The tribal community's perception on tuberculosis: A community based qualitative study in Tamil Nadu, India.
Tuberculosis is a highly contagious bacterial infection. It is a major public health issue with India being the highest prevalent country in the world. The nation has a large and heterogeneous tribal population of approximately 104 million people which accounts for 8.6% of the total population. This study focuses on assessing the tuberculosis scenario amongst the tribal population their perceptions on risk factors of TB, general health problems, health seeking behavior, and challenges faced by them. The study was conducted using in-depth interviews and focus group discussions in the three sampled study districts namely Nilgiris, Namakkal, and Villipuram of Tamil Nadu, India. A thematic analysis was performed to identify the major emerging themes. Following thematic analysis, an interventional strategy for improving the overall knowledge and awareness among the community health education was imparted. The conducted in-depth interviews and focus group discussions identified major themes that emerged from the codes which included stigma and discrimination, association with HIV, detection of symptoms, health seeking behavior, knowledge and awareness of TB, acculturation, treatment adherence and lack of lab facility. This qualitative study has captured the overall perception towards tuberculosis from the tribal community as a whole as well as from the health workers. The tribal community stigmatized and discriminated people suffering from TB which had an impact on the health seeking behavior as well as on the treatment adherence. The primary care providers were aware of the situation of TB in tribes but were poorly equipped. Primary healthcare providers should in fact, have a crucial role in identification of at-risk subjects, for prompt referrals, and delivery of treatment services.


Non-histone chromatin proteins of B lymphocytes stimulated by lipopolysaccharide. II. Phosphorylation.
Stimulation of mouse lymphocytes with the B lymphocyte specific mitogen lipopolysaccharide results in an increased rate of phosphorylation of non-histone chromatin proteins. An initial small increase in phosphorylation occurs during the first 2 h and a much larger increase after 24 h of culture with mitogen. The phosphorylated nuclear and cytoplasmic proteins were analysed by polyacrylamide gel electrophoresis and the stimulation index of each prominent peak measured. It was inferred that selective stimulation of the phosphorylation of individual proteins had occurred from: (1) the range of stimulation indices for different proteins, and (2) the appearance, after 8 h stimulation of an apparently newly phosphorylated non-histone chromatin protein of molecular weight 115 000. The pool size of ATP was monitored and showed only small changes during the first 24 h of exposure to lipopolysaccharide. Phosphatase activity was found to be associated with lymphocyte chromatin and nucleoplasm and may help to regulate the level of phosphorylation of non-histone chromatin proteins in vivo. To preserve phosphorylated proteins during their isolation phosphatase activity was inhibited by Na2MoO4. The selective changes in phosphorylation of nuclear proteins precede, and continue during, the stimulation of immunoglobulin and DNA synthesis. Our results are thus consistent with the hypothesis that phosphorylation of non-histone chromatin proteins plays a role in the regulation of gene expression in B lymphocytes.


Event-related potentials to repeated speech in 9-month-old infants at risk for autism spectrum disorder.
Atypical neural responses to repeated auditory and linguistic stimuli have been reported both in individuals with autism spectrum disorder (ASD) and their first-degree relatives. Recent work suggests that the younger siblings of children with ASD have atypical event-related potentials (ERPs) to repeated tones at 9 months of age; however, the functional significance is unclear, and it is unknown whether this atypicality is also present in response to linguistic stimuli. We analyzed ERPs to repetitive and deviant consonant-vowel stimuli at 9 months in 35 unaffected high-risk-for-autism (HRA) infant siblings of children with ASD and 45 low-risk control (LRC) infants. We examined a positive component, the P150, over frontal and central electrode sites and investigated the relationships between this component and later behavior. Over frontal electrodes, HRA infants had larger-amplitude ERPs to repetitions of the standard than LRC infants, whereas ERPs to the deviant did not differ between HRA and LRC infants. Furthermore, for HRA infants, the amplitude of ERPs to the standards was positively correlated with later language ability. Our work suggests that atypical ERPs to repeated speech during infancy are a possible endophenotype of ASD but that this atypicality is associated with beneficial, rather than disordered, language development. Potential mechanisms driving these relationships and implications for development are discussed.


Altered hippocampal plasticity by prenatal kynurenine administration, kynurenine-3-monoxygenase (KMO) deletion or galantamine.
Glutamate receptors sensitive to N-methyl-D-aspartate (NMDA) are involved in embryonic brain development but their activity may be modulated by the kynurenine pathway of tryptophan metabolism which includes an agonist (quinolinic acid) and an antagonist (kynurenic acid) at these receptors. Our previous work has shown that prenatal inhibition of the pathway produces abnormalities of brain development. In the present study kynurenine and probenecid (both 100mg/kg, doses known to increase kynurenic acid levels in the brain) were administered to female Wistar rats on embryonic days E14, E16 and E18 of gestation and the litter was allowed to develop to post-natal day P60. Western blotting revealed no changes in hippocampal expression of several proteins previously found to be altered by inhibition of the kynurenine pathway including the NMDA receptor subunits GluN1, GluN2A and GluN2B, as well as doublecortin, Proliferating Cell Nuclear Antigen (PCNA), sonic hedgehog and unco-ordinated (unc)-5H1 and 5H3. Mice lacking the enzyme kynurenine-3-monoxygenase (KMO) also showed no changes in hippocampal expression of several of these proteins or the 70-kDa and 100-kDa variants of Disrupted in Schizophrenia-1 (DISC1). Electrical excitability of pyramidal neurons in the CA1 region of hippocampal slices was unchanged, as was paired-pulse facilitation and inhibition. Long-term potentiation was decreased in the kynurenine-treated rats and in the KMO(-/-) mice, but galantamine reversed this effect in the presence of nicotinic receptor antagonists, consistent with evidence that it can potentiate glutamate at NMDA receptors. It is concluded that interference with the kynurenine pathway in utero can have lasting effects on brain function of the offspring, implying that the kynurenine pathway is involved in the regulation of early brain development.


Transport of alpha-p-nitrophenylgalactoside by the lactose carrier of Escherichia coli.
alpha-p-Nitrophenylgalactoside was found to be accumulated by the lactose transport-system of Escherichia coli. This fact may help to resolve the differences in the reported number of sugar binding sites of the lactose transport protein in nonenergized and energized membrane vesicles.


Whither community-based health care?
This paper identifies implications for community-based health care (CBHC). Sustainability of CBHC depends on effective community involvement, power sharing, adequate resources and, above all else careful planning with the community expected to benefit from CBHC.


Mapping implementation strategies of evidence-based interventions for three preselected phenomena in people with dementia-a scoping review.
Caring for people with dementia is complex, and there are various evidence-based interventions. However, a gap exists between the available interventions and how to implement them. The objectives of our review are to identify implementation strategies, implementation outcomes, and influencing factors for the implementation of evidence-based interventions that focus on three preselected phenomena in people with dementia: (A) behavior that challenges supporting a person with dementia in long-term care, (B) delirium in acute care, and (C) postacute care needs. We conducted a scoping review according to the description of the Joanna Briggs Institute. We searched MEDLINE, CINAHL, and PsycINFO. For the data analysis, we conducted deductive content analysis. For this analysis, we used the Expert Recommendations for Implementation Change (ERIC), implementation outcomes according to Proctor and colleagues, and the Consolidated Framework for Implementation Research (CFIR). We identified 362 (A), 544 (B), and 714 records (C) on the three phenomena and included 7 (A), 3 (B), and 3 (C) studies. Among the studies, nine reported on the implementation strategies they used. Clusters with the most reported strategies were adapt and tailor to context and train and educate stakeholders. We identified one study that tested the effectiveness of the applied implementation strategy, while ten studies reported implementation outcomes (mostly fidelity). Regarding factors that influence implementation, all identified studies reported between 1 and 19 factors. The most reported factors were available resources and the adaptability of the intervention. To address dementia-specific influencing factors, we enhanced the CFIR construct of patient needs and resources to include family needs and resources. We found a high degree of homogeneity across the different dementia phenomena, the evidence-based interventions, and the care settings in terms of the implementation strategies used, implementation outcomes measured, and influencing factors identified. However, it remains unclear to what extent implementation strategies themselves are evidence-based and which intervention strategy can be used by practitioners when either the implementation outcomes are not adjusted to the implementation strategy and/or the effects of implementation strategies are mostly unknown. Future research needs to focus on investigating the effectiveness of implementation strategies for evidence-based interventions for dementia care. The review protocol was prospectively published (Manietta et al., BMJ Open 11:e051611, 2021).


Increasing the antinociceptive effect of ingested glycinamide in female rats by increasing its palatability.
These studies were undertaken to investigate whether the ingestion of glycinamide, a precursor of glycine, made more palatable by mixing with a chocolate suspension, improves antinociception in rats. Two nociception threshold models were employed: the tail-flick latency and vocalization to tail shock, in restricted and freely-moving rats. Glycinamide in a highly palatable commercial chocolate aqueous suspension was provided for ad-lib ingestion after 24 hours of water deprivation. Antinociception threshold testing was performed before and 10, 30, 60, 90, 120, 180, and 240 minutes after the ingestion of the chocolate-glycinamide mixture. Ingestion of the glycinamide-in-chocolate suspension induced antinociception based on the tail shock vocalization and tail-flick latency tests. Ingestion of the glycinamide-in-chocolate suspension induced an 80% elevation in the antinociceptive threshold that persisted for 4 hours. Rats readily ingest the glycine precursor, glycinamide, in an aqueous chocolate mixture, which induces potent and prolonged antinociception.


Participation in healthcare behavior by adolescents with epilepsy and factors that influence it during the transition period: A cross-sectional study in China.
Given the importance of adolescents' participation in the care of their chronic diseases during their transitional period in the healthcare system, the present study investigated the degree of participation in healthcare behavior by Chinese adolescents with chronic epilepsy and identified factors that should be addressed by health interventions. The study used a convenience sample of 1238 adolescent patients with epilepsy, who were hospitalized in 17 tertiary A-level children or maternal and child specialty hospitals in China between January 2017 and March 2020. Several scales were used to measure their degree of participation in healthcare behavior and the factors that influence it. Data collection was conducted after uniform training of the investigators. The adolescents who met the inclusion and exclusion criteria could scan the QR code of the questionnaire via a mobile phone. The age of the participants ranged from 12.2 to 17.8 years (mean 14.2 years), and the sample had a male-to-female ratio of 1.25:1. The patients' average total score of participation in healthcare behavior was 125.58 (SD = 12.25), which was lower than the norm for China. Their scores on the six dimensions of participation were highest for information interaction, followed in descending order by medical decision-making, treatment and care, appeal, diagnosis and treatment decision-making, and questioning supervision. Multiple linear regression found significant associations between health-care participation and five personal and disease variables (gender, age, course of disease, number of comorbid diseases, type of family structure), self-efficacy, and coping styles (cognitive-palliative and acceptance), which explained 52.1% of the variance in patients' total scores on participating in healthcare behavior. The participation of young Chinese patients with epilepsy in transitional healthcare behavior needs to be improved. Participation was positively associated with being female, a longer course of disease, fewer comorbidities, and living in a nuclear family. Patients who used cognitive-palliative and acceptance coping styles and those who had higher self-efficacy also had significantly higher levels of participation in healthcare behavior. The study provides useful reference points for adolescents with chronic disease to participate in healthcare programs, in order to achieve a smooth transition from childhood to adulthood.


