete SOM pools, showing changes in labile, recalcitrant and refractory carbon in the bulk soil and particle size fractions which track the vegetation changes. Analysis of evolved gases (by QMS) from thermal decomposition, rather than observed weight loss, proved essential in determining the temperature at which SOM decomposes, because smectite and kaolinite clays contribute to observed weight losses. The delta(13)C analyses of the CO(2) evolved at different temperatures for bulk soil and particle size-separates showed that most of the labile SOM under the more recent woody vegetation was C(3)-derived carbon whereas the delta(13)C values in the recalcitrant SOM showed greater C(4) contributions. This indicated a shift from grass (C(4))- to tree (C(3))-derived carbon in the woodland, which was also supported by the two-phase (13)C enrichment with depth, i.e. C(3) vegetation dominated the top soil (0-10 cm), but the C(4) contribution increased with depth (more gradual). This is perturbed by the inclusion of charcoal from forest fires ((14)C age incursions) and by the deep incorporation of C(3) carbon due to root penetration.


Conduct problems in Russian adolescents: the role of personality and parental rearing.
The purpose of the present study was 1) to assess the predictive value of conduct problems prior to the age of 12 for the severity of antisocial behaviour during adolescence, and 2) to investigate the relationships between personality traits/parental rearing and childhood conduct problems/teenage antisocial behaviour. A group of 193 delinquents was assessed by means of the Antisocial Behavior Checklist (ABC), the Retrospective Childhood Problems (RETROPROB), the Temperament and Character Inventory (TCI) and the EMBU questionnaire on parental rearing. The extreme groups of delinquents as defined by childhood conduct problems, differed significantly on the experience of a rejecting father and a self-directed character. Furthermore, some specific predictive patterns for current antisocial behaviour by childhood conduct disorder and both personality dimensions and parental rearing factors emerged. The findings are discussed in the light of the interactive nature of relations between personality and parental rearing in the development of antisocial behaviour among adolescents.


Inadequate reimbursement for care management to primary care offices.
Care management in primary care can be effective in helping patients with chronic disease improve their health; however, primary care practices are often challenged to identify revenue to pay for it. This study explored the impact of direct reimbursement on the provision of care management in a primary care physician organization. Using data on expenses and health plan reimbursement during the initial 16 months of care management implementation at 5 practices, we calculated the percentage of related costs that were covered by payments. Qualitative data from interviews with practice members were used to identify their perceived barriers to care management reimbursement and the impact of current reimbursement strategies on service delivery. Direct reimbursement for care management covered only 21% of the costs. Reimbursement varied by care manager background, patient diagnoses, insurer, and indication for the visit. Barriers to gaining reimbursement included patient resistance to copay, clinician hesitation to bill for care management visits (for fear the patient may receive a bill), differential reimbursement policies of insurers, and general lack of reimbursement for care management in many cases. Although practice-level quality improvement incentives were an alternative means of supporting care management, because these incentives were not directly tied to the service of care management, they were used for other activities ultimately supporting patient care. This study highlights the need for sufficient reimbursement to initiate and maintain care management for patients in primary care as proposed for service reforms under the Affordable Care Act.


Enhanced radiation-mediated cell killing of human cervical cancer cells by small interference RNA silencing of ataxia telangiectasia-mutated protein.
The ataxia telangiectasia-mutated (ATM) protein, which is mutated in the inherited disease ataxia telangiectasia (AT), is a key activator of cell cycle checkpoint, initiating cell response to DNA damage and ensuring genomic stability. AT cells exhibit defects in all cellular responses to ionizing radiation and radiomimetic chemicals. Inactivation of ATM may therefore make cells fail to execute many responses to DNA damage and improve the cells' sensitivity to radiation. Recent developments in the use of small interference RNA molecules (siRNAs) to inhibit specific protein expression have highlighted the potential use of siRNA as a therapeutic agent. In this study, we have designed and exogenously delivered plasmids encoding siRNAs targeting ATM to human cervical carcinoma SiHa cells and generated a stable cell line, SiHa(ATM). SiHa(ATM) cells displayed minimal levels of ATM protein and showed a marked increase in sensitivity to radiation. Together, these data provide strong evidence for the potential use of siRNA as a novel radiation/chemotherapy-sensitizing agent.


A multi-center trial of exercise and testosterone therapy in women after hip fracture: Design, methods and impact of the COVID-19 pandemic.
Up to 75% of hip fracture patients never recover to their pre-fracture functional status. Supervised exercise that includes strength training can improve functional recovery after hip fracture. The role of testosterone replacement for augmenting the effects of exercise in older women after hip fracture is unknown. The Starting Testosterone and Exercise after Hip Injury (STEP-HI) Study is a 6-month Phase 3 multicenter randomized placebo-controlled trial designed to compare supervised exercise (EX) plus 1% testosterone topical gel, with EX plus placebo gel, and with enhanced usual care (EUC). Female hip fracture patients age ≥ 65 years are being recruited from clinical centers across the United States. Participants are community dwelling and enrolled within 24 weeks after surgical repair of the fracture. The EX intervention is a center-based program of progressive resistance training. The EUC group receives a home exercise program and health education. Participants receive dietary counseling, calcium and vitamin D. The primary outcome is the Six Minute Walk Distance. Secondary outcomes include physical performance measures, self-reported function and quality of life, and dual energy x-ray absorptiometry measures of body composition and bone mineral density. Enrollment, interventions, and follow-up are ongoing. We describe the impact of the coronavirus disease 2019 pandemic on the trial, including modifications made to allow continuation of the interventions and outcome data collection using remote video and audio technology. Results from the STEP-HI study are expected to have important clinical and public health implications for management of the growing population of hip fracture patients.


CheS-Mapper - Chemical Space Mapping and Visualization in 3D.
Analyzing chemical datasets is a challenging task for scientific researchers in the field of chemoinformatics. It is important, yet difficult to understand the relationship between the structure of chemical compounds, their physico-chemical properties, and biological or toxic effects. To that respect, visualization tools can help to better comprehend the underlying correlations. Our recently developed 3D molecular viewer CheS-Mapper (Chemical Space Mapper) divides large datasets into clusters of similar compounds and consequently arranges them in 3D space, such that their spatial proximity reflects their similarity. The user can indirectly determine similarity, by selecting which features to employ in the process. The tool can use and calculate different kind of features, like structural fragments as well as quantitative chemical descriptors. These features can be highlighted within CheS-Mapper, which aids the chemist to better understand patterns and regularities and relate the observations to established scientific knowledge. As a final function, the tool can also be used to select and export specific subsets of a given dataset for further analysis.


Embryological considerations of distinctive feature theory.
The role of the physiology is emphasized here, perhaps to the eventual denial of the importance of the acoustic cues involved at these stages. The acoustic cues are the result of the physiology and are a further development of the features of speech. The selection of the sounds of babbling is a function of the physiological readiness and is an internal function [Locke, 1983]. Sounds are produced that are not used in final adult speech [Locke, 1983]. It is the acoustic cues of the environment that perhaps cause the 'babbling drift' toward adult speech of the environment [Brown, 1958]. In line with the above-mentioned ideas regarding branchial arch development, most of the components of the outer and middle ear are derivatives of the first branchial arch, which though limited musculature is involved, especially for sound perception, might downplay the role of acoustics at these earliest stages even further. If it can be said that cortical organization and representation development follow a similar sequence as is evidenced from the branchial arches and their derivatives, the importance of acoustic stimuli, at this point, would be even further questioned for these early stages. The assumption should be made that a muscle or muscle group does not function prior to this established branchial arch pair sequence. The major distinction here has been utilization of the structures in a 'conscious', deliberate, voluntary manner with a specific goal in mind. The babbling and even feeding that children undergo provides evidence that these structures function perhaps long before any sequence of branchial arch pair developmental sequence can be applied.(ABSTRACT TRUNCATED AT 250 WORDS)


The First Slow Step: Differential Effects of Object and Word-Form Familiarization on Retention of Fast-Mapped Words.
Recent research demonstrated that although twenty-four month-old infants do well on the initial pairing of a novel word and novel object in fast-mapping tasks, they are unable to retain the mapping after a five-minute delay. The current study examines the role of familiarity with the objects and words on infants' ability to bridge between the initial fast mapping of a name and object, and later retention in the service of slow mapping. Twenty-four-month-old infants were familiarized with either novel objects or novel names prior to the referent selection portion of a fast-mapping task. When familiarized with the novel objects, infants retained the novel mapping after a delay, but not when familiarized with the novel words. This suggests familiarity with the object versus the word form leads to differential encoding of the name-object link. We discuss the implications of this finding for subsequent slow mapping.


Statistical Properties of SGR 1900+14 Bursts.
We study the statistics of soft gamma repeater (SGR) bursts using a database of 187 events detected with BATSE and 837 events detected with the Rossi X-Ray Timing Explorer Proportional Counter Array; all events are from SGR 1900+14 during its 1998-1999 active phase. We find that the fluence or energy distribution of bursts is consistent with a power law of index 1.66, over 4 orders of magnitude. This scale-free distribution resembles the Gutenberg-Richter law for earthquakes and gives evidence for self-organized criticality in SGRs. The distribution of time intervals between successive bursts from SGR 1900+14 is consistent with a lognormal distribution. There is no correlation between burst intensity and the waiting times till the next burst, but there is some evidence for a correlation between burst intensity and the time elapsed since the previous burst. We also find a correlation between the duration and the energy of the bursts, but with significant scatter. In all these statistical properties, SGR bursts resemble earthquakes and solar flares more closely than they resemble any known accretion-powered or nuclear-powered phenomena. Thus, our analysis lends support to the hypothesis that the energy source for SGR bursts is internal to the neutron star and plausibly magnetic.


Genetic blockade of the dopamine D3 receptor enhances hippocampal expression of PACAP and receptors and alters their cortical distribution.
Dopamine D3 receptors (D3Rs) are implicated in several aspects of cognition, but their role in aversive conditioning has only been marginally uncovered. Investigations have reported that blockade of D3Rs enhances the acquisition of fear memories, a phenomenon tightly linked to the neuropeptide pituitary adenylate cyclase-activating peptide (PACAP). However, the impact of D3R ablation on the PACAPergic system in regions critical for the formation of new memories remains unexplored. To address this issue, levels of PACAP and its receptors were compared in the hippocampus and cerebral cortex (CX) of mice devoid of functional D3Rs (D3R(-/-)) and wild-types (WTs) using a series of comparative immunohistochemical and biochemical analyses. Morphometric and stereological data revealed increased hippocampal area and volume in D3R(-/-) mice, and augmented neuronal density in CA1 and CA2/3 subfields. PACAP levels were increased in the hippocampus of D3R(-/-) mice. Expression of PACAP receptors was also heightened in mutant mice. In the CX, PACAP immunoreactivity (IR), was restricted to cortical layer V in WTs, but was distributed throughout layers IV-VI in D3R(-/-) mice, along with increased mRNAs, protein concentration and staining scores. Consistently, PAC1, VPAC1 and VPAC2 IRs were variably redistributed in CX, with a general upregulation in cortical layers II-IV in knockout animals. Our interpretation of these findings is that disturbed dopamine neurotransmission due to genetic D3R blockade may enhance the PACAP/PAC1-VPAC axis, a key endogenous system for the processing of fear memories. This could explain, at least in part, the facilitated acquisition and consolidation of aversive memories in D3R(-/-) mice.


Plantarflexory osteotomy for a plantar flexed first ray? A cross-sectional study of the relationship between frontal plane forefoot deformity and lateral intermetatarsal angle in 190 patients.
Many surgeons consider performing plantarflexory osteotomy when a lateral weightbearing radiograph shows an elevated first metatarsal. In our study, we clinically evaluated the first metatarsal position in terms of the forefoot-to-rearfoot relationship and radiographically evaluated the lateral intermetatarsal angle in 190 patients. We divided the subjects into forefoot varus, valgus, and neutral groups and compared their mean lateral intermetatarsal angle. The mean lateral intermetatarsal angle for those with forefoot varus, valgus, and neutral was 1.4° ± 3.10°, 1.3° ± 3.30°, and 0.4° ± 2.67°, respectively. Neither analysis of variance nor post hoc tests showed any significant difference among the groups. We hypothesized that the ground reacting force alters the first ray position on the weightbearing radiographs; thus, it would not be advisable to rely solely on this angular measurement for surgical decision-making.


The relevance of urodynamic studies for Urge syndrome and dysfunctional voiding: a multicenter controlled trial in children.
The objective of this study was to compare prospectively, in urge syndrome and dysfunctional voiding, clinical patterns with urodynamic patterns, to assess changes in urodynamic patterns after treatment, and to correlate urodynamic patterns and parameters with treatment outcome. In the European Bladder Dysfunction Study 97 children with clinically diagnosed urge syndrome received standard treatment, to which was randomly added placebo, oxybutynin or bladder training with online feedback. In a separate branch 105 children with clinically diagnosed dysfunctional voiding were randomly allocated to standard treatment or standard treatment plus pelvic floor training with online feedback. In all children urodynamic studies were performed before and immediately after treatment. In urge syndrome detrusor overactivity was present in 33% of cases before and 27% after treatment (of which 65% were de novo). Detrusor overactivity did not correlate with treatment outcome. In dysfunctional voiding increased pelvic floor activity during voiding, which was present in 67% of cases before and 56% after treatment (of which 45% were de novo), did not correlate with treatment outcome. In urge syndrome as well as in dysfunctional voiding neither maximum detrusor pressure during voiding, cystometric bladder capacity, bladder compliance nor free flow patterns correlated with treatment outcome. Neither detrusor overactivity nor increased pelvic floor activity during voiding correlated with treatment outcome. Standard treatment could be the first choice in urge syndrome as well as in dysfunctional voiding, reserving urodynamic studies for patients in whom this first approach fails.


Kinematic and Coordination Variability in Individuals With Acute and Chronic Patellofemoral Pain.
Altered gait variability occurs in those with patellofemoral pain and may be relevant to pain progression. We examined gait kinematic and coordination variability between individuals with acute and chronic patellofemoral pain and healthy controls. Eighty-three patellofemoral pain runners (37 men and 46 women) and 142 healthy controls (52 men and 90 women) ran on a treadmill while 3-dimensional lower limb kinematic data were collected. Patellofemoral pain runners were split into acute (n = 22) and chronic (n = 61) subgroups based on pain duration (< and ≥3 mo, respectively). Approximate entropy assessed continuous hip, knee, and ankle kinematic variability. Vector coding calculated coordination variability for select joint couplings. Variability measures were compared between groups using 1-way analysis of variance and post hoc comparisons with Cohen d effect sizes. The chronic patellofemoral pain subgroup displayed higher frontal plane knee kinematic variability compared with controls (P = .0004, d = 0.550). No statistically significant effects for any coordination variability couplings were identified. Minimal differences in gait variability were detected between those with acute and chronic patellofemoral pain and healthy controls.


Chromatin structure at the replication origins and transcription-initiation regions of the ribosomal RNA genes of Tetrahymena.
The chromatin structure of regulatory regions of the extrachromosomal rRNA genes of Tetrahymena thermophila was probed by nuclease treatment of isolated nuclei. The chromatin near the origins of replication contains hypersensitive sites for micrococcal nuclease, DNAase I, and DNAase II. These sites persist in starved cells, consistent with the origins' being maintained in an altered chromatin structure independent of DNA replication. The region between the two origins of replication is organized into a phased array of seven nucleosomes, the fourth of which is centered at the axis of symmetry of the palindromic rDNA. The entire transcribed region and 150 bp upstream from the initiation site are generally accessible to nucleases; any histone proteins associated with these regions are clearly not in a highly organized nucleosomal array as seen in the central region. Comparison of the chromatin structures of the central spacer of T. thermophila and T. pyriformis rDNA reveals that deletion or insertion of DNA has occurred in increments of 200 bp. This is taken to imply that there are constraints on the evolution of spacer DNA sequences at the level of the nucleosome.


Health status, job satisfaction, job stress, and life satisfaction among academic and clinical faculty.
The present study compares academic and clinical faculty affiliated with a major teaching hospital in terms of work characteristics, job stress, conflict between work and personal life, job and life satisfaction, and perceived health. There were no significant differences between the two physician groups on job satisfaction, total stress, anxiety, or depression scores. However, academic faculty reported working longer hours, taking less vacation time, and spending more time in research and teaching, but seeing fewer outpatients. Academic physicians experienced more conflict between work and personal life, were burdened by a variety of time pressures, and were less satisfied with their finances, but experienced fewer recent episodes of physical illness than clinical faculty. However, compared with what is known about the general population, both physician samples seemed equally or more satisfied with their health and their lives.