[Special aspects of abdominal sepsis].
Abdominal sepsis remains a major cause of perioperative morbidity and mortality in surgical intensive care units. It must be considered a life-threatening condition and requires multidisciplinary coordination of intensive care. Apart from the local abdominal infection (peritonitis), abdominal sepsis is defined by extraperitoneal systemic reactions potentially leading to septic shock and death in the further course. Early and radical focus sanitation as well as aggressive systemic antimicrobial therapy remain the causal therapy strategies of abdominal sepsis.


Vertebrate hairy and Enhancer of split related proteins: transcriptional repressors regulating cellular differentiation and embryonic patterning.
The basic-helix-loop-helix (bHLH) proteins are a superfamily of DNA-binding transcription factors that regulate numerous biological processes in both invertebrates and vertebrates. One family of bHLH transcriptional repressors is related to the Drosophila hairy and Enhancer-of-split proteins. These repressors contain a tandem arrangement of the bHLH domain and an adjacent sequence known as the Orange domain, so we refer to these proteins as bHLH-Orange or bHLH-O proteins. Phylogenetic analysis reveals the existence of four bHLH-O subfamilies, with distinct, evolutionarily conserved features. A principal function of bHLH-O proteins is to bind to specific DNA sequences and recruit transcriptional corepressors to inhibit target gene expression. However, it is likely that bHLH-O proteins repress transcription by additional mechanisms as well. Many vertebrate bHLH-O proteins are effectors of the Notch signaling pathway, and bHLH-O proteins are involved in regulating neurogenesis, vasculogenesis, mesoderm segmentation, myogenesis, and T lymphocyte development. In this review, we discuss mechanisms of action and biological roles for the vertebrate bHLH-O proteins, as well as some of the unresolved questions about the functions and regulation of these proteins during development and in human disease.


Tris(ethyl-enediamine-κN,N')cobalt(III) aqua-tris-(oxalato-κO,O)indate(III).
In the cation of the title compound, [Co(C(2)H(8)N(2))(3)][In(C(2)O(4))(3)(H(2)O)], the Co(III) atom is coordinated by six N atoms from three ethyl-enediamine mol-ecules. The Co(III)-N bond lengths lie in the range 1.956 (4)-1.986 (4) Å. In the anion, the In(III) atom is seven-coordinated by six O atoms from three oxalate ligands and by a water mol-ecule. The cations and anions are linked by extensive O-H⋯O and N-H⋯O hydrogen bonds, forming a supermolecular network.


Laparoscopic cholecystectomy in the grossly obese: 4 years experience and review of literature.
Conventional abdominal surgery in grossly obese patients is associated with an increased rate of postoperative complications; thus, laparoscopic surgery may be preferred in these patients. A prospective analysis was performed of 20 grossly obese patients who underwent laparoscopic cholecystectomy between April 1996 and April 2000 for symptomatic non-complicated gallstone disease. Technical problems at operation included difficulty with induction of pneumoperitoneum and introduction of the most lateral subcostal port, retraction of the gallbladder fundus, the need for longer instruments and the closure of the fascia. Laparoscopic cholecystectomy was successfully completed in 19 patients, but one patient required conversion to open operation. There were no anaesthetic difficulties. Two patients developed minor chest infections. The mean hospital stay was 2.9 days. Laparoscopic cholecystectomy is feasible and can be recommended for symptomatic gallstone disease in grossly obese patients.


[Determination of the endotoxin content of egg products using a miniaturized chromogenic Limulus test].
A chromogenic Limulus amoebocyte lysate assay was applied to monitor endotoxin concentration in egg products. Analysis of differently contaminated whole egg probes revealed a strong correlation of endotoxin concentration to total bacterial count 6 x 10(4) cfu x ng-1, where cfu = colony-forming unit) as well as to number of Enterobacteriaceae (1 ng/7 x 10(2) cfu). Similar relations were also found for egg white and egg yolk probes. A significant influence of heat pretreatment of egg probes (65 degrees C, 60 min) on endotoxin detection could be excluded. Up to a concentration of 10 mg x ml-1 endotoxin-free whole egg material did not interfere with the test system. A miniaturized version of the chromogenic Limulus test, which can be carried out in microtiter plates, is described.


Adjuvant high-dose interferon for cutaneous melanoma is most beneficial for patients with early stage III disease.
Evidence from randomized trials in the pre-sentinel lymph node biopsy era indicate that adjuvant treatment with high-dose interferon-alpha (IFN) increases recurrence-free survival (RFS) in patients with high-risk melanoma. However, to the authors' knowledge, the role of this treatment in selected patients with early stage III disease has not been well studied. The clinical and pathologic characteristics of 486 patients undergoing surgical treatment for stage III melanoma were evaluated and the authors compared outcomes for those given adjuvant treatment with IFN with those patients who had surgery alone. A particular focus was on the effect of IFN therapy on RFS and overall survival (OS) among those patients with stage IIIA disease. The median follow-up for the entire cohort was 5.2 years; the 5-year RFS and OS rates for the entire group were 41% and 53%, respectively. Adjuvant IFN was given to 141 patients (29%). On multivariate analysis, IFN was found to be the only independent predictor for RFS in patients with stage IIIA disease (hazards ratio of 0.4; 95% confidence interval, 0.2-0.9 [P = .02]). IFN was not found to be associated with increased RFS in patients with more advanced lymph node disease (stage IIIB and stage IIIC). IFN appeared to have no effect on OS in any patient with stage III disease. Adjuvant treatment with IFN improves RFS in melanoma patients with early stage III disease. The results of the current study should help guide management when considering adjuvant treatment for these patients.


Correction to: Unlocking the Value of Anti-TNF Biosimilars: Reducing Disease Burden and Improving Outcomes in Chronic Immune-Mediated Inflammatory Diseases: A Narrative Review.
In the original article, under the "Access to treatment" heading.


Ortho- and retronasal olfactory performance in rhinosurgical procedures: a longitudinal comparative study.
Testing olfaction should be an integral part of a clinical work-up in rhinosurgical procedures. Importantly, intact olfactory experience also includes retronasally perceived odors (retronasal olfaction). This study aimed at comprehensively assessing olfaction in patients undergoing rhinosurgical procedures in a comparative manner and evaluating relations to patient-reported outcome measurements (PROMs). Each nostril odor threshold and discrimination, and birhinal identification were tested using Sniffin' Sticks in 14 subjects assigned for septoplasty (SP), 21 for septorhinoplasty (SRP), and 30 for endoscopic sinus surgery (ESS). The 27-Candy-Smell-Test was used to quantify retronasal abilities. Tests were repeated 3 months after surgery. Olfactory dysfunction was preoperatively present in 21% of SP, in 47.6% of SRP, and in 80% of ESS patients. Odor threshold side differences were most frequently found in SRP. Frequently, SRP and ESS patients showed severely impaired retronasal olfaction. Half of included subjects re-visited after 3 months, but olfactory function did not improve overall and rarely on an individual basis to a meaningful extent. Subjective ratings on nasal patency and PROMs were not associated with olfaction nor with changes in olfactory scores. Olfactory function can decisively be impaired a priori not only in patients awaiting sinus surgery, but also in those assigned for functional septorhinoplasty. This impairment may not improve in the short term, which has to be taken into account in patient counseling. This study adds to the current literature on olfaction in rhinosurgery with the extension of retronasal testing.


Rabies virus binding at neuromuscular junctions.
Morphological, immunocytochemical, biochemical, and immunological techniques have been used to describe rabies virus binding to a sub-cellular unit and molecular complex at the neuromuscular junction (NMJ). Early after infection in vivo, virus antigen and virus particles were found by immunofluorescence, electron microscopy and immunoelectron microscopy in regions of high density acetylcholine receptors (AChR) at NMJs. One monoclonal antibody (alpha-Mab) to the alpha subunit of the AChR blocked attachment of radio-labeled rabies virus to cultured muscle cells bearing high density patches of AChR. A sub-cellular structure, resembling an array of AChR monomers, bound both rabies virus antigens and alpha-Mab. By immunoblotting with electrophoretically transferred motor endplate proteins, rabies virus proteins and alpha-Mab bound to two proteins of 43 000 and 110 000 daltons. A rabies virus glycoprotein antibody detected virus antigen bound to the 110 000 dalton protein. An auto-immune (anti-idiotypic) response followed immunization of mice with rabies virus glycoprotein antigen; the antibody was directed to the 110 000 dalton protein. This auto-antibody altered the kinetics of neutralization by rabies virus antibody and induced the formation of rabies virus antibody after inoculation of mice. These results define, at the neuromuscular junction, a rabies virus receptor which may be part of the acetylcholine receptor complex.


"Security loop" tie: a new technique to overcome loosening of surgical knots.
Sutures require knots so as to ensure optimal tissue closure strength. Loosening of surgical knots during or after tying can lead to an ineffective suture and compromise the final result. Loosening is affected mainly by the type of suture material and nature of surgical field. In palatal surgery, tying secure knots is a major consideration and may present a technical challenge. In this article, and after a review of the literature, we present a new modification of the usual knot-tying technique to maximize knot security and prevent knot loosening after the first throw is done. This technique was found to be effective, simple, fast, easy to learn, and saves time and material.