Practical applications of nutritional scores.
Any intensive therapy requires individual adaptation, despite the standardization of the concepts that support them. Among these therapies, nutritional care has repeatedly been shown to influence clinical outcome. In order to evaluate the risk of malnutrition among critically ill patients and to identify those patients who may benefit from medical nutrition therapy is imperative to have a validated screening tool to optimize nutritional care.The scope of this review is to analyze the recent literature on the management of nutritional scores for patients admitted to the ICU. Critically ill patient staying for more than 24-48 h in the ICU, if unable to eat, should be considered at risk for malnutrition. Several nutritional tools have been proposed but not all are validated to screening those patients. The limitations of existing screening tools are described. Nutritional scores should be routinely performed at ICU admission according to recommended guidelines. An approach to incorporate these tools into everyday clinical practice is suggested.


The importance of monitoring adverse drug reactions in pediatric patients: the results of a national surveillance program in Italy.
To gain information on safety of drugs used in pediatrics through a 4-year post-marketing active pharmacovigilance program. The program sampled the Italian population and was termed 'Monitoring of the Adverse Effects in Pediatric population' (MEAP). Adverse drug reactions (ADRs) were collected for individuals aged 0 - 17 years treated in hospitals and territorial health services in Lombardy, Tuscany, Apulia and Campania; located to gain an appropriate sampling of the population. ADRs were evaluated using the Adverse Drug Reaction Probability Scale (Naranjo) and analyzed with respect to time, age, sex, category of ADR, seriousness, suspected medicines, type of reporter and off-label use. We collected and analyzed reports from 3539 ADRs. Vaccines, antineoplastic and psychotropic drugs were the most frequently pharmacotherapeutic subgroups involved. Seventeen percent of reported ADRs were serious; of them fever, vomiting and angioedema were the most frequently reported. Eight percent of ADRs were associated with off-label use, and 10% were unknown ADRs. Analysis of these revealed possible strategies of therapy optimization. The MEAP project demonstrated that active post-marketing pharmacovigilance programs are a valid strategy to increase awareness on pediatric pharmacology, reduce underreporting and provide information on drug actions in pediatrics. This information enhances drug therapy optimization in the pediatric patients.


New cochlear implant coding strategy for tonal language speakers.
Accurate pitch perception on the basis of fundamental frequency patterns is essential for the processing of lexical tones in tonal languages such as Cantonese. Speech intelligibility in Cantonese-speaking CI recipients was compared using current signal processing strategies, which typically result in poor pitch perception, and a new strategy, known as the multi-channel envelope modulation (MEM) strategy, was designed to enhance temporal periodicity cues to the fundamental frequency. Performance of nine postlingually hearing-impaired adult cochlear implant users was measured twice using each strategy, initially after a four week trial, and again after two weeks of use with each strategy. Speech intelligibility in speech-spectrum shaped noise was measured using the Cantonese hearing in noise test. A fixed noise level of 65 dB A was used and the signal-to-noise ratios were fixed at either +10, +15, or +20 dB, depending on the baseline performance of individual subjects using the clinical processor. Self-reported benefit in 18 listening situations and overall preference for strategies were obtained at the end of these trial periods. Results showed poorer speech intelligibility with CIS while results obtained using ACE and MEM were comparable. Unfamiliar place coding might have contributed to poorer performance using CIS. Self-reported benefit across strategies did not differ in most listening situations. Participants preferred ACE for listening overall in daily situations, and a few preferred MEM in noise. Whilst the results did not demonstrate any advantages for speech recognition in noise when using MEM compared to ACE, no degradation in performance was observed. This implies that the form of processing employed by MEM retains similar segmental information to that provided by ACE and that potentially, future variations/optimizations of MEM may lead to some improvement in tone perception.


Association between perceived racism and physiological stress indices in Native Hawaiians.
The association between racism and the physical health of native U.S. populations has yet to be examined despite their high risk for stress-related disorders and a history of discrimination toward them. We examined the correlation between perceived racism and the two physiological stress indices of cortisol level and blood pressure in 146 adult Native Hawaiians. Attributed and felt racism were assessed with a 10-item shortened version of the Oppression Questionnaire. Height, weight, blood pressure, and salivary cortisol samples (AM and PM) were collected and analyzed along with information on Hawaiian ancestry, BMI, age, sex, marital status, education level, general psychological stress, and ethnic identity. The results indicated that Native Hawaiians reporting more attributed racism had significantly (P < .05) lower average cortisol levels than those reporting less attributed racism, after adjusting for socio-demographic, biological, and psychosocial confounders. Native Hawaiians reporting more felt racism had a significantly higher systolic blood pressure than those reporting less, but this association was not significant after adjusting for the aforementioned confounders. Racism appears to be a chronic stressor that can "get under the skin" of Native Hawaiians by affecting their physical health and risk for stress-related diseases, possibly, through mechanisms of cortisol dysregulation.


Local Adjuvant Treatment with Low-Dose CpG-B Offers Durable Protection against Disease Recurrence in Clinical Stage I-II Melanoma: Data from Two Randomized Phase II Trials.
Purpose: Although risk of recurrence after surgical removal of clinical stage I-II melanoma is considerable, there is no adjuvant therapy with proven efficacy. Here, we provide clinical evidence that a local conditioning regimen, aimed at immunologic arming of the tumor-draining lymph nodes, may provide durable protection against disease recurrence (median follow-up, 88.8 months).Experimental Design: In two randomized phase II trials, patients, diagnosed with stage I-II melanoma after excision of the primary tumor, received local injections at the primary tumor excision site within 7 days preceding re-excision and sentinel lymph node (SLN) biopsy of either a saline placebo (n = 22) or low-dose CpG type B (CpG-B) with (n = 9) or without (n = 21) low-dose GM-CSF.Results: CpG-B treatment was shown to be safe, to boost locoregional and systemic immunity, to be associated with lower rates of tumor-involved SLN (10% vs. 36% in controls, P = 0.04), and, at a median follow-up of 88.8 months, to profoundly improve recurrence-free survival (P = 0.008), even for patients with histologically confirmed (i.e., pathologic) stage I-II disease (P = 0.02).Conclusions: Potentially offering durable protection, local low-dose CpG-B administration in early-stage melanoma provides an adjuvant treatment option for a large group of patients currently going untreated despite being at considerable risk for disease recurrence. Once validated in a larger randomized phase III trial, this nontoxic immunopotentiating regimen may prove clinically transformative. Clin Cancer Res; 23(19); 5679-86. ©2017 AACR.


Role of protein degradation in the regulation of cellular protein content and amino acid pools.
A decrease in the rate of protein degradation contributes to the accumulation of cellular protein during growth or storage of dietary amino acids. Examples of this process in the liver of live mice are reviewed. One aspect of this regulation is the direct effect of amino acids on the rate of protein breakdown. At least in the case of histidine starvation in Chinese hamster ovary cells, the regulatory mechanism recognizes the level of aminoacylation of tRNA.


The role of home-visitation programs in improving health outcomes for children and families. American Academy of Pediatrics. Council on Child and Adolescent Health.
Traditional pediatric care is often based on the assumption that parents have th basic knowledge and resources to provide a nurturing, safe environment and to provide for the emotional, physical, developmental, and health care needs of their infants and young children. Unfortunately, many families have insufficient knowledge of parenting skills and an inadequate support system of friends, extended family, or professionals to help with these vital tasks. Home-visitation programs offer an effective mechanism to ensure ongoing parental education, social support, and linkage with public and private community services. This statement reviews the history and current research on home-visitation programs and provides recommendations about the pediatrician's role in supporting and using home visitation.


Quantum-orbit analysis for yield and ellipticity of high order harmonic generation with elliptically polarized laser field.
We perform a quantum-orbit analysis for the dependence of high-order-harmonic yield on the driving field ellipticity and the polarization properties of the generated high harmonics. The electron trajectories responsible for the emission of particular harmonics are identified. It is found that, in elliptically polarized driving field, the electrons have ellipticity-dependent initial velocities, which lead to the decrease of the ionization rate. Thus the harmonic yield steeply decreases with laser ellipticity. Besides, we show that the polarization properties of the harmonics are related to the complex momenta of the electron. The physical origin of the harmonic ellipticity is interpreted as the consequence of quantum-mechanical uncertainty of the electron momentum. Our results are verified with the experimental results as well as the numerical solutions of the time dependent Schrödinger equation from the literature.


Citizen science in the marine environment: estimating common dolphin densities in the north-east Atlantic.
Citizen science is increasingly popular and has the potential to collect extensive datasets at lower costs than traditional surveys conducted by professional scientists. Ferries have been used to collect data on cetacean populations for decades, providing long-term time series for monitoring of cetacean populations. One cetacean species of concern is the common dolphin, which has been found stranded around the north-east Atlantic in recent years, with high numbers on French coasts being attributed to fisheries bycatch. We estimate common dolphin densities in the north-east Atlantic and investigate the ability of citizen science data to identify changes in marine mammal densities and areas of importance. Data were collected by citizen scientists on ferries between April and October in 2006-2017. Common dolphin sightings data from two ferry routes across three regions, Bay of Biscay (n = 569); south-west United Kingdom to the Isles of Scilly in the Celtic Sea (n = 260); and English Channel (n = 75), were used to estimate density across ferry routes. Two-stage Density Surface Models accounted for imperfect detection, and tested the influence of environmental (chlorophyll a, sea surface temperature, depth, and slope), spatial (latitude and longitude) and temporal terms (year and Julian day) on occurrence. Overall detection probability was highest in the areas sampled within the English Channel (0.384) and Bay of Biscay (0.348), and lowest on the Scilly's route (0.158). Common dolphins were estimated to occur in higher densities on the Scilly's route (0.400 per km2) and the Bay of Biscay (0.319 per km2), with low densities in the English Channel (0.025 per km2). Densities on the Scilly's route appear to have been relatively stable since 2006 with a slight decrease in 2017. Densities peaked in the Bay of Biscay in 2013 with lower numbers since. Densities in the English Channel appear to have increased over time since 2009. This study highlights the effectiveness of citizen science data to investigate the distribution and density of cetaceans. The densities and temporal changes shown by this study are representative of those from wider-ranging robust estimates. We highlight the ability of citizen science to collect data over extensive periods of time which complements dedicated, designed surveys. Such long-term data are important to identify changes within a population; however, citizen science data may, in some situations, present challenges. We provide recommendations to ensure high-quality data which can be used to inform management and conservation of cetacean populations.


Study of cytotoxic chemotherapy as an adjuvant to surgery in carcinoma of the bronchus. Report by a Medical Research Council Working Party.
This report gives the findings after two years of a study of long-term oral cytotoxic chemotherapy with busulphan or cyclophoshamide in carcinoma of the bronchus compared with two placebos, identical in appearance to the drug-containing tablets. A total of 753 patients who had had a total resection of the tumour, who had no detectable extrathoracic metastasis, and who were able to attend chest clinics monthly were admitted to the study from January 1965 to January 1968. Twenty-seven patients were excluded from all the analyses.The 217 patients admitted up to December 1965 form the "early" intake, the remaining 509 the "late" intake. There were no significant differences between the series in either intake period in a number of pretreatment factors studied. At 24 months 46% of the busulphan, 44% of the cyclophosphamide, and 49% of the placebo series were alive in the early intake, as were 49%, 50%, and 50% respectively in the late intake. There were no important differences between the series in survival related to pretreatment condition, cause of death, time of detection of metastases, and condition of the survivors at 24 months. Maintenance chemotherapy was interrupted to a greater extent in the busulphan than in the cyclophosphamide series and least in the placebo series.In both intakes clinical toxicity was more frequent in the cyclophosphamide series and similar in frequency in the busulphan and placebo series. Haematological toxicity was particularly frequent and severe in the busulphan series, especially in the early intake, platelet depression being the predominant manifestation.It is concluded that there is no evidence that either of the two cytotoxic drugs in the dosage prescribed improved survival for the two-year period of observation, though a final evaluation of the adjuvant chemotherapy as studied in this investigation will have to await the results at five years.


Influence of morphine on TLR4/ NF-kB signaling pathway of MCF-7 cells.
Morphine affects the risk of metastasis in cancer. The TLR4 gene promotes migration in adenocarcinoma cells. We investigated the effect of morphine on TLR4, MyD88 and NF-κ B-expression and migration. Migration of estrogen receptor-positive MCF7 breast cancer cells was studied after 24 and 48 hours incubation with morphine, with boyden chamber method. Morphine effect on TLR4, MyD88 and NF-κB mRNA expression was determined by quantitative Real-Time polymerase chain reaction. Migration was reduced at the doses of 0.5 and 5 µM (p < 0.05). However, TLR4, MyD88 and NF-κBmRNA expression was decreased at the doses of 0.5, 5 and 500 µM. Morphine at the dose of 50 µM increased the expression of mentioned genes. MCF-7 cell line after 48 hours incubation with the dose of 0.5 µM morphine decreased the migration and at the dose of 0.5 µM down-regulated the mRNA expression of TLR4, MyD88 and NF-κB, however, the higher doses increased the expression of TLR4, MyD88 and NF-κB. Morphine affects TLR4expression in breast cancer cell, which depends on time and concentration (Tab. 1, Fig. 5, Ref. 24).


Cisplatin inhibits bone healing during distraction osteogenesis.
Osteosarcoma (OS) is the most common malignant bone tumor affecting children and adolescents. Many patients are treated with a combination of chemotherapy, resection, and limb salvage protocols. Surgical reconstructions after tumor resection include structural allografts, non-cemented endoprostheses, and distraction osteogenesis (DO), which require direct bone formation. Although cisplatin (CDP) is extensively used for OS chemotherapy, the effects on bone regeneration are not well studied. The effects of CDP on direct bone formation in DO were compared using two dosing regimens and both C57BL/6 (B6) and tumor necrosis factor receptor 1 knockout (TNFR1KO) mice, as CDP toxicity is associated with elevated TNF levels. Detailed evaluation of the five-dose CDP regimen (2 mg/kg/day), demonstrated significant decreases in new bone formation in the DO gaps of CDP treated versus vehicle treated mice (p < 0.001). Further, no significant inhibitory effects from the five-dose CDP regimen were observed in TNFR1KO mice. The two-dose regimen significantly inhibited new bone formation in B6 mice. These results demonstrate that CDP has profound short term negative effects on the process of bone repair in DO. These data provide the mechanistic basis for modeling peri-operative chemotherapy doses and schedules and may provide new opportunities to identify molecules that spare normal cells from the inhibitory effects of CDP.


Plastic versus metal stents for inoperable gallbladder cancer with hilar biliary obstruction: the jury is still out.
In unresectable malignant hilar obstruction, adequate biliary drainage can be achieved with endoscopic placement of plastic or metal stents. Stent patency and patient survival may differ, depending on the primary disease, disease progression and stent type. Metal and plastic stents were compared in patients with malignant hilar strictures in several studies, but these studies mainly included patients who had cholangiocarcinoma, without taking into consideration potential differences in the invasion properties of tumor cells, histological differentiation and the biological behavior of different tumors. Gallbladder cancer (GBC) is the most common malignancy of the biliary tract, especially in the Indian subcontinent and Latin America. About half the patients with GBC present with jaundice, which usually means the tumor is inoperable. Palliative endoscopic stenting remains the first-line treatment of unresectable GBC with biliary obstruction. Primary disease progression is faster in GBC compared to cholangiocarcinoma. There is a paucity of data on the selection of stents for inoperable GBC with hilar biliary obstruction. This review focuses on the published literature related to the selection of stents for unresectable GBC with hilar obstruction.


Social tenants' health: evaluating the effectiveness of landlord interventions.
The National Health Service (NHS) scores well internationally on access to healthcare. But access has been measured on methods likely to undersample the more disadvantaged. Social landlords have access to more disadvantaged groups and may be able to improve health outcomes for their tenants and reduce their NHS usage by simple interventions. This is a randomised controlled trial of 547 London social housing 'general needs' tenants over 50 years of age. Participants were given a health assessment, then split into a control group or one of two treated groups. Following early assessment 25 participants had to be withdrawn to receive intensive treatment because of currently untreated major health problems. Participants were followed up over 18 months and changes in health outcomes and NHS usage measured. Compared with the control the most intensively treated group showed non-significant improvements on health outcomes but a significant reduction in NHS resource use, on conventional costings worth some £760 per person. All 25 participants transferred to the most intensively treated group after their early health assessments showed improvement on all health outcomes at final assessment, but these improvements were not statistically significant. Drawing a sample from disadvantaged but not the most seriously disadvantaged groups in London revealed 4.5% of the population to have very serious untreated health problems. The reason for lack of treatment was mainly non-registration with a general practitioner or psychiatric issues. Simple interventions to a targeted group were found to produce significant reductions in NHS usage and other, although non-significant, health benefits. ID ISRCTN96259142.