Comparison of up-front cash cards and checks as incentives for participation in a clinician survey: a study within a trial.
Evidence is needed regarding effective incentive strategies to increase clinician survey response rates. Cash cards are increasingly used as survey incentives; they are appealing because of their convenience and because in some cases their value can be reclaimed by investigators if not used. However, their effectiveness in clinician surveys is not known. In this study within the BRCA Founder OutReach (BFOR) study, a clinical trial of population-based BRCA1/2 mutation screening, we compared the use of upfront cash cards requiring email activation versus checks as clinician survey incentives. Participants receiving BRCA1/2 testing in the BFOR study could elect to receive their results from their primary care provider (PCP, named by the patient) or from a geneticist associated with the study. In order to understand PCPs' knowledge, attitudes, experiences and willingness to disclose results we mailed paper surveys to the first 501 primary care providers (PCPs) in New York, Boston, Los Angeles and Philadelphia who were nominated by study participants to disclose their BRCA1/2 mutation results obtained through the study. We used alternating assignment stratified by city to assign the first 303 clinicians to receive a $50 up-front incentive as a cash card (N = 155) or check (N = 148). The cash card required PCPs to send an activation email in order to be used. We compared response rates by incentive type, adjusting for PCP characteristics and study site. In unadjusted analyses, PCPs who received checks were more likely to respond to the survey than those who received cash cards (54.1% versus 41.9%, p = 0.046); this remained true when we adjusted for provider characteristics (OR for checks 1.61, 95% CI 1.01, 2.59). No other clinician characteristics had a statistically significant association with response rates in adjusted analyses. When we included an interaction term for incentive type and city, the favorable impact of checks on response rates was evident only in Los Angeles and Philadelphia. An up-front cash card incentive requiring email activation may be less effective in eliciting clinician responses than up-front checks. However, the benefit of checks for clinician response rates may depend on clinicians' geographic location. ClinicalTrials.gov ( NCT03351803 ), November 24, 2017.


Corrigendum: TRPV1 and TRPV1-Expressing Nociceptors Mediate Orofacial Pain Behaviors in a Mouse Model of Orthodontic Tooth Movement.
[This corrects the article DOI: 10.3389/fphys.2019.01207.].


Evaluation of clinical efficacy of integrated traditional Chinese and Western medicine in the treatment of acute respiratory distress syndrome.
Acute respiratory distress syndrome (ARDS) is a common disease in critically ill patients that has a high incidence and mortality rate worldwide. At present, there is no specific treatment for ARDS. Traditional Chinese medicine has been shown to have good potential in preventing and treating ARDS, especially in reducing the dosages of Western medicines and therefore, adverse drug reactions. The purpose of this study is to compare the clinical efficacy of integrated Chinese and Western medicine to that of Western medicine alone in the treatment of ARDS. We are proposing a prospective, multicenter, randomized, double-blind, placebo-controlled study in which 110 eligible patients would be enrolled and randomly divided into a Western medicine treatment group and an integrated Chinese and Western medicine treatment group. After 2 weeks of interventions and 1 year of follow-up, the clinical efficacy and safety of Jiawei qianyang dan in ARDS patients would be observed. The outcomes measured would include the Traditional Chinese medicine symptom score, the oxygenation index (PɑO2/FiO2), extravascular pulmonary water index, duration of mechanical ventilation, number of ICU hospitalization days, and the 28-day mortality rate for the 2 groups before and after treatment. The all-cause mortality rate, respiratory failure mortality rate, and readmission rate after 1 year of follow-up will be statistically analyzed and safety will be evaluated. In this study, we aim to demonstrate the greater clinical efficacy of integrated traditional Chinese and Western medicine in the treatment of ARDS compared to that of Western medicine alone. In order to do this, we hope to provide evidence for the clinically supportive effect of the Jiawei qianyang dan in the treatment of ARDS and therefore demonstrate a more effective treatment.


[Repeated failure of the suture line of an aortic valve prosthesis. Treatment by implantation of a valvular tube in the supra-coronary position].
We present our 7 years' experience in the treatment of repeated stitch failure of the suture line on aortic valve replacements. We used a valved tube placed in the supra-coronary position. This technique prevented further stitch failure and also prevented postop infections. Of eight patients operated on, five had survived.


Genome-wide aggregated trans-effects on risk of type 1 diabetes: A test of the "omnigenic" sparse effector hypothesis of complex trait genetics.
The "omnigenic" hypothesis postulates that the polygenic effects of common SNPs on a typical complex trait are mediated through trans-effects on expression of a relatively sparse set of effector ("core") genes. We tested this hypothesis in a study of 4,964 cases of type 1 diabetes (T1D) and 7,497 controls by using summary statistics to calculate aggregated (excluding the HLA region) trans-scores for gene expression in blood. From associations of T1D with aggregated trans-scores, nine putative core genes were identified, of which three-STAT1, CTLA4 and FOXP3-are genes in which variants cause monogenic forms of autoimmune diabetes. Seven of these genes affect the activity of regulatory T cells, and two are involved in immune responses to microbial lipids. Four T1D-associated genomic regions could be identified as master regulators via trans-effects on gene expression. These results support the sparse effector hypothesis and reshape our understanding of the genetic architecture of T1D.


A prospective study of maternal serum insulin-like growth factor-I in pregnancies with appropriately grown or growth restricted fetuses.
To determine whether there is a relationship between maternal serum insulin-like growth factor-I and fetal growth, consistent with the hypothesis that insulin-like growth factor-I influences maternal constraint upon fetal growth by controlling placental transfer. A prospective, observational study. Fetal medicine unit and antenatal clinic of a large teaching hospital. One hundred and forty-one pregnant women identified as having small or normally grown fetuses. Fetuses were scanned every two weeks with maternal venesection at each visit. Cases (birthweight < 5th centile) were assigned to two groups: fetal growth restriction due to placental dysfunction (umbilical artery Doppler, growth velocity pulsatility index > +2 SD; n = 25) and normal small-for-gestational-age (normal Doppler, growth velocity and amniotic fluid; n = 27). Eighty-nine controls had birthweights between the 5th and the 95th centiles, normal Doppler, growth velocity and amniotic fluid. Insulin-like growth factor-I was measured by radioimmunoassay, and its relationship to gestational age and birthweight was assessed by regression analysis. Comparisons between case groups were made by Student's t test or analysis of covariance to allow for the effect of birthweight. The last insulin-like growth factor-I level before delivery within the different subgroups. In controls, maternal insulin-like growth factor-I increased with gestational age (r = 0.40; P = 0.0001) but did not correlate with birthweight. Insulin-like growth factor-I was low in the mothers of growth restricted fetuses (-1.56 SD; P = 0.0001), but not in those with small-for-gestational age fetuses. The control and small-for-gestational-age data suggest that maternal insulin-like growth factor-I is not associated with endocrine control of normal placental function. Low insulin-like growth factor-I relates to poor placental transfer, as indicated by Doppler, rather than to low birthweight. Whether this is a regulatory mechanism, a cause or a consequence of placental dysfunction needs further study.


Intra tester reliability of sympathetic skin responses in subjects with primary palmar hyperhidrosis.
Primary palmar hyperhidrosis (PPH) is a disorder related to sympathetic dysfunction. Iontophoresis can be used to reduce sweating rate. Sympathetic skin response (SSR) is commonly used to evaluate the sympathetic system. However, scarce evidence exists about the reliability of SSR parameters. To assess the relative and absolute reliability of SSR before and after the application of iontophoresis with aluminum chloride hexahydrate (ACH) gel or tap water in subjects with PPH. Twenty subjects were randomized to receive either iontophoresis with ACH gel or tap water. Three SSRs (amplitude and latency) with 5 s intervals from both hands in both groups were recorded before and after the application of iontophoresis for 30 min. Reliability of amplitude and latency of the SSR was assessed using intraclass correlation coefficient (ICC) with 95% confidence intervals, standard error of measurement (SEM), and minimal detectable change (MDC). Amplitudes and latencies of SSR showed good to excellent test-retest reliability for ICC in both groups before iontophoresis. Except for right hand latency which was moderate (0.5-0.75). After iontophoresis, the ACH gel group still showed good to excellent agreement for SSR parameters, while the reliability of SSR parameters in the tap water group was reduced. Subjects with PPH showed high intra-rater reliability for SSR parameters which was maintained after ACH gel iontophoresis and decreased after tap water iontophoresis. It seems that media used for iontophoresis or the state of media (gel vs liquid) may affect the reliability of SSR. Further research is recommended.


Correction: Implementation of a COVID-19 screening tool in a southern Nigerian tertiary health facility.
[This corrects the article DOI: 10.1371/journal.pgph.0000578.].


Western blot detection of epidermal growth factor receptor from plasmalemma of culture cells using 125I-labeled epidermal growth factor.
We have developed a novel Western blot procedure for the detection of epidermal growth factor (EGF) receptors within a complex mixture of membrane proteins. Purified cell membranes from either human placenta or cultured A431 cells were solubilized, resolved by electrophoresis, and electroblotted onto nitrocellulose paper. With 5-15% gradient gels, electroblotting was completed in 2 h and both the high- and low-molecular-weight proteins were transferred evenly onto the nitrocellulose, as indicated by the radiolabeled protein markers. Upon hybridization with 125I-EGF, the membrane receptor was identified as two adjoining bands on the nitrocellulose of 150 and 170 kDa. Binding of 125I-EGF to the immobilized membrane receptor was specific and was displaced by excess unlabeled EGF. The receptor signal on the autoradiogram was optimized when 1% hemoglobin and 0.05% Tween 20 were present during the hybridization. The ligand-binding activity of the immobilized receptor was not affected by sodium dodecyl sulfate detergent or ethylene glycol bis(beta-aminoethyl ether) N,N,N',N'-tetraacetic acid, but was drastically reduced by either heat denaturation or the addition of dithiothreitol to the membrane samples. Using this method, we were able to demonstrate that no noticeable difference was observed between the pre- and postphosphorylated EGF receptors in their ability to bind to 125I-EGF. Because it allows both identification and purification of a receptor from a mixture of proteins, this protocol should have general application in characterizing various receptor-ligand systems.


Characterizing and demonstrating the role of Klebsiella SSN1 exopolysaccharide in osmotic stress tolerance using neutron radiography.
Exopolysaccharides (EPS) are organic macromolecules naturally secreted by many microorganisms. EPS is increasingly used for agriculture and industrial purposes. This study focuses on isolate Klebsiella pneumonia SSN1, Klebsiella quasipeumonniae SGM81 isolated from rhizosphere to explore its water retention efficiency under drought conditions. Neutron Radiography was used to visualise water distribution in the sand under normal and drought conditions in the presence and absence of EPS producing bacteria. The EPS production was studied by applying Box Behnken design (BBD) under drought stress which was artificially induced by using polyethene glycol 6000 under osmotic stress condition 3.65% w/v of EPS dry weight was obtained. The relative water content (RWC) is used to calculate the amount of water present in the sand and was further studied by Neutron Radiography imaging with appropriate controls. FTIR and HPLC were also carried out for the characterisation of the extracted EPS. The sand experiments revealed that after 24 h of evaporation, the highest RWC was maintained by SSN1 at 29.7% compared to SGM81 (19.06%). SSN1 was found to release L-arabinose as the main sugar of its EPS under drought stress conditions by HPLC method. The FTIR data indicated the presence of β-glucans and polysaccharide α-pyranose between wavenumber 700 cm-1-1500 cm-1 and 1017 cm-1-1200 cm-1 respectively. The HPLC characterization of extracted EPS from osmotic stressed cells (run 3) displayed a peak designated to L-arabinose at 10.3 retention time (RT) for 132.4 mM concentration. While from run 5 with the controlled condition indicated the presence of L-rhamnose at 7.3 RT for 87 mM concentration. Neutron radiography enables the visualisation of water distribution in the sand as well as water transport in root-soil systems in situ. SSN1 has elicited EPS production in drought conditions with a low level of nitrogen and carbon.