Phylloplane bacteria increase seedling emergence, growth and yield of field-grown groundnut (Arachis hypogaea L.).
To isolate and characterize groundnut-associated bacterial isolates for growth promotion of groundnut in field. Three hundred and ninety-three groundnut-associated bacteria, representing the geocarposphere, phylloplane and rhizosphere, and endophytes were applied as seed treatment in greenhouse. Maximum increase in plant biomass (up to 26%) was observed following treatment with a rhizosphere isolate identified as Bacillus firmis GRS 123, and two phylloplane isolates Bacillus megaterium GPS 55 and Pseudomonas aeruginosa GPS 21. There was no correlation between the production of L-tryptophan-derived auxins and growth promotion by the test isolates. Actively growing cells and peat formulations of GRS 123 and GPS 55, and actively growing cells of GPS 21, significantly increased the plant growth and pod yield (up to 19%) in field. Rifampicin-resistant mutants of GRS 123 and GPS 21 colonized the ecto- and endorhizospheres of groundnut, respectively, up to 100 days after sowing (DAS), whereas GPS 55 was recovered from both the habitats at 100 DAS. Seed bacterization with phylloplane isolates promoted groundnut growth indicating the possibility of isolating rhizosphere beneficial bacteria from different habitats. Identification of phylloplane bacteria as effective plant growth-promoting rhizobacteria (PGPR) broadens the spectrum of PGPR available for field application.


Edatrexate (10-ethyl-deaza-aminopterin) (NSC #626715) with or without leucovorin rescue for malignant mesothelioma. Sequential phase II trials by the cancer and leukemia group B.
The Cancer and Leukemia Group B (CALGB) conducted sequential Phase II multicenter trials to evaluate the activity of edatrexate alone (E) or with leucovorin rescue (EL) in patients with malignant pleural mesothelioma (CALGB Protocol 9131). Twenty patients were accrued to the E portion of the study and received edatrexate, 80 mg/m(2), intravenously over 20-30 minutes weekly. After a protocol amendment precipitated by excessive toxic events with E, 40 patients were enrolled in the EL arm and received the same dose of edatrexate with leucovorin, 15 mg orally, every 6 hours for 4 doses beginning 24 hours after edatrexate. Eligibility criteria included a CALGB performance status of 0-2 and no prior chemotherapy. A central pathology review was performed. Of the 58 patients included in this analysis (20 receiving E and 38 receiving EL), 36 had epithelial cell type and 22 had mixed or sarcomatous cell types. There were 31 patients with measurable disease and 27 with evaluable disease. The overall response rate was 25% for E (95% confidence interval [95% CI], 9-49%) and 16% for EL (95% CI, 6-31%). There was a 5% complete response [CR] rate, a 10% partial response [PR] rate, and a 10% regression [R] rate for E and a 0% CR rate, a 3% PR rate, and a 13% R rate for EL. The median survival duration from study entry was 9.6 months and 6.6 months, respectively, for E and EL; 1-year survival was 50% and 32%, respectively, for E and EL. There were four early deaths with the E regimen (including two from neutropenic sepsis) and one early death with the EL regimen (from progressive disease). Principal toxicities included mu cositis, myelosuppression, and rash, which were less frequent with leucovorin rescue. Moderate antitumor activity has been observed with both regimens. Leucovorin rescue ameliorated the mucosal, hematologic, and dermatologic toxicities of edatrexate, but also may have reduced its efficacy.


Health care inequality in free access health systems: The impact of non-pecuniary incentives on diabetic patients in Danish general practices.
Indicators of deprivation based on income and education might offer a blunt tool for inequality analysis in universal health systems with free access to care and thereby preventing the identification of groups experiencing the largest inequality. Also, analysis methods based on ranking the population by income or education, such as concentration curves and indices, are unsuitable for evaluating the impact of a health programme on inequality. This paper uses a new method for inequality analysis based on the Health Care Deprivation profiles' approach, allowing for: (1) considering multi-dimensional aspects of deprivation in the inequality analysis, (2) a graphical representation of the distribution of inequality, and (3) a range of additive decomposable inequality indices consistent with dominance. We apply this method and a Difference in Differences approach to evaluate the impact of a disease management programme aiming at reducing underutilisation of GP services for diabetic patients in Denmark. The programme introduced a set of non-pecuniary incentives empowering GPs with feedback reports on their performance and comparisons with other peers. Our study population includes 93,849 diabetic patients aged 18 + registered in 563 GP practices in Denmark; a total of 246 of these practices joined the programme, and 317 are used as control. The results show that patients experiencing the largest inequality in the top quintile of the distribution are characterised by deprivation in multiple socio-economic and morbidity dimensions that are not captured fully by income and education. The programme significantly reduced inequality in access to pivotal services, such as blood tests and preventive visits, for all patients and, with greater magnitude, for the most-deprived patients. Non-pecuniary incentives may be an effective tool for GPs to improve access to care in the most vulnerable patients.


People with neuromuscular diseases and their relatives' perspectives on challenges in everyday life and healthcare.
Objective: People with a neuromuscular disease (NMD) often experience challenges in everyday life and healthcare. Aim: To investigate experiences of and perspectives on challenges in everyday life and healthcare of people with NMDs and their relatives to gain new insights into how life-long rehabilitation can be tailored. Patients & methods: The design was qualitative using the interpretive description methodology and the Sense of Coherence theory. An ethnographic fieldwork was conducted where 45 persons with NMD and their relatives were included for interviews and participant observations. Results & conclusion: People with NMDs continually adapt to a changing functioning and balance their need for knowledge with their dependency on help when navigating the healthcare system. Structured, professionally facilitated peer support is needed.


Uptake and release of amino acids in the fetal-placental unit in human pregnancies.
The current concepts of human fetal-placental amino acid exchange and metabolism are mainly based on animal-, in vitro- and ex vivo models. We aimed to determine and assess the paired relationships between concentrations and arteriovenous differences of 19 amino acids on the maternal and fetal sides of the human placenta in a large study sample. This cross-sectional in vivo study included 179 healthy women with uncomplicated term pregnancies. During planned cesarean section, we sampled blood from incoming and outgoing vessels on the maternal (radial artery and uterine vein) and fetal (umbilical vein and artery) sides of the placenta. Amino acid concentrations were measured by liquid chromatography-tandem mass spectrometry. We calculated paired arteriovenous differences and performed Wilcoxon signed-rank tests and Spearman's correlations. In the umbilical circulation, we observed a positive venoarterial difference (fetal uptake) for 14 amino acids and a negative venoarterial difference (fetal release) for glutamic acid (p<0.001). In the maternal circulation, we observed a positive arteriovenous difference (uteroplacental uptake) for leucine (p = 0.005), isoleucine (p = 0.01), glutamic acid (p<0.001) and arginine (p = 0.04) and a negative arteriovenous difference (uteroplacental release) for tyrosine (p = 0.002), glycine (p = 0.01) and glutamine (p = 0.02). The concentrations in the maternal artery and umbilical vein were correlated for all amino acids except tryptophan, but we observed no correlations between the uteroplacental uptake and the fetal uptake or the umbilical vein concentration. Two amino acids showed a correlation between the maternal artery concentration and the fetal uptake. Our human in vivo study expands the current insight into fetal-placental amino acid exchange, and discloses some differences from what has been previously described in animals. Our findings are consistent with the concept that the fetal supply of amino acids in the human is the result of a dynamic interplay between fetal and placental amino acid metabolism and interconversions.


Epidural analgesia and intrapartum fever: placental findings.
To assess whether epidural analgesia is associated with fever, independent of maternal infection, by evaluating the relationship between epidural analgesia and inflammation of the placenta. Placentas collected prospectively from women with singleton gestations, who delivered 6 hours or more after membrane rupture, were evaluated systematically for histologic inflammation by an investigator blinded to all clinical information. Maternal and neonatal markers of infection were assessed in the cohorts who did and did not receive epidural analgesia. One hundred forty-nine consecutive placentas were analyzed, and 80 (54%) of these women received epidural analgesia. On univariate analysis, significant differences between epidural and no epidural groups were found with respect to maternal fever 38C or greater (46% versus 26%, P = .01), placenta inflammation (61% versus 36%, P = .002), and length of labor (11.8 hours versus 9.6 hours, P = .03). The combination of maternal fever plus placental inflammation was significantly more common in the epidural group (35% versus 17% P = .02). However, maternal fever in the absence of supporting evidence of infection, in the form of placental inflammation, was not increased after epidural analgesia (11% versus 9%, P = .61). Epidural analgesia is associated with intrapartum fever, but only in the presence of placental inflammation. This suggests that the fever reported with epidural analgesia is due to infection rather than the analgesia itself.


Progressive chest radiographic changes in wet lung disease.
Delayed clearance of fetal lung fluid, or wet lung disease (WLD), is a common, well described clinico-radiographic diagnosis. Unusual chest roentgenographic findings in six infants with WLD are reported. All infants had either delayed development of pleural fluid collections or transient apparent worsening of pulmonary parenchymal infiltrates simulating infection. Five of the six patients were treated with antibiotics. The patients were clinically well, radiographically normal, and culture negative by 72 hours. Our findings suggest that worsening of pulmonary parenchymal opacities and the appearance of pleural effusions can be part of the WLD spectrum. An initial radiographic impression of neonatal pneumonia can be changed to WLD and antibiotics stopped after 72 hours if subsequent radiographs show clearing, cultures are negative, and clinical findings resolve as they did in our patients.


Bone loss and bone turnover in acute and chronic spinal cord injured patients.
To investigate bone loss and the rate of bone turnover in individuals with spinal cord injury (SCI), and to compare the results with those healthy controls. This cross-sectional, controlled study was performed between January and December 2005, in the Istanbul Physical Medicine and Rehabilitation Training Hospital, Istanbul, Turkey. Forty-eight patients with SCI were included in the study. The control group consisted of 47 age and sex matched healthy subjects. Bone density was measured at the proximal hip region by dual-energy X-ray absorptiometry. Serum levels of osteocalcin (OC) and C telopeptide of type 1 collagen (CTX) were measured. Femur neck and femur total bone mineral density values in the SCI patients and control group were 0.894 (0.188), 0.911 (0.185), and 0.994 (0.116), 1.063 (0.132) (p<0.03, p<0.000). Serum levels of OC and CTX were significantly increased in patients (p<0.015, p<0.000). Femur bone density in both neck and total regions showed a significant decrease in the SCI patients with longer injury duration (p<0.001, p<0.000). Serum CTX levels were markedly elevated in the first year of SCI. However, serum OC level showed no difference for the injury duration. Significant bone loss was found at the proximal hip in SCI patients. Serum biochemical markers were also significantly higher in the patient group than the healthy controls. The bone density was lower in the long-standing SCI patients, although serum CTX levels were higher in the first 12 months after injury.


The effect of calcitonin on beta-endorphin levels in postmenopausal osteoporotic patients with back pain.
The purpose of this study was to evaluate the efficacy of calcitonin on beta-endorphin levels in female patients experiencing back pain associated with postmenopausal osteoporosis. The secondary purpose was to assess the pain and quality of life in these patients. There were 30 patients with a mean age of 58.2+/-5.4 years in the treatment group and 26 patients with a mean age of 58.8+/-5.2 years in the placebo group in this randomized, placebo-controlled study. The patients subcutaneously received 100 IU salmon calcitonin or placebo injections and 1,000 mg elementary calcium for 2 weeks. Baseline plasma beta-endorphin levels were measured and repeated after 2 weeks. Patients' pain and quality of life (QOL) were evaluated by using the Visual Analogue Scale, Modified Face Scale, Beck Depression Index, and Nottingham Health Profile. Patients' global assessment of disease activity was also performed at baseline and at the end of the first and second week. We found that plasma beta-endorphin levels in the treatment group were significantly higher than the placebo group at the end of the second week (p<0.001). Although pain and QOL scores were improved at the end of the second week in both groups (p<0.05), the improvement in the treatment group was more significant when compared with the placebo group (p<0.05). Therefore, calcitonin is an analgesic agent, as it increases the plasma beta-endorphin levels in patients with postmenopausal osteoporosis, which consequently improves QOL.


Smell test predicts performance on delayed recall memory test in elderly with depression.
Elderly with depression are at increased risk for cognitive dysfunction and dementia. Smell tests are correlated with performance on cognitive tests in the elderly and therefore might serve as a screening test for cognitive impairment in depressed elderly. To assess the validity of the CC-SIT (Cross-Cultural Smell Identification Test) as a screening test for cognitive impairment in elderly with depression. Forty-one patients, aged 60 and over, were assessed with the CC-SIT and CVLT (California Verbal Learning Test) after 3 months treatment of a Major Depressive Episode (DSM-IV) at the Day Hospital for Depression, Baycrest. Patients already diagnosed with dementia, or other psychiatric and neurological disorders, were excluded. Receiver Operating Characteristics (ROC) analysis was applied to assess the CC-SIT's accuracy in identifying individuals with impairment (2 SD below the mean for age and education or less) on CVLT delayed recall trials. Forty-one patients (33 women and eight men) were assessed. Mean age was 76.8 (SD: 6.5), mean HRSD scores before treatment was 22.0 (SD: 5.1). Nine patients had impairment on CVLT delayed recall measures. The area under the ROC curve was 0.776 (95% CI = 0.617-0.936). Our results support the use of the CC-SIT as a screening tool for cognitive impairment among elderly with depression as an indicator for the need of a comprehensive neuropsychological evaluation. Replication with larger samples is necessary.


Haptic synthesis of shapes and sequences.
Haptic perception of shape is based on kinesthetic and tactile information synthesized across space and time. We studied this process by having subjects move along the edges of multisided shapes and then remember and reproduce the shapes. With eyes closed, subjects moved a robot manipulandum whose force field was programmed to simulate a quadrilateral boundary in a horizontal plane. When subjects then reproduced the quadrilateral using the same manipulandum, with eyes still closed but now with the force field set to zero, they made consistent errors, overestimating the lengths of short segments and underestimating long ones, as well as overestimating acute angles and underestimating obtuse ones. Consequently their reproductions were more regular than the shapes they had experienced. When subjects felt the same quadrilaterals with the same manipulandum but drew them on a vertical screen with visual feedback, they made similar errors, indicating that their distortions reflected mainly perceptual rather than motor processes. In a third experiment, subjects explored the 3 sides of an open shape in a fixed order. The results revealed a temporal pattern of interactions, where the lengths and angles of previously explored segments influenced the drawing of later segments. In all tasks, our subjects were as accurate as subjects in earlier studies who haptically explored only single lines or angles, suggesting that the mental processes that synthesize haptic data from multiple segments into complete shapes do not introduce any net error.


Clinical characteristics and outcomes of COVID-19 in people living with HIV in Belgium: A multicenter, retrospective cohort.
The aim of this study was to describe the clinical characteristics and outcomes of coronavirus disease 2019 (COVID-19) among people living with HIV (PLWH) in Belgium. We performed a retrospective multicenter cohort analysis of PLWH with either laboratory-confirmed, radiologically diagnosed, or clinically suspected COVID-19 between February 15, 2020 and May 31, 2020. The primary endpoint was outcome of COVID-19. Secondary endpoints included rate of hospitalization and length of hospital stay and rate of Intensive Care Unit (ICU) admission and mechanical ventilation. One hundred and one patients were included in this study. Patients were categorized as having either laboratory-confirmed (n = 65), radiologically-diagnosed (n = 3), or clinically suspected COVID-19 (n = 33). The median age was 51.3 years (interquartile range [IQR] 41.3-57.3) and 44% were female. Ninety-four percent of patients were virologically suppressed and 67% had a CD4+ cell count more than or equal to 500 cells/µl. Overall, 46% of patients required hospitalization and the median length of hospital stay was 6 days (IQR 3-15). Age more than or equal to 50 years, Black Sub-Saharan African patients, and being on an integrase strand transfer inhibitor-based regimen were associated with being hospitalized. ICU admission and mechanical ventilation was required for 15% and 10% of all patients respectively. Overall, 9% of patients died while 78 (77%) patients made a full recovery. HIV patients with COVID-19 experienced a high degree of hospitalization despite having elevated CD4+ cell counts and a high rate of virologic suppression. Matched case-control studies are warranted to measure the impact that HIV may have on patients with COVID-19.