Studies on the synthesis and subcellular distribution of dopamine in the rat adrenal medulla.
Rats received intravenous injections of 3H-tyrosine and were killed at various time intervals thereafter. 3H-dopamine (DA) in the adrenals reached a maximum within 1.5 min after the administration of 3h=tyrosine. From the 15th min it disappeared with an apparent half life of 90 min. 3H-Adrenaline (A) plus 3H-noradrenaline(NA) increased much more slowly and reached a plateau 120-240 min after the injection. The approximate synthesis rate of adrenal A plus NA, calculated from the specific activity curves, ranged from 0.3 to 2.2 nmoles/h per kg b.w. The highest value was noted the first few minutes, the lowest 1-2 hrs after the administration of 3H-tyrosine. In some experiments subcellular fractionation of the adrenals was performed. In untreated animals the amount of DA and A plus NA recovered from the supernatant fraction was about 10 and 8 per cent, respectively, of the total amount recovered from the supernatant and particulate fractions. In the adrenals of animals receiving 3H-tyrosine 3.75 or 60 min beforehand these figures were significantly elevated whereas the DA and A plus NA of the particulate fraction did not deviate significantly from control values. The specific activities of 3H-DA were the same in the supernatant and particulate fractions within 3.75 min after the injection of 3H-tyrosine.


Establishment and characterization of NCC-GCTB5-C1: a novel cell line of giant cell tumor of bone.
Giant cell tumor of bone (GCTB), is a rare intermediate malignant bone tumor with high local infiltrative ability, and is genetically characterized by mutation in the H3-3A gene. Standard treatment is curative surgical tumor resection. GCTB demonstrates both local recurrence and pulmonary metastasis after surgical treatment, and effective systematic chemotherapy is yet to be established. Therefore, development of novel chemotherapies for GCTB is necessary. Although patient-derived tumor cell lines are potent tools for preclinical research, 15 GCTB cell lines have been reported to date, and only four are publicly available. Thus, this study aimed to establish and characterize a novel GCTB cell line for preclinical studies on GCTB. Herein, we described the establishment of a cell line, NCC-GCTB5-C1, from the primary tumor tissue of a patient with GCTB. NCC-GCTB5-C1 was shown to harbor a mutation in the H3-3A gene, which is typical of GCTB; thus, it has useful properties for in vitro studies. We conducted the largest integrated screening analysis of 214 antitumor agents using NCC-GCTB5-C1 along with four GCTB cell lines. Romidepsin (a histone deacetylase inhibitor), camptothecin, and actinomycin D (topoisomerase inhibitors) demonstrated remarkable antitumor effects, suggesting that these antitumor agents are potential therapeutic candidates for GCTB treatment. Therefore, the NCC-GCTB5-C1 cell line could potentially contribute to the elucidation of GCTB pathogenesis and the development of novel GCTB treatments.


Cutaneous manifestations of metabolic diseases: uncommon presentations.
Metabolic diseases are common diseases in the Western world. Many of these diseases, including diabetes mellitus, hyperlipoproteinemia, gout, calcinosis, and hemochromatosis, are associated with skin diseases or often present with specific cutaneous signs. A knowledge of cutaneous manifestations helps to identify patients at risk, establish the internal diagnosis, and monitor the adverse effects of therapy.


Retraction: Kim et al. Advantage of Species Diversification to Facilitate Sustainable Development of Aquaculture Sector. Biology 2022, 11, 368.
Biology retracts the article "Advantage of Species Diversification to Facilitate Sustainable Development of Aquaculture Sector" cited above [...].


4-[N,N-Bis(2-cyanoethyl)amino]pyridine.
The title compound, 3,3'-(4-pyridylimino)dipropanenitrile, C(11)H(12)N(4), has a twofold axis and consists of a pyridine ring head and two cyanoethyl tails, the three groups being linked by an N atom. The planar geometry around the amino N atom suggests conjugation with the pi-system of the pyridine ring. The molecules are stacked in a layer structure via relatively weak to very weak intermolecular C-H.pi and C-H.N hydrogen-bond interactions.


Segmentation of nerve fibers using multi-level gradient watershed and fuzzy systems.
This paper presents an algorithm based on multi-level watershed segmentation combined with three fuzzy systems to segment a large number of myelinated nerve fibers in microscope images. The method can estimate various geometrical parameters of myelinated nerve fibers in peripheral nerves. It is expected to be a promising tool for the quantitative assessment of myelinated nerve fibers in related research. A novel multi-level watershed scheme iteratively detects pre-candidate nerve fibers. At each immersion level, watershed segmentation extracts the initial axon locations and obtains meaningful myelinated nerve fiber features. Thereafter, according to a priori characteristics of the myelinated nerve fibers, fuzzy rules reject unlikely pre-candidates and collect a set of candidates. Initial candidate boundaries are then refined by a fuzzy active contour model, which flexibly deforms contours according to the observed features of each nerve fiber. A final scan with a different set of fuzzy rules based on the a priori properties of the myelinated nerve fibers removes false detections. A particle swarm optimization method is employed to efficiently train the large number of parameters in the proposed fuzzy systems. The proposed method can automatically segment the transverse cross-sections of nerve fibers obtained from optical microscope images. Although the microscope image is usually noisy with weak or variable levels of contrast, the proposed system can handle images with a large number of myelinated nerve fibers and achieve a high fiber detection ratio. As compared to manual segmentation by experts, the proposed system achieved an average accuracy of 91% across different data sets. We developed an image segmentation system that automatically handles myelinated nerve fibers in microscope images. Experimental results showed the efficacy of this system and its superiority to other nerve fiber segmentation approaches. Moreover, the proposed method can be extended to other applications of automatic segmentation of microscopic images.


The progression of renal disease.
The diversity of its causes, the unpredictability of its clinical course, and our expanding knowledge of the conditions that may exacerbate or retard its progression suggest that glomerular sclerosis cannot be attributed to a single aberration in glomerular physiology. Nonetheless, the welter of clinical and experimental observations is beginning to yield a pattern. Agents or conditions injurious to glomerular epithelium tend to cause glomerular sclerosis. Agents or conditions that induce short-term or long-term activation of mesangial cells may lead to glomerular sclerosis. Indeed, one contribution of the healthy epithelium may be to serve as a tonic inhibitor of the intraglomerular processes arising from mesangial-cell activation. Long-term activation of the mesangium is associated with the proliferation and infiltration of cells and with the expansion of the mesangial matrix--the antecedents of sclerosis. We anticipate that different diseases associated with glomerular sclerosis will be found to depend to varying extents on these two potential mechanisms of sclerosis. Beyond a certain threshold of glomerular injury, glomerular diseases share an additional factor: the capacity of both intrinsic cells and infiltrating cells to alter the microenvironment of the glomerulus so that sclerosis progresses inexorably long after the disappearance of the initiating insult. Several potential risk factors may contribute to the progression of chronic renal disease. These factors include systemic hypertension, proteinuria, hyperlipidemia, high protein intake, and probably conditions that lead to glomerular hypertrophy. Interventions designed to minimize the potential contribution of these factors to the progression of renal insufficiency may halt or slow the loss of function of the kidney. Clinical trials designed to examine the effects of these factors on the progressive course of renal insufficiency will help to establish their role and relative importance in humans.


Two-Photon Absorbing Properties of Ultraviolet Phase-Matchable Crystals at 264 and 211 nm.
We investigated the intensity-dependent loss properties of nonlinear crystals by using subpicosecond laser pulses at 264 and 211 nm. Two-photon absorption coefficients for potassium dihydrogen phosphate, beta-barium borate, and lithium triborate crystals were obtained from the intensity-dependent transmission measurements.


Substance P is a functional neurotransmitter in the rat parotid gland.
The technique of electrical field stimulation was employed to stimulate the intrinsic nerves of isolated rat parotid gland fragments. Responses to field stimulation were recorded as changes in enzyme secretion (amylase release), radiolabelled ion fluxes (86Rb efflux) and electrophysiological effects (changes in acinar cell membrane potential and input resistance). All effects of field stimulation were abolished by the neurotoxin, tetrodotoxin (TTX). Selective use of pharmacological antagonists revealed that both the sympathetic and parasympathetic nerves to this tissue were being excited by field stimulation. Importantly a significant component of the response to field stimulation persisted in the presence of combined autonomic receptor blockade by atropine, phentolamine and propranolol, i.e. due to release of a non-cholinergic, non-adrenergic neurotransmitter. The non-cholinergic, non-adrenergic neurotransmitter evoked amylase release, 86Rb efflux and electrophysiological effects seen as changes in acinar cell membrane potential and conductance, i.e. stimulus-permeability coupled. Two biologically active peptides, substance P (SP) and vasoactive intestinal polypeptide (VIP) were shown to evoke amylase release in the presence of combined autonomic blockade. VIP however did not evoke any increase in 86Rb efflux, i.e. not stimulus-permeability coupled. All the effects of the non-cholinergic, non-adrenergic transmitter were mimicked by substance P which evokes 86Rb efflux and electrophysiological effects in addition to amylase release. The non-cholinergic, non-adrenergic field stimulus effects on amylase release and 86Rb efflux were abolished or markedly attenuated in tissues which had been desensitized by prior exposure to exogenous substance P. In the presence of VIP, however, the non-cholinergic, non-adrenergic effects persisted and were apparently potentiated. Acute application of the neurotoxin capsaicin first stimulated a transient release of amylase and subsequently abolished the non-cholinergic, non-adrenergic field stimulus-evoked enzyme release. The putative substance P antagonist, D-Pro2, D-Trp7,9 substance P, reversibly blocked the response to both non-cholinergic, non-adrenergic nerve stimulation and exogenous substance P. It was demonstrated however that prolonged exposure to this antagonist is associated with non-reversible and, importantly, non-specific neurotoxic effects. It is concluded that substance P or a closely related peptide is a functional neurotransmitter in the rat parotid gland.