A human placenta-specific ATP-binding cassette gene (ABCP) on chromosome 4q22 that is involved in multidrug resistance.
We characterized a new human ATP-binding cassette (ABC) transporter gene that is highly expressed in the placenta. The gene, ABCP, produces two transcripts that differ at the 5' end and encode the same 655-amino acid protein. The predicted protein is closely related to the Drosophila white and yeast ADP1 genes and is a member of a subfamily that includes several multidrug resistance transporters. ABCP, white, and ADP1 all have a single ATP-binding domain at the NH2 terminus and a single COOH-terminal set of transmembrane segments. ABCP maps to human chromosome 4q22, between the markers D4S2462 and D4S1557, and the murine gene (Abcp) is located on chromosome 6 28-29 cM from the centromere. ABCP defines a new syntenic segment between human chromosome 4 and mouse chromosome 6. The abundant expression of this gene in the placenta suggests that the protein product has an important role in transport of specific molecule(s) into or out of this tissue.


Role of hysterectomy and its alternatives in benign uterine diseases.
There is a rising trend of hysterectomy rate as too frequently it is being performed now for conditions like symptomatic fibroids and dysfunctional uterine bleeding which can be treated alternatively. Hysterectomy, as with all other major surgeries, is also associated with increased mortality and morbidity risks. Various medical and surgical lines of management, other than hysterectomy, are presently accessible for the above conditions. Availability of safer and newer treatment options is great boon for women with changing attitudes towards child-bearing and uterine conservation.


Critical indirect effects of climate change on sub-Antarctic ecosystem functioning.
Sub-Antarctic islands represent critical breeding habitats for land-based top predators that dominate Southern Ocean food webs. Reproduction and molting incur high energetic demands that are sustained at the sub-Antarctic Prince Edward Islands (PEIs) by both inshore (phytoplankton blooms; "island mass effect"; autochthonous) and offshore (allochthonous) productivity. As the relative contributions of these sustenance pathways are, in turn, affected by oceanographic conditions around the PEIs, we address the consequences of climatically driven changes in the physical environment on this island ecosystem. We show that there has been a measurable long-term shift in the carbon isotope signatures of the benthos inhabiting the shallow shelf region of the PEIs, most likely reflecting a long-term decline in enhanced phytoplankton productivity at the islands in response to a climate-driven shift in the position of the sub-Antarctic Front. Our results indicate that regional climate change has affected the balance between allochthonous and autochthonous productivity at the PEIs. Over the last three decades, inshore-feeding top predators at the islands have shown a marked decrease in their population sizes. Conversely, population sizes of offshore-feeding predators that forage over great distances from the islands have remained stable or increased, with one exception. Population decline of predators that rely heavily on organisms inhabiting the inshore region strongly suggest changes in prey availability, which are likely driven by factors such as fisheries impacts on some prey populations and shifts in competitive interactions among predators. In addition to these local factors, our analysis indicates that changes in prey availability may also result indirectly through regional climate change effects on the islands' marine ecosystem. Most importantly, our results indicate that a fundamental shift in the balance between allochthonous and autochthonous trophic pathways within this island ecosystem may be detected throughout the food web, demonstrating that the most powerful effects of climate change on marine systems may be indirect.


EXO modifies sucrose and trehalose responses and connects the extracellular carbon status to growth.
Plants have the capacity to adapt growth to changing environmental conditions. This implies the modulation of metabolism according to the availability of carbon (C). Particular interest in the response to the C availability is based on the increasing atmospheric levels of CO2. Several regulatory pathways that link the C status to growth have emerged. The extracellular EXO protein is essential for cell expansion and promotes shoot and root growth. Homologous proteins were identified in evolutionarily distant green plants. We show here that the EXO protein connects growth with C responses. The exo mutant displayed altered responses to exogenous sucrose supplemented to the growth medium. Impaired growth of the mutant in synthetic medium was associated with the accumulation of starch and anthocyanins, altered expression of sugar-responsive genes, and increased abscisic acid levels. Thus, EXO modulates several responses related to the C availability. Growth retardation on medium supplemented with 2-deoxy-glucose, mannose, and palatinose was similar to the wild type. Trehalose feeding stimulated root growth and shoot biomass production of exo plants whereas it inhibited growth of the wild type. The phenotypic features of the exo mutant suggest that apoplastic processes coordinate growth and C responses.


Coping with Work-related Traumatic Situations among Crime Scene Technicians.
Crime scene technicians collect evidence related to crime and are therefore exposed to many traumatic situations. The coping strategies they use are thus very important in the process of facing the psychological consequences of such work. The available literature shows that crime scene technicians are an understudied subgroup of police workers. Our study is therefore the first unfolding insights into technicians' coping strategies, post-traumatic symptomatology and somatic health, based on a sample of 64 male crime scene technicians (85% of all Slovene technicians). Crime scene technicians mainly use avoidance coping strategies. Approach strategies that are more effective in the long-term-i.e. lead to a larger buffering of the effects of traumatic stress-are more frequently used if technicians are familiar with the nature of the task, when they have time to prepare for it, and if they feel that past situations have been positively resolved. Behavioural avoidance strategies were found to be least effective when dealing with traumatic experiences and are also related to more frequent problems of physical health. Results indicate that appropriate trainings for future technicians would facilitate the use of more effective coping strategies and consequently lead to a more effective and satisfied worker. Copyright © 2014 John Wiley & Sons, Ltd.


Utility of contrast-enhanced ultrasound for the assessment of the carotid artery wall in patients with Takayasu or giant cell arteritis.
Carotid contrast-enhanced ultrasound (CEUS) was recently proposed for the evaluation of large-vessel vasculitides (LVV), particularly to assess vascularization within the vessel wall. The aim of this pilot study was to evaluate the potential of carotid colour Doppler ultrasound (CDUS) and CEUS in patients with LVV. This prospective study included seven patients (mean age 48 ± 14 years, all females) with established LVV (Takayasu arteritis or giant cell arteritis). All patients underwent CDUS and CEUS (14 carotid arteries). Intima-media thickness, lumen diameter, Doppler velocities, vessel wall thickening, and lesion thickness were assessed. CEUS was used to improve visualization of the lumen-to-vessel wall border, and to visualize carotid wall vascularization. Four (57%) patients [7 (50%) carotid arteries] exhibited lesions, and the average lesion thickness was 2.0 ± 0.5 mm. According to the Doppler peak systolic velocity, 5 (35%) carotid arteries had a <50% stenosis, 1 (7%) had a 50-70% stenosis, and 1 (7%) had a ≥70% stenosis. The contrast agent improved the image quality and the definition of the lumen-to-vascular wall border. Carotid wall vascularization was observed in 5 (71%) patients [9 (64%) carotid arteries]. Five (36%) carotid arteries had mild-to-moderate vascularization, and 4 (29%) had severe wall vascularization. Carotid CDUS allows the assessment of anatomical features of LVV, including vessel wall thickening and degree of stenosis. Carotid CEUS improves the visualization of the lumen border, and allows dynamic assessment of carotid wall vascularization, which is a potential marker of disease activity in patients with LVV.


Carbohydrate-active enzyme profiles of Lactiplantibacillus plantarum strain 84-3 contribute to flavor formation in fermented dairy and vegetable products.
Microbes are critical for flavor formation in fermented foods; however, their mechanisms of action are not fully understood. The microbial composition of 51 dairy and 47 vegetable products was functionally annotated and the carbohydrate-active enzyme (CAZyme) profiles of Lactiplantibacillus plantarum 84-3 (Lp84-3), isolated from dairy samples, can promote resistant starch (RS) degradation, were analyzed. Lactobacillus, Streptococcus, and Lactococcus were the predominant genera in dairy products, whereas the major genera in vegetables were Lactobacillus, Weissella, and Carnimonas. Phages from Siphoviridae, Myoviridae, and Herelleviridae were also present in dairy products. Additionally, the glycosyl hydrolase (GHs) family members GH1 and GH13 and the glycosyltransferase (GTs) family members GT2 and GT4 were abundant in Lp84-3. Moreover, Lp84-3 was enriched in butanoate metabolism enzymes and butanoate metabolite compounds. Therefore, fermented food microbes, especially Lp84-3, have an abundant repertoire of enzymes that promote flavor production, as starter improving the flavor of fermented dairy and vegetable products.