Positive human contact on the first day of life alters the piglet's behavioural response to humans and husbandry practices.
This experiment examined the effects of positive human contact at suckling on the first day of life on the behavioural and physiological responses of piglets to both humans and routine husbandry procedures. Forty litters from multiparous sows were randomly allocated to one of two treatments: Control (CC, minimal human interaction with day-old piglets) or Positive Contact (PC, human talking and caressing piglets during 6 suckling bouts on their first day of life, day 1). In each litter, 2 males and 2 females were randomly selected and their behavioural responses to tail docking (day 2), and to an experimenter (day 35) were studied. Escape behaviour at tail docking was assessed according to intensity (on a scale from 0 to 4 representing no movement to high intensity movement) and duration (on a scale from 0 to 3 representing no movement to continuous movement). At day 15 of age, a human approach and avoidance test was performed on focal piglets and at day 15, escape behaviour to capture before and after testing was recorded again. Blood samples for cortisol analysis were obtained from the focal piglets 30 min after tail docking and 1 h after weaning. Escape behaviour to tail docking of the PC piglets was of shorter duration than that of the CC piglets (P = 0.05). There was a tendency for the escape behaviour both before and after testing at day 15 to be of a lower intensity (P = 0.11 and P = 0.06, respectively) and a shorter duration (P = 0.06 and P = 0.08, respectively) in the PC piglets. There was a tendency for PC piglets to have higher cortisol concentrations after tail docking than the CC piglets (P = 0.07). Male piglets had higher cortisol concentrations after tail docking and after weaning than female piglets (P = 0.02 and P = 0.03). The results indicate that Positive Contact treatment reduced the duration of escape behaviour of piglets to tail docking. The role of classical conditioning, habituation and developmental changes in the observed effects of the Positive Contact treatment is unclear. Nonetheless, this experiment demonstrated that brief positive human contacts early in life can alter the behavioural responses of piglets to subsequent stressful events.


A personalised approach to prostate cancer screening based on genotyping of risk founder alleles.
To evaluate whether genotyping for 18 prostate cancer founder variants is helpful in identifying high-risk individuals and for determining optimal screening regimens. A serum PSA level was measured and a digital rectal examination (DRE) was performed on 2907 unaffected men aged 40-90. Three hundred and twenty-three men with an elevated PSA (≥4 ng ml⁻¹) or an abnormal DRE underwent a prostate biopsy. All men were genotyped for three founder alleles in BRCA1 (5382insC, 4153delA and C61G), for four alleles in CHEK2 (1100delC, IVS2+1G>A, del5395 and I157T), for one allele in NBS1 (657del5), for one allele in HOXB13 (G84E), and for nine low-risk single-nucleotide polymorphisms (SNPs). On the basis of an elevated PSA or an abnormal DRE, prostate cancer was diagnosed in 135 of 2907 men (4.6%). In men with a CHEK2 missense mutation I157T, the cancer detection rate among men with an elevated PSA or an abnormal DRE was much higher (10.2%, P=0.0008). The cancer detection rate rose with the number of SNP risk genotypes observed from 1.2% for men with no variant to 8.6% for men who carried six or more variants (P=0.04). No single variant was helpful on its own in predicting the presence of prostate cancer, however, the combination of all rare mutations and SNPs improved predictive power (area under the curve=0.59; P=0.03). These results suggest that testing for germline CHEK2 mutations improves the ability to predict the presence of prostate cancer in screened men, however, the clinical utility of incorporating DNA variants in the screening process is marginal.


Comparison of active and combined passive/active immunization of Navajo children against Haemophilus influenzae type b.
In a high risk Navajo population we compared the immunogenicity of a new Haemophilus influenzae type b mutant-diphtheria toxic conjugate vaccine (HbOC) with simultaneous active (HbOC) and passive immunization with bacterial polysaccharide immunoglobulin prepared from adults immunized with H. influenzae b, pneumococcal and meningococcal vaccines. Only 7 of 26 (27%) 2-month-olds had an increase in H. influenzae b capsular polysaccharide antibody after a single dose of HbOC, a proportion similar to that of saline controls (9 of 25, 36%). After a second HbOC dose at 4 months 88% had antibody concentrations of 0.15 microgram or more, and after a third dose at 6 months all had antibody levels greater than or equal to 0.15 microgram/ml. The group receiving both HbOC and bacterial polysaccharide immunoglobulin at 2 months uniformly had H. influenzae b CP antibody concentrations of greater than or equal to 0.15 microgram/ml at 4 months (P less than 0.001 relative to "HbOC alone" group) and subsequently responded similarly to second and third doses of HbOC vaccine as did also the "HbOC alone" group. We conclude that combined passive/active immunization with bacterial polysaccharide immunoglobulin and HbOC at 2 months maintains antibody at concentrations thought to be protective (greater than or equal to 0.15 microgram/ml) without interfering with the active antibody response to second and third doses of HbOC at 4 and 6 months of age.


Undescended testis in inguinal canal detected incidentally on fluorodeoxyglucose PET/CT imaging.
The differential diagnosis at the inguinal region is very important for hypermetabolic foci because of the possibility of metastasis at this level in cancer patients ongoing PET imaging for detection of metastases. It is important to distinguish this activity from other possible malignant and benign conditions such as lymph node activity, testicular cancer, metastatic disease activity, inflammation and urine skin contamination artefact. A 66-year-old male patient with operated colon cancer and liver metastasis was referred for PET/CT examination for re-staging because of suspicious metastases. Findings of PET/CT imaging with undescended testis detected incidentally was presented.


Prevalence of allergic rhinitis and asthma in patients with chronic rhinosinusitis and gastroesophageal reflux disease.
An association between chronic rhinosinusitis (CRS) and gastroesophageal reflux disease (GERD) has been previously reported; however, the underlying factors linking CRS and GERD remain to be elucidated. To assess the association of GERD and CRS using prospective and retrospective approaches. The retrospective study comprised a large cohort of CRS cases, whereas the prospective arm evaluated a series of CRS cases and controls. In the retrospective arm of the study, of the 1066 patients with CRS, 112 (10.5%) had GERD. Among patients with CRS, GERD was associated with higher body mass index, older age, and female sex. The odds ratios (ORs) for asthma and allergic rhinitis in the CRS group with GERD compared with the CRS group without GERD were 2.89 (95% confidence interval [CI], 1.905-4.389) and 2.021 (95% CI, 1.035-3.947). Furthermore, GERD was associated with a greater duration of CRS. Ninety patients with CRS and 81 controls were enrolled in the prospective arm of the study. In the CRS group, GERD was associated with asthma (OR, 4.77; 95% CI, 1.27-18.01). Patients with CRS and GERD had a longer duration and a younger age at onset of CRS. In controls, no association was found between GERD and asthma (OR, 0.67; 95% CI, 0.09-5.19) or allergic rhinitis (OR, 0.35; 95% CI, 0.05-2.59). Patients with CRS and GERD are more likely to have atopic conditions and asthma when compared with patients with CRS but without GERD. One of the potential explanations of this link is that comorbid GERD and atopic disease are potential risk factors for development of CRS.


Attention and scintillation.
The scintillating grid is a recently discovered visual illusion, created by superimposing white discs on the intersections of orthogonal gray bars on a black background. Even though the entire display is stationary, observers perceive dark spots appearing and disappearing rapidly within some of the white discs. This scintillation effect is correlated with eye position and eye movements. Here we investigate whether covert shifts of attention, as revealed by cueing and visual search paradigms, can also affect the illusion. We find that the chance of a particular intersection scintillating is directly correlated with distance from the attentional focus, regardless of the location of the fixation point. This suggests that the dynamics of this illusion might reflect the distribution of attention in space and time.


Long-term skeletal and soft-tissue responses after advancement genioplasty.
The objectives of this cephalometric study were to assess the skeletal stability of advancement genioplasty 3 years after surgery and to evaluate the predictability of soft-tissue changes. The subjects comprised 21 consecutive patients who had no additional orthognathic surgical procedures. Lateral cephalograms were taken at 5 times: immediately preoperative, immediately postoperative, 6 months postoperative, and 1 and 3 years postoperative. Mean surgical advancement at pogonion was 8.4 mm. Three years after surgery, mean relapse at pogonion was 8% of the surgical advancement. Part of this change was most likely due to bone remodeling. No patient demonstrated a clinically significant postoperative change at pogonion. The soft tissue of the chin was found to follow bony movement in a ratio of 0.9:1. Great individual variability was observed. The mentolabial fold depth increased as a result of the treatment. Effects of advancement genioplasty on the lips were small. A prediction ratio based on long-term skeletal changes is likely to generate an estimate that is more appropriate to present to the patient.


Mycophenolate mofetil for non-renal manifestations of systemic lupus erythematosus: a systematic review.
To summarize the evidence for the use of mycophenolate mofetil (MMF) in non-renal manifestations of systemic lupus erythematosus (SLE). Treatment trials in human SLE from 1990 to 2006 that have been published in the English literature were searched by Medline using the keywords 'lupus', 'mycophenolate', 'neuropsychiatric', 'neurological', 'hematological', 'dermatological', 'cutaneous', 'skin', 'hemolytic' and 'thrombocytopenia'. Laboratory studies were excluded. Twenty relevant studies were summarized. All were case series or open-labelled trials. The main indications for MMF were refractory haematological and dermatological lupus. Data regarding MMF in neuropsychiatric SLE were scant. Favourable results were reported with haematological disease. Evidence regarding the efficacy of MMF in refractory lupus skin lesions was conflicting. The efficacy of MMF in neuropsychiatric lupus was only modest and could not be separated from that of concomitant therapies. In one uncontrolled study, MMF was reported to be effective in preventing clinical flares in patients with persistently active serological markers. MMF was well tolerated in these reports. Limited evidence suggests that MMF may be effective in refractory haematological and dermatological manifestations of SLE. Because of the possibility of publication bias, the efficacy of MMF in these manifestations has to be confirmed with controlled trials. The efficacy of MMF in neuropsychiatric SLE is unproven and should be restricted to those patients who are refractory and intolerant to, or reluctant for, cyclophosphamide. Finally, the current level of evidence does not support treating serology alone in SLE by MMF.


[We have to stop talking about "non compliant" patients but rather about patients with difficulties of medication adherence].
Medication adherence can be defined as the link between "what the patient implements" and "what the patient and his doctor have decided together after negotiating without constrains". This definition should be put into perspective with the chronology of the disease and the way the patient experiences it. Counselling actions should always be adapted to the situation and negotiated with the patient, all along the process of care. This article proposes a model for this process and offers options pour tailored counselling. Key elements for pharmacist's practice are: simplify the prescription; communicate with the patient according to his stage of acceptation of the disease; get adequate training for motivational interviewing.


Prognostic Importance of Left Ventricular Global Longitudinal Strain in Patients with Severe Aortic Stenosis and Preserved Ejection Fraction.
Impaired left ventricular (LV) speckle-tracking-derived global longitudinal strain (GLS) magnitude (GLS worse than 14.7%) has been associated with poor outcome in patients with severe aortic stenosis (AS) and preserved LV ejection fraction (EF). To test the hypothesis that GLS magnitude ≤ 15% obtained with vendor-independent speckle-tracking strain software may be able to identify patients with severe AS who are at higher risk of death, despite preserved LVEF and no or mild symptoms. GLS was retrospectively obtained in 332 patients with severe AS (aortic valve area indexed [AVAi] < 0.6 cm2/m2), no or mild symptoms, and LVEF ≥ 50%. Absolute values of GLS were collected. Survival analyses were carried out to study the impact of GLS magnitude on all-cause mortality. During a median follow-up period of 42 (37-46) months, 105 patients died. On multivariate analysis, and after adjustment of known clinical and/or echocardiographic predictors of outcome and aortic valve replacement as a time-dependent covariate, GLS magnitude ≤ 15% was independently associated with mortality during follow-up (all P < .01). Adding GLS magnitude ≤ 15% (adjusted hazard ratio = 1.99 [1.17-3.38], P = .011) to a multivariate model including clinical and echocardiographic variables of prognostic importance (aortic valve replacement, aortic valve area, LV stroke volume index < 30 mL/m2, and LVEF<60%) improved the predictive performance with improved global model fit, reclassification, and better discrimination. After propensity score matching (n = 196), increased risk of mortality persisted among patients with GLS magnitude ≤ 15% compared with those with GLS > 15% (hazard ratio = 2.10; 95% confidence interval, 1.20-3.68; P = .009). In this series of patients with severe AS, no or mild symptoms, and LVEF ≥ 50%, GLS obtained with vendor-independent speckle-tracking strain software was an effective tool to identify patients with a poor outcome. Detection of myocardial dysfunction by identifying GLS magnitude < 15% in patients with severe AS, no or mild symptoms, and LVEF ≥ 50%, can aid in risk assessment.


General medium for the autotrophic cultivation of acetogens.
Syngas fermentation, a microbial process in which synthesis gas serves as a substrate for acetogens, has attracted increasing interest in the last few years. For the purposeful selection of acetogens for various applications, it would be useful to characterize and compare the process performances of as many autotrophic strains as possible under identical process conditions. Unfortunately, all the media compositions so far recommended for syngas fermentation differ considerably with respect to each individual strain. Therefore, a general medium for syngas fermentation was designed. The suitability of this new general-acetogen medium (GA-medium) was proven based on the autotrophic batch cultivation of Acetobacterium fimetarium, Acetobacterium wieringae, Blautia hydrogenotrophica, Clostridium magnum, Eubacterium aggregans, Sporomusa acidovorans, Sporomusa ovata and Terrisporobacter mayombei in anaerobic flasks with an initial gas phase of H2:CO2 (66:34) (P = 200 kPa). A comparison of the autotrophic batch processes with this medium revealed T. mayombei as the bacterium with the highest maximum growth rate of 5.77 day(-1) which was more than 10 times higher than the lowest identified maximum growth rate of A. fimetarium. The maximum growth rates of A. wieringae, C. magnum and S. acidovorans were all in the same order of magnitude around 1.7 day(-1). The newly designed GA-medium offers the possibility to compare autotrophic process performances of different acetogens under similar conditions absent the effects of various media compositions.


Determination of citrulline in human plasma, red blood cells and urine by electron impact (EI) ionization gas chromatography-mass spectrometry.
A method was developed by using gas chromatography-mass spectrometry in the electron impact ionization mode to quantify citrulline in plasma, red blood cells (RBC) and urine. For all three fluids, citrulline was extracted on ion exchange resins, before derivatization to its propyl-heptaflorobutyryl-ester. Assay precision (coefficient of variation, CV) was <5%, recovery% was >90% and the within- and between-day CV were <10% on 200 microL of plasma and RBC, and 400 microL of urine. The current method allows for the detection of 20 pmol of natural citrulline in aqueous standards, and small volumes (<100 microL) of biological fluids.


Proximal Tubular Vacuolization and Hypersensitivity to Drug-Induced Nephrotoxicity in Male Mice With Decreased Expression of the NADPH-Cytochrome P450 Reductase.
The effect of variations in the expression of cytochrome P450 reductase (CPR or POR) is determined in mice with decreased POR expression to identify potential vulnerabilities in people with low POR expression. There is an age-dependent appearance of increasing vacuolization in the proximal tubules of the renal cortex in 4- to 9-month-old male (but not female) Cpr-low (CL) mice. These mice have low POR expression in all cells of the body and upregulation of lysosome-associated membrane protein 1 expression in the renal cortex. Vacuolization is also seen in extrahepatic CL and extrarenal CL male mice, but not in mice with tissue-specific Por deletion in liver, intestinal epithelium, or kidney. The occurrence of vacuolization is accompanied by increases in serum blood-urea-nitrogen levels. Male CL mice are hypersensitive to cisplatin- and gentamicin-induced renal toxicity at 3 months of age, before proximal tubular (PT) vacuoles are detectable. At doses that do not cause renal toxicity in wild-type mice, both drugs cause substantial increases in serum blood-urea-nitrogen levels and PT vacuolization in male but not female CL mice. The hypersensitivity to drug-induced renal toxicity is accompanied by increases in circulating drug levels. These novel findings demonstrate deficiency of renal function in mice with globally reduced POR expression and suggest that low POR expression may be a risk factor for drug-induced nephrotoxicity in humans.


Two novel species isolated from wheat rhizospheres in Serbia: Pseudomonas serbica sp. nov. and Pseudomonas serboccidentalis sp. nov.
Pseudomonas strains IT-194P, IT-215P, IT-P366T and IT-P374T were isolated from the rhizospheres of wheat grown in soils sampled from different fields (some of them known to be disease-suppressive) located near Mionica, Serbia. Phylogenetic analysis of the 16S rRNA genes and of whole genome sequences showed that these strains belong to two potentially new species, one containing strains IT-P366T and IT-194P and clustering (whole genome analysis) next to P. umsongensis DSM16611T, and another species containing strains IT-P374T and IT-215P and clustering next to P. koreensis LMG21318T. Genome analysis confirmed the proposition of novel species, as ANI was below the threshold of 95% and dDDH below 70% for strains IT-P366T (compared with P. umsongensis DSM16611T) and IT-P374T (compared with P. koreensis LMG21318T). Unlike P. umsongensis DSM16611T, strains of P. serbica can grow on D-mannitol, but not on pectin, D-galacturonic acid, L-galactonic acid lactone and α-hydroxybutyric acid. In contrary to P. koreensis LMG21318T, strains of P. serboccidentalis can use sucrose, inosine and α-ketoglutaric acid (but not L-histidine) as carbon sources. Altogether, these results indicate the existence of two novel species for which we propose the names Pseudomonas serbica sp. nov., with the type strain IT-P366T (=CFBP 9060 T = LMG 32732 T = EML 1791 T) and Pseudomonas serboccidentalis sp. nov., with the type strain IT-P374T (=CFBP 9061 T = LMG 32734 T = EML 1792 T). Strains from this study presented a set of phytobeneficial functions modulating plant hormonal balance, plant nutrition and plant protection, suggesting a potential as Plant Growth-Promoting Rhizobacteria (PGPR).


Orthodontic treatment of a Class II/1 malocclusion with extremely enlarged overjet.
Orthodontic non-extraction treatment of a Class II malocclusion with an extremely enlarged overjet in a 9-year-old boy is demonstrated.


Protective effect of Melothria maderaspatana leaf fraction on electrolytes, catecholamines, endothelial nitric oxide synthase and endothelin-1 peptide in uninephrectomized deoxycorticosterone acetate-salt hypertensive rats.
This study was designed to investigate the protective effect of ethyl acetate fraction of Melothria maderaspatana (EAFM) leaf on electrolytes, catecholamines, endothelial nitric oxide synthase (eNOS) and endothelin-1 (ET-1) peptide in uninephrectomized deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Administration of DOCA-salt significantly increased the systolic and diastolic blood pressure and treatment with EAFM significantly lowered the blood pressure. In DOCA-salt rats, the levels of sodium and chloride increased significantly while potassium level decreased and administration of EAFM brought these parameters to normality. The levels of epinephrine and norepinephrine increased significantly in DOCA-salt rats and administration of EAFM significantly decreased these parameters to normality. DOCA-salt hypertensive rats exhibited significantly decreased L: -arginine and nitrite + nitrate levels and administration of EAFM brought these parameters to normality. DOA-salt hypertensive rats showed down-regulation of eNOS and up-regulation of ET-1 protein expressions in heart and kidney, and treatment with EAFM prevented down-regulation of eNOS and significantly down-regulated the ET-1 protein expressions. In conclusion, EAFM provides good blood pressure control by enhancing potassium and decreasing sodium levels, decreasing levels of epinephrine and norepinephrine, and preventing down-regulation of eNOS and significantly down-regulating ET-1 protein expression.


Experimental radiofrequency (RF) coagulation with computer-based on line monitoring of temperature and power.
The safety and reliability of radiofrequency coagulative techniques are questioned after each coagulation, especially in functional neurosurgery. In spite of the high level of technical development of modern surgical RF generators there is still uncertainty about the character of the coagulative lesion. For the present study, a 500 kHz RF generator was connected through a module for analog/digital conversion and for regulation to a personal computer provided with a software programme for the graphic display in real time of the RF power and of the temperature/time curves. The effects of thermocoagulation were studied in fresh egg white, and monopolar lesions were made in the subcortical white matter of rabbits with a probe with a 0.5 mm diameter and a bare tip of 3 mm in length. The regularity of thermocoagulation depends on the accurate temperature reading at the tip of the electrode. The ideal course of the temperature is a smoothly ascending curve from the level of 37 degrees C to the level present for coagulation, followed by a straight horizontal line. With too slow a response of the probe to temperature changes there is an inherent danger of overheating in the initial phase of the procedure. Additionally the power level has to be adjusted for each probe. On line monitoring with graphic display of the physical parameters provides a direct control of the course of the coagulation. Regular curves of the physical parameters without temperature overshoot correspond to reproducible lesions in vitro and in vivo.