Biotin uptake into human peripheral blood mononuclear cells increases early in the cell cycle, increasing carboxylase activities.
Cells respond to proliferation with increased accumulation of biotin, suggesting that proliferation enhances biotin demand. Here we determined whether peripheral blood mononuclear cells (PBMC) increase biotin uptake at specific phases of the cell cycle, and whether biotin is utilized to increase biotinylation of carboxylases. Biotin uptake was quantified in human PBMC that were arrested chemically at specific phases of the cell cycle, i.e., biotin uptake increased in the G1 phase of the cycle [658 +/- 574 amol biotin/(10(6) cells x 30 min)] and remained increased during phases S, G2, and M compared with quiescent controls [200 +/- 62 amol biotin/(10(6) cells x 30 min)]. The abundance of the sodium-dependent multivitamin transporter (SMVT, which transports biotin) was similar at all phases of the cell cycle, suggesting that transporters other than SMVT or splicing variants of SMVT may account for the increased biotin uptake observed in proliferating cells. Activities of biotin-dependent 3-methylcrotonyl-CoA carboxylase and propionyl-CoA carboxylase were up to two times greater in proliferating PBMC compared with controls. The abundance of mRNA encoding 3-methylcrotonyl-CoA carboxylase and propionyl-CoA carboxylase paralleled carboxylase activities, suggesting that PBMC respond to proliferation with increased expression of genes encoding carboxylases. Similarly, expression of the gene encoding holocarboxylase synthetase (which catalyzes binding of biotin to carboxylases) increased in response to proliferation, suggesting that cellular capacity to biotinylate carboxylases was increased. In summary, these findings suggest that PBMC respond to proliferation with increased biotin uptake early in the cell cycle, and that biotin is utilized to increase activities of two of the four biotin-requiring carboxylases.


Memory is Not Enough: The Neurobiological Substrates of Dynamic Cognitive Reserve.
Changes in the residual memory variance are considered as a dynamic aspect of cognitive reserve (d-CR). We aimed to investigate for the first time the neural substrate associated with changes in the residual memory variance overtime in patients with amnestic mild cognitive impairment (aMCI). Thirty-four aMCI patients followed-up for 36 months and 48 healthy elderly individuals (HE) were recruited. All participants underwent 3T MRI, collecting T1-weighted images for voxel-based morphometry (VBM). They underwent an extensive neuropsychological battery, including six episodic memory tests. In patients and controls, factor analyses were used on the episodic memory scores to obtain a composite memory score (C-MS). Partial Least Square analyses were used to decompose the variance of C-MS in latent variables (LT scores), accounting for demographic variables and for the general cognitive efficiency level; linear regressions were applied on LT scores, striping off any contribution of general cognitive abilities, to obtain the residual value of memory variance, considered as an index of d-CR. LT scores and d-CR were used in discriminant analysis, in patients only. Finally, LT scores and d-CR were used as variable of interest in VBM analysis. The d-CR score was not able to correctly classify patients. In both aMCI patients and HE, LT1st and d-CR scores showed correlations with grey matter volumes in common and in specific brain areas. Using CR measures limited to assess memory function is likely less sensitive to detect the cognitive decline and predict the evolution of Alzheimer's disease. In conclusion, d-CR needs a measure of general cognition to identify conversion to Alzheimer's disease efficiently.


Crying abnormalities in congenital hypothyroidism: preliminary spectrographic study.
The aim of this preliminary study was to evaluate the acoustic patterns of the cries of hypothyroid newborns at the time of diagnosis and after the beginning of therapy. Cries were recorded at the nursery of the San Raffaele Hospital, Milan, Italy from 12 full-term subjects (three boys and nine girls) affected by congenital hypothyroidism. Results show that untreated hypothyroid infants at first recording had fewer voiceless and partially voiced cries than normal controls. The percent distribution of this pattern did not change at the second recording after the onset of substitutive therapy. Also, untreated hypothyroid infants had many more cry units showing a vibrato contour than did controls, and this pattern did not change after the onset of treatment. Starting, maximum, minimum, and end frequencies measured on the fundamental were significantly lower in the hypothyroid sample. Four hypothyroid subjects recorded before therapy and within 4 weeks after therapy onset significantly augmented their fundamental frequency parameters; however, in 25% of the sample, sound parameters remained unaltered after 3 or more weeks of treatment. To our knowledge the present preliminary study is the first one performed on follow-up of hypothyroid newborns and indicates that both central and peripheral damage might influence the pattern of crying in untreated hypothyroid infants.


Fate and biodegradability of sulfonated aromatic amines.
Ten sulfonated aromatic amines were tested for their aerobic and anaerobic biodegradability and toxicity potential in a variety of environmental inocula. Of all the compounds tested, only two aminobenzenesulfonic acid (ABS) isomers, 2- and 4-ABS, were degraded. The observed degradation occurred only under aerobic conditions with inocula sources that were historically polluted with sulfonated aromatic amines. Bioreactor experiments, with non-sterile synthetic wastewater, confirmed the results from the aerobic batch degradation experiments. Both ABS isomers were degraded in long-term continuous experiment by a bioaugmented enrichment culture. The maximum degradation rate in the aerobic bioreactor was 1.6-1.8 g 1(-1) d(-1) for 2-ABS and a somewhat lower value for 4-ABS at hydraulic retention times (HRT) of 2.8-3.3 h. Evidence for extensive mineralization of 2- and 4-ABS was based on oxygen uptake and carbon dioxide production during the batch experiments and the high levels of chemical oxygen demand (COD) removal in the bioreactor. Furthermore, mineralization of the sulfonate group was demonstrated by high recovery of sulfate. The sulfonated aromatic amines did not show any toxic effects on the aerobic and anaerobic bacterial populations tested. The poor biodegradability of sulfonated aromatic amines indicated under the laboratory conditions of this study suggests that these compounds may not be adequately removed during biological wastewater treatment.


Molecular characterization of dsRNA segments 2 and 5 and electron microscopy of a novel reovirus from a hypovirulent isolate, W370, of the plant pathogen Rosellinia necatrix.
A hypovirulent isolate, W370, of the white root rot fungus Rosellinia necatrix has previously been shown to harbour 12 dsRNA segments. In this study, complete nucleotide sequences of segments 2 and 5 of W370 dsRNAs were determined. The nucleotide sequence of genome segment 2 was 3773 bases long with a single long open reading frame (ORF) encoding 1226 amino acid residues with a predicted molecular mass of approximately 138.5 kDa. The nucleotide sequence of segment 5 was 2089 bases long with a single long ORF, whose deduced polypeptide contained 646 amino acid residues with a predicted molecular mass of about 72 kDa. Comparative analysis showed that the deduced protein sequence of segment 2 had significant homology with the putative VP2 of Colorado tick fever virus (CTFV) and European Eyach virus (EYAV) in the genus Coltivirus, but the deduced protein sequence of segment 5 had no similarity with other virus proteins. Double-shelled spherical particles approximately 80 nm in diameter associated with W370 dsRNAs were observed in a preparation from the mycelial tissue of isolate W370. The results demonstrated that the virus associated with W370 dsRNAs is a novel reovirus of the family Reoviridae. The virus was named Rosellinia anti-rot virus (RArV).


Oct4/Sox2-regulated miR-302 targets cyclin D1 in human embryonic stem cells.
Oct4 and Sox2 are transcription factors required for pluripotency during early embryogenesis and for the maintenance of embryonic stem cell (ESC) identity. Functional mechanisms contributing to pluripotency are expected to be associated with genes transcriptionally activated by these factors. Here, we show that Oct4 and Sox2 bind to a conserved promoter region of miR-302, a cluster of eight microRNAs expressed specifically in ESCs and pluripotent cells. The expression of miR-302a is dependent on Oct4/Sox2 in human ESCs (hESCs), and miR-302a is expressed at the same developmental stages and in the same tissues as Oct4 during embryogenesis. miR-302a is predicted to target many cell cycle regulators, and the expression of miR-302a in primary and transformed cell lines promotes an increase in S-phase and a decrease in G(1)-phase cells, reminiscent of an ESC-like cell cycle profile. Correspondingly, the inhibition of miR-302 causes hESCs to accumulate in G(1) phase. Moreover, we show that miR-302a represses the productive translation of an important G(1) regulator, cyclin D1, in hESCs. The transcriptional activation of miR-302 and the translational repression of its targets, such as cyclin D1, may provide a link between Oct4/Sox2 and cell cycle regulation in pluripotent cells.