The MFMU Cesarean Registry: factors affecting the success of trial of labor after previous cesarean delivery.
The purpose of this study was to determine which factors influence the likelihood of successful trial of labor (TOL) after 1 previous cesarean delivery (CD). We performed a multicenter 4-year prospective observational study (1999-2002) of all women with previous CD undergoing TOL. Women with term singleton pregnancies with 1 previous low transverse CD or unknown incision were included for analysis. Fourteen thousand five hundred twenty-nine women underwent TOL, with 10,690 (73.6%) achieving successful VBAC. Women with previous vaginal birth had an 86.6% success rate compared with 60.9% in women without such a history (odds ratio [OR] 4.2; 95% CI 3.8-4.5; P < .001). TOL success rates were affected by previous indication for CD, need for induction or augmentation, cervical dilation on admission, birth weight, race, and maternal body mass index. Multivariate logistic regression analysis identified as predictive of TOL success: previous vaginal delivery (OR 3.9; 95% CI 3.6-4.3), previous indication not being dystocia (CPD/FTP) (OR 1.7; 95% CI 1.5-1.8), spontaneous labor (OR 1.6; 95% CI 1.5-1.8), birth weight <4000 g (OR 2.0; 95% CI 1.8-2.3), and Caucasian race (OR 1.8, 95% CI 1.6-1.9) (all P < .001). The overall TOL success rate in obese women (BMI > or = 30) was lower (68.4%) than in nonobese women (79.6%) (P < .001), and when combined with induction and lack of previous vaginal delivery, successful VBAC occurred in only 44.2% of cases. Previous vaginal delivery including previous VBAC is the greatest predictor for successful TOL. Previous indication as dystocia, need for labor induction, or a maternal BMI > or = 30 significantly lowers success rates.


Left ventricular hypertrophy in athletes: morphologic features and clinical correlates.
The athlete's heart is a constellation of cardiac morphologic changes, including increased left ventricular volume, increased left ventricular mass, increased left atrial volume, and right ventricular structural changes as a physiologic response to exercise training. These structural changes fall within the normal reference ranges of appropriately matched control subjects for most trained individuals; however, there are significant numbers of athletes who have "abnormal" measurements. The ability to distinguish between physiologic changes associated with the athlete's heart and structural abnormalities that may represent underlying cardiac disease is of paramount importance. Structural heart disease significantly increases risk for morbidity, mortality, and sudden death, especially during exercise or physical stress. This article reviews the morphologic changes associated with the athlete's heart.


New experimental setup for studying strictly noninvasively skeletal muscle function in rat using 1H-magnetic resonance (MR) imaging and 31P-MR spectroscopy.
Traditional setups for in situ MR investigation of skeletal muscle function in animals use invasive systems for muscle stimulation and force measurement. These systems require surgical preparation and therefore exclude repetitive investigations on the same animal. This article describes a new experimental setup allowing strictly noninvasive MR investigations of muscle function in contracting rat gastrocnemius muscle using 1H-MR imaging and 31P-MR spectroscopy. The novelty of this setup is the integration of two noninvasive systems allowing muscle contraction by transcutaneous stimulation and force measurement with a dedicated ergometer. Muscle function was investigated in 20 rats (275-300 g) through a fatiguing stimulation protocol, either with this noninvasive setup (n = 10) or with a traditional MR setup (n = 10). T2-weighted images demonstrated that transcutaneous stimulation activated mainly the gastrocnemius muscle. Moreover, the changes in force development and in energy metabolism obtained with the noninvasive setup were qualitatively and quantitatively similar to those obtained with the traditional setup. This noninvasive setup is thus suitable for investigating skeletal muscle function in situ. It offers the possibility to repeat investigations in the same animal, avoiding individual variability and enabling longitudinal follow-up studies. This opens up new perspectives in various research areas including pharmaceutical research.


A big STEP for treatment of heart failure with preserved ejection fraction.
In the STEP-HFpEF trial, 2.4 mg semaglutide produced marked improvements in heart failure-related symptoms, physical limitations, and exercise function, and reduced inflammation and body weight in individuals with obesity HFpEF phenotype. These data usher in a new paradigm of targeting obesity as a therapeutic strategy in HFpEF.


Myocardial work-A new tool for early detection of rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone chemotherapy induced-cardiotoxicity in hematological patients.
Rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (RCHOP) chemotherapy in non-Hodgkin's lymphoma (NHL) has risk of cardiotoxicity. To determine the role of myocardial work and biomarkers in subclinical diagnosis and prediction of cardiotoxicity. The 130 NHL patients (52 ± 9 years, 62% men) scheduled for RCHOP, with LVEF>50%, were evaluated at baseline, after third cycle and chemotherapy completion for 3D LVEF, 2D myocardial deformation (longitudinal, radial, circumferential strain - LS, RS, CS) and myocardial work (global constructive work, waste work, work index and work efficiency - GCW, GWW, GWI, GWE). NT-pro-BNP and troponin I were determined. After chemotherapy ended, 37 patients (28%) (group I) developed asymptomatic cardiotoxicity (8 mild form, 25 moderate form, 4 severe form); 93 patients (group II) did not. After third cycle, all patients had decreased LS, CS, RS, GCW, GWI, GWE and increased GWW, persistent after chemotherapy completion, with significant changes in group I. After third cycle, GWE and GCW were the best independent predictors for LVEF reduction; GWE decrease with>5% after third cycle predicted cardiotoxicity after chemotherapy completed (91% sensitivity, 94% specificity). In NHL, myocardial work can diagnose subclinical cardiotoxicity and predict LVEF decline. These parameters should be used for sensitive evaluation of myocardial function during chemotherapy.


Tumor progression, histologic grading and DNA-ploidy as predictive factors of lymphogenous metastasis in primary carcinoma of the Fallopian tube.
The bad prognosis of primary carcinoma of the Fallopian tube (FTC), with 5-year overall survival rates of only 35%, is particularly ascribed to lymphogenous metastasis. Yet, we know very little on the pathophysiologic factors on which this lymphogenous metastasis is based. The present study, therefore, aims at evaluating the influence of intra-abdominal tumor progression and tumor-cell anaplasia on lymphogenous metastasis in FTC. We studied 41 cases of FTC, who had been subjected to radical lymphadenectomy during primary operation in a retrospective analysis. Staging was done by International Federation of Gynecology and Obstetrics-classification. Histologic grading and nuclear DNA-content (DNA-index) were used for evaluating tumor-cell anaplasia. Histologic grading discriminated between highly differentiated (G1), moderately dedifferentiated (G2), and dedifferentiated (G3) tumors. According to their DNA-indices, tumors were separated into three groups: DNA-index < or =1.1 (euploid cases), DNA-indices between 1.1 and 2.0 (cases of intermediate ploidy), and DNA-index >2.0 (aneuploid cases). The overall incidence of lymph node metastases was 43.9%. There was no correlation between histologic grading and DNA-index (P=0.98). Lymphogenous metastasis set in after the tumor had transgressed the tube (intra-abdominal stage II). Further intra-abdominal tumor progression (including omentum, liver, or peritoneum) significantly increases the incidence of lymph node metastases (P=0.02). There was only a single G1-tumor that had already disseminated into the lymph, all other cases of lymph node metastases were found in G2- or G3-tumors. DNA-index and the extent of lymphogenous metastases were not found to be correlated (P=0.74). The extent of lymphogenous metastases in FTC depends above all on intra-abdominal tumor progression. This fact has clinical consequences as the indication for lymphadenectomy can be obtained directly during operation. The results of histologic grading are of no impact on the surgical proceedings; the determination of DNA-ploidy is negligible.


The University of Michigan experience with percutaneous nephrostolithotomy for urinary matrix calculi.
To evaluate commonalities in presentation and long-term efficacy of treatment by percutaneous nephrostolithotomy of matrix stones, a rare form of urinary calculi. The clinical data of 9 consecutive patients with urinary matrix calculi in 11 kidneys treated at our institution between 1995 and 2007 were retrospectively reviewed. The matrix component in all 11 kidneys was successfully treated with percutaneous nephrostolithotomy, with few complications. Among 8 patients (9 kidneys) with follow-up, none has had recurrence of matrix stones after a mean follow-up of 3.8 years. Along with previously known risk factors for matrix stones, such as urinary tract infections and renal insufficiency, we identified smoking as another possible risk factor. Long-term antimicrobial prophylaxis was used in only 1 patient and thus does not seem necessary for prevention of recurrence. Matrix stone treatment with percutaneous nephrostolithotomy is durable and should remain the treatment modality of choice.


[Cutaneous metastases of bronchial carcinoma under the histological picture of an eccrine porocarcinoma].
A metastatic bronchogenic carcinoma to the skin, occupying the dermis and invading the epidermis is reported, which showed similar histologically feature to an eccrine porocarcinoma. Pigmented dendritic cells in certain parts of the metastatic carcinomas are considered to enter the tumor parenchyma secundarily.


Long-term therapy with the acorn cardiac support device normalizes gene expression of growth factors and gelatinases in dogs with heart failure.
Passive mechanical containment of the failing left ventricle with the Acorn Cardiac Support Device (CSD) was shown to prevent progressive left ventricular dilation in dogs with heart failure and increase left ventricular ejection fraction. To examine possible mechanisms for improved cardiac function with a CSD, we examined the effect of CSD therapy on the mRNA gene expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), matrix metalloproteinases (MMP) 2 and 9, and tissue inhibitors of metalloproteinases (TIMP) 1 and 2. Heart failure was produced in 12 dogs by multiple sequential intracoronary microembolizations. Six dogs were implanted with the CSD and 6 served as concurrent controls. Left ventricular tissue from 6 normal dogs was used for comparison. Compared with normal dogs, dogs with untreated heart failure showed downregulation of mRNA expression for VEGF and bFGF, whereas upregulation of mRNA expression for MMP-2 and MMP-9 was observed. Normalization of mRNA expression for all these genes was seen after treatment with the CSD. This study shows that preventing left ventricular dilation and myocardial stretch with the CSD promotes normalization of growth factor and MMP gene expression. These results suggest that modulation of gene activity may, in part, contribute to the improvement of left ventricular function observed with CSD therapy.


Z-scheme Au decorated carbon nitride/cobalt tetroxide plasmonic heterojunction photocatalyst for catalytic reduction of hexavalent chromium and oxidation of Bisphenol A.
Au/g-C3N4/Co3O4 plasmonic heterojunction photocatalyst was successfully prepared by in-situ forming Co3O4 nanocubes on the Au/g-C3N4 nanosheets. The catalytic activities of the photocatalysts were systematically studied through the catalytic reduction of hexavalent chromium (Cr6+) and oxidation of Bisphenol A (BPA) under visible light irradiation, while according to the degradation products determined by GC-MS, the catalytic degradation pathway of BPA was proposed. 4Au/g-C3N4/Co3O4 sample exhibits the most efficient catalytic activities, and the photocatalytic reduction and photocatalytic oxidation efficiencies can obtain 85.6% and 90.3%, respectively. The main reasons of the enhancing catalytic performance are the high absorption capability to visible light generated by localized surface plasmon resonance and the effective interface charge separation. Finally, we speculated that the Au/g-C3N4/Co3O4 sample followed Z-scheme charge transfer mechanism in this study, which is verified by the analysis of experiment and theoretical calculation results.


Meet the parents: Parental interactions, social influences, and college drinking.
Previous research suggests that, even in college, parents influence the alcohol consumption of their children directly and indirectly through peers. However, research has not tested whether face-to-face interactions with parents buffer students against social influences on drinking. In the current study, 1168 undergraduate students selected 5 people they contact regularly and then completed a 30-day daily diary reporting on interactions with those people and drinking behavior. The 401 students who selected a parent drank less and less often than those who did not select a parent as a frequent contact. In addition, on evenings when these students had met with their parents, they drank less alcohol and the association between others' drinking and participant drinking was weakened. This adds to evidence suggesting that parents continue to influence emerging adults after they have left home and may be helpful in informing future intervention efforts.


Cross-talk among AFAP1-AS1, ACVR1 and microRNA-384 regulates the stemness of pancreatic cancer cells and tumorigenicity in nude mice.
Pancreatic cancer (PC) represents one of the most aggressive forms of cancer. The role of long non-coding RNAs (lncRNAs) has been highlighted in various malignancies including PC. The aim of the present study was to investigate the effects associated with actin filament-associated protein 1 antisense RNA 1 (AFAP1-AS1) on the progression of PC and the underlying mechanism. Microarray-based gene expression profiling of PC was performed to identify PC-related lncRNAs, after which the expression of AFAP1-AS1 and cancer stem cell (CSC) markers in PC tissues and cells were determined accordingly. The potential microRNA-384 (miR-384) capable of binding to AFAP1-AS1, in addition to its ability to regulate activin receptor A type I (ACVR1) were analyzed. In order to investigate the effect of the AFAP1-AS1/miR-384/ACVR1 axis on self-renewal ability, tumorigenicity, invasion, migration and stemness of PC cells, shRNA-AFAP1-AS1, miR-384 mimic and inhibitor were cloned into cells. High expression of AFAP1-AS1 and ACVR1 with low expression of miR-384 were detected in PC tissues. ACVR1 was determined to be down-regulated when miR-384 was overexpressed, while the inhibition of AFAP1-AS1 decreased its ability to binding competitively to miR-384, resulting in the down-regulation of ACVR1 and enhancing miR-384 expression, ultimately inhibiting the progression of PC. The knockdown of AFAP1-AS1 or overexpression of miR-384 was confirmed to impair PC cell self-renewal ability, tumorigenicity, invasion, migration and stemness. Taken together, AFAP1-AS1 functions as an endogenous RNA by competitively binding to miR-384 to regulate ACVR1, thus conferring inhibitory effects on PC cell stemness and tumorigenicity.


Sulfated modification, characterization, and potential bioactivities of polysaccharide from the fruiting bodies of Russula virescens.
The water-soluble polysaccharide from fruiting bodies of Russula virescens (RVP) was sulfated using sulfur trioxide·pyridine complex method under different reaction conditions. Five sulfated RVP derivatives (SRVP1-5, SRV1-10, SRVP1-15, SRVP1-20 and SRVP1-25) with different degrees of substitution (DS) ranging from 0.34 to 0.73 were prepared. Several structural features of RVP and SRVPs including chemical structure, monosaccharide composition, molecular weight and chain conformation were investigated. The spectra results indicated that the sulfate groups were successfully introduced on RVP. The molecular weights of SRVP decreased with the increasing DS. Both RVP and SRVPs were mainly composed of mannose, glucose and galactose, with different molar ratios. The triple-helical conformation was broken down into a random coil when the DS exceeded 0.34. In vitro activity test results indicated that the SRVPs showed better antioxidant, anticoagulant, antibacterial and anti-tumor activities compared with RVP. Among the five sulfated derivatives, SRVP1-25 exhibited the strongest ABTS and hydroxyl radical scavenging activities and anticoagulant activity, while SRVP1-20 showed the best antibacterial activity and anti-tumor activity. These results demonstrated that the SRVPs could be developed as one of potential antioxidant, anticoagulant, antibacterial and anti-tumor agents for industrial and biomedical use.


Combined transcriptomic and metabolomic analyses elucidate key salt-responsive biomarkers to regulate salt tolerance in cotton.
Cotton is an important industrial crop and a pioneer crop for saline-alkali land restoration. However, the molecular mechanism underlying the cotton response to salt is not completely understood. Here, we used metabolome data and transcriptome data to analyze the salt tolerance regulatory network of cotton and metabolic biomarkers. In this study, cotton was stressed at 400 m M NaCl for 0 h, 3 h, 24 h and 48 h. NaCl interfered with cotton gene expression, altered metabolite contents and affected plant growth. Metabolome analysis showed that NaCl stress increased the contents of amino acids, sugars and ABA, decreased the amount of vitamin and terpenoids. K-means cluster analysis of differentially expressed genes showed that the continuously up-regulated genes were mainly enriched in metabolic pathways such as flavonoid biosynthesis and amino acid biosynthesis. The four metabolites of cysteine (Cys), ABA(Abscisic acid), turanose, and isopentenyladenine-7-N-glucoside (IP7G) were consistently up-regulated under salt stress, which may indicate that they are potential candidates for cotton under salt stress biomarkers. Combined transcriptome and metabolome analysis revealed accumulation of cysteine, ABA, isopentenyladenine-7-N-glucoside and turanose were important for salt tolerance in cotton mechanism. These results will provide some metabolic insights and key metabolite biomarkers for salt stress tolerance, which may help to understanding of the metabolite response to salt stress in cotton and develop a foundation for cotton to grow better in saline soil.


Efficient degradation of Congo red by persulfate activated with different particle sizes of zero-valent copper: performance and mechanism.
In this study, Congo red (CR) was degraded by different particle sizes of zero-valent copper (ZVC) activated persulfate (PS) under mild temperature. The CR removal by 50 nm, 500 nm, 15 μm of ZVC activated PS was 97%, 72%, and 16%, respectively. The co-existence of SO42- and Cl- promoted the degradation of CR, and HCO3- and H2PO4- were detrimental to the degradation. With the reduction of ZVC particle size, the effect of coexisting anions on degradation grew stronger. The high degradation efficiency of 50 nm and 500 nm ZVC was achieved at pH=7.0, while the high degradation of 15 μm ZVC was achieved at pH=3.0. It was more favorable to leach copper ions for activating PS to generate reactive oxygen species (ROS) with the smaller particle size of ZVC. The radical quenching experiment and electron paramagnetic resonance (EPR) analysis indicated that SO4-•, •OH and •O2- existed in the reaction. The mineralization of CR reached 80% and three possible paths were suggested for the degradation. Moreover, the degradation of 50 nm ZVC can still reach 96% in the 5th cycle, indicating promising application potential in dyeing wastewater treatment.


Recent advancement in EUS-guided fine needle sampling.
EUS-guided tissue acquisition technique plays an essential role for evaluation of gastrointestinal tumors. Several components affect the yield of EUS-guided tissue acquisition outcomes such as sampling techniques, use of ROSE (rapid onsite evaluation), training and experience, and needle designs. In this review we discuss advancement in EUS-guided fine needle sampling.


X-linked adrenoleukodystrophy: first report of the Italian Study Group.
In this paper we report Italian data on X-linked adrenoleukodystrophy (ALD) collected from 1985 to 1997. This disease appears to be the most common of the peroxisomal disorders and is associated with a functional defect of the peroxisomal very long chain fatty acid (VLCFA) oxidation. In Italy 117 cases have been recognized, but many cases may be unrecognized due to the heterogeneous clinical manifestations that vary from mild to very severe forms. To control the devastating course of this disease two therapeutic approaches are under evaluation: bone marrow transplantation (BMT) and dietary treatment based on a mixture of glyceroyl trioleate (GTO) and glyceroyl trierucate (GTE). Our experience of 68 subjects submitted to dietary treatment shows that almost all patients with signs of cerebral involvement at the beginning of treatment worsened or died, patients with the milder form, adrenomyeloneuropathy (AMN), remained stable, while 4 of the 15 presymptomatic subjects developed neurological signs of the disease. In recent years a more accurate selection of patients and donors for BMT has given favourable results, but some strict criteria should be respected.


Redox signaling triggers protection during the reperfusion rather than the ischemic phase of preconditioning.
In ischemic preconditioning (IPC) brief ischemia/reperfusion renders the heart resistant to infarction from any subsequent ischemic insult. Protection results from binding of surface receptors by ligands released during the preconditioning ischemia. The downstream pathway involves redox signaling as IPC will not protect in the presence of a free radical scavenger. To determine when in the IPC protocol the redox signaling occurs, seven groups of isolated rabbit hearts were studied. All hearts underwent 30 min of coronary branch occlusion and 2 h of reperfusion. IPC groups were subjected to 5 min of regional ischemia followed by 10 min of reperfusion prior to the 30-min coronary occlusion. The Control group had only the 30-min occlusion and 2-h reperfusion. In the second group IPC preceded the index coronary occlusion. The third group was also preconditioned, but the free radical scavenger N-2-mercaptopropionyl glycine (MPG 300 microM) was infused during the 10-min reperfusion and therefore was present in the myocardium in the distribution of the snared coronary artery during the entire reperfusion phase and also during the subsequent 30-min ischemia. In another preconditioned group MPG was added to the perfusate before the preconditioning ischemia and therefore was present in the tissue only during the preconditioning ischemia and then was washed out during reperfusion. In the fifth group MPG was added to the perfusate for only the last 5 min of the preconditioning reperfusion and therefore was present in the tissue during the last minutes of the reperfusion phase and the 30 min of ischemia. In an additional group of IPC hearts MPG was infused for only the initial 5 min of the preconditioning reperfusion and then allowed to wash out so that the scavenger was present for only the first half of the reperfusion phase. Infarct and risk zone sizes were measured by triphenyltetrazolium staining and fluorescent microspheres, resp. IPC reduced infarct size from 31.3 +/- 2.7% of the ischemic zone in control hearts to only 8.4 +/- 1.9%. MPG completely blocked IPC's protection in the third (39.4 +/- 2.8%) and sixth (36.1 +/- 7.7%) groups but did not affect its protection in groups 4 (8.1 +/- 1.5%) or 5 (7.8 +/- 1.1%). When deoxygenated buffer was used during IPC's reperfusion phase in the seventh group of hearts, protection was lost and infarct size was increased over that seen in control hearts (74.5 +/- 9.0%). Hence redox signaling occurs during the reperfusion phase of IPC, and the critical component in that reperfusion phase appears to be molecular oxygen.